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6568c2955bc9fcb5c9bf5f51
|
10.26434/chemrxiv-2023-rnbb6
|
Ultrafast Hot Exciton Nonadiabatic Excited-State Dynamics in Green Fluorescent Protein Chromophore Analogue
|
The ultrafast high-energy nonadiabatic excited-state dynamics of benzylidenedimeth-ylimidazolinone (BDI) chromophore dimer has been investigated using an electronic structure method coupled with on-the-fly quantitative wave function analysis to gain an insight into the photophysics of hot excitons in biological systems. The dynamical simulation provides a rationalization of the behavior of exciton in dimer after photoabsorption of light to higher energy states. The results suggest that hot exciton localization within the manifold of excited states is caused by the hindrance of ΦI- and ΦP - torsional rotation in the monomeric units of a dimer. This hindrance arises due to weak π-π stacking interaction in the dimer resulting in an energetically uphill excited-state barrier for ΦI- and ΦP - twisted rotation impeding the isomerization process in chromophore. Thus, the study highlights the potential impact of the weak π-π interaction regulating the photodynamics of the green fluorescent protein chromophore derivatives.
|
Bittu Lama; Manabendra Sarma
|
Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Photochemistry (Physical Chem.); Physical and Chemical Processes
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-12-01
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6568c2955bc9fcb5c9bf5f51/original/ultrafast-hot-exciton-nonadiabatic-excited-state-dynamics-in-green-fluorescent-protein-chromophore-analogue.pdf
|
6750aa7a7be152b1d0f62a04
|
10.26434/chemrxiv-2024-rjrnd
|
Solvent channels and proton transfer pathways in peroxidase catalysis
|
The active site architecture of all heme enzymes is designed for fully controlled formation of highly reactive heme intermediates for oxidative catalysis. Finely tuned proton delivery to and from the heme, substrates and active site water molecules is essential, yet the mechanisms of proton delivery and the sources of protons are poorly understood in all heme enzymes. This information is important if the power of heme enzymes is to be exploited for bespoke catalysis. Here, proton transfer pathways in a heme peroxi-dase enzyme (ascorbate peroxidase) are identified using molecular dynamics (MD) simulations, DFT calculations, QM(DFT)/MM calculations and QM(DFTB2)/MM MD simulations. The results show that an active site arginine residue, Arg38, is predominantly positively charged but can transiently deprotonate and adopt different tautomeric states, potentially accepting and donating pro-tons to nearby water molecules, depending on the instantaneous local environment. Extensive MD simulations identify two hy-drated tunnels through which protons from solvent can access the active site from the - and -edges of the heme. In the active site, dynamic proton exchange can occur, assisted by an active site distal histidine residue, and relayed to the substrate via Arg38. QM/MM free energy calculations demonstrate the feasibility of the transfer of a proton from solvent to His42 via distal water molecules. Rather than a simplistic model for proton delivery – where a single substrate provides a single proton (and an electron) – the data instead indicate multiple possible routes for proton delivery during reaction.
|
Reynier Suardiaz; Hanna Kwon; Marc van der Kamp; Lola González-Sánchez; Peter Moody; Emma Raven; Adrian Mulholland
|
Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Catalysis; Biochemistry; Computational Chemistry and Modeling; Biocatalysis
|
CC BY NC 4.0
|
CHEMRXIV
|
2024-12-13
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6750aa7a7be152b1d0f62a04/original/solvent-channels-and-proton-transfer-pathways-in-peroxidase-catalysis.pdf
|
624b5f50855ee56f7ae22c7e
|
10.26434/chemrxiv-2022-vpjgf
|
Selected Ion Monitoring Using Low-Cost Mass Spectrum Detectors Provide a Rapid, General, and Accurate Method for Enantiomeric Excess Determination in High Throughput Experimentation
|
High-Throughput Experimentation (HTE) workflows are efficient means of surveying a broad array of chiral catalysts in the development of catalytic asymmetric reactions. However, use of traditional HPLC-UV/vis methodology to determine enantiomeric excess (ee) from the resulting reactions is often hampered by coelution of other reaction components, resulting in erroneous ee determination when crude samples are used, and ultimately requiring product isolation prior to ee analysis. In this study, using four published reactions selected as model systems, we demonstrate that the use of LC-MS, SFC-MS, and selected ion monitoring (SIM) mass chromatography provides a highly accurate means to determine ee of products in crude reaction samples using commonplace, low-cost MS detectors. By using ion selection, co-eluting signals can be deconvoluted to provide accurate integrations of the target analytes. We also show that this method is effective for samples lacking UV/vis chromophores, making it ideal for HTE workflows in asymmetric catalysis.
|
Katerina Korch; Jacob Hayes; Raphael Kim; Jessica Sampson; Austin Kelly; Donald Watson
|
Organic Chemistry; Catalysis; Organometallic Chemistry; Homogeneous Catalysis; Catalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2022-04-05
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/624b5f50855ee56f7ae22c7e/original/selected-ion-monitoring-using-low-cost-mass-spectrum-detectors-provide-a-rapid-general-and-accurate-method-for-enantiomeric-excess-determination-in-high-throughput-experimentation.pdf
|
60c749d2f96a00cb5c287308
|
10.26434/chemrxiv.12114063.v1
|
Manuscript-C-dots assembly at interface-041020.pdf
|
We describe a
systematic investigation of carbon dots (C-dots) assemblies fabricated at the
liquid/air interface because of the surface tension gradient. This gradient is
originally created by capillary action and increased by addition of sodium
dodecyl sulfate (SDS) surfactant or
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) phospholipid to the
surface of C-dots aqueous mixture. The
arrangement of carbon dots in liquid bulk phase (before self-assembly) and at
the surface region (after self-assembly) was examined by TEM microscopy. The
presence of SDS surfactant and POPC phospholipid at the air/water interface
induced the C-dots compression. In addition, molecular dynamics simulation was conducted
to obtain the structure of C-dots at liquid/vapor interface. The orientation of
C-dots is evaluated quantitatively at water/vapor surface by using bivariate
analysis.
|
Amin Reza Zolghadr; Behnam Rostami
|
Interfaces; Self-Assembly; Surface
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-04-13
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c749d2f96a00cb5c287308/original/manuscript-c-dots-assembly-at-interface-041020-pdf.pdf
|
60c741db4c8919c7f3ad2363
|
10.26434/chemrxiv.8144294.v1
|
Hindered Dialkyl Ether Synthesis via Electrogenerated Carbocations
|
<p>Hindered ethers represent an underexplored area of chemical space due to the difficulty and inoperability associated with conventional reactions, despite the high-value of such structural motifs in a variety of societal applications. Demonstrated herein is an exceptionally simple solution to this problem that leverages the power of electrochemical oxidation to liberate high-energy carbocations from simple carboxylic acids. The controlled formation of these reactive intermediates takes place with low electrochemical potentials under non-acidic conditions to capture an alcohol donor thereby producing a range (>80) of ethers that would be extremely difficult to otherwise access. Simple nucleophiles can also intercept such cations, leading to hindered alcohols and even alkyl fluorides. This method has been field tested to solve the synthetic bottlenecks encountered on twelve real-world chemical scaffolds with documented societal impact, resulting in a dramatic reduction in step-count and labor required, accompanied with a higher yield (average step-count, time, and yield = 6.3, ca. 100 h, 19% vs. 1.5, 9.8 h, 43%). Finally, the use of molecular probes coupled to kinetic studies support the proposed mechanism and role of additives in the conditions employed.</p>
|
Jinbao Xiang; Ming Shang; Yu Kawamata; Helena Lundberg; Solomon Reisberg; Miao Chen; Pavel Mykhailiuk; Gregory Beutner; Michael Collins; Alyn Davies; Matthew Del Bel; Gary Gallego; Jillian Spangler; Jeremy T. Starr; Shouliang Yang; Donna Blackmond; Phil Baran
|
Organic Compounds and Functional Groups; Organic Synthesis and Reactions
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2019-05-20
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c741db4c8919c7f3ad2363/original/hindered-dialkyl-ether-synthesis-via-electrogenerated-carbocations.pdf
|
60c7426c337d6c4dbee26a6e
|
10.26434/chemrxiv.8281082.v1
|
Molecular Dynamics Simulations of the “Breathing” Phase Transformation of MOF Nanocrystallites
|
One of the intriguing features of certain metal-organic frameworks (MOFs) is the large volume change upon external stimuli like pressure or guest molecule adsorption, referred to as “breathing”. This displacive phase transformation from an open to a closed pore has been investigated intensively by theoretical simulations within periodic boundary conditions (PBC). However, the actual free energy barriers for the transformation under real conditions and the impact of surface effects on it can only be studied beyond PBC for nanocrystallites. In this work, we used the first-principles parameterized forcefield MOF-FF to investigate the thermal- and pressure induced transformations for nanocrystallites of the pillared-layer DMOF-1 (Zn<math>
<mrow>
<msub><mrow></mrow>
<mrow><mn>2</mn>
</mrow>
</msub>
</mrow></math>(bdc)<math>
<mrow>
<msub><mrow></mrow>
<mrow><mn>2</mn>
</mrow>
</msub>
</mrow></math>(dabco); bdc: 1,4-benzenedicarboxylate; dabco: 1,4-diazabicyclo[2.2.2]octane) as a model system. By heating of prepared closed pore nanocrystallites of different size, a spontaneous opening is observed within a few tenth of picoseconds with an interface between the closed and open pore phase moving with a velocity of several 100 m/s<math><mrow><mrow><mi></mi> </mrow><mrow><mi></mi>
</mrow>
</mrow></math> through the system. The critical nucleation temperature for the opening transition raises with size. On the other hand, by forcing the closing transition with a distance restraint between paddle-wheel units placed on opposite edges of the crystallite, the free energy barrier can be determined by umbrella sampling. As expected, this barrier is substantially lower than the one determined for a concerted process under PBC. Interestingly, the barrier reduces with the size of the crystallite, indicating a hindering surface effect. The results demonstrate the need consider domain boundaries and surfaces, for example by simulations that go beyond PBC and to large system sizes in order to properly predict and describe first order phase transitions in MOFs.<div>
</div>
|
Julian Keupp; Rochus Schmid
|
Hybrid Organic-Inorganic Materials; Computational Chemistry and Modeling
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2019-06-17
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7426c337d6c4dbee26a6e/original/molecular-dynamics-simulations-of-the-breathing-phase-transformation-of-mof-nanocrystallites.pdf
|
60c746e5bdbb8955cba38cb9
|
10.26434/chemrxiv.11426994.v1
|
Functionalized NIR-II Semiconducting Polymer Nanoparticles for Single-Cell to Whole-Organ Imaging of PSMA-Positive Prostate Cancer
|
<p>Development of specific
molecular probes holds great promise for early diagnosis of aggressive prostate
cancer (PCa). Here, 2-[3-(1,3-dicarboxypropyl) ureido] pentanedioic acid
(DUPA)-conjugated ligand and bis-isoindigo-based polymer (BTII) are synthesized
to formulate semiconducting polymer nanoparticles (BTII-DUPA SPN) as a
prostate-specific membrane antigen (PSMA)-targeted probe for PCa imaging in the
NIR-II window. Insights into the interaction of the imaging probes with the
biological targets from single-cell to whole-organ levels are obtained by
transient absorption microscopy (TAM) and photoacoustic tomography (PAT). The
targeting mechanism, kinetics, and specificity of BTII-DUPA SPN to PSMA-positive
PCa cells are revealed at cellular level with TAM. At the organ level, PAT imaging
of BTII-DUPA SPN in the NIR-II window demonstrates superior penetration depth
and imaging contrast. By intravenous administration, BTII-DUPA SPN demonstrates
selective accumulation and retention in the PSMA-positive tumor, allowing
noninvasive PAT detection of PSMA overexpressing PCa. The distribution of
nanoparticles at tissue level is further analyzed through TAM. These results collectively
demonstrate a new SPN for targeted cancer detection by TAM and PAT imaging.</p>
|
Jiayingzi Wu; Hyeon-Jeong Lee; Liyan You; Xuyi Luo; Tsukasa Hasegawa; Kai-Chih Huang; Peng Lin; Timothy Ratliff; Minoru Ashizawa; Jianguo Mei; Ji-Xin Cheng
|
Conducting polymers
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2019-12-23
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c746e5bdbb8955cba38cb9/original/functionalized-nir-ii-semiconducting-polymer-nanoparticles-for-single-cell-to-whole-organ-imaging-of-psma-positive-prostate-cancer.pdf
|
63f4c392fcfb27a31f2b02bf
|
10.26434/chemrxiv-2023-55tgl
|
Latent Pronucleophiles in Lewis Base Catalysis: Enantioselective Allylation of Silylated Stabilized Carbon Nucleophiles with Allylic Fluorides
|
Lewis base catalyzed allylations of C-centered nucleophiles have been largely limited to the niche substrates with acidic C-H substituted with C-F bonds at the stabilized carbanionic carbon. Here we report that the concept of latent pronucleophiles serves to overcome these limitations and allow for a variety of common silylated stabilized C-nucleophiles to undergo enantioselective allylations using allylic fluorides. The reactions of silyl enol ethers afford the allylation products in good yields and with high degree of regio / stereoselectivity as well as diastereoselectivity when cyclic silyl enol ethers are used. Further examples of silylated stabilized carbon nucleophiles that undergo efficient allylation speak in favor of the broad applicability of this concept in the arena of C-centered nucleophiles.
|
Suresh Kumar; Markus Lange; You Zi; Helmar Görls; Ivan Vilotijevic
|
Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Base Catalysis; Organocatalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-02-22
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63f4c392fcfb27a31f2b02bf/original/latent-pronucleophiles-in-lewis-base-catalysis-enantioselective-allylation-of-silylated-stabilized-carbon-nucleophiles-with-allylic-fluorides.pdf
|
64521e631ca6101a45b5625b
|
10.26434/chemrxiv-2023-7mm1f
|
Computational Discovery for Crafting Multi-dimensional and Multi-functional Metal-Organic Framework Composites
|
Rational design of multiple material components to create composite materials for synergistic enhancement is a crucial strategy in materials science. The combination of two-dimensional (2D) and three-dimensional (3D) metal-organic frameworks (MOFs) has great potential for creating multi-dimensional and multi-functional composites, expanding the material space for various applications. In this study, we developed a novel screening algorithm to construct 2D-MOF@3D-MOF composite structures using the intrinsic geometrical information of each MOF. Our algorithm was designed to prioritize synthesizability and identified several pairs of 2D-MOFs and 3D-MOFs. The screening results revealed that Ni-HHTP@UiO-66, a previously synthesized composite material, was among the potential candidates. Furthermore, the 2D-MOF@3D-MOF composite candidate that passed our algorithm exhibited superior mechanical strength compared to the mismatched composite. Our research advances the field of MOF by providing a practical screening algorithm for identifying suitable 2D-MOF@3D-MOF composite candidates and paves the way for the discovery of new materials with enhanced properties.
