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662c1181418a5379b0d1d57e
|
10.26434/chemrxiv-2024-bfgk0
|
Computational design of drugs for Epilepsy using a novel guided evolutionary algorithm for enhanced Blood Brain Barrier permeability
|
Epilepsy is a common disorder of the Central Nervous System. Although several drugs are available for treatment of epilepsy, none of them are applicable for all cases, and some have serious adverse affects. The rational design of small molecule drugs for disorders of the Central Nervous System is a difficult process because the majority of small molecules are unable to cross the Blood- Brain-Barrier. Although many methods have been developed for computer aided drug design, only a few of these are focused on the specific requirements of Central Nervous System drugs. To address these limitations, a validated free and open source drug design package, Autogrow4, was modified to guide the evolution of the population, for generation of molecules with improved permeability across the Blood-Brain-Barrier. This method has the potential for application in computer aided drug design for other Central Nervous System disorders such as Addiction, Alzheimer’s disease, Bipolar disorder, Depression, Gliomas, and Tuberculous meningitis. This method was applied for the design of inhibitors of g-Amino Butyric Acid Transaminase, which is a validated target for the treatment of epilepsy. The ligands designed with this method were predicted to have high binding affinity for the target as well as high permeability across the Blood-Brain-Barrier. The designed molecules were assessed by using the SWISS-ADME webserver which predicted that the designed molecules were Blood-Brain-Barrier permeable, did not have any violation of Lipinsky’s rules and were chemically synthesizable.
|
Sekhar Talluri
|
Theoretical and Computational Chemistry; Physical Chemistry; Biological and Medicinal Chemistry; Bioinformatics and Computational Biology; Drug Discovery and Drug Delivery Systems; Chemoinformatics - Computational Chemistry
|
CC BY 4.0
|
CHEMRXIV
|
2024-04-29
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/662c1181418a5379b0d1d57e/original/computational-design-of-drugs-for-epilepsy-using-a-novel-guided-evolutionary-algorithm-for-enhanced-blood-brain-barrier-permeability.pdf
|
60c743d2842e65a6e6db233c
|
10.26434/chemrxiv.9641990.v1
|
Hysteretic Thermal Spin-Crossover and Symmetry Breaking in Heteroleptic Fe(II) Complexes Using Alkyl Chain Substituted 2,2’-Dipyridylamine Ligands
|
The alkyl chain carrying ligands N,N-di(pyridin-2-yl)butanamide (LC4) and N,N-di(pyridin-2-yl)decanamide (LC10) were combined with NCS- co-ligands to form the neutral heteroleptic Fe(II) complexes trans-[FeII(LC4)2(NCS)2] (1C4) and trans [FeII(LC10)2(NCS)2] (1C10). Variable temperature crystallographic studies revealed that 1C4 is in the orthorhombic space group Pna21 between 85-200 K whereas 1C10 is in the monoclinic space group P21/c between 85-105 K before undergoing a crystallographic phase transition to the triclinic space group P1 by 140 K. The average Fe-N bond lengths suggest that at 85 K 1C4 contains LS Fe(II) centres; However, the ca. 0.18 Å increase in the average Fe-N bond lengths between 85 and 120 K suggests a spin-transition occurs within this temperature interval and the HS state is predominant beyond this. 1C10 contains LS Fe(II) centres between 85 and 105 K. Upon warming from 105 to 140 K the average Fe-N bond lengths increase by ca. 0.19 Å, which suggests that a spin-transition to the HS accompanies the P21/c to P1 crystallographic phase transition. Solid-state magnetic susceptibility measurements showed that 1C4 undergoes semi-abrupt spin-crossover with T1/2 = 127.5 K and a thermal hysteresis of ca. 13 K whereas, 1C10 undergoes an abrupt spin-crossover with T1/2 = 119.0 K, and is also accompanied by thermal hysteresis of ca. 4 K. The crystallographic and magnetic data show that the length of the complex’s alkyl chain substituents can have a large impact on the structure of the crystal lattice as well as a subtle effect on the T1/2 value for thermal spin-crossover.
|
Blaise Geoghegan; Wasinee Phonsri; Peter Horton; James Orton; Simon Coles; Keith Murray; Peter Cragg; Marcus Dymond; Ian Gass
|
Coordination Chemistry (Inorg.); Magnetism; Crystallography – Inorganic
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2019-08-19
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c743d2842e65a6e6db233c/original/hysteretic-thermal-spin-crossover-and-symmetry-breaking-in-heteroleptic-fe-ii-complexes-using-alkyl-chain-substituted-2-2-dipyridylamine-ligands.pdf
|
655c2f0a6e0ec7777f5cd0cb
|
10.26434/chemrxiv-2023-4z7z6
|
Synthesizing Aza[n]helicenes to the Limit: Hydrogen-bond-assisted Solubility and Benzannulation Strategy
|
Synthetic challenges toward anomalous structures and electronic states often involve handling problems such as insolubility in common organic solvents and oxida-tive degradation under aerobic conditions. We de-signed benzo-annulated aza[n]helicenes, which bene-fit from both the suppressed elevation of HOMO ener-gies and high solubility due to hydrogen-bonding with solvent molecules to overcome these challenges. This strategy enabled the synthesis of six new aza[n]helicenes ([n]AHs) of different lengths (n = 9–19) from acyclic precursors via one-shot oxidative fu-sion reactions. The structures of all the synthesized aza[n]helicenes were determined by X-ray diffraction (XRD) analysis, and their electrochemical potentials were measured by cyclic voltammetry. Among the syn-thesized aza[n]helicenes, [17]AH and [19]AH are the first heterohelicenes with a triple-layered helix. The noncovalent interaction (NCI) plots confirm the exist-ence of an effective π-π interaction between the layers. The absorption and fluorescence spectra red-shifted as the helical lengths increased, without any distinct satu-ration points. The optical resolutions of N-butylated [9]AH, and [11]AH were accomplished and their circu-lar dichroism (CD) and circularly polarized lumines-cence (CPL) were measured. Thus, the structural, (chir)optical, and electrochemical properties of the aza[n]helicenes were comprehensively analyzed.
|
Yusuke Matsuo; Masayuki Gon; Kazuo Tanaka; Shu Seki; Takayuki Tanaka
|
Organic Chemistry; Organic Synthesis and Reactions; Physical Organic Chemistry
|
CC BY 4.0
|
CHEMRXIV
|
2023-11-22
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/655c2f0a6e0ec7777f5cd0cb/original/synthesizing-aza-n-helicenes-to-the-limit-hydrogen-bond-assisted-solubility-and-benzannulation-strategy.pdf
|
624564e13affe4aa393bc16d
|
10.26434/chemrxiv-2022-0v5sc
|
Using auxiliary electrochemical working
electrodes as probe during contact glow
discharge electrolysis: A proof of concept study
|
Plasma in-liquid by means of anodic contact
glow discharge electrolysis (aCGDE) is a grow-
ing research field allowing the selective modifi-
cation of the electrode and the electrolyte. The
aim of this proof of concept study is to demon-
strate that auxiliary electrochemical electrodes
placed in vicinity to the plasma electrode, can
be modified by aCGDE. Furthermore, we illus-
trate in how far such auxiliary electrodes can be
used as a probe to detect products (in particu-
lar H2 , H2O2 , and O2 ) formed in the solution by
aCGDE via electrochemical techniques. In this
work aCGDE is achieved by applying a voltage
of 580 V to a small Pt wire (plasma electrode)
vs. a large stainless steel counter electrode. An
auxiliary Pt electrochemical working electrode,
operated in a three electrode configuration, is
placed at different distances from the plasma
working electrode. Depending on the distance,
we find small changes in the electrode struc-
ture. More importantly, we will show that in
principle the local H2 O2 concentration in the
electrolyte can be monitored operando. After
aCGDE the concentration changes with time
and depends on the distance from the plasma
electrode.
|
Albert Kilian Engstfeld; Evelyn Artmann; Lukas Forschner; Timo Jacob
|
Physical Chemistry; Catalysis; Electrocatalysis; Physical and Chemical Processes; Physical and Chemical Properties
|
CC BY 4.0
|
CHEMRXIV
|
2022-04-04
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/624564e13affe4aa393bc16d/original/using-auxiliary-electrochemical-working-electrodes-as-probe-during-contact-glow-discharge-electrolysis-a-proof-of-concept-study.pdf
|
64e5ceaedd1a73847f5778eb
|
10.26434/chemrxiv-2023-0kjx4
|
Graph neural network-accelerated multitasking genetic algorithm for optimizing PdxTi1–xHy surface under various CO2 reduction reaction conditions
|
Palladium (Pd) hydride-based catalysts have been reported to have excellent performance for CO2 reduction (CO2RR) and hydrogen evolution reactions (HER). Our previous doped-PdH and alloy hydride works showed that Ti-doped and Ti-alloyed Pd hydride could improve the performance of the CO2 reduction reaction compared to pure Pd hydride. Compositions and chemical orderings of the surfaces with only one adsorbate under certain reaction condition are linked to their stablity, activity, and selectivity towards CO2RR and HER in our previous work. In fact, various coverages, types, and mixture of the adsorbates as well as state variable such as, temperature, pressure, applied potential, and chemical potential could have an impact on their stability, activity, and selectivity. However, these factors are usually fixed at common values in order to reduce the complexity of structures and complexity of reaction conditions in most theoretical work. To address the above complexities and thus huge search space, a deep learning-assisted multitasking genetic algorithm is used to screen for PdxTi1-xHy surfaces containing multiple adsorbates for CO2RR under different reaction conditions in this work. The ensemble deep learning model can greatly speed up the structure relaxations and keep a high accuracy and low uncertainty of energy and forces. The multitasking genetic algorithm is used to simultaneously globally find stable surface structures at each reaction condition. Finally, 23 stable structures are screened out under different reaction conditions. Among them, Pd0.56Ti0.44H1.06+25%CO, Pd0.31Ti0.69H1.25+50%CO, Pd0.31Ti0.69H1.25+25%CO, and Pd0.88Ti0.12H1.06+25%CO are found to be very active for CO2RR and suitable to generate syngas consisting of CO2 and H2.
|
Changzhi Ai; Shuang Han; Xin Yang; Tejs Vegge; Heine Anton Hansen
|
Theoretical and Computational Chemistry; Materials Science; Catalysis; Catalysts; Computational Chemistry and Modeling; Electrocatalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-08-25
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64e5ceaedd1a73847f5778eb/original/graph-neural-network-accelerated-multitasking-genetic-algorithm-for-optimizing-pdx-ti1-x-hy-surface-under-various-co2-reduction-reaction-conditions.pdf
|
65723bce5bc9fcb5c9512cb9
|
10.26434/chemrxiv-2023-w1s3m-v2
|
A Bulky Imidodiphosphorimidate Brønsted Acid Enables Highly Enantioselective Prins-semipinacol Rearrangements
|
The development of BINOL-derived Brønsted acid catalysts has been profoundly guided by rational design, with carefully implemented structural changes leading to unique generations of catalysts with enhanced reaction capabilities. This approach to catalyst optimization has promoted the integration of knowledge gathered in optimizing prior eras of Brønsted acids and ultimately, the molecular features that have contributed to the success of previous designs are preserved. Of these, the large substituents at the 3 and 3’ positions of the BINOL backbone are the most critical with almost every newly developed structure possessing this feature. However, imidodiphosphorimidate (IDPi) catalysts are not synthetically well-suited to contain the same sterically bulky groups associated with the high selectivity imparted by previously implemented catalyst structures. Herein, we have leveraged the moderate size (as compared to TRIP and 9-anthryl) but high applicability of the 9-phenanthryl substituent to synthesize a sterically demanding IDPi. Using computed descriptors, we survey the catalyst properties of known structures to demonstrate this catalyst to be both unique and one of the bulkiest IDPi yet synthesized. The applicability of the catalyst was evaluated in the construction of stereochemically dense spirocycles generated via an asymmetric Prins-semipinacol reaction sequence. Transition state calculations were deployed to interrogate the origins of the superior enantioselectivity and these demonstrate the mechanistic hallmarks of the 9-phenanthryl substituent can be generalized to a genuinely different class of Brønsted acid catalyst. Ultimately, providing the basis for the development of general catalyst design principles and the translation of “privileged” substituents across unique eras of Brønsted acid catalyst structures.
|
Junshan Lai; Jolene Reid
|
Theoretical and Computational Chemistry; Organic Chemistry; Catalysis; Stereochemistry; Computational Chemistry and Modeling; Organocatalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-12-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65723bce5bc9fcb5c9512cb9/original/a-bulky-imidodiphosphorimidate-br-nsted-acid-enables-highly-enantioselective-prins-semipinacol-rearrangements.pdf
|
66e8f73951558a15ef33d5a3
|
10.26434/chemrxiv-2024-2v5l6-v3
|
Hydrogen Absorption Promoted by Surface Melting: Guidelines for High-Pressure Superhydride Synthesis
|
The synthesis of new superhydrides with high superconducting Tc is challenging due to the high temperatures and pressures required. Here, we used machine-learning potential molecular dynamics simulations to investigate the initial stage of superhydride formation in calcium hydrides. Upon contact with high-pressure H2, the surface of CaH2 melts, leading to CaH4 formation. High pressure reduces the formation enthalpy for liquid superhydride as an intermediate state. Consequently, excess pressure above equilibrium shifts the balance towards superhydride formation and lowers the activation energy, promoting the hydrogenation reaction. Based on these thermodynamic insights, we propose superhydride synthesis guidelines focused on bulk properties: superhydride (product) melting temperature and pressure-dependent hydrogenation enthalpy, readily determined through supplementary calculations during structure prediction workflows.
|
Ryuhei Sato; Lewis Conway; Di Zhang; Chris Pickard; Kazuto Akagi; Kartik Sau; Li Hao; Shin-ichi Orimo
|
Physical Chemistry; Materials Science; Interfaces; Thermodynamics (Physical Chem.)
|
CC BY 4.0
|
CHEMRXIV
|
2024-09-17
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66e8f73951558a15ef33d5a3/original/hydrogen-absorption-promoted-by-surface-melting-guidelines-for-high-pressure-superhydride-synthesis.pdf
|
60c744e6842e65357edb2527
|
10.26434/chemrxiv.9923363.v1
|
Extracellular Electron Transfer Mediated by a Cytocompatible Redox Polymer Lengthens the Circadian Period of Mammalian Cells
|
The crosstalk among the circadian clock, cellular metabolism, and cellular redox state has attracted much attention. To elucidate this crosstalk, chemical compounds have been used to perturb cellular metabolism and the redox state. However, extracellular electron transfer (EET) with an electron mediator has not been used to study the mammalian circadian clock due to potential cytotoxic effects of the mediator. Here, we describe the use of EET mediated by pMFc, a cytocompatible redox polymer, on human U2OS cells. EET mediated by oxidized pMFc (ox-pMFc) extracted intracellular electrons, resulting in a longer circadian period. Analyses of the metabolome and intracellular redox species suggest that ox-pMFc receives an electron from glutathione, thereby inducing pentose phosphate pathway activation. We anticipate that redox perturbation via EET will provide new insights into the crosstalk among the circadian clock, metabolism, and redox state, which may lead to the development of new treatments for circadian clock disorders.
|
Masahito Ishikawa; Kazuki Kawai; Masahiro Kaneko; Kenya Tanaka; Shuji Nakanishi; Katsutoshi Hori
|
Chemical Biology
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2019-10-02
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c744e6842e65357edb2527/original/extracellular-electron-transfer-mediated-by-a-cytocompatible-redox-polymer-lengthens-the-circadian-period-of-mammalian-cells.pdf
|
60c748160f50dbe0dc39670c
|
10.26434/chemrxiv.11856036.v1
|
Grids to Illustrate Induction and Resonance Effects: Aromatic Acidity and Basicity
|
The effect of substituents on the acidity of benzoic acids and anilines has been organized in grids to demonstrate the inductive and resonance effects. The relation between structure and pKa is emphasized by a new educational process: the Search-Organize-Predict (SOP) procedure.
|
Guy Lamoureux; Carlos Árias-Alvarez
|
Physical Organic Chemistry; Chemical Education - General
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-02-18
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c748160f50dbe0dc39670c/original/grids-to-illustrate-induction-and-resonance-effects-aromatic-acidity-and-basicity.pdf
|
60c75706bb8c1a77903dc70b
|
10.26434/chemrxiv.14216666.v1
|
Formation of Formic Acid from Glucose with Simultaneous Conversion of Ag2O to Ag under Mild Hydrothermal Conditions
|
<p>Formation of
formic acid from renewable biomass resources is of great interest since formic
acid is a widely used platform chemical and has recently been regarded as an
important liquid hydrogen carrier. Herein, a novel approach is reported for the
conversion of glucose, the constituent carbohydrate from cellulose fraction of
biomass, to formic acid under mild hydrothermal conditions with simultaneous
reduction of Ag<sub>2</sub>O to Ag. Results showed that glucose was selectively
converted to formic acid with an optimum yield of 40.7% at a mild reaction
temperature of 135
for 30 min. In addition, Ag<sub>2</sub>O was
used as a solid oxidant for the glucose oxidation, which avoids the use of
traditionally dangerous liquid oxidant H<sub>2</sub>O<sub>2</sub>. Furthermore,
complete conversion of Ag<sub>2</sub>O to Ag can be achieved. This study not
only developed a new method for value-added chemical production from renewable
biomass but also explored an alternative low-carbon and energy-saving route for
silver extraction and recovery.</p>
|
Runtian He; Jing Xu; Teng Ma; Jiong Cheng; Binbin Jin
|
Environmental Science
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-04-05
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75706bb8c1a77903dc70b/original/formation-of-formic-acid-from-glucose-with-simultaneous-conversion-of-ag2o-to-ag-under-mild-hydrothermal-conditions.pdf
|
6787774cfa469535b918fa96
|
10.26434/chemrxiv-2024-9fm01-v2
|
Evaluating the Diversity and Target Addressability of DELs using Scaffold Analysis and Machine Learning
|
DNA-encoded libraries (DELs) enable efficient experimental screening of vast combinatorial molecular libraries, making it a powerful platform for drug discovery. Apart from ensuring the druglike physicochemical properties, other key parameters to maximize the success rate of DEL designs include the scaffold diversity and target addressability. While several computational tools have been developed to evaluate DEL chemical diversity, a dedicated tool that combines both parameters is currently lacking. In this work, we developed a computational approach to systematically evaluate both the scaffold diversity and target-orientedness of DELs using Bemis-Murcko (BM) scaffold analysis and machine learning. To demonstrate its utility, we present a case study using two of our in-house produced libraries. We show that our workflow can effectively distinguish between a generalist and a focused library. Furthermore, we show that although focused libraries tend to have higher compound-based addressability, they could suffer from lower scaffold-based addressability relative to a generalist library. Consequently, we illustrate how our tool can guide medicinal chemists in deciding which library to screen as a function of the objective, whether it is hit-finding or hit-optimization. To facilitate utilization, this tool is freely available both as a web application and as a Python script at https://github.com/novalixofficial/NovaWebApp.
|
Yaelle Fischer; Ruel Cedeno; Dhoha Triki; Bertrand Vivet; Philippe Schambel
|
Theoretical and Computational Chemistry; Biological and Medicinal Chemistry
|
CC BY NC 4.0
|
CHEMRXIV
|
2025-01-16
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6787774cfa469535b918fa96/original/evaluating-the-diversity-and-target-addressability-of-de-ls-using-scaffold-analysis-and-machine-learning.pdf
|
654d15a62c3c11ed71171bbc
|
10.26434/chemrxiv-2023-3hbvq
|
Apparent nitrous acid dissociation across environmentally relevant temperatures in freshwater and seawater
|
Nitrite is a ubiquitous compound found across aquatic systems and an intermediate in both the oxidative and reductive metabolisms transforming fixed nitrogen in the environment. Yet, the abiotic cycling of nitrite is often overlooked in favor of biologically mediated reactions. Here we quantify the apparent acid dissociation constant (pKa) between nitrous acid and nitrite in both freshwater and seawater systems across a range of environmentally-relevant temperatures (5–35 ºC) using potentiometric-based titration. We find substantial effects of both salinity and temperature on the pKa, with colder and fresher water manifesting higher values and thus a greater proportion of protonated nitrite at any given pH. Because nitrous acid is unstable and decomposes to nitric oxide, a toxic free radical gas but also a potential antioxidant and biological signaling compound, the implications for the nitrous acid pKa on ecosystem function are broad.