|
Mingyu Jeon; Ohmin Kwon; Jihan Kim
|
Theoretical and Computational Chemistry; Computational Chemistry and Modeling
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-05-04
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64521e631ca6101a45b5625b/original/computational-discovery-for-crafting-multi-dimensional-and-multi-functional-metal-organic-framework-composites.pdf
|
60c74cea4c8919fd96ad370f
|
10.26434/chemrxiv.12566963.v1
|
Expanding the Chemical Repertoire of DNA Nanomaterials Generated by Rolling Circle Amplification
|
<p>Rolling circle amplification (RCA) is a powerful tool for the construction of DNA nanomaterials such as hydrogels, high-performance scaffolds and DNA nanoflowers (DNFs), hybrid materials formed of DNA and magnesium pyrophosphate. Such DNA nanomaterials have great potential in therapeutics, imaging, protein immobilisation, and drug delivery, yet limited chemistry is available to expand their functionality. Here, we present an orthogonal strategy to produce densely modified RCA products and DNFs. We show that it is possible to selectively functionalise the DNA component of these materials, their protein cargo, or both, thereby greatly expanding the chemical repertoire available to these systems. We then use this methodology to construct DNFs bearing multiple surface aptamers capable of binding to cancer cells that overexpress the HER2 oncobiomarker, demonstrating the therapeutic and diagnostic potential of this chemistry.</p>
|
Ysobel Baker; Liyiwen Yuan; jinfeng Chen; Roman Belle; Robert Carlisle; Afaf El-Sagheer; Tom Brown
|
Bioorganic Chemistry; Nanostructured Materials - Materials; Drug Discovery and Drug Delivery Systems
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-06-26
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74cea4c8919fd96ad370f/original/expanding-the-chemical-repertoire-of-dna-nanomaterials-generated-by-rolling-circle-amplification.pdf
|
6766de6881d2151a027f8d02
|
10.26434/chemrxiv-2024-255g9
|
Optimization of Hydrogen Evolution Reaction Efficiency: Entropy and External Pressure Effects on High-Density Fish Patch Single-Atom Catalysts
|
Hydrogen has the blueprint as the next generation energy. Despite the considerable promise of Single atom catalysts (SACs) for hydrogen evolution, it is crucial to address the environmental concerns associated with these catalysts to advance their application in renewable energy technologies. In line with the Second law of thermodynamics we report the findings from a first principle examination of a novel high-density fish patch single-atom catalyst for HER. We employed DMOL3 and MATLAB for the molecular modelling and computation while MATLAB was used to determine the overpotential constant. With a focus on the effect of the entropy on the reaction rate for Hydrogen evolution reaction (HER), the optimum entropy for efficient HER was determine. Applying an external pressure of (0, 0.1333, 0.2667 and 0.4 Pascal) on the system and studying the Gibbs free energy, the study revealed that 0.2667 Pa, is the best position for efficient HER. At this value, ΔGH2 and ΔGH -0.25369 and -0.25883 eV.
|
Chidi Daniel
|
Catalysis; Energy; Heterogeneous Catalysis; Nanocatalysis - Reactions & Mechanisms; Fuels - Energy Science
|
CC BY 4.0
|
CHEMRXIV
|
2024-12-26
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6766de6881d2151a027f8d02/original/optimization-of-hydrogen-evolution-reaction-efficiency-entropy-and-external-pressure-effects-on-high-density-fish-patch-single-atom-catalysts.pdf
|
60c750369abda2263df8d9bd
|
10.26434/chemrxiv.12999770.v1
|
The Surface Composition of Amino Acid - KCl Solutions is pH-Dependent
|
The manuscript based on X-ray photoelectron spectroscopy on aqueous solutions containing KCl and different amino acids. Our analysis suggests that the presence of the inorganic ions at the surface of the liquid is strongly dependent on the pH of the solution and the type of amino acid.
|
Geethanjali Gopakumar; Isaak Unger; Clara-Magdalena Saak; Gunnar Öhrwall; Arnaldo Naves de Brito; Tulio Costa Rizuti da Rocha; Christophe Nicolas; Carl Caleman; Olle Björneholm
|
Interfaces; Physical and Chemical Properties; Spectroscopy (Physical Chem.); Surface
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-09-28
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c750369abda2263df8d9bd/original/the-surface-composition-of-amino-acid-k-cl-solutions-is-p-h-dependent.pdf
|
65ef093e9138d2316135f661
|
10.26434/chemrxiv-2024-489l5
|
The Enol of Isobutyric Acid
|
We present the gas-phase synthesis of 2-methyl-prop-1-ene-1,1-diol, an unreported higher energy tautomer of isobutyric acid. The enol was captured in an argon matrix at 3.5 K and characterized using IR and UV/Vis spectroscopy, combined with density functional theory computations. Upon irradiation the enol rearranges to form isobutyric acid and dimethylketene. Moreover, we also identified propene, photochemically formed from dimethylketene.
|
Akkad Danho; Artur Mardyukov; Peter Richard Schreiner
|
Organic Chemistry
|
CC BY 4.0
|
CHEMRXIV
|
2024-03-26
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65ef093e9138d2316135f661/original/the-enol-of-isobutyric-acid.pdf
|
63d27b686bc5ca354a1bd4a6
|
10.26434/chemrxiv-2022-h9bq3-v2
|
Cyclopropylcarbinyl-to-homoallyl carbocation equilibria influence the stereospecificity in the nucleophilic substitution of cyclopropylcarbinols
|
The synthesis of quaternary homoallylic halides and trichloroacetates from cyclopropylcarbinols, as reported by Marek in 2020 (J. Am. Chem. Soc. 2020, 142, 5543-5548), is one of the few reported examples of stereospecific nucleophilic substitution involving chiral bridged carbocations. However, for the phenyl-substituted substrates the stereoselectivity of the reaction is poor and a mixture of diastereomers is obtained. In order to understand the nature of the intermediates involved in this transformation and explain the loss of selectivity for certain substrates, we have performed a Density Functional Theory investigation of the reaction mechanism at the DLPNO-CCSD(T)/Def2TZVPP level of theory. Our results indicate that cyclopropylcarbinyl cations are stable intermediates in this reaction, while bicyclobutonium structures are high-energy transition structures and as such are not involved, regardless of the substitution pattern on the substrate. Instead, multiple rearrangement pathways of cyclopropylcarbinyl cations have been located, including rotations around their π-bonds and ring openings to homoallylic cations. Importantly, the relative energies of these homoallylic cations and of the activation barriers to reach them are correlated to the nature of the substituents. While direct nucleophilic attack on the chiral cyclopropylcarbinyl cation is kinetically favored for most systems, the rearrangements become competitive with nucleophilic attack for the phenyl-substituted systems, leading to a loss of selectivity through a mixture of rearranged carbocation intermediates. As such, it appears that stereospecific reactions of chiral cyclopropylcarbinyl cations depend on the ability of these cations to access homoallylic structures, from which selectivity is not guaranteed.
|
Sean Larmore; Pier Alexandre Champagne
|
Theoretical and Computational Chemistry; Organic Chemistry; Organic Synthesis and Reactions; Stereochemistry; Computational Chemistry and Modeling
|
CC BY NC 4.0
|
CHEMRXIV
|
2023-01-27
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63d27b686bc5ca354a1bd4a6/original/cyclopropylcarbinyl-to-homoallyl-carbocation-equilibria-influence-the-stereospecificity-in-the-nucleophilic-substitution-of-cyclopropylcarbinols.pdf
|
6262ba4e1033885ba5f6a21e
|
10.26434/chemrxiv-2022-tq6zk
|
Photoactivated Formal [3 + 2] Cycloaddition of N-Aryl Cycloprop-ylamines
|
Organic transformations initiated by photochemical activation have been at the forefront of reaction discovery. We have seen the [2+2] photocycloaddition performed upon excitation of α,β-unsaturated carbonyl compounds, and more recently [3 + 2] cycloadditions of aryl cyclopropyl ketones have been reported. These methodologies required a photocatalyst and/or external activators, adding some limitations to the substrates used. Herein, we report a formal photochemical [3 + 2] cycloaddition using N-aryl cyclopropylamines and α,β-unsaturated carbonyl systems without the use of photocatalysts or additives. This simple method proceeding through a Single Electron Transfer (SET) offers a wide scope for the synthesis of N-arylaminocycloalkyl compounds in good to excellent yields.
|
Louis Barriault; Montserrat Zidan
|
Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Photocatalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2022-04-25
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6262ba4e1033885ba5f6a21e/original/photoactivated-formal-3-2-cycloaddition-of-n-aryl-cycloprop-ylamines.pdf
|
60c74798f96a00a01a286f6c
|
10.26434/chemrxiv.11743017.v1
|
Macrolactonization Driven by Supramolecular Interactions
|
Macrolactones constitute a privileged class of natural
and synthetic products with a broad range of applications in the fine chemicals
and pharmaceutical industry. Despite all the
progresses made towards their synthesis, notably from <i>seco</i>-acids, a macrolactonization promoter system that is effective,
selective, flexible, readily available, and, insofar as possible, compatible
with manifold functional
groups is still lacking. Herein, we describe an alternative strategy
relying on a speculated supramolecular template to enable a convenient access
to macrolactones, macrodiolides and esters with a versatility that had not been
reached with classic methods.
|
guillaume force; david leboeuf
|
Organic Synthesis and Reactions
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-01-29
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74798f96a00a01a286f6c/original/macrolactonization-driven-by-supramolecular-interactions.pdf
|
6753b4db7be152b1d031afe9
|
10.26434/chemrxiv-2024-9wfb9
|
Testing a heterogeneous polarizable continuum model against exact Poisson boundary conditions
|
The polarizable continuum model (PCM) is a computationally efficient way to incorporate dielectric boundary conditions into electronic structure calculations, via a boundary-element reformulation of Poisson's equation. This transformation is only rigorously valid for an isotropic dielectric medium. To simulate anisotropic solvation, as encountered at an interface or when parts of a system are solvent-exposed while other parts are assumed to be in a nonpolar environment, ad hoc modifications to the PCM formalism have been suggested, in which a dielectric constant is assigned separately to each atomic sphere that contributes to the solute cavity. The accuracy of this "heterogeneous" PCM (HetPCM) method is tested here for the first time, by comparison to results from a generalized Poisson equation solver. The latter is a more expensive and cumbersome approach to incorporate arbitrary dielectric boundary conditions, but one that corresponds to a well-defined scalar permittivity function, epsilon(r). We examine simple model systems for which a model function epsilon(r) can be constructed in a manner that maps reasonably well onto a dielectric constant for each atomic sphere, using a solvent-exposed dielectric constant epsilon_solv = 78 and a variety of smaller values to represent a hydrophobic environment. For nonpolar dielectric constants epsilon_nonp <= 2, differences between the HetPCM and Poisson solvation energies are large compared to the effect of anisotropy on the solvation energy. For epsilon_nonp = 4 and epsilon_nonp = 10, however, HetPCM and anisotropic Poisson solvation energies agree to within 2 kcal/mol in most cases. As a realistic use case, we apply the HetPCM method to predict solvation energies and pKa values for a blue copper protein. The HetPCM method affords pKa values that are more in line with experimental results as compared to either gas-phase calculations or homogeneous (isotropic) PCM results.
|
Paige Bowling; Montgomery Gray; Suranjan Paul; John Herbert
|
Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Biochemistry; Computational Chemistry and Modeling; Theory - Computational
|
CC BY 4.0
|
CHEMRXIV
|
2024-12-10
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6753b4db7be152b1d031afe9/original/testing-a-heterogeneous-polarizable-continuum-model-against-exact-poisson-boundary-conditions.pdf
|
64de4aab01042bc1cc36ec04
|
10.26434/chemrxiv-2023-41kt8
|
High throughput identification of complex rutile alloys for the acidic oxygen evolution reaction
|
Efficient and durable catalysis of the oxygen evolution reaction in acidic media remains a grand challenge at the intersection of electrochemistry and materials discovery. Antimony-based rutile oxides have shown great promise but suffer from poor durability at high concentration of activity-promoting elements such as Mn. We use combinatorial methods to realize a new family of catalysts wherein combinations of Sn, Ti, and Sb enable activity in rutile oxides with Mn concentration less than 40%.
|
Lan Zhou; Aniketa Shinde; Ming-Chiang Chang; R Bruce van Dover; Michael Thompson; John Gregoire
|
Materials Science; Catalysis; Energy; Fuels - Materials; Thin Films; Electrocatalysis
|
CC BY 4.0
|
CHEMRXIV
|
2023-08-22
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64de4aab01042bc1cc36ec04/original/high-throughput-identification-of-complex-rutile-alloys-for-the-acidic-oxygen-evolution-reaction.pdf
|
63cc0c8d1a1ead04b8b2bedf
|
10.26434/chemrxiv-2023-c4q7f
|
Identification of the Veterinary Sedative Medetomidine in Combination with Opioids and Xylazine in Maryland
|
Public health, public safety, and forensic science personnel continue to face the emergence of new compounds into the drug market. While focus is often put on the detection of new analogs of known illicit drugs, monitoring the changes in cutting agents and other compounds can be equally as important. Over the last year, near real-time monitoring of the drug supply in Maryland has been completed through a public health – public safety partnership whereby residue from suspected drug packaging or used paraphernalia is collected and analyzed. Through this project, we have recently detected the presence of the veterinary sedative medetomidine in a small number of samples. The presence of medetomidine has been identified in both public health and law enforcement samples and in the presence of fentanyl and xylazine – another veterinary sedative that has been widely observed over the last year. While the rate at which medetomidine has been detected remains low, it is concerning and worthy of continued monitoring.
|
Edward Sisco; Meghan Appley
|
Analytical Chemistry; Mass Spectrometry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-01-23
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63cc0c8d1a1ead04b8b2bedf/original/identification-of-the-veterinary-sedative-medetomidine-in-combination-with-opioids-and-xylazine-in-maryland.pdf
|
63107e95eadd9ac1a189927a
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10.26434/chemrxiv-2022-zbjzl
|
Conjugation-Modulated Excitonic Coupling Brightens Multiple Triplet Excited States
|
The design and regulation of multiple room-temperature phosphorescence (RTP) processes are formidably challenging due to the restrictions imposed by Kasha’s rule. Here we report a general design principle for materials that show multiple RTP processes, which is informed by our study of four compounds where there is modulation of the linker hybridization between donor (D) and acceptor (A) groups. Theoretical modeling and photophysical experiments demonstrate that multiple RTP processes can be achieved in sp3 C-linked D-A compounds due to the arrest of intramolecular electronic communication between the T2 and T1 states. However, for the sp2 C-linked D-A counterparts, only RTP from T1 is observed because of enhanced excitonic coupling between the T2 and T1 states. Single-crystal and reduced density gradient analyses reveal the influence of molecular packing on the coincident phosphorescence processes and the origin of the observed aggregate phosphorescence. These findings provide insight into high-lying triplet excited state dynamics and into a fundamental design principle for designing compounds that show multiple RTP.
|
Tao Wang; Abhishek Kumar Gupta; Sen Wu; Alexandra Slawin; Eli Zysman-Colman
|
Organic Chemistry; Materials Science; Physical Organic Chemistry; Dyes and Chromophores; Optical Materials
|
CC BY 4.0
|
CHEMRXIV
|
2022-09-02
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63107e95eadd9ac1a189927a/original/conjugation-modulated-excitonic-coupling-brightens-multiple-triplet-excited-states.pdf
|
67974aabfa469535b9061de5
|
10.26434/chemrxiv-2025-6b2mp
|
Enzyme-membrane-reactors: recent trends and applications for the production of fine chemicals and pharmaceutical building-blocks
|
Biocatalysis has gained attention in recent decades as a green and efficient method for producing high-value chemicals. Enzymes, notably due to their high selectivity, offer significant advantages for organic synthesis. However, industrial implementation remains limited due to challenges such as free enzyme instability, enzyme inhibition, and difficulties in catalyst recovery and reuse. The coupling of biocatalysis with membrane technology in enzyme-membrane-reactors (EMR) holds significant potential for process intensification, as it paves the way to continuous flow synthesis concatenated with product purification, and biocatalyst recovery. By allowing flow hybrid processes (i.e. simultaneous biocatalytic reactions and membrane operations in one-pot), EMR have the potential to increase reaction yields and kinetics, and reduce downstream processing requirements. This review explores recent trends and advancements in EMR for the production of pharmaceutical building blocks and fine chemicals. We examine the combination of enzymes with both polymeric and ceramic membranes, highlighting their respective benefits and limitations. We cover both EMR processes where free enzymes are used separately from membrane devices, and EMR processes employing membrane-immobilized enzymatic reactors. As enzyme immobilization in/on solid supports has emerged as an effective approach for enhancing enzyme stability and reusability, we argue that the development of such membrane-immobilized enzyme reactors is of prime importance for the pharmaceutical industry. These insights aim to provide a comprehensive overview of the role and recent applications of EMRs in advancing biocatalytic processes within the fine chemistry and pharmaceutical industry.
|
Hippolyte Meersseman Arango; Tom Leyssens; Patricia Luis; Damien Debecker
|
Catalysis; Chemical Engineering and Industrial Chemistry; Pharmaceutical Industry; Reaction Engineering; Biocatalysis
|
CC BY 4.0
|
CHEMRXIV
|
2025-01-28
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67974aabfa469535b9061de5/original/enzyme-membrane-reactors-recent-trends-and-applications-for-the-production-of-fine-chemicals-and-pharmaceutical-building-blocks.pdf
|
60c759289abda21861f8ea4f
|
10.26434/chemrxiv.14663883.v1
|
Water-Assisted and Protein-Initiated Ring-Opening Polymerization of Proline N-Carboxyanhydride
|
<p>The production of poly-<sub>L</sub>-proline (PLP) via
the ring-opening polymerization (ROP) of <sub>L</sub>-proline <i>N</i>-carboxyanhydride (ProNCA) is
challenging due to a combination of factors, including the stringent
requirement of moisture-free conditions, slow monomer conversion, poor control
of the molar mass, and premature precipitation of the product in the form of
polyproline type I helix. Here, we report water-assisted ROP of ProNCA, which affords
well-defined PLP in polyproline II helix in 2-5 minutes. Density functional
theory reveals an as-yet-unreported role of water in facilitating proton shift
that significantly lowered the energy barrier of the chain propagation. Protein-mediated
ROP of ProNCA conveniently affords various protein-PLP conjugates via a
grafting-from approach. PLP conjugation not only preserves the biological
activities of the native proteins, but also enhances the stability of proteins against
extreme conditions. This work provides a simple means and new mechanistic
insight to solve a longstanding problem in PLP synthesis and will offer
valuable guidance for the development of water-resistant ROP of other NCAs. The
facile access of PLP can greatly boost the application potentials of PLP-based
functional materials.<b></b></p>
|
Yali Hu; Zi-You Tian; wei xiong; HUA LU
|
Biopolymers; Polymerization (Polymers)
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-05-25
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c759289abda21861f8ea4f/original/water-assisted-and-protein-initiated-ring-opening-polymerization-of-proline-n-carboxyanhydride.pdf
|
67c3a55c81d2151a02a86017
|
10.26434/chemrxiv-2025-6vgg9
|
Insights from designing an artificial cascade catalysis system using principles from substrate channeling in enzymes
|
Generalizing the key requirements of highly-selective, multi-step chemical conversions involving spatially separated reaction centers remains one of the grand challenges of chemistry. Much work towards this effort has focused on decomposing multi-step conversions into their constituent reactions, whose intermediates are successively upgraded in a chemical cascade via diffusion from center to center. This approach for synthesizing more complex molecules takes its cues from biochemical networks, where near-unit conversion of even complex carbohydrates is achieved by upgrading chemical precursors via enzymatic cascades. In this computational study we examine a simple cascade involving coupled Ag and Cu catalysts that sequentially converts CO2 to CO and then CO2 and CO to reduced products, generically named CO2Product and COProduct. The system architecture is inspired by the phenomenon of biological substrate channeling, and components are examined to evaluate their effects on conversion efficiency in the cascade. Aside from a substrate channel linking two reaction centers, we find efficient cascades must also incorporate directional substrate diffusion, compartmentalization of the reaction centers, and proper timing of substrate arrival at the active center. We make explicit linkages between these requirements and chemical conversion in known biological systems, revealing additional control elements that could be incorporated.
|
Frances Houle; Peter Agbo; Junko Yano
|
Physical Chemistry; Physical and Chemical Processes
|
CC BY NC 4.0
|
CHEMRXIV
|
2025-03-04
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67c3a55c81d2151a02a86017/original/insights-from-designing-an-artificial-cascade-catalysis-system-using-principles-from-substrate-channeling-in-enzymes.pdf
|
66c31755f3f4b052905579a6
|
10.26434/chemrxiv-2024-pglww
|
Ketonization of Valeric Acid to 5-Nonanone over Metal Oxides catalysts
|
Valeric acid (VA), readily obtainable in the biorefinery from sugary biomass streams, can be upgraded to 5-nonanone, a versatile chemical building block with numerous applications. This study investigates the performance of nine metal oxide catalysts (SnO2, SiO2, Y2O3, CeO2, ZrO2, TiO2, La2O3, Cr2O3, and Al2O3) in the gas-phase ketonization of VA to 5-nonanone in the 350-450°C range. This screening reveals a correlation between the metal oxides lattice energy and their catalytic activity for valeric acid ketonization. ZrO2, TiO2, and La2O3, char-acterized by high lattice energy, demonstrate the highest catalytic activity. Y2O3, SnO2, SiO2, showing low lattice energy, are barely active. However, exceptions to this trend were ob-served: Cr2O3 and Al2O3 displayed poor catalytic performance despite their elevated lattice energy. The comprehensive characterization of the catalysts, encompassing XRD, N2-physisorption, NH3-TPD, and CO2-TPD analyses, has unveiled the crucial role of important parameters including acid-base properties in addition to lattice energy. Only oxides showing amphoteric properties can catalyse the reaction effectively. Interestingly, low-lattice energy and amphoteric oxides such as SnO2 (showing poor performance) became significantly active at higher temperature (500°C). Analysis of by-products by online GC-MS and spent catalyst characterization indicated that in this case the ketonization mechanism changed from the so-called surface mechanism to the so-called bulk mechanism. This study contributes to a refined understanding of catalyst properties governing ketonization efficiency, paving the way for optimizing the conversion of biomass-derived carboxylic acids into valuable biofuel precursors.
|
Ali Alizadeh Eslami; François Devred; Damien P Debecker
|
Catalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-08-21
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66c31755f3f4b052905579a6/original/ketonization-of-valeric-acid-to-5-nonanone-over-metal-oxides-catalysts.pdf
|
60c744f60f50db5294396199
|
10.26434/chemrxiv.9932366.v1
|
Gas-Phase Bioproduction of a High-Value-Added Monoterpenoid (E)-Geranic Acid by Metabolically Engineered Acinetobacter Sp. Tol 5
|
Gas-phase bioproduction, in which immobilized biocatalysts are employed and chemical reactions are performed in a gas phase, has attracted researchers’ attention as a green process. However, there is difficulty in the employment of whole cell catalysts for gas-phase bioproduction due to the lack of a suitable cell immobilization method. <i>Acinetobacter</i> sp. Tol 5 is a unique bacterium, which is remarkably sticky and can be easily immobilized onto various material surfaces through the adhesive bacterionanofiber protein AtaA. In this study, we demonstrate the gas-phase bioproduction of (<i>E</i>)-geranic acid (GA), a high-value-added monoterpenoid, from geraniol using immobilized Tol 5 transformant cells, into which a gene involved in a (<i>E</i>)-GA synthetic pathway was introduced. Time course analysis of the liquid-phase bioproduction of (<i>E</i>)-GA revealed the inherent metabolism of Tol 5 involved in the degradation of (<i>E</i>)-GA. By disrupting the <i>fadD4</i>-ortholog gene, which encodes a key enzyme of the (<i>E</i>)-GA degradation, we successfully generated a (<i>E</i>)-GA-accumulating strain, Tol 5 Δ<i>fadD4</i> (pGeoA). The immobilized cells of this mutant strain on a polyurethane support enabled the production of (<i>E</i>)-GA with a passive supply of gaseous geraniol in a batch gas-phase reaction. A major fraction of the (<i>E</i>)-GA, which was produced, was adsorbed onto the polyurethane support but easily extracted into ethanol, a safe solvent without environmental impact. This is the first example of gas-phase bioproduction of a complex and high-value-added compound. Tol 5 is a highly promising platform for gas-phase bioproduction.
|
Atsushi Usami; Masahito Ishikawa; Katsutoshi Hori
|
Biocatalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2019-10-04
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c744f60f50db5294396199/original/gas-phase-bioproduction-of-a-high-value-added-monoterpenoid-e-geranic-acid-by-metabolically-engineered-acinetobacter-sp-tol-5.pdf
|
60c747ff337d6c525fe27448
|
10.26434/chemrxiv.11823684.v1
|
Preferential Control of Forward Reaction Kinetics in Hydrogels Crosslinked with Reversible Conjugate Additions
|
<p>Molecular substitutions were used to demonstrate preferential control
over the kinetic rate constants in a poly(ethylene glycol)-based hydrogel with
two different reversible thia-conjugate addition reactions. A strong electron
withdrawing nitrile group on the conjugate acceptor showed a 20-fold increase
in the forward rate constant over a neutral withdrawing group, while the
reverse rate constant only increased 6-fold. Rheometry experiments demonstrated
that the hydrogel plateau modulus was primarily dictated by reaction
equilibrium, while the stress relaxation characteristics of the hydrogel were
dominated by the reverse rate constant. Furthermore, the dynamic crosslinking
allowed the hydrogel to rapidly and spontaneously self-heal. These results
indicate that decoupling the kinetic rate constants of bond exchange allow
systematic control over dynamic covalent hydrogel bulk properties, such as
their adaptability, stress relaxation ability, and self-healing properties.</p>
|
Thomas FitzSimons; Felicia Oentoro; Tej V. Shanbhag; Eric Anslyn; Adrianne Rosales
|
Hydrogels
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-02-10
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c747ff337d6c525fe27448/original/preferential-control-of-forward-reaction-kinetics-in-hydrogels-crosslinked-with-reversible-conjugate-additions.pdf
|
66b00fc301103d79c5c07d8b
|
10.26434/chemrxiv-2024-c0xng
|
An Integrated Study of Pd(0)-Halide Interactions in Pd Oxidative Addition to Organic Halides: Uncovering the “Super Iodine” Character of Pd(0)
|
Pd(0) oxidative addition (OA) to organic halides is a fundamental step in many catalytic organic transformations. Previous mechanistic studies have shown that the electronic/steric nature of ligand, metal coordination unsaturation, halide identity and the presence of an additive all have sizable influences on reaction reactivity and selectivity. A single parameter-based rational design fully integrating all important factors in a quantitative manner remains elusive, due to the complex nature of Pd(0) OA. To address this challenge, a study of Pd(0)-halide interactions which are crucial for the 3-centered concerted mechanism, is initiated in this work by integrating the key progress in organometallic chemistry and the relatively well-established halogen bonding knowledge, mimicking the “data-driven” method. The achieved advanced understanding of the mechanisms in this work includes five key parts: 1) uncovering the “super iodine” character of Pd(0), 2) uncovering the bonding nature of Pd-halide (organic halide) interaction and its essential role in Pd(organic halide) precomplex before OA; 3) a molecular mechanism for the additive effect, and a theoretical prediction of a halogen transfer pathway for OA to specific organic halides; 4) demystifying the known super reactivity of the ligand-controlled Pd catalysis with inactive aryl chlorides; and ultimately 5) proposing a proof-of-concept of surface molecule electrostatic potential-based rational design of OA.