|
Benedict Borer; Eric Bi; Ryan Woosley; Andrew Babbin
|
Physical Chemistry; Earth, Space, and Environmental Chemistry; Hydrology and Water Chemistry; Physical and Chemical Properties
|
CC BY NC 4.0
|
CHEMRXIV
|
2023-11-10
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/654d15a62c3c11ed71171bbc/original/apparent-nitrous-acid-dissociation-across-environmentally-relevant-temperatures-in-freshwater-and-seawater.pdf
|
65a926d59138d231613622f0
|
10.26434/chemrxiv-2022-dsbm5-v3
|
Transfer learning with graph neural networks for improved molecular property prediction in the multi-fidelity setting
|
We investigate the potential of graph neural networks for transfer learning and improving molecular property prediction on sparse and expensive to acquire high-fidelity data by leveraging low-fidelity measurements as an inexpensive proxy for a targeted property of interest. This problem arises in discovery processes that rely on screening funnels for trading off the overall costs against throughput and accuracy. Typically, individual stages in these processes are loosely connected and each one generates data at different scale and fidelity. We consider this setup holistically and demonstrate empirically that existing transfer learning techniques for graph neural networks are generally unable to harness the information from multi-fidelity cascades. Here, we propose several effective transfer learning strategies and study them in transductive and inductive settings. Our analysis involves a novel collection of more than 28 million unique experimental protein-ligand interactions across 37 targets from drug discovery by high-throughput screening and 12 quantum properties from the dataset QMugs. The results indicate that transfer learning can improve the performance on sparse tasks by up to eight times while using an order of magnitude less high-fidelity training data. Moreover, the proposed methods consistently outperform existing transfer learning strategies for graph-structured data on drug discovery and quantum mechanics datasets.
|
David Buterez; Jon Paul Janet; Steven Kiddle; Dino Oglic; Pietro Liò
|
Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Machine Learning; Chemoinformatics - Computational Chemistry
|
CC BY 4.0
|
CHEMRXIV
|
2024-01-19
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65a926d59138d231613622f0/original/transfer-learning-with-graph-neural-networks-for-improved-molecular-property-prediction-in-the-multi-fidelity-setting.pdf
|
60c74d674c8919b61aad37ff
|
10.26434/chemrxiv.12236240.v2
|
Detection of Perfluorooctane Sulfonate by Ion-Transfer Stripping Voltammetry at an Array of Microinterfaces Between Two Immiscible Electrolyte Solutions
|
We present an analytical approach for the detection of perfluorooctane sulfonate (PFOS) by ion transfer stripping voltammetry at an array of micro-interfaces between two immiscible electrolyte solutions. With this approach, picomolar concentrations are detected and environmental matrix effects are evaluated.
|
Benjamin N. Viada; L. Mabel Yudi; Damien Arrigan
|
Electrochemical Analysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-07-02
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74d674c8919b61aad37ff/original/detection-of-perfluorooctane-sulfonate-by-ion-transfer-stripping-voltammetry-at-an-array-of-microinterfaces-between-two-immiscible-electrolyte-solutions.pdf
|
6638864d91aefa6ce145605f
|
10.26434/chemrxiv-2024-x7h6z
|
Stoichiometric constraints for detection of EV-borne biomarkers in blood
|
Stochiometric issues, encompassing both the quantity and heterogeneity of extracellular vesicles (EVs) derived from tumor or other tissues in blood, pose important challenges across various stages of biomarker discovery and detection, affecting the integrity of data, introducing losses and artifacts during blood processing, EV purification, and analysis. These challenges shape the diagnostic utility of EVs especially within the framework of established and emerging methodologies. By addressing these challenges, we aim to delineate crucial parameters and requirements for tumor-specific EV detection, or more precisely, for tumor identification via EV based assays. Our endeavor involves a comprehensive examination of the layers that mask or confound the traceability of EV markers such as nucleic acids and proteins, and focus on "Low abundance - low occupancy" scenario. Finally, we evaluate the advantages vs. limitations of digital technologies over more conventional bulk assays, suggesting that the combined use of both to capture and interpret the EV signals, in particular the EV surface displayed proteins, may ultimately provide quantitative information on their absolute abundance and distribution.
|
Nataša Zarovni; Danilo Mladenović; Dario Brambilla; Federica Panico; Marcella Chiari
|
Biological and Medicinal Chemistry; Analytical Chemistry; Nanoscience; Biochemical Analysis; Bioengineering and Biotechnology; Cell and Molecular Biology
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-05-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6638864d91aefa6ce145605f/original/stoichiometric-constraints-for-detection-of-ev-borne-biomarkers-in-blood.pdf
|
635b9e1fac45c720879be18d
|
10.26434/chemrxiv-2022-3qwcj
|
Characterisation of a newly available marine dissolved organic matter reference material (TRM-0522)
|
Recent methodological advances have greatly increased our ability to characterise aquatic dissolved organic matter (DOM) using high resolution instrumentation, including nuclear magnetic resonance (NMR) and mass spectrometry (HRMS). Reliable DOM reference materials are required for further method development and dataset alignment, but do not currently exist for the marine environment. This presents a major limitation for marine biogeochemistry and related fields, including natural product discovery. To fill this resource gap, we have prepared a marine DOM reference material (TRM-0522) from 45 m deep coastal seawater obtained ~ 1 km offshore of Sweden’s west coast. Over 3000 molecular formulas were assigned by direct infusion HRMS, confirming sample diversity, and the distribution of formulas in van Krevelen space was typical for a marine sample, with the majority of formulas in the region H/C 1-1.5 and O/C 0.3-0.7. The extracted DOM pool was more nitrogen (N) and sulfur (S) rich than a typical terrestrial reference material (SRFA). MZmine3 processing of UPLC-HRMS/MS data revealed 494 resolvable features (233 in negative mode; 261 in positive mode) over a wide range of retention times and masses. NMR data indicated low contributions of the aromatic protons, and generally speaking lignin, humic, and fulvic substances associated with terrestrial samples. Instead, carboxylic-rich aliphatic molecules (CRAM) were the most abundant components, followed by carbohydrates and aliphatic functionalities. This is consistent with a very low specific UV absorbance SUVA254 value of 1.36 L mg C-1 m-1. When combined with comparisons with existing terrestrial reference materials (SRFA and PLFA), these results suggest that TRM-0522 is a useful and otherwise unavailable reference material for use in marine DOM biogeochemistry.
|
Stacey Felgate; Alexander Craig; Lindon Moodie; Jeffrey Hawkes
|
Analytical Chemistry; Earth, Space, and Environmental Chemistry; Environmental Science; Environmental Analysis; Mass Spectrometry
|
CC BY 4.0
|
CHEMRXIV
|
2022-10-31
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/635b9e1fac45c720879be18d/original/characterisation-of-a-newly-available-marine-dissolved-organic-matter-reference-material-trm-0522.pdf
|
60c752f59abda2b6f1f8ded9
|
10.26434/chemrxiv.13369454.v1
|
In Silico Screening of Natural Products Isolated from Mexican Herbal Medicines Against COVID-19
|
<p>We performed a
chemoinformatic screening with 100 compounds isolated from Mexican natural
products to seek active molecules with the potential to be implemented in the pharmacological
treatment of such disease (either as a drug itself or as an inspiring molecule
to developed active compounds against SARS-CoV-2). We found ten
compounds with leadlikeness and
Lipinski's potential. However, after the docking and toxicoinformatic analysis,
only Cichoriin was safe and docked with high affinity to the main targets of
SARS-CoV-2. Additionally we performed a PBPK simulation which showed that this compound might
reach acceptable levels in plasma and highest concentration in the lung when
administered IV at 100 mg/Kg. Our work suggests that Cichoriin may be a potential
candidate in treating severe COVID-19.</p>
|
Juan Carlos Gomez Verjan; Nadia Alejandra Rivero-Segyra
|
Drug Discovery and Drug Delivery Systems
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-12-15
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c752f59abda2b6f1f8ded9/original/in-silico-screening-of-natural-products-isolated-from-mexican-herbal-medicines-against-covid-19.pdf
|
660380bd9138d2316163942d
|
10.26434/chemrxiv-2024-xrtp1
|
Pyrene-Based AIE System: A Bridge Model to Regulate Aggregate Structures
|
The bridging role of aggregate between single-molecule structures and macroscopic photophysical properties has attracted intense attention. Pyrene (Py), as the simplest dimer candidate, is a proper model for studying accurate structure-property relationships of aggregates. Herein, a series of Py and derivatives were systematically investigated. With a largely planar and conjugated conformation, Py shows anomalous aggregation-induced emission (AIE) characteristics due to the oxygen quenching at the molecular level but turn-on fluorescence in the aggregate state because of the oxygen isolation. Although introducing substituents induces molecular motion and weakened luminescence in the molecular state, the impact of substituents on the aggregate-state photophysical properties enormously differs. A small and electron-conjugated substituent (-CHO) can generate long-range ordered dimer stacking, leading to redshifted and weakened emission. Meanwhile, the larger substituent (-CyA) can disrupt long-range stacking and result in discrete dimers, leading to blue-shifted but enhanced emission. Further, incorporating a natural and bulky alicyclic structure (-DAA) inhibits dimer formation and activates strong molecular motions in the crystalline state, resulting in the shortest wavelength and weakest emission. Interestingly, crystalline Py-DAA exhibits both mechanochromic and acidichromic properties, which can be synergistically applied in dynamic encryption-decryption. These results indicate that substituents significantly affect their fluorescent behaviors due to the complexity of aggregate structures. This work not only elucidates the unique AIE performance of Py for the first time but also applies it as an accurate model for regulating the aggregate structures, offering precise molecular design strategies for aggregate-state luminescent materials.
|
Xu-Min Cai; Yuting Lin; Jianyu Zhang; Zhenguo Tang; Shouji Li; Weiren Zhong; Ziyue Ye; Feng Gao; Wen-Jin Wang; Xing Feng; Zheng Zhao; Qiang Yong; Ben Zhong Tang
|
Materials Science; Dyes and Chromophores; Optical Materials; Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-03-27
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/660380bd9138d2316163942d/original/pyrene-based-aie-system-a-bridge-model-to-regulate-aggregate-structures.pdf
|
638fa3220a81270275d5f6da
|
10.26434/chemrxiv-2022-3k5d5
|
Copper reductase activity and free radical chemistry by cataract-associated human lens γ-crystallins
|
Cataracts are caused by high-molecular weight aggregates of human eye lens proteins that scatter light, causing lens opacity. Metal ions have emerged as important potential players in the etiology of cataract disease, as human lens γ-crystallins are susceptible to metal-induced aggregation. Here, the interaction of Cu2+ ions with γD-, γC-, and γS- crystallins, the three most abundant γ-crystallins in the lens, has been evaluated. Cu2+ ions induced non-amyloid aggregation in all three proteins. Solution turbidimetry, SDS-PAGE, circular dichroism and differential scanning calorimetry showed that the mechanism for Cu-induced aggregation involves: i) loss of beta-sheet structure in the N-terminal domain; ii) decreased thermal and kinetic stability; iii) formation of metal-bridged species; and iv) formation of disulfide-bridged dimers. Electron paramagnetic resonance (EPR) revealed two distinct Cu2+ binding sites in each protein. Spin quantitation demonstrated reduction of γ-crystallin-bound Cu2+ ions to Cu+ under aerobic conditions, while X-ray absorption spectroscopy (XAS) confirmed the presence of linear or trigonal Cu+ binding sites in γ-crystallins. Our EPR and XAS studies revealed that γ-crystallins’ Cu2+ reductase activity yields a protein-based free radical that is likely a Tyr-based species in human γD-crystallin. This unique free radical chemistry carried out by distinct redox-active Cu sites in human lens γ-crystallins likely contributes to the mechanism of copper-induced aggregation. In the context of an aging human lens, γ-crystallins could be acting, not only as structural proteins, but also as key players for metal and redox homeostasis.
|
Giovanni Palomino-Vizcaino; Jose A. Domínguez-Calva; Nils Schuth; Eduardo Martínez-Jurado; Oscar Rodríguez-Meza; Eugene Serebryany; Jonathan A. King; Thomas Kroll; Miguel Costas; Liliana Quintanar
|
Biological and Medicinal Chemistry; Inorganic Chemistry; Bioinorganic Chemistry; Spectroscopy (Inorg.); Biochemistry
|
CC BY NC 4.0
|
CHEMRXIV
|
2022-12-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/638fa3220a81270275d5f6da/original/copper-reductase-activity-and-free-radical-chemistry-by-cataract-associated-human-lens-crystallins.pdf
|
60c73d92ee301c2133c785aa
|
10.26434/chemrxiv.5355937.v2
|
Measuring the conductivity of very dilute electrolyte solutions, drop by drop
|
The study of the conductivity
of electrolyte solutions is important for practical applications and
for the understanding of ion mobility. Because of that, undergraduate
experiments on ionic conductivity are common practice in first year
general chemistry or more advanced physical chemisdegreetry
laboratories. Often, the conductivities are measured for solutions
prepared for various salts, in a range of concentrations, and the
relationship between solution conductivity and concentration is
interpreted in terms of the Kohlrausch
law. Extrapolation of the molar conductivities to infinite dilution
allows the study of the individual ionic conductivities. In practice,
the preparation of dilute solutions for these experiments can be
cumbersome, because small electrolyte contaminations can dominate the
conductivity of the solutions. Additionally, significant amounts of
reactants, particularly deionized water, must be used. Here, a simple
experimental procedure is proposed to obtain the concentration
dependence of ionic conductivities for very dilute (sub-millimolar)
electrolyte solutions. The experiment consists in measuring the
conductivity of solutions of increasing concentration prepared by
dropping the electrolyte solution into a single initial vessel of
deionized water. The range of concentrations achieved is one in which
the conductivities vary linearly with the concentrations, such that the
molar conductivities can be obtained directly without the use of the Kohlrausch
equation. The simplicity of the experimental procedure leads the
students to obtain very good quality results using minimal amounts of
materials. Examples are presented for the conductivities of various
strong electrolytes, and for weak acetic acid electrolyte, for which the conductivity is dependent on the degree of dissociation even at very low concentrations
|
Leandro Martinez
|
Chemical Education - General
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2017-11-20
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d92ee301c2133c785aa/original/measuring-the-conductivity-of-very-dilute-electrolyte-solutions-drop-by-drop.pdf
|
60c75371702a9b29fe18c37e
|
10.26434/chemrxiv.13490460.v1
|
Ultrathin Films of Pentacene on Ag(111): Charge-Transfer Bonding and Inter-Adsorbate Interactions
|
Temperature programmed desorption (TPD) was used to examine the surface binding and intermolecular interactions of mono- and multi-layer thin films of the polycyclic aromatic acene, pentacene, deposited on a Ag(111) surface. The TPD spectra of sub-monolayer cov- erages revealed the presence of three distinct phases (denoted as α1, α2, and α3). The α1 phase was attributed to adsorption on step sites, while the α2 and α3 phases were assigned to adsorption on terrace sites under different local molecular densities. A physical model was constructed to describe the desorption kinetics from each of the three monolayer phases, including intermolecular repulsion from interfacial dipoles produced as a result of charge transfer bonding between pentacene and the Ag substrate. Fit analysis of the sub-monolayer spectra revealed desorption energies in the zero-coverage limit of 218±8, 166±8, and 162±9 kJ/mol for the α1, α2, and α3 phases, respectively. The interface dipoles of the α2 and α3 terrace adsorption sites were found to be effectively invariant (within error) and deduced as 18±7 and 23±10 D, respectively. These values suggest a partial charge transfer of 0.6 to 0.7 electrons from each pentacene molecule to the Ag substrate and is equivalent to 0.13 electrons per aromatic ring. The TPD spectra from the multilayer films also exhibited three phases. Leading edge analysis of the lowest temperature multilayer peak yielded a desorption energy of 121±15 kJ/mole, while simulations predicted desorption energies ca. 10-15 kJ/mole higher for the higher temperature phases. The three multilayer phases were assigned, from lowest to highest temperature, as an amorphous bulk film, a thin film, and polycrystalline structures.
|
Thomas Rockey; Michael Wilhelm; Hai-Lung Dai
|
Thin Films; Interfaces; Surface
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-01-04
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75371702a9b29fe18c37e/original/ultrathin-films-of-pentacene-on-ag-111-charge-transfer-bonding-and-inter-adsorbate-interactions.pdf
|
619ce2b07c891627fb41a06a
|
10.26434/chemrxiv-2021-lfn0b
|
Liquid amine–solid carbamic acid phase-separation system for direct capture of CO2 from air
|
The phase separation between a liquid amine and the solid carbamic acid exhibited >99% CO2 removal efficiency under a large-scale gas stream of 400 ppm CO2. Isophorone diamine [IPDA; 3-(aminomethyl)-3,5,5-trimethylcyclohexylamine] reacted with CO2 in the CO2/IPDA molar ratio of ≥ 1 even in H2O as a solvent. The captured CO2 was completely desorbed at 333 K because the disolved carbamate ion releases CO2 at low temperature. The reusability of IPDA under CO2 adsorption-and-desorption cycles without degradation, the >95% efficinecy kept for 100 hours under direct air capture condition, and high CO2 capture rate (214 mmol/h for 1 mol amine) suggest that the phase separation system using IPDA is robust and durable for practical use.
|
Soichi Kikkawa; Kazushi Amamoto; Yu Fujiki; Jun Hirayama; Gen Kato; Hiroki Miura; Tetsuya Shishido; Seiji Yamazoe
|
Energy
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-11-26
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/619ce2b07c891627fb41a06a/original/liquid-amine-solid-carbamic-acid-phase-separation-system-for-direct-capture-of-co2-from-air.pdf
|
60c74d24842e65e939db33e9
|
10.26434/chemrxiv.12589013.v1
|
SERS Background Imaging – a Versatile Tool Towards More Reliable SERS Analytics
|
<div>Surface-enhanced Raman scattering (SERS) is a highly selective and sensitive straightforward analytical method, which is however not yet established in routine analysis due to a lack of reliability and reproducibility. Here we utilise the broad SERS continuum background (SERS-BG) accompanying every SERS measurement as a versatile tool towards more reliable SERS analytics. We apply a heterogeneous gold SERS substrate immersed with an adenosine triphosphate solution to show that the integrated SERS-BG distinctly correlates with the intensity of the analyte signals in the SERS spectrum. Based on this relationship we introduce an easy-to-handle, automatable and more reliable SERS measurement procedure starting with fast and high-contrast imaging of the SERS substrate followed by hot spot localisation and recording of highly enhanced SERS spectra at the centre of the diffraction-limited spot. We further demonstrate the applicability of SERS-BG imaging by combining it with other optical modalities and electron microscopy to assess structure-property relationships. Additionally, we perform Monte-Carlo simulations to evaluate the sampling error in SERS experiments highlighting the advantages of our method over conventional SERS experiments.</div>
|
Paul Ebersbach; Ute Münchberg; Erik Freier
|
Imaging; Microscopy; Spectroscopy (Anal. Chem.); Optics; Spectroscopy (Physical Chem.); Surface
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-05-20
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74d24842e65e939db33e9/original/sers-background-imaging-a-versatile-tool-towards-more-reliable-sers-analytics.pdf
|
65e5cb489138d23161a40164
|
10.26434/chemrxiv-2024-vgbxq
|
Actionable predictions of human pharmacokinetics at the drug design stage
|
We present a novel computational approach for predicting human pharmacokinetics (PK) that addresses the challenges of early-stage drug design. Our study introduces and describes a large-scale dataset of 11 clinical PK endpoints, encompassing over 2700 unique chemical structures to train machine learning models. To that end multiple advanced training strategies are compared, including the integration of in vitro data and a novel self-supervised pre-training task. In addition to the predictions, our final model provides meaningful epistemic uncertainties for every data point. This allows us to successfully identify regions of exceptional predictive performance, with an Absolute Average Fold Error (AAFE/GMFE) of less than 2.5 across multiple endpoints. These advancements represent a significant leap towards actionable PK predictions, which can be utilized early on in the drug design process to expedite development and reduce reliance on nonclinical
studies.
|
Leonid Komissarov; Nenad Manevski; Katrin Groebke Zbinden; Torsten Schindler; Marinka Zitnik; Lisa Sach-Peltason
|
Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Machine Learning; Artificial Intelligence; Chemoinformatics - Computational Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-03-06
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65e5cb489138d23161a40164/original/actionable-predictions-of-human-pharmacokinetics-at-the-drug-design-stage.pdf
|
6341564c0e3c6a2a093936ef
|
10.26434/chemrxiv-2022-p60cn
|
Journey of plants natural products from plants to bioactive products
|
Secondary metabolites present in medicinal plants having intrinsic functions in the host also possess vast and versatile pharmacological effects along with a crucial role in the herbal, food, cosmetics, and chemical industry sector. Traditional knowledge of medicinal plants provides the clues for the target-specific research by implementing botanical, phytochemical, analytical, biological, and biotechnological tools which can ultimately lead to the discovery of lead molecules. The structural complexity and molecular diversity of plant-based specialized metabolites make them potential drug-like candidates. Multivariate analytical and chromatographic techniques assists in phytochemical analysis and facilitates the isolation of secondary metabolites from plants. This review is mainly focused on covering fundamental aspects involved in the phytochemical study of plants starting from approaches used for the selection of particular plants for research, biosynthesis of the different classes of compounds owing to a diverse range and complexity, and complete steps involved from raw plant material to pure bioactive molecule along with tools used for structure elucidation and quality assessment of plants.