|
Liuqun Gu
|
Organic Chemistry; Catalysis; Organometallic Chemistry; Physical Organic Chemistry; Homogeneous Catalysis; Kinetics and Mechanism - Organometallic Reactions
|
CC BY NC 4.0
|
CHEMRXIV
|
2024-08-06
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66b00fc301103d79c5c07d8b/original/an-integrated-study-of-pd-0-halide-interactions-in-pd-oxidative-addition-to-organic-halides-uncovering-the-super-iodine-character-of-pd-0.pdf
|
612db736d5f08081b4b6e2b6
|
10.26434/chemrxiv-2021-1p0wp
|
Accessing Three Oxidation States of Cobalt in M6L3 Nanoprisms with Cobalt-Porphyrin Walls
|
Nanocages with porphyrin walls are common, but studies of such structures hosting redox-active metals are rare. Pt-linked M6L3 nanoprisms with cobalt-porphyrin walls were prepared and their redox properties were evaluated electrochemically and chemically, leading to the first time that cobalt-porphyrin nanocages have been characterized in Co(I), Co(II), and Co(III) states.
|
P. Thomas Blackburn; Iram F. Mansoor; Kaitlyn G. Dutton; Alexei M. Tyryshkin; Mark C. Lipke
|
Inorganic Chemistry; Organometallic Chemistry; Nanoscience; Electrochemistry; Reaction (Inorg.); Supramolecular Chemistry (Inorg.)
|
CC BY NC 4.0
|
CHEMRXIV
|
2021-09-07
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/612db736d5f08081b4b6e2b6/original/accessing-three-oxidation-states-of-cobalt-in-m6l3-nanoprisms-with-cobalt-porphyrin-walls.pdf
|
60c749e0469df4860ef43c54
|
10.26434/chemrxiv.12119040.v1
|
Critical Assessment of Artificial Intelligence Methods for Prediction of hERG Channel Inhibition in the ‘Big Data’ Era
|
The rise of novel artificial intelligence methods necessitates a comparison of this wave of new approaches with classical machine learning for a typical drug discovery project. Inhibition of the potassium ion channel, whose alpha subunit is encoded by human Ether-à-go-go-Related Gene (hERG), leads to prolonged QT interval of the cardiac action potential and is a significant safety pharmacology target for the development of new medicines. Several computational approaches have been employed to develop prediction models for assessment of hERG liabilities of small molecules including recent work using deep learning methods. Here we perform a comprehensive comparison of prediction models based on classical (random forests and gradient boosting) and modern (deep neural networks and recurrent neural networks) artificial intelligence methods. The training set (~9000 compounds) was compiled by integrating hERG bioactivity data from ChEMBL database with experimental data generated from an in-house, high-throughput thallium flux assay. We utilized different molecular descriptors including the latent descriptors, which are real-valued continuous vectors derived from chemical autoencoders trained on a large chemical space (> 1.5 million compounds). The models were prospectively validated on ~840 in-house compounds screened in the same thallium flux assay. The deep neural networks performed significantly better than the classical methods with the latent descriptors. The recurrent neural networks that operate on SMILES provided highest model sensitivity. The best models were merged into a consensus model that offered superior performance compared to reference models from academic and commercial domains. Further, we shed light on the potential of artificial intelligence methods to exploit the chemistry big data and generate novel chemical representations useful in predictive modeling and tailoring new chemical space.<br />
|
Vishal Babu Siramshetty; Dac-Trung Nguyen; Natalia J. Martinez; Anton Simeonov; Noel T. Southall; Alexey Zakharov
|
Computational Chemistry and Modeling; Machine Learning; Artificial Intelligence; Chemoinformatics - Computational Chemistry
|
CC BY 4.0
|
CHEMRXIV
|
2020-04-16
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c749e0469df4860ef43c54/original/critical-assessment-of-artificial-intelligence-methods-for-prediction-of-h-erg-channel-inhibition-in-the-big-data-era.pdf
|
67d8b3436dde43c9082dde89
|
10.26434/chemrxiv-2025-mz223
|
Data-driven discovery of water-stable metal-organic
frameworks with high water uptake capacity
|
Metal-organic frameworks (MOFs) are promising candidate materials for applications that would benefit from precise chemical patterning, such as desalination and atmospheric water harvesting, but many MOFs suffer from poor stability in water. In addition to water stability, high water uptake capacity in ambient conditions is expected to be necessary for water-related practical applications of MOFs, motivating large-scale search that can only be achieved computationally. Here, we take a combined machine learning and high-throughput screening approach to identifying water-stable MOFs with high water uptake capacities. Starting from a subset of previously curated MOFs with experimentally known exceptionally high stability in water, we explore the effect of linker functionalization with twelve diverse hydrophilic
functional groups expected to further tune water uptake. For these 736 MOFs, we use grand canonical Monte Carlo (GCMC) simulations to compute their water uptake capacity. We observe strong positive correlations between MOF pore features (e.g., the largest cavity diameter and
volumetric pore volume) and water uptake capacity, although we notice breakdowns of such correlations in MOFs with extremely hydrophobic linkers that repel water molecules despite having large pores. Finally, we develop machine learning models to screen new MOFs simultaneously for water stability and water uptake capacity. From a pool of hypothetical and experimental MOFs, we identify 74 promising materials within the domain of applicability of the machine learning models that are predicted to be both water-stable and have high water uptake.
|
Akash Ball; Gianmarco Terrones; Shuwen Yue; Heather Kulik
|
Theoretical and Computational Chemistry; Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2025-03-19
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67d8b3436dde43c9082dde89/original/data-driven-discovery-of-water-stable-metal-organic-frameworks-with-high-water-uptake-capacity.pdf
|
60c7499f0f50dbd394396928
|
10.26434/chemrxiv.12092265.v1
|
Highly-Excited State Properties of Cumulenone Chlorides in the Vacuum-Ultraviolet
|
<div><div><div><p>Recent observations of chloromethane in interstellar environments suggest that other organohalo- gens, which are known to be critically important in Earth′s atmosphere, may also be of significance beyond our own terrestrial veil. This raises the question of how such molecules behave under extreme conditions such as when exposed to vacuum ultraviolet (VUV) radiation. VUV photons promote molecules to highly excited states that fragment in non-statistical patterns controlled by the initial femtosecond dynamics. A detailed understanding of VUV-driven photochemistry in complex organic molecules that consist of more than one functional group is a particularly challenging task. This quantum chemical analysis reports the electronic states and ionization potentials up to the VUV range (6 - 11 eV) of the chlorine-substituted cumulenone series molecules. The valence and Rydberg properties of lone-pair terminated, π-conjugated systems are explored for their potential resonance with lone pairs from elsewhere in the system. The carbon chain elongation within the family ClHCnO, where n=1-4, influences the electronic excitations, associated wavefunctions, and ionization poten- tials of the molecules. The predicted geometries and ionization potentials are in good agreement with the available experimental photoelectron spectra for formyl chloride and chloroketene, n=1-2. Furthermore, comparison between the regular cumulenone species and the corresponding chlorinated derivatives exhibit similar behaviors especially for n=3, where the allene backbone in propadienone chloride is severely bent. Most notably for the excited states is that the Rydberg character becomes more dominant as the energy increases, with some retaining valence characters.</p></div></div></div>
|
Quynh Nguyen; William Peters; Ryan Fortenberry
|
Theory - Computational
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-04-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7499f0f50dbd394396928/original/highly-excited-state-properties-of-cumulenone-chlorides-in-the-vacuum-ultraviolet.pdf
|
62975e36a6101b28b4d72926
|
10.26434/chemrxiv-2022-p8l62
|
Recent Advancement in Palladium Catalysed C-C bond Activation of Strained Ring Systems: Three and four-membered carbocycles as prominent C3/C4 building blocks
|
In recent years, transition metal catalysed strong C-C bond activation has significantly attracted the attention of synthetic chemists. This enables simultaneous and direct functionalization of two different M-C bonds. Among different types of C-C bond activation strategies, strain-driven C-C bond activation has resulted in a variety of transformations, which is otherwise impossible. In this context, palladium catalyst has been extensively used and studied due to its robust nature in terms of its reactivity and selectivity. Herein, we have provided a brief discussion about palladium catalysed C-C bond activation of three and four-membered cycloalkane derivatives.
|
Tanmayee Nanda; Muhammed Fastheem ; Astha Linda; Bedadyuti Vedvyas Pati; Shyam Kumar Banjare; Pragati Biswal; Ponneri C. Ravikumar
|
Organic Chemistry; Catalysis; Organic Synthesis and Reactions
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2022-06-02
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62975e36a6101b28b4d72926/original/recent-advancement-in-palladium-catalysed-c-c-bond-activation-of-strained-ring-systems-three-and-four-membered-carbocycles-as-prominent-c3-c4-building-blocks.pdf
|
673496637be152b1d0f00418
|
10.26434/chemrxiv-2024-f13l1
|
A Self-Driving Lab for Nano- and Advanced Materials Synthesis
|
The recent emergence of self-driving labs (SDL) and material acceleration platforms (MAPs) demonstrates the ability of these systems to change the way chemistry and material syntheses will be performed in the future. Especially in conjunction with nano and advanced materials which are generally recognized for their great potential in solving current material science challenges, such systems can make disrupting contributions. Here, we describe in detail MINERVA - an SDL specifically built and designed for the synthesis, purification, and in line characterization of nano and advanced materials. By fully automating these three process steps for seven different materials from five representative, completely different classes of nano and advanced materials (metal, metal oxide, silica, metal organic framework, and core-shell particles) that follow different reaction mechanisms, we demonstrate the great versatility and flexibility of the platform. We further study the reproducibility and particle size distributions of these seven representative materials in depth and show the excellent performance of the platform when synthesizing these material classes. Lastly, we discuss the design considerations as well as the hardware and software components that went into building the platform and make all components publicly available.
|
Mohammad Zaki; Carsten Prinz; Bastian Ruehle
|
Materials Science; Nanoscience; Nanostructured Materials - Materials; Nanostructured Materials - Nanoscience; Materials Chemistry
|
CC BY 4.0
|
CHEMRXIV
|
2024-12-09
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/673496637be152b1d0f00418/original/a-self-driving-lab-for-nano-and-advanced-materials-synthesis.pdf
|
61c337e47f367e246d5c2cea
|
10.26434/chemrxiv-2021-kbdcz
|
Assessment of carotenoid degradation of grits from orange corn packaged in high barrier thermosealed pouches
|
Genetically improved maize varieties with high carotenoid levels and dark orange color have been developed to increase dietary consumption of macular carotenoids. However, postharvest and food processing conditions can cause isomerization and oxidation of carotenoids, reducing their potential impact on consumers' health. The purpose of this study was to assess the effectiveness of high barrier pouches in reducing carotenoid losses during the storage of dry-milled corn products. Orange corn grits were packaged in paper pouch bags, and three types of low-oxygen and low-moisture permeable (LOMP) pouches. Grits were packaged in each type of LOMP pouch with (LOMP-oxy) and without (LOMP-noxy) an oxygen scavenger. For six months, all pouches were stored at semi-controlled environmental conditions (22.5 ± 1.3°C, 32 ± 18% RH). After the storage period, orange corn grits stored in paper pouch bags lost 55% of total xanthophylls, whereas grits packaged in LOMP pouches only lost 8% of total xanthophylls. Orange Corn grits packaged in LOMP-oxy pouches had slightly higher carotenoid content than in LOMP-noxy pouches. Relative humidity fluctuation in the storeroom could have caused fluctuation in moisture content in the orange corn grits packaged in paper pouches, which may affect the rate of carotenoid degradation in the orange corn grits. Therefore, an effective control of the moisture content of the packaged dry-milled product and effective control of the temperature of pouches during storage conditions is essential to maximize carotenoid retention during the storage of dry-milled high carotenoid orange corn grits.
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Darwin Ortiz; Ingrid Aragón; Sean Renwick; Jhoan Rodriguez-Yara; Tyler Lawson; Evan Rocheford; Torbert Rocheford
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Agriculture and Food Chemistry; Food
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CC BY NC ND 4.0
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CHEMRXIV
|
2021-12-24
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61c337e47f367e246d5c2cea/original/assessment-of-carotenoid-degradation-of-grits-from-orange-corn-packaged-in-high-barrier-thermosealed-pouches.pdf
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60c756a7bdbb8999cea3aa7a
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10.26434/chemrxiv.14166866.v2
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Phytoalexins and Signalling Metabolites Produced in the Wild Crucifer Neslia Paniculata: Camalexins and Arabidopsides
|
The metabolites produced in elicited leaves of the
wild crucifer <i>Neslia paniculata</i> (L.)
Desv. were investigated in
abiotically stressed plants. Herein the phytoalexins camalexin,
7-methoxycamalexin and 6,7-dimethoxycamalexin together with the signalling
metabolites arabidopsides A and D are reported. This is the first report of occurrence
of 7-methoxy and 6,7-dimethoxycamalexins <i>in planta</i> and
the third example of
synchronized biosynthesis of phytoalexins and galacto-oxylipins. It is
suggested that arabidopsides and structurally similar metabolites functioning as signalling molecules are likely to occur in a much larger number of plant
species than originally hypothesized. <i>N. paniculata</i> is potentially useful to generate hybrid plants
resistant to blackleg disease caused by <i>Leptosphaeria maculans.</i>
|
M. Soledade C. Pedras; Mahla Alavi; Abbas Abdoli
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Natural Products; Plant Biology
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CC BY NC ND 4.0
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CHEMRXIV
|
2021-03-19
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c756a7bdbb8999cea3aa7a/original/phytoalexins-and-signalling-metabolites-produced-in-the-wild-crucifer-neslia-paniculata-camalexins-and-arabidopsides.pdf
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64823a3fbe16ad5c57a97637
|
10.26434/chemrxiv-2023-qc8sp
|
Unambiguous molecular characterization of solid
electrolyte interphase species on graphite negative
electrodes
|
Performances of lithium-ion batteries (LIBs) are closely related to the control of solid-electrolyte interface (SEI) stability. To decrease the capacity losses linked to the build-up of this interface or potentially reverse such losses, electrolyte formulations have been continuously optimized over years to evaluate how they affect SEI. However, direct molecular characterization of the diverse interphases remains extremely challenging. Herein, we report the molecular imaging of SEI components formed on graphite electrodes by laser desorption ionization (LDI) coupled to ultrahigh-resolution Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS). By exploiting the surface analysis offered by LDI combined with the molecular formula attributions provided by the FT-ICR MS, it is possible to unambiguously identify/exclude suspected molecules in the SEI such as lithium ethylene dicarbonate and lithium ethylene mono carbonate. Moreover, thousands of unknown species were observed, which could be exploited for further understanding of the surface composition. We believe this methodology to be a critical advance for the design of high-performance LiBs.
|
Julien Florent Maillard; Julien Demeaux; Charlotte Mase; Antonin Gajan; Cécile Tessier; Patrick Bernard; Carlos Afonso; Pierre Giusti
|
Analytical Chemistry; Energy; Imaging; Mass Spectrometry; Energy Storage
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-06-09
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64823a3fbe16ad5c57a97637/original/unambiguous-molecular-characterization-of-solid-electrolyte-interphase-species-on-graphite-negative-electrodes.pdf
|
6503399599918fe537f39753
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10.26434/chemrxiv-2023-9m257
|
Nickel-Bound 5-Membered N-Heterocyclic Arynes: Access to Previously “Inaccessible” 7-Aza-2,3-indolynes
|
N-Heteroaromatics are key elements of life-saving pharmaceuticals, potent agrochemicals, and vital materials. N-Heteroarynes provide a scaffold to build these essential molecules but are underutilized because 5-membered N-heteroarynes have been computed to be inaccessible to synthetic chemists due to the strain of a triple bond in a 5-membered ring. Using principles of metal-ligand interactions that are foundational to organometallic chemistry, herein is reported the first access to a previously inaccessible 5-membered N-heteroaryne. A series of 1,2-bis(dicyclohexylphosphino)ethane nickel 7-azaindol-2,3-yne complexes are synthesized and characterized crystallographically and spectroscopically. In order to showcase the synthetic potential, a difunctionalization of N-methyl-7-azaindol-2,3-yne to form two new C-C bonds is performed. By overcoming a 120-year old limitation, we have unlocked a new synthon for the synthesis of difunctionalized N-heteroaromatics for transformative synthesis.
|
Jenna Humke; Roman Belli; Erin Plasek; Sallu Kargbo; Annabel Ansel; Courtney Roberts
|
Inorganic Chemistry; Organometallic Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-09-19
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6503399599918fe537f39753/original/nickel-bound-5-membered-n-heterocyclic-arynes-access-to-previously-inaccessible-7-aza-2-3-indolynes.pdf
|
6631088d418a5379b01aaf90
|
10.26434/chemrxiv-2024-1c3xs
|
Mechanochemically-Driven Self-Assembly of a Chiral Mono-Biotinylated Hemicucurbit[8]uril
|
Hemicucurbiturils are macrocycles formed by connecting ethyleneurea moieties with methylene bridges. This study presents the development of self-assembled chiral mono-biotinylated hemicucurbit[8]urils (mixHC[8]) in the solid state. The mixHC[8]s were synthesized in a single preparative step by a mechanochemically-assisted condensation reaction of D-biotin, (R,R)- or (S,S)-cyclohexa-1,2-diylurea and formaldehyde. Dynamic covalent library of over 100 identified oligomers was generated via ball milling under perchloric or hexafluorophosphoric acid catalysis. Rigorous analysis of intermediates, including formation kinetics of short oligomers, revealed key processes and chemical parameters influencing self-assembly. We found that self-organization of about 50,000 theoretically predicted oligomers can be directed to formation of 8-membered hemicucurbiturils in 75% yield, consisting of a 1:1 mixture of chimeric mixHC[8] and homomeric cyclohexanohemicucurbit[8]uril (cycHC[8], 38% and 37% yields, respectively), or predominantly homomeric cycHC[8] (up to a 72% yield). The developed procedure was used for synthesis of diastereomeric (−)- and (+)-mixHC[8] suitable for anion binding and derivatization. Immobilization of mixHC[8] on a surface of aminated silica produced a functional material capable of selective capture of anions, as demonstrated by efficient perchlorate removal from a spiked mineral matrix.
|
Elina Suut-Tuule; Tatsiana Jarg; Priit Tikker; Ketren-Marlein Lootus; Jevgenija Martõnova; Rauno Reitalu; Lukaš Ustrnul; James Ward; Vitalijs Rjabovs; Kirill Shubin; Jagadeesh V. Nallaparaju; Marko Vendelin; Sergei Preis; Mario Öeren; Kari Rissanen; Dzmitry Kananovich; Riina Aav
|
Physical Chemistry; Organic Chemistry; Analytical Chemistry; Organic Synthesis and Reactions; Supramolecular Chemistry (Org.); Self-Assembly
|
CC BY 4.0
|
CHEMRXIV
|
2024-05-02
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6631088d418a5379b01aaf90/original/mechanochemically-driven-self-assembly-of-a-chiral-mono-biotinylated-hemicucurbit-8-uril.pdf
|
61781105d7e1ee8e3c357541
|
10.26434/chemrxiv-2021-jt414
|
Conversion of carboxylic acids to potassium acyltrifluoroborates (KATs) by Cu-catalyzed borylation of mixed anhydrides
|
We report the preparation of potassium acyltrifluoroborates (KATs) from widely-available carboxylic acids. Mixed anhydrides of carboxylic acids were prepared using isobutyl chloroformate and transformed to the corresponding KATs using a commercial copper catalyst, B2(pin)2 and aqueous KHF2. This method allows for the facile preparation of aliphatic, aromatic, and amino acid-derived KATs and is compatible with a variety of functional groups including alkenes, esters, halides, nitriles, and protected amines.
|
Pinku Tung; Anne Schuhmacher; Philipp Schilling; Jeffrey Bode; Neal Mankad
|
Organic Chemistry; Organometallic Chemistry; Organic Synthesis and Reactions; Catalysis; Main Group Chemistry (Organomet.)
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-10-27
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61781105d7e1ee8e3c357541/original/conversion-of-carboxylic-acids-to-potassium-acyltrifluoroborates-ka-ts-by-cu-catalyzed-borylation-of-mixed-anhydrides.pdf
|
60c73eda469df4affff42967
|
10.26434/chemrxiv.7133885.v1
|
Evaluation of Cross-Validation Strategies in Sequence-Based Binding Prediction Using Deep Learning
|
Binding prediction between targets and drug-like compounds through Deep Neural Networks have generated promising results in recent years, outperforming traditional machine learning-based methods. However, the generalization capability of these classification models is still an issue to be addressed. In this work, we explored how different cross-validation strategies applied to data from different molecular databases affect to the performance of binding prediction proteochemometrics models. These strategies are: (1) random splitting, (2) splitting based on K-means clustering (both of actives and inactives), (3) splitting based on source database and (4) splitting based both in the clustering and in the source database. These schemas are applied to a Deep Learning proteochemometrics model and to a simple logistic regression model to be used as baseline. Additionally, two different ways of describing molecules in the model are tested: (1) by their SMILES and (2) by three fingerprints. The classification performance of our Deep Learning-based proteochemometrics model is comparable to the state of the art. Our results show that the lack of generalization of these models is due to a bias in public molecular databases and that a restrictive cross-validation schema based on compounds clustering leads to worse but more robust and credible results. Our results also show better performance when representing molecules by their fingerprints.
|
Angela Lopez-del Rio; Alfons Nonell-Canals; David Vidal; Alexandre Perera-Lluna
|
Bioinformatics and Computational Biology; Drug Discovery and Drug Delivery Systems; Machine Learning; Chemoinformatics - Computational Chemistry
|
CC BY 4.0
|
CHEMRXIV
|
2018-09-27
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73eda469df4affff42967/original/evaluation-of-cross-validation-strategies-in-sequence-based-binding-prediction-using-deep-learning.pdf
|
66fe9a8251558a15eff3445e
|
10.26434/chemrxiv-2024-gngkq
|
Nickel-Catalyzed Stereospecific Alkylation of Vinylsiloxanes Using Pyridinium salts
|
A methodology for radical cross-coupling with vinylsiloxanes and pyridinium salts under nickel catalysis is described. Easily implemented from inexpensive and abundant primary amines and terminal alkynes, this modern Hiyama coupling provides efficient access to (E), (Z), and 1,1’-alkenes with configuration retention. Operating under mild conditions, this robust strategy applies to a broad range of functional groups with diverse double bond stereochemistries. This versatile reaction is scalable and straightforward, accommodating both secondary and primary alkyl groups. A radical mechanism involving hypervalent silicon intermediates is proposed.
|
Logan Salamone; Xavier Vanderbiest; Olivier Riant
|
Organic Chemistry; Catalysis; Homogeneous Catalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-10-04
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66fe9a8251558a15eff3445e/original/nickel-catalyzed-stereospecific-alkylation-of-vinylsiloxanes-using-pyridinium-salts.pdf
|
65233545bda59ceb9a2371e9
|
10.26434/chemrxiv-2023-q5r9g-v3
|
Transition-metal free boron triiodide-mediated reduction of nitroarenes from simple borohydride reagents
|
The reduction of nitroarenes using KBH4 and I2 is described. BI3 is generated in situ, which was shown to be the active reductant. Conditions were optimized for BI3 generation, and then applied to a wide range of nitroarenes, including traditionally challenging substrates. The method constitutes a practical reduction option which produces low toxicity boric acid and potassium iodide upon workup.
|
Florence Williams; Andrej Corkovic; Thomas Chiarella
|
Organic Chemistry; Organic Synthesis and Reactions
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-10-09
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65233545bda59ceb9a2371e9/original/transition-metal-free-boron-triiodide-mediated-reduction-of-nitroarenes-from-simple-borohydride-reagents.pdf
|
674dded45a82cea2fabc93bd
|
10.26434/chemrxiv-2024-r7k45-v2
|
MTDL-GAN: De novo Design of Multi-Target Directed Ligands for Alzheimer’s Disease from Unpaired Sets of Target-Focused Chemical Library
|
BACKGROUND. Alzheimer’s disease (AD), the most common form of dementia, causes memory loss, cognitive decline, and behavioural changes, affecting over 32 million people globally. Current AD treatments that focus on single-target intervention often fail to significantly slow disease progression and may not be effective for all patients. Given AD's complex nature, a more effective approach may involve targeting multiple pathways simultaneously. METHODS. This study proposes the use of a cycle-consistent adversarial network to design multi-target directed ligands (MTDL-GAN), drugs designed to inhibit two primary AD target enzymes simultaneously. Our targets of interest are acetylcholinesterase (AChE), beta-secretase 1 (BACE1), and glycogen synthase kinase 3 beta (GSK3), which are known to have significant impacts on the progression and development of AD, each with a different mechanism of action. Inhibitor libraries were curated from ChEMBL27 and further characterized to represent each inhibitor domain, resulting in 69 AChE, 572 BACE1, and 246 GSK3 inhibitors. The MTDL-GAN was trained on these unpaired datasets to generate MTDL-like molecules. During the model training, all generated molecular structures were stored to create in silico MTDL libraries. From each MTDL library, 300 molecules were sampled for further analysis. Tanimoto similarity scores were computed to assess the structural similarity of the generated molecules to the target inhibitor domain, and molecular docking simulations were carried out to validate their \textit{in silico} binding affinities to the target enzymes. RESULTS. The proposed method effectively transformed molecules from the original inhibitor domains into MTDL-like molecules while maintaining their structural similarity to the original inhibitors. Less than 0.15% of the generated molecules have a Tanimoto similarity score above 0.85 to the known bioactive molecules in ChEMBL27, highlighting their structural novelty and potential for exploring new chemical space. Further investigation revealed that the sampled MTDLs demonstrate promising in silico dual-binding affinity while having favourable physicochemical properties and synthetic tractability. Among these, several MTDLs surpassed the in silico binding affinities of investigational drugs in phase 2/3 clinical trials. Molecular structures of these hit MTDLs are publicly available for academic research.
|
Taeyeub Lee
|
Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Computational Chemistry and Modeling; Artificial Intelligence; Chemoinformatics - Computational Chemistry
|
CC BY NC 4.0
|
CHEMRXIV
|
2024-12-03
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/674dded45a82cea2fabc93bd/original/mtdl-gan-de-novo-design-of-multi-target-directed-ligands-for-alzheimer-s-disease-from-unpaired-sets-of-target-focused-chemical-library.pdf
|
66ecbd5bcec5d6c14299cac6
|
10.26434/chemrxiv-2024-l35x3
|
Flow-gel approach enables rapid extraction of pure magnesium phase from seawater
|
Current methods for separating critical materials from feedstock solutions remain chemistry- and energy-intensive. We demonstrate the rapid extraction of a pure magnesium phase from seawater via precipitation with sodium hydroxide in a flow-gel device. Our approach is scalable, suitable for high-throughput extraction, and does not rely on specialty chemicals.
|
Pravalika Butreddy; Andrew Ritchhart; Qingpu Wang; Heather Job; Maria Sushko; Jaehun Chun; Elias Nakouzi
|
Materials Science; Energy; Chemical Engineering and Industrial Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-09-24
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66ecbd5bcec5d6c14299cac6/original/flow-gel-approach-enables-rapid-extraction-of-pure-magnesium-phase-from-seawater.pdf
|
60c74622f96a00088c286ced
|
10.26434/chemrxiv.10728086.v1
|
Design of AIEgens for Near-Infrared IIb Imaging Through Structural Modulation at Molecular and Morphological Levels
|
<p>Fluorescence
imaging in near-infrared IIb (NIR-IIb, 1500-1700 nm) spectrum holds a
considerable promise for tissue imaging with deep penetration and high spatial
resolution owing to the minimized autofluorescence and suppressed photon
scattering. While few inorganic NIR-IIb fluorescent probes have been reported,
their organic counterparts are still underdeveloped, possibly due to the lack
of efficient materials with long emission wavelength. Herein, we propose a new
molecular design philosophy to develop organic NIR-IIb fluorophores with high
quantum yield (QY) by manipulation of the effects of twisted intramolecular
charge transfer and aggregation-induced emission at the molecular and morphological
levels. A pure organic fluorescent dye emitting up to 1600 nm with a QY of
14.2% in the NIR-II region (1000-1600 nm) is developed. For the first time, NIR-IIb fluorescence imaging of blood vessels and
deeply-located intestinal tract of live mice based on organic dyes is achieved.