|
Anmol -; Gaurav Aggarwal; Mehak Sharma; Raman Singh; Shivani -; Upendra Sharma
|
Biological and Medicinal Chemistry; Analytical Chemistry; Agriculture and Food Chemistry; Mass Spectrometry; Separation Science; Food
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2022-10-10
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6341564c0e3c6a2a093936ef/original/journey-of-plants-natural-products-from-plants-to-bioactive-products.pdf
|
6659890591aefa6ce171dc76
|
10.26434/chemrxiv-2024-g1cq3-v2
|
Chemical catalyst manipulating cancer epigenome and transcription
|
Post-translational modification (PTM) of histones dynamically regulates gene transcription and is closely related to cancer development. Altering the epigenome is thus a promising strategy for cancer chemotherapy. However, there have been no methods to artificially introduce physiologically relevant histone PTMs and their transcription profile without genetic engineering in living cells. Here we report a cell-permeable histone acetylation catalyst, BAHA-LANA-PEG-CPP44, enabling cancer epigenome manipulation. The catalyst selectively entered leukemia cells, bound to chromatin, and selectively acetylated H2BK120 of endogenous histones in a short reaction time. The catalytic histone acetylation attenuated chromatin binding of negative elongation factor E (NELFE), an RNA polymerase II regulatory factor, and changed the transcription profile in leukemia cells. The in-cell chemical catalysis slowed proliferation of leukemia cells and reduced their tumorigenic potential in mice. As this approach requires no genetic engineering and is orthogonal to canonical epigenetic drugs, it may represent a new modality of cancer chemotherapy.
|
Yuki Yamanashi; Shinpei Takamaru; Atsushi Okabe; Satoshi Kaito; Yuto Azumaya; Yugo Kamimura; Kenzo Yamatsugu; Tomoya Kujirai; Hitoshi Kurumizaka; Atsushi Iwama; Atsushi Kaneda; Shigehiro Kawashima; Motomu Kanai
|
Biological and Medicinal Chemistry; Cell and Molecular Biology; Chemical Biology
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-05-31
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6659890591aefa6ce171dc76/original/chemical-catalyst-manipulating-cancer-epigenome-and-transcription.pdf
|
60c75776f96a0044cb288c84
|
10.26434/chemrxiv.14368607.v1
|
Cyclic(Alkyl)(Amino)Carbene Ligands Enable Cu-Catalyzed Markovnikov Protoboration and Protosilylation of Terminal Alkynes: A Versatile Portal to Functionalized Alkenes
|
Regioselective hydrofunctionalization of alkynes represents a straightforward route to access alkenyl boronate and silane building blocks. In previously reported catalytic systems, high selectivity is achieved with a limited scope of substrates and/or reagents, with general solutions lacking. Herein, we describe a selective copper-catalyzed Markovnikov hydrofunctionalization of terminal alkynes that is facilitated by strongly donating cyclic (alkyl)(amino)carbene (CAAC) ligands. Using this method, both alkyl- and aryl-substituted alkynes are coupled with a variety of boryl and silyl reagents with high α-selectivity. The reaction is scalable, and the products are versatile intermediates that can participate in various downstream transformations. Preliminary mechanistic experiments shed light on the role of CAAC ligands in this process.
|
Yang Gao; Sima Yazdani; Aaron Kendrick; Glen Junor; Douglas Grotjahn; Guy Bertrand; Rodolphe Jazzar; Keary Engle
|
Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Physical Organic Chemistry; Ligand Design; Ligands (Organomet.)
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-04-13
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75776f96a0044cb288c84/original/cyclic-alkyl-amino-carbene-ligands-enable-cu-catalyzed-markovnikov-protoboration-and-protosilylation-of-terminal-alkynes-a-versatile-portal-to-functionalized-alkenes.pdf
|
67837f42fa469535b9a54e1e
|
10.26434/chemrxiv-2024-896n0-v2
|
A photoactive nickel complex provides evidence for a general Ni(I)/Ni(III) paradigm in cross-coupling catalysis
|
Advances in nickel catalysis have significantly broadened the synthetic chemists’ toolbox, particularly through methodologies leveraging paramagnetic nickel species via photoredox catalysis or electrochemistry. Key to these reactions are oxidation state modulations of nickel via single electron transfer events. Recent mechanistic studies provided evidence that (Csp2)–heteroatom bond formations proceed through NiI/NiIII cycles. Related C(sp2)–C(sp3) cross-couplings were proposed to operate via generation of C-centered radicals and a catalytic cycle that involves Ni0, NiI and NiIII species. However, the exact mechanism of C(sp2)–C(sp3) couplings is still under debate. We demonstrate that light-mediated C(sp2)–C(sp3) bond formations can operate via a NiI/NiIII manifold without C-centered radical intermediates. In a pursuit to expand the scope of C(sp2)–heteroatom couplings using donor-acceptor ligands, we identified a photoactive nickel complex capable of catalyzing C(sp2)–C(sp3) cross-couplings between aryl halides and benzyltrifluoroborate salts without involving photoredox reactivity. Mechanistic investigations unveiled an unprecedented direct transmetalation between a NiI intermediate and the organoboron species that serves as the crucial catalytic step. Our study demonstrates that light-mediated C(sp2)–heteroatom and C(sp2)–C(sp3) cross-couplings can both proceed through similar NiI/NiIII cycles. This new paradigm for light-mediated nickel catalysis will be pivotal for the rational design of photoactive ligands and novel cross-coupling methodologies.
|
Lucia Anghileri; Haralds Baunis; Aleksander R. Bena; Christos Giannoudis; John H. Burke; Susanne Reischauer; Christoph Merschjann; Rachel F. Wallik; Callum E. Adams; Gianluca Simionato; Sergey Kovalenko; Tarek Al Said; Luca Dell’Amico; Renske M. van der Veen; Bartholomäus Pieber
|
Organic Chemistry; Catalysis; Organometallic Chemistry; Photochemistry (Org.); Homogeneous Catalysis; Ligand Design
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2025-01-16
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67837f42fa469535b9a54e1e/original/a-photoactive-nickel-complex-provides-evidence-for-a-general-ni-i-ni-iii-paradigm-in-cross-coupling-catalysis.pdf
|
63e6027ffcfb27a31f871819
|
10.26434/chemrxiv-2023-qklh1-v2
|
Optimization of Instrument Parameters for Efficient Phosphopeptide Identification and Localization by Data-dependent Analysis Using Orbitrap Tribrid Mass Spectrometers
|
The analysis of protein phosphorylation site identification by mass spectrometry-based methods continues to improve with increased efficiency at multiple points of the pipeline including affinity isolation, sample handling with automated protein digestion and phosphopeptide extraction routines, and more sensitive phosphopeptide detection capabilities. The role mass spectrometry parameters play in the quantity and quality of results is understudied, with some reports presenting improvements without sufficient details of how these parameters were derived, nor how they were fully optimized. Here, we systematically scrutinize and optimize parameters of two Orbitrap Tribrid mass spectrometers by varying instrument parameters at both the MS1 and MS2 levels using Titanium IMAC-enriched phosphopeptide samples to illustrate how the recovery of phosphopeptides, and the confidence of phosphosite localizations, vary accordingly. These optimized values are then used to compare different IMAC beads for phosphopeptide-enrichment, and optimal bead combinations used to further improve phosphopeptide detection. These results have implications for planning detailed phosphoprotein identification and quantitation experiments to provide confidence in detection, site localization and reproducibility.
|
Seamus R. Morrone; Michael R. Hoopmann; David D. Shteynberg; Ulrike Kusebauch; Robert L. Moritz
|
Biological and Medicinal Chemistry; Analytical Chemistry; Biochemical Analysis; Mass Spectrometry; Biochemistry
|
CC BY NC 4.0
|
CHEMRXIV
|
2023-02-10
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63e6027ffcfb27a31f871819/original/optimization-of-instrument-parameters-for-efficient-phosphopeptide-identification-and-localization-by-data-dependent-analysis-using-orbitrap-tribrid-mass-spectrometers.pdf
|
60c745c4567dfe408eec44fc
|
10.26434/chemrxiv.10262912.v1
|
Thermal Atomic Layer Deposition of Gold Nanoparticles: Controlled Growth and Size Selection for Photocatalysis
|
Gold nanoparticles have been extensively studied
for their applications in catalysis. For Au nanoparticles to be catalytically
active, controlling the particle size is crucial. Here we present a low
temperature (105 °C) thermal atomic layer deposition approach for depositing
gold nanoparticles on TiO<sub>2</sub> with controlled size and loading using
trimethylphosphino-trimethylgold (III) and two co-reactants (ozone and water)
in a fluidized bed reactor. We show that the exposure time of the precursors is
a variable that can be used to decouple the Au particle size from the Au
loading. Longer exposures of ozone narrow the particle size distribution while longer
exposures of water broaden it. By studying the photocatalytic activity of
Au/TiO<sub>2</sub> nanocomposites we show how the ability to control particle
size and loading independently can be used not only to enhance performance but
also to investigate structure-property relationships. This study provides
insights into the mechanism underlying formation and evolution of Au
nanoparticles via a vapor phase technique which eliminates the shortcomings of
conventional liquid-base processes.
|
Fatemeh Sadat Minaye Hashemi; Fabio Grillo; Vikram Ravikumar; dominik Benz; Ankit Shekhar; Matt Griffiths; Sean Barry; J. Ruud van Ommen
|
Nanostructured Materials - Materials; Nanostructured Materials - Nanoscience; Photocatalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2019-11-15
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c745c4567dfe408eec44fc/original/thermal-atomic-layer-deposition-of-gold-nanoparticles-controlled-growth-and-size-selection-for-photocatalysis.pdf
|
60c74ce40f50db2cb1396f30
|
10.26434/chemrxiv.12497693.v2
|
High Performance Computing Prediction of Potential Natural Product Inhibitors of SARS-CoV-2 Key Targets
|
This work describes using a supercomputer to perform virtual screening of natural products and natural products derivatives against several conformations of 3 proteins of SARS-CoC-2 : papain-like protease, main protease and spike protein. We analyze the common chemical features of the top molecules predicted to bind and describe the pharmacophores responsible for the predicted binding.
|
Kendall Byler; Joseph Landman; Jerome Baudry
|
Bioinformatics and Computational Biology; Computational Chemistry and Modeling
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-06-19
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74ce40f50db2cb1396f30/original/high-performance-computing-prediction-of-potential-natural-product-inhibitors-of-sars-co-v-2-key-targets.pdf
|
6349859b2a709181fb5ca77e
|
10.26434/chemrxiv-2022-cd8xm
|
Electrochemical Properties and Local Structure of the TEMPO/TEMPO+ Redox Pair in Ionic Liquids
|
Redox-active organic species play an important role in catalysis, energy storage, and biotechnology. One of the representatives is 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical, used as a mediator in organic synthesis and considered a safe alternative to heavy metals. In order to develop a TEMPO-based system with well-controlled electrochemical and catalytic properties, a reaction medium should be carefully chosen. Being highly conductive, stable, and low flammable fluids, ionic liquids (ILs) seem to be promising solvents with easily adjustable physical and solvation properties. In this work, we give an insight into the local structure of ILs around TEMPO and its oxidized form, TEMPO+, underlining striking differences in solvation of these two species. The analysis is coupled with a study of thermodynamics and kinetics of oxidation in the frame of Marcus theory. Our systematic investigation includes imidazolium, pyrrolydinium, and phosphonium families combined with anions of different size, polarity, and flexibility, opting to provide a clear and comprehensive picture of the impact of the nature of IL ions on the behavior of radical/cation redox pair. The obtained results will help to explain experimentally observed effects and to rationalize the design of TEMPO/IL systems.
|
Kateryna Goloviznina; Mathieu Salanne
|
Theoretical and Computational Chemistry; Physical Chemistry; Catalysis; Computational Chemistry and Modeling; Homogeneous Catalysis; Redox Catalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2022-10-17
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6349859b2a709181fb5ca77e/original/electrochemical-properties-and-local-structure-of-the-tempo-tempo-redox-pair-in-ionic-liquids.pdf
|
6564265a29a13c4d47133b2f
|
10.26434/chemrxiv-2023-gxm6p
|
Converting inorganic sulfur into degradable thermoplastics and adhesives by copolymerization with cyclic disulfides
|
Converting elementary sulfur into sulfur-rich polymers provides a sustainable strategy to replace fossil-fuel-based plastics. However, the low ring strain of eight-membered rings, i.e., S8 monomers, compromises their ring-opening polymerization (ROP) due to lack of an enthalpic driving force and as a consequence, poly(sulfur) is inherently unstable. Here we report that copolymerization with cyclic disulfides, e.g., 1,2-dithiolanes, can enable a simple and energy-saving way to convert elementary sulfur into sulfur-rich thermoplastics. The key strategy is to combine two types of ROP — both mediated by disulfide bond exchange — to tackle the thermodynamic instability of poly(sulfur). Meanwhile, the readily modifiable sidechain of the cyclic disulfides provides chemical space to engineer the mechanical properties and dynamic functions over a large range, e.g., self-repairing ability and degradability. Thus, this simple and robust system is expected to be a starting point for the organic transformation of inorganic sulfur toward sulfur-rich functional and green plastics.
|
Yuanxin Deng; Zhengtie Huang; Ben Feringa; He Tian; Qi Zhang; Da-Hui Qu
|
Polymer Science; Earth, Space, and Environmental Chemistry; Organic Polymers; Polymerization (Polymers); Wastes; Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-11-28
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6564265a29a13c4d47133b2f/original/converting-inorganic-sulfur-into-degradable-thermoplastics-and-adhesives-by-copolymerization-with-cyclic-disulfides.pdf
|
61491b1ea7b2492d1c32daf5
|
10.26434/chemrxiv-2021-stnt5
|
Charge Induced Chi(3) Susceptibility in Interfacial Nonlinear Optical Spectroscopy Beyond the Bulk Aqueous Contributions: The Case for Silica/Water Interface
|
The electric field induced (EFI) bulk Chi(3) contribution to the second harmonic generation (SHG) signal from charged interfaces was discovered and applied to study the interfacial chemistry of various charged interfaces three decades ago. For both the buried fused silica/water interface and the exposed charged monolayer covered air/water interface, such bulk Chi(3) contribution was all attributed to the Chi(3) term of the polarized water molecules near the charged interfaces. The puzzling experimental observation of the more than one-order of magnitude difference of the EFISHG intensity between the fully charged silica/water interface and the charged molecular covered air/water interface was generally overlooked in the EFISHG literature. Nevertheless, this significant signal difference suggests additional source for the Chi(3) contribution at the fully charged silica/water interface other than the polarized water molecules as in the case of charged monolayer covered air/water interface. In this report, we re-examine the treatment of the Chi(3) mechanism at the charged silica/water interface by including the contributions from the bulk silica using proper boundary condition and image charge distributions for the change screening effects inside bulk silica phase. We show that the Chi(3) contribution from the bulk silica is in similar form as that of the aqueous bulk phase, and it is with more than one-order of magnitude and with opposite sign. The treatment reported here can be extended to other charged interfaces.
|
Hui Wang; Xiaohua Hu; Hongfei Wang
|
Physical Chemistry; Interfaces
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-09-22
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61491b1ea7b2492d1c32daf5/original/charge-induced-chi-3-susceptibility-in-interfacial-nonlinear-optical-spectroscopy-beyond-the-bulk-aqueous-contributions-the-case-for-silica-water-interface.pdf
|
60c75852bdbb89c2b8a3ad4d
|
10.26434/chemrxiv.14538426.v1
|
Observation and Rationalization of Nitrogen Oxidation Enabled Only by Coupled Plasma and Catalyst
|
<div>
<div>
<div>
<p>Heterogeneous catalysts coupled with non-thermal plasma (NTP) are known to achieve reaction yields that exceed the contributions of the individual components. Rationalization of
the enhancing potential of catalysts, however, remains challenging because the background
contributions from NTP are often non-negligible. Here, we first demonstrate nitrogen (N2)
oxidation by radio frequency plasma and platinum (Pt) combination at conditions in which nitric oxide (NO) yield from plasma or Pt is vanishingly small. We then develop reactor
models based on reduced NTP- and surface-microkinetic mechanisms to identify the features of each that lead to the synergy between NTP and Pt. At experimental conditions,
NO yields from NTP and thermal catalysis are suppressed by radical reactions and inhibited
by high N2 dissociation barrier, respectively. Pt catalyzes NTP-generated radicals and vibrationally excited molecules to produce NO. The model construction further illustrates that
the optimization of yield and energy efficiency involves tuning of plasma species, catalysts
properties, and the reactor configurations to couple the two. These results provide unambiguous evidence of the benefits of combining plasma and catalysts and open approaches to
design the coupled system.
</p>
</div>
</div>
</div>
|
Hanyu Ma; Rakesh Sharma; Stefan Welzel; M.C.M. van de Sanden; Michail Tsampas; William
F. Schneider
|
Heterogeneous Catalysis
|
CC BY 4.0
|
CHEMRXIV
|
2021-05-06
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75852bdbb89c2b8a3ad4d/original/observation-and-rationalization-of-nitrogen-oxidation-enabled-only-by-coupled-plasma-and-catalyst.pdf
|
622886ef97f210129302f32a
|
10.26434/chemrxiv-2022-pjgw1
|
Solution aggregation of two carbamazepine co-crystal systems as indication of nucleation pathways
|
An investigation into the solution phase aggregation of carbamazepine/saccharin and carbmazepine/nicotinamide shows weak and strong interaction, respectively, though both systems co-crytallise easily. The strong self-aggregation of saccharin molecules restricts the interaction between carbamazepine and saccharin. The strength of interaction can be connected to different nucleation pathways.
|
Yichun Shen; Katharina Edkins
|
Physical Chemistry; Materials Science; Analytical Chemistry; Aggregates and Assemblies; Self-Assembly; Structure
|
CC BY NC 4.0
|
CHEMRXIV
|
2022-03-11
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/622886ef97f210129302f32a/original/solution-aggregation-of-two-carbamazepine-co-crystal-systems-as-indication-of-nucleation-pathways.pdf
|
60c73cc0f96a004d04285c7f
|
10.26434/chemrxiv.14742840.v1
|
Inverse Material Search and Synthesis Verification by Hand Drawings via Transfer Learning and Contour Detection
|
Nanomaterials of various morphologies and chemistry
have an extensive use <a>as photonic devices, advanced
catalysts, sorbents for water purification, agrochemicals, platforms for drug
delivery</a> as well as imaging systems to name a few. However, search for
synthesis routes giving custom nanomaterials for particular needs with the desired
structure, shape, and size remains a challenge and is often implemented by
manual research articles screening. Here, we develop for the first time scanning
and transmission electron microscopy (SEM/TEM) reverse image search and hand
drawing-based search <i>via</i> transfer learning (TL), namely, VGG16
convolutional neural network (CNN) repurposing for image features extraction
and subsequent image similarity determination. Moreover, we demonstrate case
use of this platform on calcium carbonate system, where sufficient amount of
data was acquired by random high throughput multiparametric synthesis, as well
as on Au nanoparticles (NPs) data extracted from the articles. This approach can
be not only used for advanced nanomaterials search and synthesis procedure
verification, but also can be further combined with machine learning (ML)
solutions to provide data-driven novel nanomaterials discovery.
|
Nikita Serov; Vladimir Vinogradov
|
Nanostructured Materials - Materials; Nanostructured Materials - Nanoscience; Machine Learning; Artificial Intelligence
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-06-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73cc0f96a004d04285c7f/original/inverse-material-search-and-synthesis-verification-by-hand-drawings-via-transfer-learning-and-contour-detection.pdf
|
65a94f5fe9ebbb4db975e402
|
10.26434/chemrxiv-2023-zl9tn-v4
|
Stability of the protactinium(V) mono-oxo cation probed by first-principle calculations
|
This study explores the distinctive behavior of Protactinium (Z = 91) within the actinide series. In contrast to neighboring elements like uranium or plutonium, Protactinium in the pentavalent state diverges by not forming the typical dioxo pro- tactinyl moiety PaO2^{+} in aqueous phase. Instead, it manifests as a monooxo PaO^{3+} cation. Employing first-principle calculations with implicit and explicit solvation, we investigate two sto- ichiometrically equivalent neutral complexes: PaO(OH)2(X)(H2O) and Pa(OH)4(X), where X represents various monodentate and bidentate ligands. Calculating the Gibbs’ free energy for the reaction PaO(OH)2(X)(H2O) −−→ Pa(OH)4(X), we find that the PaO(OH)2(X)(H2O) complex is stabilized with Cl– , Br– , I– , NCS– , NO3 – , and SO42– ligands, while it is not favored with OH–, F–, and C2O42– ligands. Quantum Theory of Atoms in Molecules (QTAIM) and Natural Bond Orbital (NBO) methods reveal the Pa mono-oxo bond as a triple bond, with significant contributions from the 5f and 6d shells. Covalency of the Pa mono-oxo bond increases with certain ligands, such as Cl–, Br–, I–, NCS–, and NO3–. These findings elucidate Protactinium’s unique chemical 1 attributes and provide insights into the conditions supporting the stability of relevant complexes.