The results show that organic fluorophore performs superb imaging ability in
both superficial blood vessels and internal organs with high resolution and
enhanced signal-to-background ratio in NIR-IIb region. We hope this
groundbreakingly study will inspire further research on the evolution of pure
organic NIR-IIb probes for in vivo imaging.</p>
|
yuanyuan li; Zhaochong Cai; shunjie liu; Haoke Zhang; sherman Wong; Jacky W. Y. Lam; Ryan Tsz Kin Kwok; Jun Qian; Ben Zhong Tang
|
Biological Materials; Optical Materials
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2019-11-29
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74622f96a00088c286ced/original/design-of-ai-egens-for-near-infrared-i-ib-imaging-through-structural-modulation-at-molecular-and-morphological-levels.pdf
|
65c0a89ce9ebbb4db9b44de3
|
10.26434/chemrxiv-2024-q9vgn
|
Rheo-SAXS study of a shear-thinning hydrogel containing clay nanoplatelets
|
Shear-induced orientation of clay nanoplatelets within a physically cross-linked hydrogel based on ionenes, positively charged polyelectrolytes, is studied here. Small angle X-ray scattering measurements (SAXS) are performed under shear within a Couette cell cylinder (rheo-SAXS). As the SAXS signal is dominated by that of the clay component, we follow the evolution of the orientational distribution of the clay nanoplatelets within the hydrogel as a function of shear. We investigate the effect of the clay volume fraction, polyelectrolyte concentration, clay charge location and clay charge density by screening three different types of clay: Wyoming and Arizona montmorillonites and Idaho beidellite. The orientational field of clay nanoplatelets in the gel is shown to strongly depend on the clay charge location and shear rate, whereas it is independent of the clay volume fraction. Approaching the critical gelation concentration of the polyelectrolyte system, these features change drastically.
|
Claire Hotton; Guylaine Ducouret; Juliette Sirieix-Plenet; Thomas Bizien; Clement Guibert; Pierre Levitz; Laurent Michot; Natalie Malikova
|
Physical Chemistry; Polymer Science; Nanoscience; Hydrogels; Polyelectrolytes - Polymers; Nanostructured Materials - Nanoscience
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-02-06
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65c0a89ce9ebbb4db9b44de3/original/rheo-saxs-study-of-a-shear-thinning-hydrogel-containing-clay-nanoplatelets.pdf
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631f4c24be03b2c20ef31735
|
10.26434/chemrxiv-2022-lb9cf
|
Selective Recognition and Sensing of Biologically Important Phosphates Using Triptycene-Based Anion Receptors
|
The overarching aim of supramolecular chemistry is to design and synthesize receptors exhibiting selectivity and efficiency comparable to that found in nature in biological receptors and enzymes. Despite the recent progress, we are still far from designing a receptor selective for a given molecular guest. Phosphate-derived anions are particularly interesting molecular targets because of their multiple cellular functions, being constituents of DNA and RNA as well as taking part in the cellular energy conversion mechanisms. Here, we present a systematic investigation of the anion binding properties of triptycene-based anion receptors, and study them in the solid-state as well as computationally using density functional theory(DFT). Titrations under fluorescence control indicate that receptor 1 is highly selective towards monophosphates derived from nucleotides such as AMP, deoxy-AMP, CMP and UMP with binding constant determined to be in the range 6637 – 100000 M-1. Contrary, phosphate anions derived from cyclic AMP and ADP were not bound by receptor 1, as indicated by no change in fluorescence spectra.
|
Ahmad F. Kassir; Daniel Lupp; Jakub Grabowski; Jaroslaw M. Granda; Janusz Jurczak
|
Physical Chemistry; Organic Chemistry; Analytical Chemistry; Physical Organic Chemistry; Supramolecular Chemistry (Org.); Physical and Chemical Properties
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2022-09-14
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/631f4c24be03b2c20ef31735/original/selective-recognition-and-sensing-of-biologically-important-phosphates-using-triptycene-based-anion-receptors.pdf
|
6610173321291e5d1d271a1d
|
10.26434/chemrxiv-2024-58031
|
Stability and Surface Functionalization of Plasmonic Group 4 Transition Metal Nitrides
|
Plasmonic transition metal nitrides (TMNs) have emerged as a low-cost and thermally and chemically robust alternatives to noble metals. While their superior thermal properties have been established, their chemical properties on the nanoscale haven’t been as well studied. Herein, the oxidative stability over time under ambient conditions and colloidal stability as function of pH was explored for plasmonic TiN, ZrN and HfN nanoparticles. It was discovered that the TMN nanoparticles made via solid-state method had a narrow pH stability range between 2 – 3. Under highly acidic conditions, the particles underwent dissolution and at pH ≥ 4, they aggregate and precipitate from the solution. Additionally, TiN nanoparticles had poor oxidative stability and oxidized to TiO2 after ~40 days. 3-Aminopropyltriethoxysilane (APTES) and dimethylsilane coated TMNs were synthesized to yield water and organic solvent dispersible particles, respectively. These functionalized colloidal suspensions showed enhanced oxidative stability over 60 days and the APTES coating widened the pH stability window of TMNs to include physiological pH. This study shows that surface functionalization using M–O–Si linkages (where M = Ti, Zr, or Hf) can greatly enhance the stability, dispersibility and therefore applicability of plasmonic TMN nanoparticles.
|
Dreenan Shea; Reem Karaballi; Samantha Jee; Mita Dasog
|
Materials Science; Nanoscience; Optical Materials; Plasmonic and Photonic Structures and Devices; Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-04-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6610173321291e5d1d271a1d/original/stability-and-surface-functionalization-of-plasmonic-group-4-transition-metal-nitrides.pdf
|
60c752adbdbb8933f7a3a326
|
10.26434/chemrxiv.13336871.v1
|
Chemoselective Copper-Mediated Radical Modification of Selenocysteines in Peptides and Proteins
|
Highly valuable bioconjugated molecules must be synthesized through efficient, chemoselective chemical modifications of peptides and proteins. Herein we report the chemoselective modification of peptides and proteins via a reaction between selenocysteine residues and aryl/alkyl radicals. <i>In situ </i>radical generation from hydrazine substrates and copper ions proceeds rapidly in neat aqueous buffer at near neutral pH (5-8), providing a variety of Se-modified linear and cyclic peptides and proteins conjugated to aryl and alkyl molecules, as well as to affinity label tag (biotin). This chemistry opens a new avenue for chemical protein modifications.
|
Zhenguang Zhao; Norman Metanis
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Chemical Biology
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-12-07
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c752adbdbb8933f7a3a326/original/chemoselective-copper-mediated-radical-modification-of-selenocysteines-in-peptides-and-proteins.pdf
|
629e2fa7468a0854134dc474
|
10.26434/chemrxiv-2022-c1cxb
|
Mechanistic Roles of Metal- and Ligand-Protonated Species in Hydrogen Evolution with [Cp*Rh] Complexes
|
Protonation reactions involving organometallic complexes are ubiquitous in redox chemistry and often result in the generation of reactive metal hydrides. However, some organometallic species supported by η5-pentamethylcyclopentadienyl (Cp*) ligands have recently been shown to undergo ligand-centered protonation by direct proton transfer from acids or tautomerization of metal hydrides, resulting in the generation of complexes bearing the uncommon η4-cyclopentadiene (Cp*H) ligand. Here, time-resolved pulse radiolysis (PR) and stopped-flow spectroscopic studies have been applied to examine the kinetics and atomistic details involved in the elementary electron- and proton-transfer steps leading to complexes ligated by Cp*H, using Cp*Rh(bpy) as a molecular model (where bpy is 2,2′-bipyridyl). Stopped-flow measurements coupled with infrared and UV-visible detection reveal that the sole product of initial protonation of Cp*Rh(bpy) is [Cp*Rh(H)(bpy)]+, an elusive hydride complex that has spectroscopically and kinetically characterized here for the first time. Tautomerization of the hydride leads to the clean formation of [(Cp*H)Rh(bpy)]+. Variable-temperature and isotopic labeling experiments further confirm this assignment, providing experimental activation parameters and mechanistic insight into metal-mediated hydride-to-proton tautomerism. Spectroscopic monitoring of the second proton transfer event reveals both the hydride and related Cp*H complex can be involved in further reactivity, showing that [(Cp*H)Rh] is not necessarily an off-cycle intermediate, but, instead, depending on the strength of the acid used to drive catalysis, an active participant in hydrogen evolution. Identification of the mechanistic roles of the protonated intermediates in the catalysis studied here will inform design of new catalytic systems supported by non-innocent cyclopentadienyl-type ligands.
|
Wade Henke; Yun Peng; Alex Meier; Etsuko Fujita; David Grills; Dmitry Polyansky; James Blakemore
|
Inorganic Chemistry; Organometallic Chemistry; Organometallic Compounds; Catalysis
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CC BY NC ND 4.0
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CHEMRXIV
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2022-06-07
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/629e2fa7468a0854134dc474/original/mechanistic-roles-of-metal-and-ligand-protonated-species-in-hydrogen-evolution-with-cp-rh-complexes.pdf
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60c743fabb8c1a6a8b3da42d
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10.26434/chemrxiv.9731279.v1
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Using Alcohols As Simple H2-Equivalents for Copper-Catalysed Transfer Hydrogenations
|
Catalytic transfer hydrogenations are among the most practical synthetic methods for the selective reduction of functional groups. Cheap and readily available dihydrogen (H2) equivalents are highly desirable for catalytic transfer hydrogenations, as inevitably, waste is generated by the formal H2 source. Copper hydride catalysis generally relies on stoichiometric use of waste-generating hydrosilanes. Here, we demonstrate that simple alcohols can be employed as H2 equivalents in stereoselective alkyne semihydrogenations, prototypical copper hydride-catalysed transformations.
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Trinadh Kaicharla; Birte Zimmermann; Martin Oestreich; Johannes F. Teichert
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Organic Synthesis and Reactions; Homogeneous Catalysis
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CC BY NC ND 4.0
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CHEMRXIV
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2019-08-27
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c743fabb8c1a6a8b3da42d/original/using-alcohols-as-simple-h2-equivalents-for-copper-catalysed-transfer-hydrogenations.pdf
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62ab11d84483980dcb77ff47
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10.26434/chemrxiv-2022-bg7gn
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Phase Separating Electrode Materials – Chemical Inductors?
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We discover presence of chemical inductive effects in phase separating ion intercalation energy storage materials, specifically in lithium iron phosphate (LFP) and also lithium titanate oxide (LTO). These materials features fast (de)intercalation and slow diffusion relaxation phenomena which are prerequisites for observing such inductive effects. Presented finding is supported by the mechanistic model and analytical reasoning indicating that all equilibrium states that lay inside the miscibility gap of the phase separating material exhibit strong inductive response in the low frequency part of spectrum. We also explain why such inductive effects are not observed outside the miscibility gap. This letter presents the first mechanistic reasoning of previously reported electrode level experimental observation of inductance during impedance measurements at low currents.
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Klemen Zelič; Igor Mele; Arghya Bhowmik; Tomaž Katrašnik
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Energy; Energy Storage
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CC BY NC 4.0
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CHEMRXIV
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2022-06-16
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62ab11d84483980dcb77ff47/original/phase-separating-electrode-materials-chemical-inductors.pdf
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65e1e99166c1381729f38788
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10.26434/chemrxiv-2024-p6bw4
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Thiolated polyglycerol sulfate as potential mucolytic for muco-obstructive lung diseases
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Increased disulfide crosslinking of secreted mucins causes elevated viscoelasticity of mucus and is a key determinant of mucus dysfunction in patients with cystic fibrosis (CF) and other muco-obstructive lung diseases. In this study, we describe the synthesis of a novel thiol-containing, sulfated dendritic polyglycerol (dPGS-SH), designed to chemically reduce these abnormal crosslinks, which we demonstrate with mucolytic activity assays in sputum from patients with CF. This mucolytic polymer, which is based on a reportedly anti-inflammatory polysulfate scaffold, additionally carries multiple thiol groups for mucolytic activity and can be produced on a gram-scale. After a physicochemical compound characterization, we compare the mucolytic activity of dPGS-SH to the clinically approved N-acetylcysteine (NAC) using Western blot studies and investigate the effect of dPGS-SH on the viscoelastic properties of sputum samples from CF patients by oscillatory rheology. We show that dPGS-SH is more effective than NAC in reducing multimer intensity of the secreted mucins MUC5B and MUC5AC and demonstrate significant mucolytic activity by rheology. In addition, we provide data for dPGS-SH demonstrating a high compound stability, low cytotoxicity, and superior reaction kinetics over NAC at different pH levels. Our data support further development of the novel reducing polymer system dPGS SH as a potential mucolytic to improve mucus function and clearance in patients with CF as well as other muco-obstructive lung diseases.
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Justin Arenhoevel; Aditi Kuppe; Annalisa Addante; Ling-Fang Wei; Nico Boback; Cosmin Butnarasu; Christine Wong; Simon Y. Graeber; Julia Duerr; Michael Gradzielski; Daniel Lauster; Marcus A. Mall; Rainer Haag
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Polymer Science; Biopolymers; Materials Chemistry
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CC BY NC 4.0
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CHEMRXIV
|
2024-03-04
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65e1e99166c1381729f38788/original/thiolated-polyglycerol-sulfate-as-potential-mucolytic-for-muco-obstructive-lung-diseases.pdf
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61f4684ac18d676ad6880090
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10.26434/chemrxiv-2022-mwjnn
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Hydroboration of Terminal Alkynes Catalysed by Sodium Triethylborohydride
|
Sodium triethylborohydride - commonly used as a reducing agent for hydroboration catalysts based on the first-row transition metal complexes with tridentate ligands, has been found a highly selective catalyst for hydroboration of terminal alkynes. Hydroboration of aromatic and aliphatic alkynes with pinacolborane in the presence of 10 mol% of NaHBEt3 proceeded in a highly selective manner to give (E)-vinylboronate esters with high yields, whereas ethynylsilanes seem to be less reactive in this process.
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Anna M. Maj; Piotr Pawluć; Maciej Zaranek
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Organic Chemistry; Catalysis; Organometallic Chemistry; Homogeneous Catalysis; Main Group Chemistry (Organomet.)