|
Tamara Shaaban; Florent Réal; Rémi Maurice; Valérie Vallet
|
Theoretical and Computational Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-01-19
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65a94f5fe9ebbb4db975e402/original/stability-of-the-protactinium-v-mono-oxo-cation-probed-by-first-principle-calculations.pdf
|
60c73f9b9abda20384f8bb11
|
10.26434/chemrxiv.7409888.v1
|
Epigenetics Recording Varied Environment and Complex Cell Events is an Origin of Cellular Aging
|
Although the phenomenal relationship between epigenetics
and aging phenotypic changes is built up, an intrinsic connection between the
epigenetics and aging requires to be theoretically illuminated. In this study,
we propose epigenetic recording of varied cell environment and complex history could
be an origin of cellular aging. Through epigenetic modifications, the environment
and historical events can induce the chromatin template into activated or repressive
accessible structure, thereby shaping the DNA template into a spectrum of
chromatin states. The inner nature of diversity and conflicts born by cell environment
and its historical events are hence recorded into the chromatin template. This
could result in a dissipated spectrum of chromatin state and chaos of overall
gene expressions. An unavoidable degradation of epigenome entropy, similar to <i>Shannon</i> entropy, would be consequently
induced. The resulted disorder in epigenome, characterized by corrosion of epigenome
entropy as reflected in chromatin template, can be stably memorized and propagated
through cell divisions. Furthermore, hysteresis nature of epigenetics responding
to emerging environment could exacerbate the degradation of epigenome entropy. Besides
stochastic errors, we propose that epigenetics disorder and chaos derived from unordered
environment and complex cell experiences play an essential role in epigenetic
drift and the as-resulted cellular aging.
|
xuejun guo; Dong Yang; Xiangyuan Zhang
|
Cell and Molecular Biology; Environmental biology
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2018-12-03
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73f9b9abda20384f8bb11/original/epigenetics-recording-varied-environment-and-complex-cell-events-is-an-origin-of-cellular-aging.pdf
|
63e126d1fcfb27a31f682bae
|
10.26434/chemrxiv-2023-cs884
|
Quantification of capture efficiency, purity, and single-cell isolation in the recovery of circulating melanoma cells from peripheral blood by dielectrophoresis
|
This paper describes a dielectrophoretic method for selection of circulating melanoma cells (CMCs), which lack reliable identifying surface antigens and are extremely rare in blood. This platform captures CMCs individually by dielectrophoresis (DEP) at an array of wireless bipolar electrodes (BPEs) aligned to overlying nanoliter-scale chambers, which isolate each cell for subsequent on-chip single-cell analysis. To determine the best conditions to employ for CMC isolation in this DEP-BPE platform, the static and dynamic dielectrophoretic response of established melanoma cell lines, melanoma cells from patient-derived xenografts (PDX) and peripheral blood mononuclear cells (PBMCs) were evaluated as a function of frequency using two established DEP platforms. Further, PBMCs derived from patients with advanced melanoma were compared with those from healthy controls. The results of this evaluation reveal that each DEP method requires a distinct frequency to achieve capture of melanoma cells and that the distribution of dielectric properties of PBMCs is more broadly varied in and among patients versus healthy controls. Based on this evaluation, we conclude that 50 kHz provides the highest capture efficiency on our DEP-BPE platform while maintaining a low rate of capture of unwanted PBMCs. We further quantified the efficiency of single-cell capture on the DEP-BPE platform and found that the efficiency diminished beyond around 25% chamber occupancy, thereby informing the minimum array size that is required. Importantly, the capture efficiency of the DEP-BPE platform for melanoma cells when using optimized conditions matched the performance predicted by our analysis. Finally, isolation of melanoma cells from contrived (spike-in) and clinical samples on our platform using optimized conditions was demonstrated. The capture and individual isolation of CMCs, confirmed by post-capture labeling, from patient-derived samples suggests the potential of this platform for clinical application.
|
Han Chen; Sommer Osman; Devon Moose; Marion Vanneste; Jared Anderson; Michael Henry; Robbyn Anand
|
Analytical Chemistry; Analytical Chemistry - General
|
CC BY NC 4.0
|
CHEMRXIV
|
2023-02-07
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63e126d1fcfb27a31f682bae/original/quantification-of-capture-efficiency-purity-and-single-cell-isolation-in-the-recovery-of-circulating-melanoma-cells-from-peripheral-blood-by-dielectrophoresis.pdf
|
6666ee6d12188379d8c4f07b
|
10.26434/chemrxiv-2024-8tlrd
|
Alkali cation stabilization of defects in 2D MXenes at ambient and elevated temperatures
|
Transition metal carbides have been adopted in energy storage, conversion, and extreme environment applications. Advancement in their 2D counterparts, known as MXenes, enables the design of unique structures at the ~1 nm thickness scale. Alkali cations have been essential in MXenes manufacturing processing, storage, and applications, however, exact interactions of these cations with MXenes are not fully understood. In this study, using Ti3C2Tx, Mo2TiC2Tx, and Mo2Ti2C3Tx MXenes, we present how transition metal vacancy sites are occupied by alkali cations, and their effect on MXene structure stabilization to control MXene’s phase transition. We examine this behavior using in situ high-temperature x-ray diffraction and scanning transmission electron microscopy, ex situ techniques such as atomic-layer resolution secondary ion mass spectrometry, and density functional theory simulations. In MXenes, this represents an advance in fundamentals of cation interactions on their 2D basal planes for MXenes stabilizations and applications. Broadly, this study demonstrates a potential new tool for ideal phase-property relationships of ceramics at the atomic scale.
|
Brian Wyatt; Matthew Boebinger; Zachary Hood; Shiba Adhikari; Paweł Michałowski; S. Kartik Nemani; Murali Gopal Muraleedharan ; Annabelle Bedford; Wyatt Highland; Paul Kent; Raymond Unocic ; Babak Anasori
|
Materials Science; Nanoscience; Ceramics; Nanostructured Materials - Materials; Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-06-11
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6666ee6d12188379d8c4f07b/original/alkali-cation-stabilization-of-defects-in-2d-m-xenes-at-ambient-and-elevated-temperatures.pdf
|
6696c15ec9c6a5c07a76460d
|
10.26434/chemrxiv-2024-h9htk
|
Harnessing free energy calculations to achieve kinome-wide selectivity in drug discovery campaigns: Wee1 case study
|
Free energy calculations are revolutionizing early-stage drug-discovery campaigns. Robust free energy methods can rapidly provide accurate on-target and off-target potency predictions to identify promising chemical matter for synthesis, thus, inspiring further rounds of ideation and optimization. Here, we present a free energy framework for efficiently achieving kinome-wide selectivity that led to the discovery of novel selective Wee1 kinase inhibitors. With ligand-based relative binding free energy calculations, multiple novel promising scaffolds were rapidly identified. With protein residue mutation free energy calculations that perturbed the Wee1 gatekeeper residue, off-target liabilities across the kinome of these promising series were efficiently reduced. With judicious identification of a selectivity handle, applying this computational strategy could effectively streamline the optimization of on-target and off-target profiles, thereby accelerating drug discovery timelines and decreasing unanticipated off-target toxicities.
|
Jennifer Knight; Anthony Clark; Jiashi Wang; Andrew Placzeck; Pieter Bos; Sathesh Bhat; Jeffrey Bell; Sarah Silvergleid; Wu Yin; Felicia Gray; Shaoxian Sun; Karen Akinsanya; Robert Abel; Aleksey Gerasyuto
|
Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems; Computational Chemistry and Modeling
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-08-20
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6696c15ec9c6a5c07a76460d/original/harnessing-free-energy-calculations-to-achieve-kinome-wide-selectivity-in-drug-discovery-campaigns-wee1-case-study.pdf
|
60c757c8ee301ca13cc7b621
|
10.26434/chemrxiv.14461932.v1
|
Synchrotron-Based Nano-XANES Reveals Intracellular Heterogeneity of Iron Species in Magnetotactic Bacteria
|
<p>This report demonstrates how scanning X-ray fluorescence microscopy
(SXFM) and nanoscale X-ray absorption near-edge structure (nano-XANES) can
spatially and chemically identify intracellular iron species at the single-cell
level, creating an opportunity to examine the role of iron storage in magnetite
biomineralization. Fe K-edge nano-XANES measurements of <i>Magnetospirillum
gryphiswaldense</i> in varied iron media conditions and iron storage capacity revealed
intracellular iron heterogeneities through a distinction between formed
magnetosomes and intracellular iron material. This work highlights the
potential of nano-XANES in providing an experimental advantage in the
multidisciplinary field of biomineralization.</p>
|
Daniel M Chevrier; Elisa Cerdá-Doñate; Yeseul Park; Fernando Cacho-Nerin; Miguel Gomez-Gonzalez; René Uebe; Damien Faivre
|
Biological Materials; Nanostructured Materials - Materials; Spectroscopy (Physical Chem.)
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-04-22
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c757c8ee301ca13cc7b621/original/synchrotron-based-nano-xanes-reveals-intracellular-heterogeneity-of-iron-species-in-magnetotactic-bacteria.pdf
|
60c74780702a9bb1dc18adc7
|
10.26434/chemrxiv.11676174.v1
|
In-Source CID Ramping (InCIDR) and Co-Variant Ion Analysis of Hydrophilic Interaction Chromatography (HILIC) Metabolomics
|
<p>A large
proportion of the complexity and redundancy of LC-MS metabolomics data comes
from adduct formation. To reduce such redundancy, many tools have been
developed to recognize and annotate adduct ions. These tools rely on
pre-defined adduct lists which are learned empirically from reverse phase LC-MS
studies. Meanwhile, hydrophilic
interaction chromatography (HILIC) is gaining popularity in metabolomics
studies due to better performance on polar compounds. HILIC methods typically
use high concentration of buffer salts for improved chromatography performance.
It is therefore necessary to analyze the adduct formation in HILIC
metabolomics. To this end, we developed <u>co</u>-<u>v</u>ariant <u>i</u>o<u>n</u>
<u>a</u>nalysis (COVINA) to investigate the metabolite adduct formation. Using
this tool, we completely annotated 201 adduct and fragment ions of 10
metabolites. Many of the metabolite adduct ions are found to contain cluster
ions of mobile phase additives. We further utilized COVINA to find the major
ionization forms of metabolites. Our results show that for some metabolites the
adduct ion signals can be >200-fold higher than the deprotonated form, offering
better sensitivity for targeted metabolomics analysis. Finally, we developed
the in-source CID ramping (InCIDR) method to analyze the intensity changes of
the adduct and fragment ions of the metabolites. Our analysis demonstrates a
promising method to distinguish the protonated/deprotonated ions of the
metabolites from the adduct and fragment ions. </p>
|
Xiaoyang Su; Eric Chiles; Sara Maimouni; Fredric Wondisford; Wei-Xing zong; Chi Song
|
Mass Spectrometry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-01-23
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74780702a9bb1dc18adc7/original/in-source-cid-ramping-in-cidr-and-co-variant-ion-analysis-of-hydrophilic-interaction-chromatography-hilic-metabolomics.pdf
|
629f5bc52e62693e7f7a8e65
|
10.26434/chemrxiv-2022-bfgzt
|
Identification of Bioactive Conformational Space of Flexible Endogenous Lipid Mediator Lysophosphoserine Based on Accessible Spaces and Activities of Conformationally Restricted Analogues
|
It is difficult to identify the bioactive conformations of flexible endogenous ligands that have a large number of rotatable bonds, but one approach is to introduce conformational restrictions. Then, by comparing the accessible conformational space and bioactivity of the analogs, it should be possible to estimate the bioactive conformational space. Here, we applied this strategy to identify the bioactive conformation of lysophosphatidylserine (LysoPS(18:1)), an endogenous lipidic ligand of the G-protein-coupled receptor GPR34. We synthesized LysoPS analogues conformationally restricted with respect to the glycerol moiety and sampled the accessible conformation spaces of two active and two inactive analogues by means of long-duration replica exchange molecular dynamics (REMD) and metadynamics (MTD) simulations. The conformational populations of these analogues and LysoPS itself were sampled with respect to two dihedral angles along the glycerol moiety. We found that REMD sampling of the whole molecule and MTD-based estimation of the free energy landscape gave similar results. Furthermore, the dihedral angles of LysoPS(18:1) in the previously identified docking pose with GPR34 were consistent with the range of dihedral angles in bioactive ligand conformations evaluated from the REMD and MTD calculations. Thus, at least with respect to the two dihedral angles of the glycerol moiety, the GPR34-bound conformation of LysoPS(18:1) corresponds well to some of the available unbound ligand conformations. Our findings are consistent with the “conformational selection” model of receptor recognition. This methodology for predicting the bioactive ligand conformation of flexible ligands should be helpful for rational drug design.
|
Sejin Jung; Nobuaki Yasuo; Misa Sayama; Luying Chen; Yuko Otani; S. Roy Kimura; Tomohiko Ohwada; Masakazu Sekijima
|
Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Chemoinformatics - Computational Chemistry
|
CC BY 4.0
|
CHEMRXIV
|
2022-06-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/629f5bc52e62693e7f7a8e65/original/identification-of-bioactive-conformational-space-of-flexible-endogenous-lipid-mediator-lysophosphoserine-based-on-accessible-spaces-and-activities-of-conformationally-restricted-analogues.pdf
|
65fe0dcb9138d231611019f9
|
10.26434/chemrxiv-2024-50l84
|
A Cellulose Encapsulated Composite Electrolyte Design: Towards Chemically and Mechanically Enhanced Solid-sodium Batteries
|
Replacing liquid electrolytes with solid ionic conductors attracts increasing attention due to the potential of improved battery safety. Solid-state batteries show potential for further increased energy/power density by eliminating the use of packaging accessories for unit cells. Sulfide- and halide-based ceramic ionic conductors exhibit comparable ionic conductivity with liquid electrolytes. These materials, however, are inherently brittle, making them unfavorable for applications. Here, we report a mechanically enhanced composite Na+ conductor that contains 92.5 wt% of sodium thioantimonate (Na3SbS4, NSS) and 7.5 wt% of sodium carboxymethylcellulose (CMC); the latter serves as the binder and an electrochemically inert encapsulation layer. The ceramic and binder constituents were integrated at the particle level, providing ceramic NSS-level Na+ conductivity in the NSS-CMC composite, the more than five-fold decrease of electrolyte thickness obtained in NSS-CMC composite electrolytes provided a five-fold increase in Na+ conductance compared to NSS ceramic pellets. Resulting from the CMC encapsulation, this NSS-CMC composite shows increased moisture resistivity and electrochemical stability, which significantly promotes the cycling performance of NSS-
based solid-state batteries, and improves ductility of the material. This work demonstrates a well-controlled, orthogonal process of ceramic-rich, composite electrolyte processing – independent streams for ceramic particle formation along and binder encapsulation in a solvent-assisted environment. This work provides insights into the interplay among the solvent, the polymeric binder, and the ceramic particles in composite electrolyte synthesis, and implies the critical importance of identifying the appropriate solvent/binder system for the precise control of this complicated process. Finally, the work also provides valuable insights into the potential of designing mechanically tailorable battery components via fundamental understanding of the effect of the constituents on the overall composite ductility.
|
Shu Dong; Geng Xie; Shihong Xu; Xuehai Tan; Madhusudan Chaudhary; Yue Zhang; Runqi Wu; Fuwei Wen; Cagri Ayranci; Vladimir Michaelis; Amanda Quirk; Scott Rosendahl; Jian Liu; Michael Fleischauer; Lingzi Sang
|
Materials Science; Energy; Composites; Energy Storage; Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-03-25
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65fe0dcb9138d231611019f9/original/a-cellulose-encapsulated-composite-electrolyte-design-towards-chemically-and-mechanically-enhanced-solid-sodium-batteries.pdf
|
663505d291aefa6ce113d9b8
|
10.26434/chemrxiv-2024-r99zr
|
Biomimetic materials to replace tubular tissues
|
Repairing tubular tissues—the trachea, the esophagus, urinary and gastrointestinal tracts, and the circulatory system—from trauma or severe pathologies that require resection, calls for new, more effective graft materials. Currently, the relatively narrow family of materials available for these applications relies on synthetic polymers that fail to reproduce the biological and physical cues found in native tissues. Mimicking the structure and the composition of native tubular tissues to elaborate functional grafts is expected to outperform the materials currently in use, but remains one of the most challenging goals in the field of biomaterials. Despite their apparent diversity, tubular tissues share extensive compositional and structural features. Here, we assess the current state of the art through a dual layer model, reducing each tissue to an inner epithelial layer and an outer muscular layer. Based on this model, we examine the current strategies developed to mimic each layer and we underline how each fabrication method stands in providing a biomimetic material for future clinical translation. The analysis provided here, addressed to materials chemists, biomaterials engineers and clinical staff alike, sets new guidelines to foster the elaboration of new biomimetic materials for effective tubular tissue repair.
|
Isabelle Martinier; Léa Trichet; Francisco Fernandes
|
Materials Science; Biocompatible Materials; Biological Materials; Materials Processing
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-05-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/663505d291aefa6ce113d9b8/original/biomimetic-materials-to-replace-tubular-tissues.pdf
|
612f1ac2b817b42b240fe1c3
|
10.26434/chemrxiv-2021-79qhk
|
Bacteria Lectin Recognition Towards Fucose Binding Motifs Highlights the Impact of Presenting Mucin Core Glycopeptides
|
Mucin glycoproteins are essential components of the mucosal protective barrier, which constantly senses and clears the host from pathogens. Throughout evolution, bacteria and virus have developed strategies to modulate and penetrate the mucosal barrier and cause virulence by interacting with the glycans of membrane-bound mucins at the epithelial cell-surface. These interactions may promote bacteria cell-adhesion, biofilm formation, protein toxin delivery, or cause an inflammatory environment. O-fucosylated glycan epitopes are commonly found on mucin glycoproteins, and are key ligands of many bacterial and viral lectins (glycan binding proteins). Herein we describe a chemoenzymatic synthesis strategy to efficiently prepare an extensive library of fucosylated mucin core tandem repeats glycopeptides to elucidate the fine fucose-binding specificities of the Pseudomonas aeruginosa lectin LecB and the Clostridium difficile toxin A. Therefore, glycan core structures were decorated with terminal Lewis and H-antigens, which play critical roles in infection biology. The fucosylated mucin glycopeptides were applied in microarray binding studies to explore the importance of the glycan and peptide backbone presentation of these terminal antigens in binding interactions with the two bacterial lectins.
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Sandra Behren; Jin Yu; Christian Pett; Manuel Shorlemer; Viktoria Heine; Thomas Fischöder; Lothar Elling; Ulrika Westerlind
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Biological and Medicinal Chemistry; Organic Chemistry; Bioorganic Chemistry; Chemical Biology
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CC BY NC ND 4.0
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CHEMRXIV
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2021-09-01
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/612f1ac2b817b42b240fe1c3/original/bacteria-lectin-recognition-towards-fucose-binding-motifs-highlights-the-impact-of-presenting-mucin-core-glycopeptides.pdf
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66f1a66112ff75c3a13f4239
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10.26434/chemrxiv-2024-4w549
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Chemoproteomic mapping of the N-terminal cysteinome
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The oxidation status of N-terminal cysteines directly dictates protein stability via arginylation and proteasomal degradation. However, only a handful of proteins have been shown to be regulated via this pathway. To date, no methods to detect N-terminal cysteine reactivity and abundance has been reported. Here, we demonstrate, for the first time, that N-terminal cysteine targeting probes can be used in living cells to bind and quantify N-terminal cysteines, discriminating their oxidation state. Using these probes, we identify hundreds of N-terminal cysteines and show that changes in reactivity and abundance under hypoxia can be directly detected. We believe the use of these types of probes will significantly expand our knowledge of this important proteolytic pathway.
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Esben Svenningsen; Fatih Demir; Florian Kromm; Anna Rahimic; David Olagnier; Markus Rinschen; Thomas Poulsen
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Biological and Medicinal Chemistry; Biochemistry; Cell and Molecular Biology; Chemical Biology
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CC BY NC ND 4.0
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CHEMRXIV
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2024-09-24
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66f1a66112ff75c3a13f4239/original/chemoproteomic-mapping-of-the-n-terminal-cysteinome.pdf
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60c74cbd702a9bec8818b71f
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10.26434/chemrxiv.12540233.v1
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A Stoichiometric and Pseudo Kinetic Model of Loop Mediated Isothermal Amplification
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<p>Loop mediated isothermal amplification (LAMP) is one of the most popular isothermal DNA amplification techniques for research and commercial applications. The LAMP mechanism is powered by strategic primer design and a strand displacement polymerase, generating products that fold over, creating loops. LAMP leads to generation of products of increasing length over time. These products containing multiple loops are conventionally called cauliflower structures. Existing literature on LAMP provides extremely limited understanding of progression of cascades of reactions involved in the reaction and it is believed that cauliflower structures of increasing length constitute a majority of the product formed in LAMP. This study presents a first of its kind stoichiometric and pseudo kinetic model to comprehend LAMP reactions in deeper depth by (i) classifying LAMP reaction products into uniquely identifiable categories, (ii) generating a condensed reaction network to depict millions of interconnected reactions occurring during LAMP, and (iii) elucidating the pathways for amplicon generation. Despite the inherent limitations of conventional stoichiometric modelling for polymerization type reactions (the network rapidly becomes too large and intractable), our model provides new theoretical understanding of the LAMP reaction pathway. The model shows that while longer length products are formed, it is the smaller length recycle amplicons that contribute more towards the exponential increase in the amount of double stranded DNA. Prediction of concentration of different types of LAMP amplicons will also contribute substantially towards informing design of probe-based assays. </p>
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Navjot Kaur; Nikhil Thota; Bhushan Toley
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Computational Chemistry and Modeling
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CC BY NC ND 4.0
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CHEMRXIV
|
2020-06-24
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74cbd702a9bec8818b71f/original/a-stoichiometric-and-pseudo-kinetic-model-of-loop-mediated-isothermal-amplification.pdf
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60c73d0ef96a0079df285cf7
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10.26434/chemrxiv.5373835.v1
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Facile Fabrication of Ultralow-Density Transparent Boehmite Nanofiber Cryogel Monoliths and Their Application in Volumetric Three-Dimensional Displays
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Low bulk density transparent porous monoliths have unique optical properties such as low refractive index and usually can be obtained via supercritical drying to prevent deformation and collapse of pore structure. We succeeded in fabricating a transparent cryogel with a bulk density of 3.5 mg cm<sup>−3</sup> by vacuum freeze drying of a monolithic wet gel composed of boehmite nanofibers. In the case of adding a functional material into the starting sol of the gel, a composite material can be obtained. We analyzed the optical properties of transparent cryogels using image processing (direct-global separation) and applied the composite with a fluorescent molecule to volumetric three-dimensional (3D) displays.
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Gen Hayase; Takuya Funatomi; Kota Kumagai
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Optical Materials; Nanostructured Materials - Nanoscience
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CC BY NC ND 4.0
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CHEMRXIV
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2018-06-25
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d0ef96a0079df285cf7/original/facile-fabrication-of-ultralow-density-transparent-boehmite-nanofiber-cryogel-monoliths-and-their-application-in-volumetric-three-dimensional-displays.pdf
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644369f8df78ec50152e17e4
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10.26434/chemrxiv-2023-nrhcf
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A tutorial mini-review on nanoporous carbons from biosourced building blocks: ordered hierarchical nanoarchitectures through benign methodologies
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Ordered hierarchically porous carbons exhibiting micro- and mesopores are state-of-the-art porous structures with extraordinary performance in a range of applications (e.g., electrochemistry, catalysis, water treatment). Nevertheless, they are mostly prepared using petroleum-based chemicals, through resource- and energy-intensive, environmentally unfriendly processes. In this tutorial mini-review, we highlight major limitations in the methodologies, and showcase important achievements towards developing more sustainable synthetic strategies. Compared to multi-step hard-templating/nano-casting procedures, soft-templating techniques can provide more efficient, benign, and direct ways to produce these nanostructures. The original soft-templating method, using Pluronic® surfactants as structure-directing agents and phenolic resins as carbon precursors, has been substantially modified over the years in light of sustainability issues. The formaldehyde crosslinker has been replaced with more benign, less toxic alternatives (e.g., glyoxal), and catalyst-free crosslinking approaches have been developed. Furthermore, the use of biobased building-blocks for the carbon precursor, such as lignin, plant-derived polyphenols (e.g., tannins), and various saccharides (e.g., D-glucose, D-fructose), has also been explored. Novel techniques, such as the coordination-induced self-assembly, mechanosynthesis, and modified hydrothermal treatment strategies are amongst the greenest processes developed so far. We give some critical comments on ongoing research in this field and point towards interesting research directions.
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Laszlo Szabo; Wim Thielemans; Jin Won Seo; Frank Buysschaert; Dionysios D. Dionysiou; Veerle Vandeginste
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Materials Science; Nanoscience; Chemical Engineering and Industrial Chemistry; Biological Materials; Carbon-based Materials; Nanostructured Materials - Materials
|
CC BY NC ND 4.0
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CHEMRXIV
|
2023-04-25
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/644369f8df78ec50152e17e4/original/a-tutorial-mini-review-on-nanoporous-carbons-from-biosourced-building-blocks-ordered-hierarchical-nanoarchitectures-through-benign-methodologies.pdf
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62322ae1d6d3ed5e42941285
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10.26434/chemrxiv-2022-606xv
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Part-per-trillion trace selective gas detection using frequency locked whispering gallery mode microtoroids
|
Rapid detection of toxic and hazardous gases at trace concentrations plays a vital role in industrial, battlefield, and laboratory scenarios. Of interest are both sensitive as well as highly selective sensors. Whispering gallery mode (WGM) microresonator-based biochemical sensors are among the most sensitive sensors in existence due to their long photon confinement times. One main concern with these devices, however, is their selectivity towards specific classes of target analytes. Here, we employ frequency locked whispering gallery mode microtoroid optical resonators covalently modified with various polymer coatings to selectively detect the chemical warfare agent surrogate diisopropyl methylphosphonate (DIMP) as well as the toxic industrial chemicals formaldehyde and ammonia at parts-per-trillion concentrations. This is 1-2 orders of magnitude better than previously reported, depending on the target, except for pristine graphene and pristine carbon nanotube sensors, which demonstrate similar detection levels but in vacuum and without selectivity. Selective polymer coatings include polyethylene glycol (PEG) for DIMP sensing, accessed by the modification of commercially available materials, and 3-(triethoxysilyl)propyl-terminated polyvinyl acetate (PVAc) for ammonia sensing. Notably, we developed an efficient one-pot procedure to access 3-(triethoxysilyl)propyl-terminated PVAc that utilizes cobalt-mediated living radical polymerization and a nitroxyl polymer-terminating agent. Alkaline hydrolysis of PVAc coatings to form polyvinyl alcohol (PVA) coatings directly bound to the microtoroid proved to be reliable and reproducible, leading to WGM sensors capable of the rapid and selective detection of formaldehyde vapors. The selectivity of these three polymer coatings as sensing media was predicted, in part, based on their functional group content and known reactivity patterns with the target analytes. Furthermore, we demonstrate that microtoroids coated with a mixture of polymers can serve as an all-in-one sensor that can detect multiple agents. We anticipate that our results will facilitate rapid early detection of chemical agents, as well as their surrogates and precursors.
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Cheng Li; Trevor Lohrey; Phuong-Diem Nguyen; Zhouyang Min; Yisha Tang; Chang Ge; Zachary Sercel; Euan McLeod; Brian Stoltz; Judith Su
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Analytical Chemistry; Environmental Analysis
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CC BY NC ND 4.0
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CHEMRXIV
|
2022-03-18
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62322ae1d6d3ed5e42941285/original/part-per-trillion-trace-selective-gas-detection-using-frequency-locked-whispering-gallery-mode-microtoroids.pdf
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653bcc60a8b423585a6038c4
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10.26434/chemrxiv-2023-x9jtz
|
Physical Separation of Enantiomeric Products by Compartmentalized Parallel Kinetic Resolution
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Accessing each enantiomers of a chiral molecule starting from a racemic mixture remains a daunting challenge in
chemistry. Indeed, until now only few solutions exist to separate enantiomers of an equimolar mixture of a chiral precursor. In this study, we establish a new strategy to prepare simultaneously and physically separate both enantioenriched enantiomers of a molecule starting from a racemic substrate. This process combines two enantiomeric catalytic systems, working in parallel and a separation by an achiral membrane with selective permeability. This unprecedented system was successfully applied to the simultaneous preparation of both enantiomers of chiral 1,2-diols starting from racemic epoxides using Jacobsen’s hydrolytic kinetic resolution (HKR) in parallel.
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Jingke Hou; Sabine Chevallier-Michaud; Marion Jean; Luc Favre; Damien Hérault; Cyril Bressy
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Organic Chemistry; Catalysis; Stereochemistry; Homogeneous Catalysis
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CC BY 4.0
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CHEMRXIV
|
2023-10-30
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/653bcc60a8b423585a6038c4/original/physical-separation-of-enantiomeric-products-by-compartmentalized-parallel-kinetic-resolution.pdf
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6627ca93418a5379b07e3b6e
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10.26434/chemrxiv-2024-h2x2b
|
More than an Amide Bioisostere: Discovery of 1,2,4-Triazole-containing Pyrazolo[1,5-a]pyrimidine Host CSNK2 Inhibitors for Combatting β-Coronavirus Replication
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The pyrazolo[1,5-a]pyrimidine scaffold is a promising scaffold to develop potent and selective CSNK2 inhibitors with antiviral activity against β-coronaviruses. Herein, we describe the discovery of a 1,2,4-triazole group to substitute a key amide group for CSNK2 binding present in many potent pyrazolo[1,5-a]pyrimidine inhibitors. Crystallographic evidence demonstrates that the 1,2,4-triazole replaces the amide in forming key hydrogen bonds with Lys68 and a water molecule buried in the ATP-binding pocket. This isosteric replacement improves potency and metabolic stability at a cost of solubility. Optimization for potency, solubility and metabolic stability led to the discovery of the potent and selective CSNK2 inhibitor 53. Despite excellent in vitro metabolic stability, rapid decline in plasma concentration of 53 in vivo was observed and may be attributed to lung accumulation, although in vivo pharmacological effect was not observed. Further optimization of this novel chemotype may validate CSNK2 as an antiviral target in vivo.
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Han Wee Ong; Xuan Yang; Jeffery Smith; Rebekah Dickmander; Jason Brown; Tammy Havener; Sharon Taft-Benz; Stefanie Howell; Marcia Sanders; Jacob Capener; Rafael Couñago; Edcon Chang; Andreas Krämer; Nathaniel Moorman; Mark Heise; Alison Axtman; David Drewry; Timothy Willson
|
Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems
|
CC BY NC ND 4.0
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CHEMRXIV
|
2024-04-24
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6627ca93418a5379b07e3b6e/original/more-than-an-amide-bioisostere-discovery-of-1-2-4-triazole-containing-pyrazolo-1-5-a-pyrimidine-host-csnk2-inhibitors-for-combatting-coronavirus-replication.pdf
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60c752479abda20e13f8ddb1
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10.26434/chemrxiv.13280471.v1
|
Unknown Knowns: Case Studies in Uncertainties in the Computation of Thermochemical Parameters
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<div>Both the computation of, and the uncertainties associated, with gas-phase molar
formation enthalpies are now quite well established for systems comprised of tens of
‘heavy’ atoms chosen from the commonest elements. The same cannot be said for
derived thermochemical quantities such as entropy, heat capacity and an enthalpy
function. Whilst the application of well known statistical thermodynamic relations is
mostly understood, the determination of the uncertainty with which such values can
be obtained has been little studied — apart, that is, for a general protocol devised by
Goldsmith et al. [J. Phys. Chem. A, 2012, 116, 9033–9057]. Specific examples from
that work are explored here and it is shown that their estimates are overly pessimistic.
It is also evident that for some species the calculated thermochemical parameters show
very little variation with either the level of theory, or basis set, or treatment of vibrational modes — this renders the inclusion of such species in databases designed to
validate new methods of limited value.<br /></div>
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John Simmie
|
Chemical Kinetics; Physical and Chemical Properties; Thermodynamics (Physical Chem.)
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CC BY NC ND 4.0
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CHEMRXIV
|
2020-11-25
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c752479abda20e13f8ddb1/original/unknown-knowns-case-studies-in-uncertainties-in-the-computation-of-thermochemical-parameters.pdf
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63d904b1d1857ca6d6a24655
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10.26434/chemrxiv-2021-m20gg-v3
|
Language models can identify enzymatic active sites in protein sequences
|
Recent advances in language modeling have tremendously impacted how we handle sequential data in science. Language architectures have emerged as a hotbed of innovation and creativity in natural language processing over the last decade, and have since gained prominence in modeling proteins and chemical processes, elucidating structural relationships from textual/sequential data. Surprisingly, some of these relationships refer to three-dimensional structural features, raising important questions on the dimensionality of the information contained in sequential data. We demonstrate that the unsupervised use of a language model architecture to a language representation of bio-catalyzed chemical reactions can capture the signal at the base of the substrate-active site atomic interactions, identifying the three- dimensional active site position in unknown protein sequences. The language representation comprises a reaction-simplified molecular-input line-entry system (SMILES) for substrate and products, and amino acid sequence information for the enzyme. This approach can recover, with no supervision, 52.12% of the active site when considering co-crystallized substrate-enzyme structures as ground truth, vastly outperforming other attention-based models.
|
Yves Gaetan Nana Teukam; Loïc Kwate Dassi; Matteo Manica; Daniel Probst; Philippe Schwaller; Teodoro Laino
|
Theoretical and Computational Chemistry; Catalysis; Machine Learning; Artificial Intelligence; Biocatalysis; Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-02-02
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63d904b1d1857ca6d6a24655/original/language-models-can-identify-enzymatic-active-sites-in-protein-sequences.pdf
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66b3977901103d79c50ec7ff
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10.26434/chemrxiv-2024-k42rz
|
Effects of Anion Size, Shape, and Solvation in Binding of Nitrate to Octamethyl Calix[4]Pyrrole
|
We present cryogenic ion vibrational spectroscopy of complexes of the anion receptor octamethyl calix[4]pyrrole (omC4P) with nitrate in vacuo. We compare the resulting vibrational spectrum with that in deuterated acetonitrile solution, and we interpret the results using density functional theory. Nitrate binds to omC4P through H-bonds between the four NH groups of the receptor and a single NO group of the nitrate ion. The shape of the ion breaks the C4v symmetry of the receptor, and this symmetry lowering is encoded in the pattern of the NH stretching modes of omC4P. We compare the spectrum of nitrate-omC4P with that of chloride-omC4P to discuss effects of ion size, shape, and solvent interaction on the ion binding behavior.
|
Lane M. Terry; Madison M. Foreman; J. Mathias WEBER
|
Physical Chemistry; Spectroscopy (Physical Chem.); Structure
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-08-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66b3977901103d79c50ec7ff/original/effects-of-anion-size-shape-and-solvation-in-binding-of-nitrate-to-octamethyl-calix-4-pyrrole.pdf
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63d1b95cfa87eb5cf354d4d3
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10.26434/chemrxiv-2023-648xm
|
Palladium responsive liposomes for triggered release of
aqueous contents
|
Palladium (Pd) is a promising metal catalyst for novel bioorthogonal chemistry and prodrug activation This report describes the first example of palladium responsive liposomes. The key molecule is a new caged phospholipid called Alloc-PE that forms stable liposomes (large unilamellar vesicles, ~220 nm diameter). Liposome treatment with PdCl2 removes the chemical cage, liberates membrane destabilizing dioleoylphosphoethanolamine (DOPE), and triggers liposome leakage of encapsulated aqueous contents. The results indicate a path towards liposomal drug delivery technologies that exploit transition metal trig-gered leakage.
|
Bradley Smith; Jordan Chasteen; Sasha Padilla-Coley; Dong-Hao Li
|
Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-01-30
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63d1b95cfa87eb5cf354d4d3/original/palladium-responsive-liposomes-for-triggered-release-of-aqueous-contents.pdf
|
67c6d9496dde43c9086f3263
|
10.26434/chemrxiv-2025-djtpm
|
Integration of Micro-encapsulated Phase Change Materials into Thin Coatings for a Passive Battery Thermal Management System
|
Exploiting the heat energy storage capability of phase change materials is emerging as a potential new strategy for managing Li-ion cell temperature changes during cycling. Phase change materials present a solution that is lighter and more energy efficient than current active battery thermal management systems. However, deploying phase change materials for battery thermal management is currently held back by the leaking of material when melted, incongruent melting, and low thermal conductivity. In order to solve these problems, micro-encapsulation, the formation of a core-shell capsule, has been used in this work. Encapsulation protects against leakage and the shell properties can be used to increase thermal conductivity. In this work, micro-encapsulated octadecane (C18H38) comprising a carbon composite-based shell made up of graphene oxide and carbon nanotubes, was selected to maintain a temperature of 27 °C. The synthesised capsules were formulated into a coating and applied onto the exterior of cylindrical,1.6 Ah, Li-ion cells. The coating delivered a heat storage capacity of 100 J·g-1, and thermal imaging of cells showed that the average peak increase in cell temperature during galvanostatic cycling was reduced by 8 °C when the coating was applied. The optimum coating thickness was found to be 3 mm, increasing the cell mass by 10-15%. Furthermore, the coatings delivered a cell temperature reduction of 4 °C during a modified European drive cycle, highlighting good functionality towards practical cell usage.
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Matthew J. Quarrell; Robert Batty; Alex R. Neale; Daniel H. S. Harvey; Dmitry Shchukin; Laurence J. Hardwick
|
Physical Chemistry; Materials Science; Electrochemistry - Mechanisms, Theory & Study
|
CC BY 4.0
|
CHEMRXIV
|
2025-03-06
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67c6d9496dde43c9086f3263/original/integration-of-micro-encapsulated-phase-change-materials-into-thin-coatings-for-a-passive-battery-thermal-management-system.pdf
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661e6dc591aefa6ce1ad2859
|
10.26434/chemrxiv-2024-g4wkt
|
Operando Photoelectron Spectroscopy Analysis of Li6PS5Cl Electrochemical Decomposition Reactions in Solid-State Batteries
|
Most solid electrolytes (SEs) which are promising for all-solid-state battery (ASSB) applications are known to have a narrow electrochemical stability window. Consequently, parasitic electrolyte reactions are observed when high-energy-density electrode materials such as lithium and silicon are employed, hindering their utilization in commercial battery systems. Therefore, it is crucial to understand at which potentials such reactions start, and which chemical species are present in the subsequently formed solid electrolyte interphase (SEI). Herein, a new operando experimental approach is introduced to investigate such reactions by employing hard X-ray photoelectron spectroscopy (HAXPES). This approach enables the examination of the SEI formed below a thin metal film (e.g., 6 nm nickel) acting as the working electrode. The feasibility of this approach is demonstrated using a sulfide-based Li6PS5Cl solid electrolyte (lithium argyrodite). It is shown that electrolyte reduction reactions start upon polarization of the working electrode to voltages below 1.75 V (vs. Li+/Li) and result in considerable Li2S formation, particularly in the voltage range of 1.5 – 1.0 V. The overall intensity trends confirm the heterogeneous/layered microstructure of the SEI (e.g., preferential Li2O and Li2S deposition near the current collector). The reversibility of side reactions is also observed, as Li2O and Li2S decompose in the 2–4 V potential window, generating oxidized sulfur species, sulfites and sulfates. The introduced experimental approach is promising for the spectroscopic investigation of electrolyte side reactions under dynamic conditions for various solid electrolyte and current collector combinations.
|
Burak Aktekin; Elmar Kataev; Luise M. Riegger; Raul Garcia-Diez; Zora Chalkley; Juri Becker; Regan G. Wilks; Anja Henss; Marcus Bär; Jürgen Janek
|
Physical Chemistry; Inorganic Chemistry; Energy; Electrochemistry; Interfaces
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-04-17
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/661e6dc591aefa6ce1ad2859/original/operando-photoelectron-spectroscopy-analysis-of-li6ps5cl-electrochemical-decomposition-reactions-in-solid-state-batteries.pdf
|
670f13aecec5d6c142453995
|
10.26434/chemrxiv-2024-6dncp
|
Inverting Conventional Chemoselectivity of Metal Carbenes with Sulfenylcarbenes for Late-Stage Functionalizations
|
Late-stage functionalization (LSF) is a crucial strategy in drug discovery, allowing the modification of complex molecules, including pharmaceuticals, to enhance chemical diversity in drug libraries. In this study, we leverage the unique reactivity of sulfenylcarbenes, which exhibit inverse chemoselectivity compared to metal carbenes. Notably, they selectively react with alkenes in the presence of more reactive functionalities like alcohols, carboxylic acids, and amines. This reactivity allows sulfenylcarbenes to insert a single carbon atom bearing diverse functional groups, transforming pyrrole, indole, and imidazole scaffolds into synthetically challenging pyridines, quinolines, and pyrimidines, respectively. Our metal-free LSF approach employs benchtop-stable sulfenylcarbene precursors compatible with various functional groups and enables late-stage modification of natural products, amino acids, and pharmaceuticals. Mechanistic studies and DFT calculations were conducted to investigate the regioselectivity outcomes.