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CC BY 4.0
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CHEMRXIV
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2022-01-31
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61f4684ac18d676ad6880090/original/hydroboration-of-terminal-alkynes-catalysed-by-sodium-triethylborohydride.pdf
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6446fd45df78ec50155556e8
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10.26434/chemrxiv-2023-1hz22
|
Phase Separation and Gelation in Solutions and Blends of Hetero-Associative Polymers
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An equilibrium statistical mechanical theory for the formation of reversible networks in two-component solutions of associative polymers is presented to account for the phase behavior due to hydrogen bonding, metal–ligand, electrostatic, or other pairwise heterotypic associative interactions. We derive explicit analytical expressions for the binding statistics, gelation condition, and free energy, in which we consider polymers of types A and B with many associating groups per chain and consider only A–B association between the groups. The free energy is approximated at the mean-field level, considering overlapping polymer chains with an ideal gas of "stickers" capable of intermolecular association. It is shown that the number of associations is maximized at stoichiometric conditions between A and B associative groups. Accordingly, homogeneous networks are most easily formed near stoichiometric conditions between A and B associative groups, resulting in a re-entrant sol–gel–sol transition as the overall composition is altered. Association and reversible network formation are found to be accompanied by a tendency for phase separation. These results demonstrate that reversibly associating polymers have a large parameter space in terms of molecular design, binding energy, and mixture compositions. Our predictions are expected to be useful in the rational design of interacting polymer mixtures and the formation of reversible networks.
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Scott Danielsen; Alexander Semenov; Michael Rubinstein
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Materials Science; Polymer Science
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CC BY NC ND 4.0
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CHEMRXIV
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2023-05-03
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6446fd45df78ec50155556e8/original/phase-separation-and-gelation-in-solutions-and-blends-of-hetero-associative-polymers.pdf
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65e589b99138d23161a0a493
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10.26434/chemrxiv-2024-mj3h8
|
An Automated Dual Modeling Approach to Accelerate Reaction Analysis and Optimization
|
In modern pharmaceutical research, the demand for expeditious development of synthetic routes to active pharmaceutical ingredients (APIs) has led to a paradigm shift towards data-rich process development. Conventional methodologies en-compass prolonged timelines for reaction and analytical model developments. Both method developments are separated into different departments and often require an iterative process to optimize the models. Addressing this issue, we intro-duce an innovative dual modeling approach, seamlessly integrating the development of a Process Analytical Technology (PAT) strategy with reaction optimization. This integrated approach is exemplified in diverse amidation reactions and the synthesis of the API benznidazole. The platform, characterized by a high degree of automation and minimal operator in-volvement, achieves PAT calibration through a “standard addition” approach. Dynamic experiments are executed to screen a broad process space and gather data for fitting kinetic parameters. Employing a Julia-coded software program facilitates rapid kinetic parameter fitting and in-situ optimization within minutes. This highly automated workflow not only expedites the understanding and optimization of chemical processes, but also holds significant promise for time and resource savings within the pharmaceutical industry.
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Peter Sagmeister; Lukas Melnizky; Jason Williams; C. Oliver Kappe
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Organic Chemistry; Analytical Chemistry; Chemical Engineering and Industrial Chemistry; Organic Synthesis and Reactions; Process Chemistry; Pharmaceutical Industry
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CC BY 4.0
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CHEMRXIV
|
2024-03-05
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65e589b99138d23161a0a493/original/an-automated-dual-modeling-approach-to-accelerate-reaction-analysis-and-optimization.pdf
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6114db5530231a5a870889c3
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10.26434/chemrxiv-2021-24dct-v2
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Characterisation of the Boson Peak from the Glass into the Liquid
|
Phenomena ranging from vitrification to crystal nucleation are governed by locally ordered structures, in otherwise disordered phases, that can either inhibit or favour the growth of macroscopic order. However, such structures are ephemeral, do not typically have distinct spectral features, and are therefore critically important but largely unobservable by current methods. Illuminating these structures therefore presents the single greatest challenge in physical chemistry. The boson peak is characteristic of glasses and represents the locally ordered structures inhibiting crystallisation but is typically obscured by other spectral contributions. Here we show that depolarised Raman scattering—obtained using femtosecond optical Kerr-effect spectroscopy—in liquids consisting of highly symmetric molecules can be used to isolate the boson peak thereby allowing detailed characterisation of the intermolecular potential-energy landscape for the first time.
|
Andrew Farrell; Mario González Jiménez; Nikita Tukachev; David A. Turton; Ben A. Russell; Sarah Guinane; Hans Martin Senn; Klaas Wynne
|
Physical Chemistry; Materials Science; Hybrid Organic-Inorganic Materials; Spectroscopy (Physical Chem.); Thermodynamics (Physical Chem.)
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CC BY NC ND 4.0
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CHEMRXIV
|
2021-08-12
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6114db5530231a5a870889c3/original/characterisation-of-the-boson-peak-from-the-glass-into-the-liquid.pdf
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60c7572c0f50dbe6383981fc
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10.26434/chemrxiv.14356970.v1
|
Customized Software Environment for Remote Learning: Providing Students a Specialized Learning Experience
|
The Covid-19 pandemic has challenged educators across the world to move their teaching and mentoring from in-person to remote. During nonpandemic semesters at their institutes (e.g. universities), educators can directly provide students the software environment needed to support their learning - either in specialized computer laboratories (e.g. computational chemistry labs) or shared computer spaces. These labs are often supported by staff that maintains the operating systems (OS) and software. But how does one provide a specialized software environment for remote teaching? One solution is to provide students a customized operating system (e.g., Linux) that includes open-source software for supporting your teaching goals. However, such a solution should not require students to install the OS alongside their existing one (i.e. dual/multi-booting) or be used as a complete replacement. Such approaches are risky because of a) the students' possible lack of software expertise, b) the possible disruption of an existing software workflow that is needed in other classes or by other family members, and c) the importance of maintaining a working computer when isolated (e.g. societal restrictions). To illustrate possible solutions, we discuss our approach that used a customized Linux OS and a Docker container in a course that teaches computational chemistry and Python3.
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Thomas Gerlach; Lukas Schauer; Michael Rademacher; Wolfgang Heiden; Karl Kirschner
|
Chemical Education - General; Computational Chemistry and Modeling
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CC BY NC ND 4.0
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CHEMRXIV
|
2021-04-07
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7572c0f50dbe6383981fc/original/customized-software-environment-for-remote-learning-providing-students-a-specialized-learning-experience.pdf
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615a7dedaef99cb0930bb9ec
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10.26434/chemrxiv-2021-s62r6
|
Tandem C–O and C–H Activation at Palladium Enables Catalytic Direct C–H Alkenylation with Enol Pivalates
|
The use of oxygen-based electrophiles in cross-coupling remains challenging for substrates with strong C–O bonds, with few examples that can combine C–O activation with an-other strong-bond activation in tandem. We report the first example of a direct, tandem C–O/C–H activation approach to C–C bond formation using palladium catalysis. This reaction combines C–O oxidative addition at enol pivalates with con-certed metallation deprotonation of functionalized heterocycles to achieve base-free direct C–H alkenylation, with pivalic acid as the only byproduct. Mechanistic studies reveal that the Pd(II) C–O oxidative addition product is the major catalyst resting state, indicating that C–H activation is the turnover-limiting step.
|
Nahiane Pipaon Fernandez; Gregory Gaube; Kyla Woelk; Mathias Burns; David Leitch
|
Organic Chemistry; Catalysis; Organometallic Chemistry; Organic Synthesis and Reactions; Homogeneous Catalysis; Bond Activation
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CC BY NC ND 4.0
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CHEMRXIV
|
2021-10-04
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/615a7dedaef99cb0930bb9ec/original/tandem-c-o-and-c-h-activation-at-palladium-enables-catalytic-direct-c-h-alkenylation-with-enol-pivalates.pdf
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639071d144ccbc04dc115814
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10.26434/chemrxiv-2022-r7gjb
|
Interpretable machine learning on metabolomics data reveals biomarkers for Parkinson’s disease
|
The use of machine learning (ML) with metabolomics provides opportunities for the early diagnosis of disease. However, the accuracy and extent of information obtained from ML and metabolomics can be limited owing to challenges associated with interpreting disease prediction models and analysing many chemical features with abundances that are correlated and ‘noisy’. Here, we report an interpretable neural network (NN) framework to accurately predict disease and identify significant biomarkers using whole metabolomics datasets without feature selection. The performance of the NN approach for predicting Parkinson’s disease (PD) from blood plasma metabolomics data was significantly higher than classical ML methods with a mean area under the curve of > 0.995. PD-specific markers that contribute significantly to early disease prediction were identified including an exogenous polyfluoroalkyl substance. It is anticipated that this accurate and interpretable NN-based approach can improve diagnostic performance for many other diseases using metabolomics and other untargeted ‘omics methods.
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J. Diana Zhang; Chonghua Xue; Vijaya B. Kolachalama; William A. Donald
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Analytical Chemistry; Analytical Chemistry - General; Mass Spectrometry
|
CC BY NC ND 4.0
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CHEMRXIV
|
2022-12-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/639071d144ccbc04dc115814/original/interpretable-machine-learning-on-metabolomics-data-reveals-biomarkers-for-parkinson-s-disease.pdf
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63773a9f3551196b9637be5d
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10.26434/chemrxiv-2022-b8t79-v4
|
From descriptors to intrinsic fish toxicity of chemicals: an alternative approach to chemical prioritization
|
The European and US chemical agencies have listed approximately 800k chemicals where knowledge on potential risks to human health and the environment are lacking. Filling these data gaps experimentally is impossible so in-silico approaches and prediction are essential. Many existing models are however limited by assumptions (e.g. linearity and continuity) and small training sets.
In this study we present a supervised direct classification model that connects molecular descriptors to toxicity. Categories can be either data-driven (using k-means clustering) or regulatory-defined. This was tested via 907 experimentally defined 96h LC50 values for acute fish toxicity. Our classification model explained ~90% of variance in our data for the training set and ~80% for the test set. This strategy gave a 5-fold decrease in the incorrect categorization compared to a QSAR regression model. Our model was subsequently employed to predict the toxicity categories of ~32k chemicals. A comparison between the model-based applicability domain (AD) and the training set AD was performed, suggesting that the training set based AD is a more adequate way to avoid extrapolation when using such models. The better performance of our direct classification model compared to QSAR methods, makes this approach a viable tool for hazard and risk assessment of chemicals.
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Saer Samanipour; Jake O'Brien; Malcolm Reid; Kevin Thomas; Antonia Praetorius
|
Earth, Space, and Environmental Chemistry; Environmental Science
|
CC BY 4.0
|
CHEMRXIV
|
2022-11-18
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63773a9f3551196b9637be5d/original/from-descriptors-to-intrinsic-fish-toxicity-of-chemicals-an-alternative-approach-to-chemical-prioritization.pdf
|
60c752fa337d6c10a0e287e6
|
10.26434/chemrxiv.13372289.v1
|
Synthesis of 4-O-Alkylated N-Acetylneuraminic Acid Derivatives
|
<p><i>N</i>-acetyl neuraminic acid<i> </i>(Neu5Ac) is a densely functionalized nine-carbon monosaccharide. It ubiquitously decorates the surface of mammalian cells were it is found in terminal positions of glycolipids and glycoproteins. This important saccharide and natural analogs play important roles in a number of processes in health and disease. Despite this few Neu5Ac based therapeutics have been developed. To further study and understand the chemistry and biology of Neu5Ac efficient protocols for synthesis of the parent natural compounds as well as synthetic analogs are required. In the manuscript, we report investigation of alkylation reactions to produce selectively modified Neu5Ac with focus on position 4. The study provides insights in the reaction and we establish robust protocols that allow selective modification of Neu5Ac for use as tool compounds and starting points for drug discovery.</p>
|
Emil Johansson; Rémi Caraballo; Mikael Elofsson
|
Natural Products; Organic Compounds and Functional Groups; Organic Synthesis and Reactions
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-12-15
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c752fa337d6c10a0e287e6/original/synthesis-of-4-o-alkylated-n-acetylneuraminic-acid-derivatives.pdf
|
60c74ea99abda2018af8d6b2
|
10.26434/chemrxiv.12781310.v1
|
Automated, Accurate, and Scalable Relative Protein-Ligand Binding Free Energy Calculations using Lambda Dynamics
|
<p>Accurate
predictions of changes to protein-ligand binding affinity in response to
chemical modifications are of utility in small molecule lead optimization.
Relative free energy perturbation (FEP) approaches are one of the most widely
utilized for this goal, but involve significant computational cost, thus
limiting their application to small sets of compounds. Lambda dynamics, also
rigorously based on the principles of statistical mechanics, provides a more
efficient alternative. In this paper, we describe the development of a workflow
to setup, execute, and analyze Multi-Site Lambda Dynamics (MSLD) calculations run
on GPUs with CHARMm implemented in BIOVIA Discovery Studio and Pipeline Pilot. The
workflow establishes a framework for setting up simulation systems for
exploratory screening of modifications to a lead compound, enabling the
calculation of relative binding affinities of combinatorial libraries. To
validate the workflow, a diverse dataset of congeneric ligands for seven
proteins with experimental binding affinity data is examined. A protocol to
automatically tailor fit biasing potentials iteratively to flatten the free
energy landscape of any MSLD system is developed that enhances sampling and
allows for efficient estimation of free energy differences. The protocol is
first validated on a large number of ligand subsets that model diverse
substituents, which shows accurate and reliable performance. The scalability of
the workflow is also tested to screen more than a hundred ligands modeled in a
single system, which also resulted in accurate predictions. With a cumulative
sampling time of 150ns or less, the method results in average unsigned errors of
under 1 kcal/mol in most cases for both small and large combinatorial libraries.