|
Prakash Kafle; Deacon Herndon; Indrajeet Sharma
|
Organic Chemistry; Organic Synthesis and Reactions
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-10-17
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/670f13aecec5d6c142453995/original/inverting-conventional-chemoselectivity-of-metal-carbenes-with-sulfenylcarbenes-for-late-stage-functionalizations.pdf
|
619741c12e10adf3a34d7205
|
10.26434/chemrxiv-2021-10hk4
|
Dynamic Catalysis Fundamentals: I. Fast calculation of limit cycles in dynamic catalysis
|
Dynamic catalysis—the forced oscillation of catalytic reaction coordinate potential energy surfaces (PES)—has recently emerged as a promising method for the acceleration of heterogeneously-catalyzed reactions. Theoretical study of enhancement of rates and supra-equilibrium product yield via dynamic catalysis has, to-date, been severely limited by onerous computational demands of forward integration of stiff, coupled ordinary differential equations (ODEs) that are necessary to quantitatively describe periodic cycling between PESs. We establish a new approach that reduces, by ≳108×, the computational cost of finding the time-averaged rate at dynamic steady state (i.e. the limit cycle for linear and nonlinear systems of kinetic equations). Our developments are motivated by and conceived from physical and mathematical insight drawn from examination of a simple, didactic case study for which closed-form solutions of rate enhancement are derived in explicit terms of periods of oscillation and elementary step rate constants. Generalization of such closed-form solutions to more complex catalytic systems is achieved by introducing a periodic boundary condition requiring the dynamic steady state solution to have the same periodicity as the kinetic oscillations and solving the corresponding differential equations by linear algebra or Newton-Raphson-based approaches. The methodology is well-suited to extension to non-linear systems for which we detail the potential for multiple solutions or solutions with different periodicities. For linear and non-linear systems alike, the acute decrement in computational expense enables rapid optimization of oscillation waveforms and, consequently, accelerates understanding of the key catalyst properties that enable maximization of reaction rates, conversions, and selectivities during dynamic catalysis.
|
Brandon Foley; Neil Razdan
|
Catalysis; Electrocatalysis; Heterogeneous Catalysis; Photocatalysis
|
CC BY NC 4.0
|
CHEMRXIV
|
2021-11-22
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/619741c12e10adf3a34d7205/original/dynamic-catalysis-fundamentals-i-fast-calculation-of-limit-cycles-in-dynamic-catalysis.pdf
|
652ee76c45aaa5fdbb376715
|
10.26434/chemrxiv-2023-79t7l
|
Electrothermal mineralization of per- and polyfluoroalkyl substances (PFAS) for soil remediation
|
Per- and polyfluoroalkyl substances (PFAS) are persistent and bioaccumulative pollutants that can easily accumulate in soil, posing threat to environment and human health. Current PFAS degradation processes often suffer from low efficiency, high energy and water consumption, or lack of generality. Here, we develop a rapid electrothermal mineralization (REM) process to remediate PFAS-contaminated soil. With environmentally compatible biochar as conductive additive, the soil temperature increases to >1000 °C within seconds by direct current pulse input, converting PFAS to calcium fluoride with inherent calcium compounds in soil. The general electrical mineralization process is applicable for remediating various PFAS contaminants in soil, with high removal efficiencies (>99.9%) and mineralization ratios (>90%). While retaining soil particle size, composition and water infiltration rate, REM facilitates an increase of exchangeable nutrient supply and arthropod survival in soil. REM has a significant reduction of energy consumption and greenhouse gas emission over existing soil remediation practices.
|
Yi Cheng; Bing Deng; Phelecia Scotland; Lucas Eddy; Arman Hassan; Bo Wang; Bowen Li; Kevin Wyss; Mine Ucak-Astarlioglu; Jinhang Chen; Tengda Si; Shichen Xu; Xiaodong Gao; Khalil JeBailey; Debadrita Jana; Mark Torres; Michael Wong; Boris Yakobson; Christopher Griggs; Matthew McCary; Yufeng Zhao; James Tour
|
Earth, Space, and Environmental Chemistry; Environmental Science; Soil Science; Wastes; Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-10-19
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/652ee76c45aaa5fdbb376715/original/electrothermal-mineralization-of-per-and-polyfluoroalkyl-substances-pfas-for-soil-remediation.pdf
|
612a8fd5abeb63cd47c2e91e
|
10.26434/chemrxiv-2021-9mh36
|
Intramolecular Charge Transfer in the Azathioprine Prodrug Quenches Intersystem Crossing to the Reactive Triplet State in 6-Mercaptopurine
|
The thiopurine prodrugs 6-mercaptopurine and azathioprine are among the world’s essential medications for acute lymphoblastic leukemia, immunosuppression, and several autoimmune conditions. Thiopurine prodrugs are efficient UVA absorbers and singlet oxygen generators and the long-term treatment with these prodrugs correlates with a high incidence of sunlight-induced skin cancer in patients. In this contribution, we show that the electronic relaxation mechanisms and photochemical properties of azathioprine are remarkably different from those of 6-mercaptopurine upon absorption of UVA radiation. UVA excitation of 6-mercaptopurine results in nearly 100% triplet yield and up to 30% singlet oxygen generation, whereas excitation of azathioprine with UVA leads to triplet yields of 15 to 3% depending on pH of the aqueous solution and less than 1% singlet oxygen generation. While photoexcitation of 6-mercaptopurine and other thiopurine prodrugs can facilitate oxidatively generated cell damage, azathioprine’s poor photosensitization ability reveals the use of interchromophoric charge transfer interactions for the molecular design of photostable prodrugs exhibiting a remarkable reduction in photocytotoxic side effects before drug metabolization.
|
Luis A. Ortiz-Rodríguez; Glesmarie Ortiz-Zayas; Marvin Pollum; Sean J. Hoehn; Steffen Jockusch; Carlos Crespo-Hernández
|
Theoretical and Computational Chemistry; Physical Chemistry; Biological and Medicinal Chemistry; Biophysics; Chemical Kinetics; Photochemistry (Physical Chem.)
|
CC BY 4.0
|
CHEMRXIV
|
2021-08-30
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/612a8fd5abeb63cd47c2e91e/original/intramolecular-charge-transfer-in-the-azathioprine-prodrug-quenches-intersystem-crossing-to-the-reactive-triplet-state-in-6-mercaptopurine.pdf
|
63b78e9474e09517dd0fe690
|
10.26434/chemrxiv-2023-81ng7
|
Post-functionalization and Mechanical Properties of Poly(lactide-cyclohexadiene oxide) Block Copolymers
|
A series of lactide (LA) and cyclohexadiene oxide (CHDO) multiblock copolymers was synthesized using a redox switchable complex, (salfen)Zr(OiPr)2 (salfen = N,N’-bis(2,4-di-tert-butylphenoxy)-1,1’-ferrocenediimine), with LA being polymerized by the reduced state, while CHDO was polymerized by the oxidized state of the catalyst. Diblock (PCHDO-PLA) and triblock (PLA-PCHDO-PLA and PCHDO-PLA-PCHDO) copolymers were prepared, and all the copolymers were post-functionalized using a thiol-ene click reaction. Dynamic mechanical analysis showed that both triblock copolymers have a better elasticity than the diblock copolymer, and all the functionalized copolymers have a better elasticity than the corresponding non-functionalized copolymers.
|
Ruxi Dai; Shijie Deng; Zihang Peng; Qibing Pei; Paula Diaconescu
|
Polymer Science; Biopolymers; Polymerization (Polymers); Polymerization catalysts
|
CC BY NC 4.0
|
CHEMRXIV
|
2023-01-06
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63b78e9474e09517dd0fe690/original/post-functionalization-and-mechanical-properties-of-poly-lactide-cyclohexadiene-oxide-block-copolymers.pdf
|
60c7442f702a9b7d9218a75d
|
10.26434/chemrxiv.9752918.v1
|
Counting the Number of Glutamate Molecules in Single Synaptic Vesicles
|
<div><p>Analytical tools for direct quantitative measurements of glutamate, the principal excitatory neurotransmitter in brain, are lacking. Here, we introduce a new enzyme-based amperometric sensor technique for direct counting of the number of glutamate molecules stored inside single synaptic vesicles. An ultra-fast enzyme-based glutamate sensor is placed into a solution of isolated synaptic vesicles, which stochastically rupture at the sensor surface in a potential dependent manner by applying a constant negative potential. High-speed (10 kHz) amperometry is used to record sub-millisecond current spikes, which represent glutamate release from single vesicles that burst open. Glutamate quantification is achieved by a calibration curve that is based on measurements of glutamate release from vesicles pre-filled with various concentrations of glutamate. Our measurements show that a single synaptic vesicle encapsulates about 8000 glutamate molecules, which is comparable to the measured exocytotic quantal glutamate release in the nucleus accumbens of mouse brain tissue. Hence, this new methodology introduces the means to quantify ultra-small amounts of glutamate and to study synaptic vesicle physiology, pathogenesis and drug treatments for neuronal disorders where glutamate is involved.</p></div>
|
Yuanmo Wang; Hoda fathali; devesh mishra; Thomas Olsson; Jacqueline Keighron; karolina skibicka; Ann-Sofie Cans
|
Electrochemical Analysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2019-09-03
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7442f702a9b7d9218a75d/original/counting-the-number-of-glutamate-molecules-in-single-synaptic-vesicles.pdf
|
669a9741c9c6a5c07adee852
|
10.26434/chemrxiv-2024-hgp3j
|
A Genetically Encoded Thiophenol Recruits Noble Metals for Designer Enzymes
|
The catalytic repertoire of nature has been expanded over the past decades by the introduction of artificial metalloenzymes. These are enzymes containing a synthetic metal complex or a non-native metal ion. However, combining noble metal catalysis and enzymes remains challenging due to the lack of suitable ligands to bind these complexes. So far, noble metal artificial metalloenzyme design mostly involves in vitro approaches of ligand anchoring, like covalent modification of a cysteine residue or via supramolecular assembly. Here, we show a facile strategy to anchor a variety of 4d and 5d-transition metal complexes via genetic incorporation of a thiophenolic metal-binding ligand. We created a methodology to efficiently incorporate 4-mercaptophenylalanine in a protein scaffold using the stop codon suppression technology. The incorporated non-canonical amino acid was capable of binding a variety of noble metal complexes. To showcase the catalytic applications of this methodology, we developed an artificial hydroaminase by binding gold ions to the thiophenol-containing protein. The benefit of in vivo incorporation of the ligand is demonstrated by the susceptibility of catalytic activity to the microenvironment around the metal site, which can be modulated by changing the position of the ligand within the protein or by mutation of residues in its proximity.
|
Mathijs J. Veen; Friso S. Aalbers; Henriëtte J. Rozeboom; Andy-Mark W. H. Thunnissen; Daniel F. Sauer; Gerard Roelfes
|
Biological and Medicinal Chemistry; Catalysis; Biochemistry; Biocatalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-07-22
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/669a9741c9c6a5c07adee852/original/a-genetically-encoded-thiophenol-recruits-noble-metals-for-designer-enzymes.pdf
|
64b7837cb605c6803bfb0834
|
10.26434/chemrxiv-2023-h7tsp-v3
|
Identification of Unknown Inverted Singlet-Triplet Cores by High--Throughput Virtual Screening
|
Molecules where the energy of the lowest excited singlet state is found below the energy of the lowest triplet state (inverted singlet-triplet molecules) are extremely rare. It is particularly challenging to discover new ones through virtual screening because the required wavefunction-based methods are expensive and unsuitable for high-throughput calculations. Here, we devised a virtual screening approach where the molecules to be considered with advanced methods are pre-selected with increasingly more sophisticated filters that include the evaluation of the HOMO-LUMO exchange integral and approximate CASSCF calculations. A final set of 7 candidates (0.05\% of the initial 15000) were verified to possess inversion between singlet and triplet states with state-of-the-art multireference methods (MS--CASPT2). One of them is deemed of particular interest because it is unrelated to other proposals made in the literature.
|
Omer Omar; Xiaoyiu Xie; Alessandro Troisi; Daniele Padula
|
Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational; Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-07-19
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64b7837cb605c6803bfb0834/original/identification-of-unknown-inverted-singlet-triplet-cores-by-high-throughput-virtual-screening.pdf
|
60c749890f50db2ba73968fe
|
10.26434/chemrxiv.12058914.v1
|
Posttranscriptional Site-Directed Spin Labeling of Large RNAs with an Unnatural Base Pair System Under Non-Denaturing Conditions
|
<div>
<p>Site-directed
spin labeling (SDSL) of large RNAs for electron paramagnetic resonance (EPR)
spectroscopy remains challenging up-to-date. We here demonstrate an efficient
and generally applicable posttranscriptional SDSL method for large RNAs under
non-denaturing conditions using an expanded genetic alphabet containing the
NaM-TPT3 unnatural base pair (UBP). An alkyne-modified TPT3 ribonucleotide
triphosphate (rTPT3<sup>CO</sup>TP) is synthesized and site-specifically
incorporated into large RNAs by <i>in vitro</i>
transcription, which allows attachment of the azide-containing nitroxide
through click chemistry. We validate this strategy using a 419-nucleotide
Ribonuclease P (RNase P) RNA
from Bacillus <i>stearothermophilus. </i>The
effects of site-directed UBP incorporation and subsequent spin labeling to
global structure and function of RNase P are marginal as evaluated by Circular
Dichroism spectroscopy, Small Angle X-ray Scattering, and enzymatic assay.
Continuous-wave EPR analyses reveal that the labeling reaction is efficient and
specific, and Pulsed Electron-Electron Double Resonance measurements yield an inter-spin distance
distribution that agrees well with the crystal structure. Thus, the labeling
strategy as presented overcomes the size constraint of RNA labeling, opening
new possibilities for application of EPR spectroscopy in investigating
structure and dynamics of large RNA.</p>
</div>
<br />
|
Yan Wang; Venkatesan Kathiresan; Yaoyi Chen; Yanping Hu; Wei Jiang; Guangcan Bai; Guoquan Liu; Peter Z. Qin; Xianyang Fang
|
Biochemistry; Biophysics; Chemical Biology
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-04-06
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c749890f50db2ba73968fe/original/posttranscriptional-site-directed-spin-labeling-of-large-rn-as-with-an-unnatural-base-pair-system-under-non-denaturing-conditions.pdf
|
675a1198f9980725cfc4d713
|
10.26434/chemrxiv-2024-51r39
|
The Effects of Chitosan Source on the Properties of 3D Printed Polymer Composites
|
Chitosan, or deacetylated chitin, is a linear polysaccharide composed of glucosamine and N-acetyl glucosamine units. Chitin is found in the cell walls of crustaceans, fungi, and insects, making chitosan the second most abundant natural polymer on earth. The broad availability of chitosan makes it an attractive material for applications in the textile, medical, and agricultural industries as well as for use in environmental waste remediation. Additive manufacturing, or 3D printing, is a technique that can be used to produce polymeric materials on demand, based on custom digital designs. Using a digital light projection (DLP) 3D printer, we incorporated chitosan from different sources into photoresins, considering different sources for their sustainability. We explored how the source of the chitosan (fungal vs. crustacean) can affect the mechanical properties, resin incorporation, and printability of the photoresin. The 3D printed materials were tested to compare the mechanical properties of the polymers with chitosan from different sources. Higher loadings of chitosan improved the strength of the printed materials. We show that chitosan with higher loading and higher molecular weights improved the mechanical properties. However, the source of the chitosan affected the incorporation and printability of the photoresins.
|
Lyndsay Ayers; Rebecca Johnson; Ariel Tolfree; Noora Al Kharji; Milinda Senarathna; Niyati Arora; Ronald Smaldone
|
Polymer Science; Biopolymers; Organic Polymers; Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-12-17
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/675a1198f9980725cfc4d713/original/the-effects-of-chitosan-source-on-the-properties-of-3d-printed-polymer-composites.pdf
|
62d455804e76bf3600934cdc
|
10.26434/chemrxiv-2022-4r4ml
|
Predicting the Partitioning Behavior of Per- and Poly-Alkyl Substances (PFAS) on Liquid-Solid Interface for Carbon and Mineral Based Surfaces using Multivariate Linear Regression Models with K-Fold Cross Validation.
|
Computational data science , especially the machine learning approach has been a major contribution to the field of engineering. In this study, data mining and machine learning were practiced estimating the partitioning of Per- and Poly-fluoroalkyl Substances (PFAS) compounds during aqueous adsorption on various adsorbent materials with a vision to potentially replace the time-consuming and labor-intensive adsorption experiments. Regression models, such as linear, tree, support vector machine (SVM), ensemble of trees, and gaussian process regression (GPR) models were trained and tested using previously published data. 290 data points and 170 data points for activated carbon and mineral adsorbents, respectively, were mined for training the models and 10 data points were used to test the trained models. Statistical parameters, such as Root-Mean-Square Error (RSME), R-Squared, Mean Average Error (MAE), Mean Squared Error (MSE), etc., were used to compare the regression models. It was found that rational quadratic GPR (R-squared = 0.9966) and fine regression tree (R-Squared = 0.9427) models had the highest estimation accuracy for carbon-based and mineral-based adsorbents, respectively. These models were then validated for prediction accuracy using 10 data points from previous studies as an outer test set. Rational quadratic GPR was able to achieve 99% prediction accuracy for carbon-based adsorbent, while fine tree regression model was able to achieve 94% prediction accuracy. Despite such high estimation accuracy, the data mining process revealed the data shortage and the need for more research on PFAS adsorption to present real-world models. This study, as one of the first, shed a light on the determination of key parameters in aquatic chemistry with data mining and machine learning approaches.
|
Harsh Patel; Hyo-shin Park; Renzun Zhao
|
Theoretical and Computational Chemistry; Organic Chemistry; Analytical Chemistry; Separation Science; Computational Chemistry and Modeling; Machine Learning
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2022-07-19
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62d455804e76bf3600934cdc/original/predicting-the-partitioning-behavior-of-per-and-poly-alkyl-substances-pfas-on-liquid-solid-interface-for-carbon-and-mineral-based-surfaces-using-multivariate-linear-regression-models-with-k-fold-cross-validation.pdf
|
66421ab491aefa6ce1dd570f
|
10.26434/chemrxiv-2024-n6w9v
|
Conjugated Small Molecules: A Promising Hole
Transport Materials in Perovskite Photovoltaics
|
There is a resurgence in the use of triphenylamine-based donor materials (TPA) in the field of perovskite photovoltaics. This work presents the synthesis of two novel conjugated small molecules (CSM's), TPA-t and TPA-t EH, which are functionalized with triisopropylsilyl groups and 2-ethylhexyl side chains. These molecules show promise as hole transport materials, which possess high hole mobilities of 1.5 × 10-4 and 2.9 × 10-3 cm2 V−1 s-1 due to self-organization. TPA-t and TPA-t EH possess HOMO energy levels at -5.38 and -5.31 eV, which is well-aligned with valence band of standard perovskite MAPbI3.This resulted in outstanding open-circuit voltages of 1100 and 1080 mV. TPA-based molecules were investigated as HTLs in n-i-p PSCs without additional doping and enabled high efficiency (17.4 %) same as for devices with state-of-the-art polytriarylamine (PTAA) HTL. The obtained results suggest that developed materials could potentially compete with PTAA when further material structure modification.
|
Ilya Martynov; aleksandra zhivchikova; Mikhail Tereshchenko; Iliya Kuznetsov; Marina Tepliakova; Alexander Akkuratov
|
Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-05-14
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66421ab491aefa6ce1dd570f/original/conjugated-small-molecules-a-promising-hole-transport-materials-in-perovskite-photovoltaics.pdf
|
678a7049fa469535b967f07a
|
10.26434/chemrxiv-2025-27pzn
|
Streamlined Identification of Metallopeptides for Intracellular Catalysis Using Positionally-Addressable Combinatorial Libraries
|
The discovery and development of artificial catalysts to carry out biorthogonal reactions in living cells is a primary goal at the interface of Chemistry and Biology. Current approaches rely on time-consuming trial-and-error methods that often fail to yield an optimal catalyst. In contrast, we show that positionally addressable combinatorial libraries (SPOT libraries) provide a significant advantage for the efficient identification of novel catalytic metallopeptides. Using these libraries, we were able to rapidly identify catalytic β-hairpin palladopeptides capable of promoting efficient depropargylation reactions, even in challenging intracellular environments.
|
Carmen González-González; Laura Martínez-Castro; Soraya Learte-Aymamí; Clara Pose-Insua; José R. Couceiro; Pau Martin-Malpartida; Maria J. Macias; Jean-Didier Maréchal; José L. mascareñas; M. Eugenio Vazquez
|
Biological and Medicinal Chemistry; Catalysis; Organometallic Chemistry; Bioinformatics and Computational Biology; Chemical Biology; Catalysis
|
CC BY NC 4.0
|
CHEMRXIV
|
2025-01-21
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/678a7049fa469535b967f07a/original/streamlined-identification-of-metallopeptides-for-intracellular-catalysis-using-positionally-addressable-combinatorial-libraries.pdf
|
6624c773418a5379b04e2ad6
|
10.26434/chemrxiv-2024-srrpj
|
Mononuclear Palladium(I) Aryl Complexes Performs Cross-Coupling Reactions with Organic Halides
|
Mononuclear Pd(I) species represent the least understood Pd intermediates in Pd-catalyzed reactions and isolable complexes of the type are exceedingly rare. Herein, we report the synthesis and characterization of mononuclear Pd(I) complexes bear-ing aryl ligands, namely [(IPr)Pd(ArTrip-R-p)] (ArTrip-R-p = 4-R-2,6-bis(2’,4’,6’-triisopropylphenyl)phenyl, R = H, CF3), as well as their reactions with organic halides. The Pd(I) aryl complexes were prepared from the reactions of [(IPr)PdCl2]2 with the corresponding aryl lithium salts and have been characterized by various spectroscopic methods. EPR spectroscopy and calculation studies suggest their Pd(I) nature. Reactivity studies using [(IPr)Pd(ArTrip-CF3-p)] as the representative revealed the capability of the Pd(I) aryl complex in activating the carbon-halogen bonds of organic iodide and benzyl halides. In the reactions with para-substituted benzyl bromides, C(aryl)-C(benzyl) cross-coupling products are formed in moderate to good yields. Kinetic studies, radical trapping experiments, and theoretical calculations point out that the cross-coupling products are likely formed from the sequential steps of stepwise oxidative addition reaction of Pd(I) aryl complex with benzyl bromide involving Pd(II) intermediate followed by reductive elimination reactions of the resulting Pd(III) intermediates.
|
Tianqi Xia; Linhong Long; Xuebing Leng; Hui Chen; Liang Deng
|
Organometallic Chemistry; Transition Metal Complexes (Organomet.)
|
CC BY 4.0
|
CHEMRXIV
|
2024-04-22
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6624c773418a5379b04e2ad6/original/mononuclear-palladium-i-aryl-complexes-performs-cross-coupling-reactions-with-organic-halides.pdf
|
60c7581d9abda20ecbf8e846
|
10.26434/chemrxiv.14501505.v1
|
Synthesis of Plakortolides E and I Enabled by Base Metal Catalysis
|
A protecting-group-free synthesis of two endoperoxide natural products, plakortolide E and plakortolide I, is reported. Key-steps feature the use of earth-abundant transition metals, consisting of a vanadium-mediated epoxidation, an iron-catalyzed allylic substitution, and a cobalt-induced endoperoxide formation. Our approach combines redox-economy, chemoselective bond-forming reactions, and telescoping into one-pot operations to forge an overall efficient synthesis.
|
Stefan Leisering; Alexandros Mavroskoufis; Patrick Voßnacker; Reinhold Zimmer; Mathias Christmann
|
Natural Products; Organic Synthesis and Reactions
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-04-29
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7581d9abda20ecbf8e846/original/synthesis-of-plakortolides-e-and-i-enabled-by-base-metal-catalysis.pdf
|
6712526451558a15ef6fcc00
|
10.26434/chemrxiv-2024-ds4gr
|
DNA scission of non-His-containing ATCUN-like peptides
|
Metallopeptides display interesting candidates for drug design from anti-cancer reagents to antimicrobials. We report the ability of non-His containing metallopeptides to perform scission of plasmid DNA exhibiting antibiotic resistance. The peptides Ac-Dap β Ala His PEG4 with an Amino-Terminal Cu(II) and Ni(II) binding (ATCUN) motif and two mutants, in which His is substituted by Ala and Asp, form complexes with Cu(II) and Ni(II) in a pH-dependent manner attributed to metal coordination. The His- and Asp-containing peptides show specificity to AT-rich DNA regions. Previously, DNA scission was only associated with His-containing ATCUN peptides of other molecular structures. Results from fluorescence displacement of Hoechst 33258 and ethidium bromide show that all three peptides bind to the DNA minor groove and this binding is enhanced in the presence of the bivalent metal ions. Molecular dynamics simulations with a DNA dodecanucleotide d(CGCGAATTCGCG) support the minor groove binding and preference for AT-rich sites for the His and Asp-containing peptides.
|
Lena Mueller; Hanna Zhdanova; Ivan Unksov; Alexander Gräwe; Joshua Stahl; Viktor Stein; Daniel Tietze; Alesia Tietze
|
Biological and Medicinal Chemistry; Bioengineering and Biotechnology; Chemical Biology
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-10-23
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6712526451558a15ef6fcc00/original/dna-scission-of-non-his-containing-atcun-like-peptides.pdf
|
676190f981d2151a020807c8
|
10.26434/chemrxiv-2024-g19fl
|
Data accessibility in the chemical sciences: an analysis of recent practice in organic chemistry journals
|
The discoverability and reusability of data is critical for machine learning to drive new discovery in the chemical sciences, and the ‘FAIR Guiding Principles for scientific data management and stewardship’ provide a measurable set of guidelines that can be used to ensure the accessibility of reusable data. We investigate the data practice of researchers publishing in specialist organic chemistry journals, by analysing the outputs of 240 randomly selected research papers from 12 top-ranked journals published in early 2023. We investigate compliance with recommended (but not compulsory) data policies, assess the accessibility and reusability of data, and if the existence of specific recommendations for publishing NMR data by some journals supports author compliance. We find that, although authors meet mandated requirements, there is very limited compliance with data sharing policies that are only recommended by journals. Overall, there is little evidence to suggest that authors’ publishing practice meets FAIR data guidance.
|
Sally Bloodworth; Cerys Willoughby; Simon J Coles
|
Organic Chemistry
|
CC BY 4.0
|
CHEMRXIV
|
2024-12-20
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/676190f981d2151a020807c8/original/data-accessibility-in-the-chemical-sciences-an-analysis-of-recent-practice-in-organic-chemistry-journals.pdf
|
665d4ac021291e5d1df1666b
|
10.26434/chemrxiv-2024-s8mlj
|
TRACER: Molecular Optimization Using Conditional Transformer for Reaction-Aware Compound Exploration with Reinforcement Learning
|
Designing molecules with desirable properties is a critical endeavor in drug discovery. Because of recent advances in deep learning, molecular generative models have been developed. However, existing compound exploration models often disregard the important issue of ensuring the feasibility of organic synthesis. To address this issue, we propose TRACER (molecular optimization using a conditional Transformer for reaction-aware compound exploration with reinforcement learning); this is a framework that integrates the optimization of molecular properties with the generation of synthetic pathways. At the core of TRACER is a conditional Transformer model trained on a dataset of chemical reactions. The model can predict the product from a given reactant under the constraints of a reaction type specified by a graph convolutional network. The results of molecular optimization on an activity prediction model targeting the dopamine receptor D2 showed that TRACER effectively generated compounds exhibiting high scores. The Transformer model, which recognizes the entire structure, captures the complexity of the organic synthesis and enables its navigation in the vast chemical space, with consideration of the real-world reactivity constraints. The source code of TRACER, the activity prediction model, and the curated dataset are available in our public repository at https://github.com/sekijima-lab/TRACER.
|
Shogo Nakamura; NOBUAKI YASUO; Masakazu Sekijima
|
Theoretical and Computational Chemistry; Organic Chemistry; Organic Compounds and Functional Groups; Computational Chemistry and Modeling; Machine Learning
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-06-03
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/665d4ac021291e5d1df1666b/original/tracer-molecular-optimization-using-conditional-transformer-for-reaction-aware-compound-exploration-with-reinforcement-learning.pdf
|
63e15dbbcdb6a7f57b451135
|
10.26434/chemrxiv-2022-xptbc-v2
|
Analysis of Resources Applied to Rationalize Elimination Mechanisms
|
Acid-base chemistry, an essential component of the undergraduate chemistry curriculum, is introduced in general chemistry and expanded on in organic chemistry. Previous research has linked student understanding of acid-base chemistry to success in organic chemistry. However, there remains a paucity of information regarding how students apply acid-base chemistry concepts in the context of organic reaction mechanisms. The purpose of this study was to analyze the resources activated in second-semester organic chemistry students understanding while solving problems on E1, E2, and E1cB elimination reactions. The resources activated were probed using a mixed-methods approach comprising survey assessments and think-aloud interviews, and the data were analyzed both quantitatively and qualitatively following a validated set of scoring criteria. The results align with existing findings that students focus upon surface level structural information and use more familiar resources when solving organic problems. Acid-base resources were activated more often than reaction-specific resources such as conformational analyses or carbocation rearrangements. Acid-base resources aid students in successfully analyzing reaction mechanisms, but in general, additional resources must be activated to rationalize specific mechanisms and explain the products formed. The implications for teaching, assessment, and future research are discussed.
|
Sean Gao; Taylor Outlaw; Jason Liang-Lin; Alina Feng; Reika Shimomura; Jennifer Roizen; Charles Cox
|
Chemical Education; Chemical Education - General
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-02-07
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63e15dbbcdb6a7f57b451135/original/analysis-of-resources-applied-to-rationalize-elimination-mechanisms.pdf
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60c73d76bb8c1ad24c3d9750
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10.26434/chemrxiv.5484073.v2
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Enhanced Grain-boundary Emission Lifetime and Additive Induced Crystal Orientation in One-Step Spin-Coated Mixed Cationic (FA/MA) Lead Perovskite Thin Films Stabilized by Zinc Iodide Doping
|
Mixed
cationic lead perovskites containing formamidinium and methylammonium can be
stabilized by incorporating ZnI<sub>2 </sub>as an “internal desiccant”. Next to
prolonged stability under ambient conditions we show with XRD that the use of an
additive, 3-chloropropyl ammonium chloride, influences crystal formation by
orienting the crystals. These ~500 nm crystals show individual photoluminescent
behavior in thin films and have a longer photoluminescence lifetime at the
grain boundaries as compared to the center of the crystal or relative to
un-doped materials without the additive made under identical conditions.
Charges recombine slower at the edges of the crystals as observed with confocal
laser scanning microscopy.
The
material can also be prepared as a black precursor powder by a solid-solid
reaction under ambient conditions.
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Loreta A. Muscarella; Dina Petrova; Rebecca Jorge Cervasio; Aram Farawar; Olivier Lugier; Charlotte McLure; Martin J. Slaman; Junke Wang; Elizabeth von Hauff; René M. Williams
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Hybrid Organic-Inorganic Materials; Thin Films
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CC BY NC ND 4.0
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CHEMRXIV
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2017-10-16
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d76bb8c1ad24c3d9750/original/enhanced-grain-boundary-emission-lifetime-and-additive-induced-crystal-orientation-in-one-step-spin-coated-mixed-cationic-fa-ma-lead-perovskite-thin-films-stabilized-by-zinc-iodide-doping.pdf
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65af2d8566c13817290cd4e4
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10.26434/chemrxiv-2024-hqwbs
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Efficient organic room-temperature phosphorescence in both solution and solid states
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Organic room-temperature phosphorescence (RTP) materials possess immense potential for a variety of applications. However, conventional RTP materials face substantial problems, such as no phosphorescence in ambient solution, and inefficient amorphous films and electroluminescence devices. To address these issues, intrinsic RTP emitters can display efficient RTP in various states and achieve multiple desired properties through the same molecule. In this work, dendrimers are first used to design of efficient intrinsic RTP materials by incorporating dendrons as triplet regulators to facilitate effective spin-orbit coupling, intersystem crossing, and triplet radiative transitions that exhibit a significant transformation from delayed fluorescence to intrinsic RTP in different states. The dendrimers exhibit long phosphorescence lifetime within milliseconds in ambient solution, photoluminescence quantum yield of 98% in doped films, and substantially high external quantum efficiency of 25.1% in the organic electroluminescence devices. Moreover, by regulating the triplet characteristics of the dendrimers, the dendrimers display up-converted anti-Kasha dual-RTP emissions and an ultra-long afterglow lifetime within seconds in rigid polymer matrixes. These results pave the way for the development of novel RTP systems for versatile optoelectronic applications.
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Chensen Li; Zhenchen Lou; Minghui Wu; Xinmeng Chen; Haozhe Tan; Zonghang Liu; Feng Gao; Zijie Qiu; Zheng Zhao; Lianrui Hu; Guohua Xie; Maoqiu Li; Yumeng Guo; Zhongjie Ren; Song Zhang; Yuchao Liu; Shouke Yan; Ryan T. K. Kwok; Jacky W. Y. Lam; Ben Zhong Tang
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Organic Chemistry; Polymer Science; Organic Polymers; Materials Chemistry
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CC BY 4.0
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CHEMRXIV
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2024-12-05
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65af2d8566c13817290cd4e4/original/efficient-organic-room-temperature-phosphorescence-in-both-solution-and-solid-states.pdf
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62628de988636cc0b91b5d32
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10.26434/chemrxiv-2022-h72gz
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Reductive anti-dimagnesiation and dialumination of alkynes: Synthesis and reactions of trans-1,2-dimetalloalkenes
|
Given the great significance of polar reactive organometallic species in synthesis for more than one century, generation and use of stereodefined 1,2-dimetallated alkenes should be fascinating yet has been very challenging. Here we report reductive anti-1,2-dimetalation of alkynes to easily and stereoselectively generate trans-1,2-dimagnesio- and 1,2-dialuminoalkenes that are difficult to prepare, reasonably stable, and thus useful for organic synthesis. The key for the success is the use of sodium dispersion as a powerful reducing agent and organomagnesium and organoaluminum halides as reduction-resistant electrophiles counterintuitively. Highly nucleophilic 1,2-dimagnesioalkenes serve as dual Grignard reagents and react with various electrophiles to afford anti-difunctionalized alkenes. Interestingly, 1,2-dialuminoalkenes react with paraformaldehyde with dearomatization of the aryl moieties to form the corresponding dearomatized 1,4-diols, the overall reaction being regarded as alkynyl-directed dearomatization of arenes. Our anti-1,2-dimetalation including structural and computational investigation provides a new powerful tool and unique insight in the development of organometallic chemistry and organic synthesis.
|
Fumiya Takahashi; Takashi Kurogi; Hideki Yorimitsu
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Organic Chemistry; Organometallic Chemistry; Organic Synthesis and Reactions; Bond Activation; Main Group Chemistry (Organomet.)
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CC BY NC 4.0
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CHEMRXIV
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2022-04-25
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62628de988636cc0b91b5d32/original/reductive-anti-dimagnesiation-and-dialumination-of-alkynes-synthesis-and-reactions-of-trans-1-2-dimetalloalkenes.pdf
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6719f9791fb27ce124632ba8
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10.26434/chemrxiv-2024-t9r77-v3
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Sustainable Development in the Plastic Industry: A Promising Future or Just a Hoax? Past, Present, and Future Perspectives from a Global Viewpoint
|
The issue of fossil-based plastics presents a paradox, with conflicting solutions proposed. While an idealistic vision promotes biodegradable plastics as the ultimate solution, the reality is that fossil-based plastics dominate production, constituting approximately 99%. Despite the conceptual appeal of biodegradable plastics, their practical implementation remains limited with minimal production. Consequently, the current plastic waste management system faces challenges, with only 25% of total plastic waste being recycled in 2023. A significant portion, around 31.2%, is incinerated, and 43.8% ends up in landfills or is improperly disposed of, reflecting a non-sustainable approach. Projections suggest a potential increase in recycling rates to nearly 44% by 2050, but incineration remains alarmingly high at close to 50%. To achieve sustainable growth and create a carbon and toxic-free environment, there is a need for a renewed commitment to accelerate the reuse and recycling of plastic waste. Failure to do so risks perpetuating the condemnation of fossil-based plastics, despite their significant historical contributions to society and the environment.
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Harendra Kumar; Akihiro Yoshida
|
Earth, Space, and Environmental Chemistry; Wastes
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CC BY NC ND 4.0
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CHEMRXIV
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2024-10-24
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6719f9791fb27ce124632ba8/original/sustainable-development-in-the-plastic-industry-a-promising-future-or-just-a-hoax-past-present-and-future-perspectives-from-a-global-viewpoint.pdf
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657c5cbde9ebbb4db9f4872b
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10.26434/chemrxiv-2023-99vx3
|
(Supra)molecular adaptation by coupled stimuli
|
Adaptation transcends scale in both natural and artificial systems, but delineating the causative
factors of this phenomenon requires urgent clarification. Herein, we unravel the molecular
requirements for adaptation and establish a link to rationalize adaptive behavior on a self-assembled level. These concepts were established by analyzing a model compound exhibiting
both light- and pH-responsive units, which enable the combined or independent application of
different stimuli. On a molecular level, adaptation arises from coupled stimuli, as the final
outcome of the system depends on their sequence of application. However, in a self-assembled
state, a single stimulus suffices to induce adaptation as a result of collective molecular behavior
and the reversibility of non-covalent interactions. Our findings go beyond state-of-the art
(multi)stimuli-responsive systems and allow us to draw up design guidelines for adaptive
behavior both at the molecular and supramolecular level, which are fundamental criteria for the
realization of intelligent matter.
|
Torsten Dünnebacke; Niklas Niemeyer; Sebastian Baumert; Sebastian Hochstädt; Lorenz Borsdorf; Michael Ryan Hansen; Johannes Neugebauer; Gustavo Fernández
|
Organic Chemistry; Polymer Science; Organic Compounds and Functional Groups; Supramolecular Chemistry (Org.); Materials Chemistry
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CC BY NC ND 4.0
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CHEMRXIV
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2023-12-18
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/657c5cbde9ebbb4db9f4872b/original/supra-molecular-adaptation-by-coupled-stimuli.pdf
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63d54989bb08ed3ed71ac4fa
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10.26434/chemrxiv-2023-stqrt
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Accelerated Chemical Reaction Optimization using Multi-Task Learning
|
Functionalization of C–H bonds is a key challenge in medicinal chemistry, particularly for fragment-based drug discovery (FBDD) where such transformations need to be executed in the presence of polar functionality necessary for fragment-protein binding. New technologies such as high-throughput experimentation and self-optimization have the potential to revolutionize synthetic approaches to challenging target molecules in FBDD. Recent work has shown the effectiveness of Bayesian optimization (BO) for the self-optimization of chemical reactions, however, in all previous cases these algorithmic procedures have started with no prior information about the reaction of interest. In this work, we explore the use of multi-task Bayesian optimization (MTBO) in several in silico case studies by leveraging reaction data collected during related historical optimization campaigns to accelerate the optimization of new reactions - this was performed for Suzuki-Miyaura and C–N couplings. This methodology was then translated to real-world, medicinal chemistry applications in the yield optimization of several pharmaceutical intermediates using an autonomous flow-based reactor platform. The use of the MTBO algorithm was shown to be successful in determining optimal conditions (both continuous and categorical variables) of unseen experimental C–H activation reactions with differing substrates, demonstrating up to a 98 % cost reduction when compared to industry-standard process optimization techniques. Our findings highlight the effectiveness of the methodology as an enabling tool in medicinal chemistry workflows, where efficient utilization of precious starting materials is particularly important. This work represents a step-change in the utilization of previously obtained reaction data and machine learning with the ultimate goal of accelerated reaction optimization.
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Connor Taylor; Kobi Felton; Daniel Wigh; Mohammed Jeraal; Rachel Grainger; Gianni Chessari; Christopher Johnson; Alexei Lapkin
|
Organic Chemistry; Organic Synthesis and Reactions
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CC BY 4.0
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CHEMRXIV
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2023-01-30
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63d54989bb08ed3ed71ac4fa/original/accelerated-chemical-reaction-optimization-using-multi-task-learning.pdf
|
67db37ef6dde43c90875df12
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10.26434/chemrxiv-2025-nt10h
|
Injectable Polymer-Based Approaches for Trabecular Bone Regeneration: Current Strategies and Future Directions
|
Trabecular bone repair presents a significant challenge in orthopedic surgery due to its complex microarchitecture and the substantial mechanical demands it endures. Injectable polymers have emerged as a promising solution, offering tunable mechanical properties, minimally invasive delivery, and excellent biocompatibility. This review comprehensively explores the trabecular bone physiology, its intrinsic healing mechanism, and conventional surgical and non-surgical methods for bone fracture management. Furthermore, it provide a detailed discussion on injectable polymers, including their classification, advantages, biomedical applications and their role in bone scaffolding. Special attention is given to the emerging field of 4D materials, which exhibit responsiveness to external stimuli like light, temperature, and pH, offering significant potential in tissue engineering. Finally, the review examines clinical studies assessing the efficacy of injectable polymers in bone repair, providing insights into future advancements in biomaterials for trabecular bone repair.
|
Amna Sadiq; Paweł Sać; Nicolas Maciejewicz-Kamiński; Agata Goszczyńska; Miroslawa El Fray
|
Biological and Medicinal Chemistry; Materials Science; Polymer Science; Biocompatible Materials; Biopolymers; Hydrogels
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CC BY 4.0
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CHEMRXIV
|
2025-03-20
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67db37ef6dde43c90875df12/original/injectable-polymer-based-approaches-for-trabecular-bone-regeneration-current-strategies-and-future-directions.pdf
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63d7dd5333b6976c48fc358e
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10.26434/chemrxiv-2023-n6qmh-v2
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Advancing the economic and environmental sustainability of the NEWgeneratorTM non-sewered sanitation system
|
Achieving safely managed sanitation and resource recovery in areas that are rural, geographically challenged, or experiencing rapidly increasing population density may not be feasible with centralized facilities due to space requirements, site-specific concerns, and high costs of sewer installation. Non-sewered sanitation (NSS) systems have the potential to provide safely managed sanitation and achieve strict wastewater treatment standards. One such NSS treatment (backend) technology is the NEWgeneratorTM, which includes an anaerobic membrane bioreactor (AnMBR), nutrient recovery via ion exchange, and electrochlorination. Although the system has been shown to achieve robust treatment of real waste streams for over 100 users, the technology’s relative life cycle sustainability across deployment locations remains unclear. This study characterizes the financial viability and life cycle environmental impacts of the NEWgeneratorTM and prioritizes opportunities to advance system sustainability through targeted improvements and deployment. The costs and greenhouse gas (GHG) emissions of the NEWgeneratorTM (general case) leveraging grid electricity were 0.139 [0.113 – 0.168] USD·cap-1·d-1 and 79.7 [55.0 – 112.3] kg CO2-eq·cap-1·yr-1, respectively. A transition to photovoltaic-generated electricity would increase costs to 0.145 [0.118 – 0.181] USD·cap-1·d-1 but decrease GHG emissions to 56.1 [33.8 – 86.2] kg CO2eq·cap-1·yr-1. The deployment location analysis demonstrated reduced median costs (relative to the general case) for deployment in China (-38%), India (-53%), Senegal (-31%), South Africa (-31%), and Uganda (-35%), but at comparable or increased GHG emissions (-2% to +16%). Examining targeted improvements revealed the relative change in median cost and GHG emissions to be -21% and -3% if loading is doubled (i.e., doubled users per unit), -30% and -12% with additional sludge drying, and +9% and -25% with the addition of a membrane contactor, respectively, with limited benefits (0-5% reductions) from an alternative photovoltaic battery, low-cost housing, or improved frontend operation. This research demonstrates the NEWgeneratorTM is a low-cost, low-emission NSS backend technology with the potential for resource recovery to increase access to safe sanitation.
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Shion Watabe; Hannah Lohman; Yalin Li; Victoria Morgan; Lewis Rowles; Tyler Stephen; Hsiang-Yang Shyu; Robert Bair; Cynthia Castro; Roland Cusick; Daniel Yeh; Jeremy Guest
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Chemical Engineering and Industrial Chemistry; Water Purification
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CC BY 4.0
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CHEMRXIV
|
2023-01-31
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63d7dd5333b6976c48fc358e/original/advancing-the-economic-and-environmental-sustainability-of-the-ne-wgenerator-tm-non-sewered-sanitation-system.pdf
|
6238ad7fa4ed95f0292823bd
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10.26434/chemrxiv-2022-x4z6k
|
Emerging Era of Biomolecular Membrane Simulations: Automated Physically-Justified Force Field Development and Quality-Evaluated Databanks
|
Molecular simulations of biological membranes and proxies thereof are entering a new era characterized by several key aspects. Progress starts with the realization that the outcome of the simulations can be only as good as the underlying force field and we actually need to know precisely how good or bad the results are. Therefore, standardized procedures for data quality evaluation are being established and will be applied to biomembrane simulations available in the literature. This provides the necessary basis and impetus for new force field development. Here, we propose to systematically build up physically well-justified models which effectively account for electronic polarization effects for all components of the biomembrane systems in aqueous environments. Such a massive task can only be achieved within a reasonable timescale by applying automated parameterization tools.
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Hanne S. Antila; Batuhan Kav; Markus S. Miettinen; Hector Martinez-Seara; Pavel Jungwirth; O. H. Samuli Ollila
|
Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Machine Learning; Biophysical Chemistry
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CC BY 4.0
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CHEMRXIV
|
2022-03-22
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6238ad7fa4ed95f0292823bd/original/emerging-era-of-biomolecular-membrane-simulations-automated-physically-justified-force-field-development-and-quality-evaluated-databanks.pdf
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6546789348dad23120121ba0
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10.26434/chemrxiv-2023-kk1p9
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Potential Prebiotic Pathways in Titan’s Atmosphere: A Computational Exploration of HCN and NH3 Reactions
|
In this study, we explore the potential for prebiotic chemistry in Titan’s atmosphere through computational modeling of reactions involving hydrogen cyanide (HCN), hydrogen isocyanide (HNC), and ammonia (NH3). Our automated reaction search identifies several key intermediates, including formamidine (A), hydrazone (B), and methanediimine (C), which serve as precursors for a variety of complex organic com- pounds. Among the products, methanamine (P5) and guanidine (P22) are highlighted for their relevance to early biological activity. The calculated low activation barriers and exothermic nature of several reactions suggest the viability of these pathways in Titan’s cold environment. Notably, the formation of molecules such as a triazole derivative (P18) and N-cyanoimidoformamide (P20), linked to biomarker cyanamide, underscores the potential for synthesizing biologically significant molecules. We pro- vide theoretical roto-vibrational spectral parameters to assist in the experimental de- tection of these species, offering insights into the molecular complexity achievable in Titan’s atmosphere and contributing to our understanding of prebiotic chemistry in extraterrestrial environments.
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Sunanda Panda; Anakuthil Anoop
|
Theoretical and Computational Chemistry; Physical Chemistry; Earth, Space, and Environmental Chemistry; Atmospheric Chemistry; Space Chemistry
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CC BY NC ND 4.0
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CHEMRXIV
|
2023-11-06
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6546789348dad23120121ba0/original/potential-prebiotic-pathways-in-titan-s-atmosphere-a-computational-exploration-of-hcn-and-nh3-reactions.pdf
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670bd9a151558a15eff0ef65
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10.26434/chemrxiv-2024-p39s0-v2
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Less for More: Enhanced Feedback-aligned Mixed LLMs for Molecule Caption Generation and Fine-Grained NLI Evaluation
|
Scientific language models drive research innovation but require extensive fine-tuning on large datasets. This work enhances such models by improving their inference and evaluation capabilities with minimal or no additional training. Focusing on molecule caption generation, we explore synergies between alignment fine-tuning and model merging in a cross-modal setup. We reveal intriguing insights into the behaviour and suitability of such methods while significantly surpassing state-of-the-art models. Moreover, we propose a novel atomic-level evaluation method leveraging off-the-shelf Natural Language Inference (NLI) models for use in the unseen chemical domain. Our experiments demonstrate that our evaluation operates at the right level of granularity, effectively handling multiple content units and subsentence reasoning, while widely adopted NLI methods consistently misalign with assessment criteria.
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Dimitris Gkoumas; Maria Liakata
|
Theoretical and Computational Chemistry
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CC BY 4.0
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CHEMRXIV
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2024-10-15
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/670bd9a151558a15eff0ef65/original/less-for-more-enhanced-feedback-aligned-mixed-ll-ms-for-molecule-caption-generation-and-fine-grained-nli-evaluation.pdf
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67acf4f9fa469535b913773a
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10.26434/chemrxiv-2025-2n40d
|
Ternary Complex Modeling, Induced Fit Docking and Molecular Dynamics Simulations as a Successful Approach for the Design of VHL-mediated PROTACs Targeting the Kinase FLT3
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Proteolysis targeting chimeras (PROTACs) have proven to be a novel approach for the degradation of disease-causing proteins in drug discovery. One of the E3 ligases for which efficient PROTACs have been described is the Von-Hippel-Lindau factor (VHL). However, the development of PROTACs has so far often relied on a minimum of computational tools, so that it is mostly based on a trial-and-error process. Therefore, there is a great need for resource- and time-efficient structure-based or computational approaches to streamline PROTAC design. In this study, we present a combined computational approach that integrates static ternary complex formation, induced fit docking, and molecular dynamics (MD) simulations. Our methodology was tested using four experimentally derived ternary complex structures of VHL PROTACs, reported for BRD4, SMARCA2, FAK and WEE1. In addition, we applied the validated approach to model a recently in-house developed FLT3-targeted PROTAC (MA49). The results show that static ternary models generated with a protein-protein docking method implemented in the software MOE have a high predictive power for reproducing the experimental 3D structures. The induced fit-docking of different active PROTACs to their respective models showed the reliability of this model for the development of new VHL-mediated degraders. In particular, the induced-fit docking was sensitive to structural changes in the PROTACs, as evidenced by the failed binding modes of the PROTAC negative controls. Furthermore, MD simulations confirmed the stability of the generated complexes and emphasized the importance of dynamic studies for understanding the relationship between PROTAC structure and function.
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Husam Nassar; Anne-Christin Sarnow; Ismail Celik; Mohamed Abdelsalam; Dina Robaa; Wolfgang Sippl
|
Theoretical and Computational Chemistry; Computational Chemistry and Modeling
|
CC BY NC ND 4.0
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CHEMRXIV
|
2025-02-14
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67acf4f9fa469535b913773a/original/ternary-complex-modeling-induced-fit-docking-and-molecular-dynamics-simulations-as-a-successful-approach-for-the-design-of-vhl-mediated-prota-cs-targeting-the-kinase-flt3.pdf
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6274668ff053df791810f351
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10.26434/chemrxiv-2022-83rhp
|
Nitrile, Imine and Amide Reduction Using Tropylium Catalyst
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We report a new method for the hydroboration reactions of nitriles, imines and amides.
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Son Hoai Doan; Thanh Vinh Nguyen
|
Organic Chemistry; Catalysis; Organocatalysis
|
CC BY NC ND 4.0
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CHEMRXIV
|
2022-05-06
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6274668ff053df791810f351/original/nitrile-imine-and-amide-reduction-using-tropylium-catalyst.pdf
|
622faf58c91cf2d4984ee8c9
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10.26434/chemrxiv-2022-hdqzr
|
Determination of Optical Density (OD) of Oligodeoxynucleotide from HPLC Peak Area
|
Oligodeoxynucleotides (ODNs) are typically purified and analysed with HPLC equipped with a UV-Vis detector. Quantities of ODNs are usually determined using a UV-Vis spectrometer separately after HPLC, and are reported as optical density at 260 nm (OD260). Here, we describe a method for direct determination of OD260 of ODNs using the area of the peaks in HPLC profiles.
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Komal Chillar; Yipeng Yin; Dhananjani Eriyagama ; Shiyue Fang
|
Organic Chemistry; Analytical Chemistry; Biochemical Analysis; Spectroscopy (Anal. Chem.)
|
CC BY 4.0
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CHEMRXIV
|
2022-03-15
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/622faf58c91cf2d4984ee8c9/original/determination-of-optical-density-od-of-oligodeoxynucleotide-from-hplc-peak-area.pdf
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67d39b74fa469535b9284832
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10.26434/chemrxiv-2025-73z9t
|
Vertical Model for Polyimide Design Assisted by Knowledge-fused Large Language Models
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Large Language Models (LLMs) show underexplored potential in specialized scientific domains. We develop domain-knowledge-fused LLMs (D-LLMs) integrated with Vertical Models (VMs) for polymer graph-structure representations. A polyimide-focused text mining assistant automatically extracted 543 experimental parameter sets from 84 articles into a structured database, achieving >91% F1 scores across 8,000 multi-parameter evaluations. Leveraging research process prompting and pre-coding toolkit, a “3T” VM was built to balance three performance parameters--Tensile Strength, Glass Transition Temperature, and Transmittance. This model was employed on an online prediction platform, as well as for the prediction of 20,424 combinations. The structural mapping aligns with high-throughput predictions, providing insights into rational experimental design. This D-LLM/VM framework demonstrates efficient design of high-performance polyimides while establishing an extensible methodology for functional materials and device innovation.
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Yu Zhang; Tongle Xu; Luling He; Weibin Ma; Xiong Li; Minjie Li; Guangrui Xu; Wei Lv; Peng Ding
|
Theoretical and Computational Chemistry; Machine Learning
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CC BY NC 4.0
|
CHEMRXIV
|
2025-03-17
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67d39b74fa469535b9284832/original/vertical-model-for-polyimide-design-assisted-by-knowledge-fused-large-language-models.pdf
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67a7e4386dde43c9081bdfc1
|
10.26434/chemrxiv-2024-gnpvz-v2
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Machine Learning-Driven Discovery of Highly Selective Antifungal Peptides Containing Non-Canonical β-Amino Acids
|
Antimicrobial peptides (AMPs) are promising compounds for the treatment and prevention of multidrug-resistant infections because of their ability to directly disrupt microbial membranes, a mechanism that is less likely to lead to resistance compared to antibiotics. Unfortunately, natural AMPs are prone to proteolytic cleavage in vivo and have relatively low selectivity for microbial versus human cells, motivating the development of synthetic peptidomimetics of AMPs with improved peptide stability, activity, and selectivity. However, a lack of understanding of structure-activity relationships for peptidomimetics constrains development to rational design or experimental predictors, both of which are cost and time prohibitive, especially when the design space of possible sequences scales exponentially with the number of amino acids. To address these challenges, we developed an iterative Gaussian process regression (GPR) approach to explore a large design space of 336,000 synthetic α/β-peptide analogues of a natural AMP, aurein 1.2, based on an initial training set of 147 sequences and their biological activities against microbial pathogens and selectivity for microbes vs. mammalian cells. We show that the quantification of prediction uncertainty provided by GPR can guide the exploration of this design space via iterative experimental measurements to efficiently discover novel sequences with up to a 52-fold increase in antifungal selectivity compared to aurein 1.2. The highest selectivity peptide discovered using this approach features an unconventional substitution of cationic amino acids in the hydrophobic face and would be unlikely to be explored by conventional rational design. Overall, this work demonstrates a generalizable approach that integrates computation and experiment to accurately predict the selectivity of AMPs containing synthetic amino acids, which we employed to discover new α/β-peptides that hold promise as selective antifungal agents to combat the antimicrobial resistance crisis.
|
Douglas Chang; Joshua Richardson; Myung-Ryul Lee; David Lynn; Sean Palecek; Reid Van Lehn
|
Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Bioengineering and Biotechnology; Machine Learning; Chemoinformatics - Computational Chemistry
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CC BY NC ND 4.0
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CHEMRXIV
|
2025-02-10
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67a7e4386dde43c9081bdfc1/original/machine-learning-driven-discovery-of-highly-selective-antifungal-peptides-containing-non-canonical-amino-acids.pdf
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60c75810bb8c1ae9013dc988
|
10.26434/chemrxiv.14495748.v1
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Fluoroalkylation of Dextromethorphan Improves CNS Exposure and Metabolic Stability
|
<p>Aryl-methyl ethers, while present in many bioactive compounds, are subject to rapid O-dealkylation that can generate bio-inactive or toxic metabolites. As an example, the cough suppressant dextromethorphan undergoes such a P450 mediated O-dealkylation to provide the psychoactive phenolic metabolite dextrorphan. This metabolite antagonizes the NMDA receptor causing hallucinations, which encourages recreational abuse. To circumvent this undesired metabolism, we have designed, synthesized, and evaluated <i>in vitro </i>and <i>in vivo</i> new fluoroalkyl analogs of dextromethorphan that display improved pharmacokinetic profiles relative to dextromethorphan and related analogs currently in clinical trials. Specifically, the fluorinated analogs minimized metabolic degradation and increased CNS exposure relative to DXM <i>in vivo</i>. Ultimately, these fluorinated motifs might be applicable to other aryl-methyl ether containing compounds as a strategy to improve pharmacokinetic profiles.<b></b></p>
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Jacob Sorrentino; Ryan Altman
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Drug Discovery and Drug Delivery Systems
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CC BY NC ND 4.0
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CHEMRXIV
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2021-04-28
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75810bb8c1ae9013dc988/original/fluoroalkylation-of-dextromethorphan-improves-cns-exposure-and-metabolic-stability.pdf
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62c426c1253021f9a589e532
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10.26434/chemrxiv-2022-4vzgh
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Large-scale synthesis of Notum inhibitor 1-(2,4-dichloro-3-(trifluoromethyl)-phenyl)-1H-1,2,3-triazole (ARUK3001185) employing a modified Sakai reaction as the key step
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1-Phenyl-1H-1,2,3-triazole 1 (ARUK3001185) was prepared on large scale from aniline 4 by application of both (1) a copper catalyzed azide-alkyne cycloaddition (CuAAC) with (trimethylsilyl)acetylene, and (2) a Clark modification of the Sakai reaction. The one-pot Sakai-Clark method with (MeO)2CHCH=NNHTos (2b) proved to be superior as it was operationally simple, metal-free, and avoided the use of aryl azide 7. The Sakai-Clark method has been reliably performed on large scale to produce >100 g of 1 in good efficiency and high purity.
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Benjamin N. Atkinson; Nicky J. Willis; Jennifer Smith; Rebecca Gill; Jody Ali; Zhou Xu; Ping-Shan Lai; Paul V. Fish
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Biological and Medicinal Chemistry; Organic Chemistry; Organic Synthesis and Reactions; Process Chemistry
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CC BY NC 4.0
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CHEMRXIV
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2022-07-06
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62c426c1253021f9a589e532/original/large-scale-synthesis-of-notum-inhibitor-1-2-4-dichloro-3-trifluoromethyl-phenyl-1h-1-2-3-triazole-aruk3001185-employing-a-modified-sakai-reaction-as-the-key-step.pdf
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62b778be8c5523138d225a32
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10.26434/chemrxiv-2022-6m0q5
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Dynamic docking in protein-ligand modeling
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Large numbers of docking jobs are used in a distributional sense to obtain computational molecular non-covalent and covalent binding information of ligands to protein cavities. A numerically calculated density of binding states is generated and used to identify binding modes, which further can be used to calculate thermal observables. With the density of states the final state non-covalent or covalent protein-ligand entropy can be calculated. Binding strengths, conformations, and individual atomic interactions are found per binding mode as well as the population of binding states that a ligand can take in interaction with a protein cavity. The binding and conformational results are analogous to what is found from molecular dynamics trajectories per protein conformation but uses a GOLD molecular model and docking. The calculation is orders of magnitude more efficient than MD simulations. Brief studies of 2 small molecules, Nirmatrelvir and BAM-15, demonstrate the protocol and the use.
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Gordon Chalmers
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Theoretical and Computational Chemistry; Computational Chemistry and Modeling
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CC BY 4.0
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CHEMRXIV
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2022-06-28
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62b778be8c5523138d225a32/original/dynamic-docking-in-protein-ligand-modeling.pdf
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60c75703f96a00a345288bad
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10.26434/chemrxiv.14039834.v3
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A Data-Driven Dimensionality Reduction Approach to Compare and Classify Lipid Force Fields
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<div><div><div><p>Molecular dynamics simulations of all-atom and coarse-grained lipid bilayer models are increasingly used to obtain insights useful for understanding the structural dynamics of these assemblies. In this context, one crucial point concerns the comparison of the performance and accuracy of classical force fields (FFs), which sometimes remains elusive. To date, the assessments performed on different classical potentials are mostly based on the comparison with experimental observables, which typically regard average properties. However, local differences of structure and dynamics, which are poorly captured by average measurements, can make a difference, but these are non-trivial to catch. Here we propose an agnostic way to compare different FFs at different resolutions (atomistic, united-atom, and coarse-grained), by means of a high-dimensional similarity metrics built on the framework of Smooth Overlap of Atomic Positions (SOAP). We compare and classify a set of 13 force fields, modeling 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. Our SOAP kernels-based metrics allows us to compare, discriminate and correlate different force fields at different model resolutions in an unbiased, high-dimensional way. This also captures differences between FFs in modeling non-average events (originating from local transitions), such as for example the liquid-to-gel phase transition in dipalmitoylphosphatidylcholine (DPPC) bilayers, for which our metrics allows to identify nucleation centers for the phase transition, highlighting some intrinsic resolution limitations in implicit vs. explicit solvent force fields.</p></div></div></div>
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Riccardo Capelli; Andrea Gardin; Charly Empereur-mot; Giovanni Doni; Giovanni M. Pavan
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Computational Chemistry and Modeling; Theory - Computational
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CC BY NC ND 4.0
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CHEMRXIV
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2021-03-23
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75703f96a00a345288bad/original/a-data-driven-dimensionality-reduction-approach-to-compare-and-classify-lipid-force-fields.pdf
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