For the multi-site systems examined, the method is estimated to be more than an
order of magnitude more efficient than contemporary FEP applications. The
results thus demonstrate the utility of the presented MSLD workflow to
efficiently screen combinatorial libraries and explore chemical space around a
lead compound, and thus are of utility in lead optimization.</p>
|
E. Prabhu Raman; Thomas J. Paul; Ryan L. Hayes; Charles L. Brooks III
|
Computational Chemistry and Modeling
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-08-10
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74ea99abda2018af8d6b2/original/automated-accurate-and-scalable-relative-protein-ligand-binding-free-energy-calculations-using-lambda-dynamics.pdf
|
66d138a2f3f4b052909537be
|
10.26434/chemrxiv-2024-m4lxq
|
Selective Inhibitor Design Against Thymidylate Synthase of Mycobacterium tuberculosis using Alchemical Simulations
|
Thymidylate synthase is an essential enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidylate synthase from Mycobacterium tuberculosis (MtbThyX) recognizes the deprotonated substrate dUMP(d) (ionized at N3, charge = -3) involving cationic side-chain of Arg199, whereas the human analog (hThyA) select the natural substrate dUMP (charge = -2) by involving polar side-chain of Asn226 in the binding pocket. Distinctly different protonation states of the substrate and the catalytic pocket architecture make MtbThyX an attractive drug target for combating Mycobacterium tuberculosis. Fluorodeoxyuridylate (FdUMP) is a known inhibitor of thymidylate synthase, which is severely limited by poor selectivity (more potent against hThyA relative to MtbThyX). Using FdUMP as a template, we designed three drug-like ligands, L1, L2, and L3, by (1) removing the proton from the Watson-Crick edge and (2) substituting the ketone/hydroxyl group by fluorine and or carboxylic moiety. The absence of a proton on the N3 atom of the ligand is intended to ensure selectivity by favoring MtbThyX binding (skipping the N3 ionization requirement) but penalizing hThyA binding (disrupting the interaction with Asn226). Ionization of the carboxyl group in the ligands was expected to increase the affinity in the cationic binding pocket of MtbThyX. Alchemical simulations confirmed that the designed ligands are strongly favored and disfavored relative to the substrate (dUMP) by MtbThyX and hThyA, respectively. In contrast to hThyA, the catalytic pocket of MtbThyX proved to be relatively dry and stabilized the relatively compact conformation of the ligand (which had a noticeable effect on the sugar puckering). Favorable protein-ligand electrostatic interaction in the dry MtbThyX pocket strongly favored ligand binding. In contrast, the interaction between the Watson-Crick edge of ligands and hThyA was compromised, resulting in water exposure. Ligand L2 is particularly advantageous for its highest affinity for MtbThyX and weak affinity for hThyA. The L2:MtbThyX complex is stabilized by a new salt-bridge interaction (COO- of L2…Arg107 of protein) and a bridging water molecule (between COO- of L2 and E92 of protein) in the binding pocket. Moreover, our estimated pKa of -8 unit of N3 (dUMP) in the MtbThyX catalytic pocket indicated the strong acidic nature of the uracil, corroborating previous experimental and computational claims. These findings provide insights into the protein-ligand binding affinity in atomic details and a rational approach for inhibitor design against MtbThyX.
|
Pallav Sengupta; PRIYADARSHI SATPATI
|
Theoretical and Computational Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-08-30
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66d138a2f3f4b052909537be/original/selective-inhibitor-design-against-thymidylate-synthase-of-mycobacterium-tuberculosis-using-alchemical-simulations.pdf
|
60c7540e4c89193b1cad440f
|
10.26434/chemrxiv.13200227.v2
|
Tuning Proton Transfer Thermodynamics in SARS-Cov-2 Main Protease: Implications for Catalysis and Inhibitor Design
|
In this computational work a hybrid quantum mechanics/molecular mechanics approach, the MD-PMM approach, is used to investigate the proton transfer reaction that activates the catalytic activity of SARS-CoV-2 main protease. The proton transfer thermodynamics is investigated for the apo ensyme (i.e., without any bound substrate or inhibitor) and in the presence of a inhibitor, N3, which was previously shown to covalently bind SARS-CoV-2 main protease.
|
Laura Zanetti-Polzi; Micholas Smith; Chris Chipot; James C. Gumbart; Diane L. Lynch; Anna Pavlova; Jeremy C. Smith; Isabella Daidone
|
Biochemistry; Biophysics; Computational Chemistry and Modeling; Theory - Computational; Biophysical Chemistry; Thermodynamics (Physical Chem.)
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-01-13
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7540e4c89193b1cad440f/original/tuning-proton-transfer-thermodynamics-in-sars-cov-2-main-protease-implications-for-catalysis-and-inhibitor-design.pdf
|
639a33a7ff465105672a9ea8
|
10.26434/chemrxiv-2022-6r17v
|
Release systems based on self-assembling RADA16-I hydrogels with a signal sequence which improves wound healing processes
|
Self-assembling peptides can be used for the regeneration of severely damaged skin. They can act as scaffolds for skin cells and as a reservoir of active compounds, to accelerate scarless wound healing. To overcome repeated administration of peptides which accelerate healing, we report development of three new peptide biomaterials based on the RADA16-I hydrogel functionalized with a sequence (AAPV) cleaved by human neutrophil elastase and short biologically active peptide motifs, namely GHK, KGHK and RDKVYR. The peptide hybrids were investigated for their structural aspects using circular dichroism, thioflavin T assay, transmission electron microscopy, and atomic force microscopy, as well as their rheological properties and stability in different fluids such as water or plasma, and their susceptibility to digestion by enzymes present in the wound environment. In addition, the morphology of the RADA-peptide hydrogels was examined with a unique technique called scanning electron cryomicroscopy. These experiments enabled us to verify if the designed peptides increased the bioactivity of the gel without disturbing its gelling processes. We demonstrate that the physicochemical properties of the designed hybrids were similar to those of the original RADA16-I. The materials behaved as expected, leaving the active motif free when treated with elastase. XTT and LDH tests on fibroblasts and keratinocytes were performed to assess the cytotoxicity of the RADA16-I hybrids, while the viability of cells treated with RADA16-I hybrids was evaluated in a model of human dermal fibroblasts. The hybrid peptides revealed no cytotoxicity; the cells grew and proliferated better than after treatment with RADA16-I alone. Improved wound healing following topical delivery of RADA-GHK and RADA-KGHK was demonstrated using a model of dorsal skin injury in mice and histological analyses. The presented results indicate further research is warranted into the engineered peptides as scaffolds for wound healing and tissue engineering.
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Sylwia Rodziewicz-Motowidło; Maria Dzierżyńska; Justyna Sawicka; Milena Deptuła; Paweł Sosnowski; Piotr Sass; Barbara Peplińska; Zuzanna Pietralik-Molińska; Martyna Fularczyk; Franciszek Kasprzykowski; Jacek Zieliński; Stefan Jurga; Maciej Kozak; Paweł Sachadyn; Michał Pikuła
|
Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems
|
CC BY 4.0
|
CHEMRXIV
|
2022-12-15
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/639a33a7ff465105672a9ea8/original/release-systems-based-on-self-assembling-rada16-i-hydrogels-with-a-signal-sequence-which-improves-wound-healing-processes.pdf
|
60c758814c89191cc5ad4be1
|
10.26434/chemrxiv.14556180.v1
|
An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome
|
<p>The tyrosine residue of proteins participates in a
wide range of activities including enzymatic catalysis, protein-protein
interaction, and protein-ligand binding. However, the functional annotation of
the tyrosine residues on a large scale is still very challenging. Here, we
report a novel method integrating azo coupling, bioorthogonal chemistry, and
multiplexed proteomics to globally investigate the tyrosine reactivity in the
human proteome. Based on the azo-coupling reaction between aryl diazonium salt
and the tyrosine residue, the two different probes were evaluated, and the
probe with the best performance was employed to specifically target the
tyrosine residues. After the reaction, tagged tyrosine containing peptides were
selectively enriched using bioorthogonal chemistry, and a small tag on the
peptides from the cleavage perfectly fits for site-specific analysis by MS. Coupling
with multiplexed proteomics, we quantified over 5,000 tyrosine sites in MCF7
cells and these quantified sites displayed a wide range of reactivity. The tyrosine
residues with high reactivity were found on functionally and structurally
diverse proteins, including those with the catalytic activity and binding
property. This method can be extensively applied to advance our understanding
of protein functions and facilitate the development of covalent drugs to
regulate protein activity.</p>
|
Fangxu Sun; Suttipong Suttapitugsakul; Ronghu Wu
|
Mass Spectrometry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-05-10
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c758814c89191cc5ad4be1/original/an-azo-coupling-based-chemoproteomic-approach-to-systematically-profile-the-tyrosine-reactivity-in-the-human-proteome.pdf
|
66e013a112ff75c3a1eed5dd
|
10.26434/chemrxiv-2024-c9w7l
|
Fabrication of superhydrophilic membranes for oil-water separation: A life cycle assessment study
|
Membrane-based technologies are widely used in oily wastewater treatment. This study selects two superhydrophilic ultrafiltration (UF) membranes (denoted M1 and M2) for oil-in-water emulsion separation and evaluates the environmental impact of membrane fabrication using life cycle assessment (LCA). Although the two membranes have similar separation performance, M1 exhibits ~40% lower environmental impacts than M2 in almost every category owing to its fewer modification steps, lower electricity use, and less solvent consumption. Electricity consumption, reactive-copolymer synthesis, and toxic-solvent use are identified as environmental hotspots in membrane fabrication. A sensitivity analysis of different energy sources reveals that coal-based electricity has the greatest environmental impact, while photovoltaic energy reduces the impact by up to 71%. Considering solvents, dimethylformamide (DMF) shows a slightly lower environmental impact than N-methyl-2-pyrrolidone (NMP).
|
Dixit V Bhalani; Qian Zhang; Yi Yang; Suresh Kumar Jewrajka; Junjie Shen
|
Chemical Engineering and Industrial Chemistry; Industrial Manufacturing; Water Purification
|
CC BY 4.0
|
CHEMRXIV
|
2024-09-13
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66e013a112ff75c3a1eed5dd/original/fabrication-of-superhydrophilic-membranes-for-oil-water-separation-a-life-cycle-assessment-study.pdf
|
6228be2e7c13f477b46d46f8
|
10.26434/chemrxiv-2022-cz4l5
|
The performance of ensemble-based free energy protocols in computing binding affinities to ROS1 kinase
|
Optimization of binding affinities for compounds to their target protein is a primary objective in drug discovery. Herein we report on a collaborative study that evaluates a set of compounds binding to ROS1 kinase. We use ESMACS (enhanced sampling of molecular dynamics with approximation of continuum solvent) and TIES (thermodynamic integration with enhanced sampling) protocols to rank the binding free energies. The predicted binding free energies from ESMACS simulations show good correlations with experimental data for subsets of the compounds. Consistent binding free energy differences are generated for TIES and ESMACS. Although an unexplained overestimation exists, we obtain excellent statistical rankings across the set of compounds from the TIES protocol, with a Pearson correlation coefficient of 0.90 between calculated and experimental activities.
|
Shunzhou Wan; Agastya P. Bhati; David W. Wright; Alexander D. Wade; Gary Tresadern; Herman van Vlijmen; Peter V. Coveney
|
Theoretical and Computational Chemistry; Computational Chemistry and Modeling
|
CC BY 4.0
|
CHEMRXIV
|
2022-03-14
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6228be2e7c13f477b46d46f8/original/the-performance-of-ensemble-based-free-energy-protocols-in-computing-binding-affinities-to-ros1-kinase.pdf
|
664d1875418a5379b0e81de2
|
10.26434/chemrxiv-2024-4l8b2
|
Solution characterization of zirconium oxo clusters
|
Group 4 metal oxo clusters are atomically precise models for colloidal nanocrystals as they consist of an inorganic core and an organic ligand shell. They are also important building blocks for MOFs, 3D-printing and polymers composites. Recently, we have elucidated their structure and ligand shell using solid state methods. Here we go one step further studying these materials in solution. Dynamic light scattering is a common technique to determine the solvodynamic diameter of nanocrystals. However, due to their small size, clusters present difficulties to the automatic data treatment, available in commercial software. Here we developed a data treatment method to fit DLS data of clusters, where we separate the signal into a contribution from the clusters itself combined with a contribution of number fluctuations. Additionally, diffusion ordered spectroscopy (DOSY) is used to study how these materials affect the viscosity of the solvent.
|
Dietger Van den Eynden; Ajmal Roshan Unniram Parambil; Sandor Balog; Jonathan De Roo
|
Inorganic Chemistry; Nanoscience; Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-05-22
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/664d1875418a5379b0e81de2/original/solution-characterization-of-zirconium-oxo-clusters.pdf
|
60c750c6bb8c1a80a53dbb6e
|
10.26434/chemrxiv.13079159.v1
|
A One Pot Photochemical Method for the Generation of Functionalized Aminocyclopentanes
|
<div>Detailed herein is the development of a photochemical intermolecular formal [3+2] cycloaddition between cyclopropylimines and substituted alkenes to generate cyclopentylimines. The Schiff base auxiliary of the cyclopropylimine was designed to enable a masked N-centered radical approach in which the requisite open-shell character was achieved upon excitation with violet light. The cycloaddition products were directly converted to N-functionalized aminocyclopentanes via N-acylation and solvolysis, thus offering a three-step, one-pot procedure for the production of diversely-substituted aminocyclopentanes. The photochemical component of this reaction sequence was demonstrated to operate in continuous flow and was amenable to gram-scale production.</div>
|
Madison Sowden; James L. Collins III; Daryl Staveness; Corey Stephenson
|
Organic Synthesis and Reactions; Photochemistry (Org.)
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-10-13
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c750c6bb8c1a80a53dbb6e/original/a-one-pot-photochemical-method-for-the-generation-of-functionalized-aminocyclopentanes.pdf
|
60c742ab0f50dbadd1395d43
|
10.26434/chemrxiv.8246966.v2
|
Synthesis-Controlled Polymorphism, Magnetic and Electrochemical Properties of Li3Co2SbO6
|
<div>Li3Co2SbO6 is found to adopt two highly distinct structural forms: a hexagonal layered O3-
LiCoO2 type phase with “honeycomb” 2:1 ordering of Co and Sb; and an orthorhombic
superstructure of rock-salt type, isostructural with Li3Co2TaO6 but with the addition of
significant Li/Co ordering. Pure samples of both phase scan be obtained by conventional
solid-state synthesis from the same precursors, Li3SbO4 and CoO, by controlling particle size
and reaction time. Both phases show relatively poor performance as lithium-ion battery
cathode materials in their as-made states, but complex and interesting low-temperature
magnetic properties. The honeycomb phase orders antiferromagnetically below TN = 14 K,
but a positive Weiss constant θw = 18.1 K points to strong ferromagnetic interactions in the
paramagnetic regime above TN; and isothermal magnetisation below TN shows evidence for a
field-induced “spin-flop” transition at H ~ 0.7 T. The rock-salt type superstructure phase
orders antiferromagnetically below TN = 112 K, then undergoes two more transitions at 80 K
and 60, suggesting close competition between at least three ground states. Consistent with
such competition, the Weiss constant θw = -181 K indicates some frustration, there is a strong
field-cooled / zero field-cooled divergence below TN, and isothermal magnetisation shows it
to be magnetically soft with low coercivity.<br /></div>
|
Alex J. Brown; Brendan J. Kennedy; Chris D. Ling
|
Electrochemistry; Magnetism; Solid State Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2019-06-17
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c742ab0f50dbadd1395d43/original/synthesis-controlled-polymorphism-magnetic-and-electrochemical-properties-of-li3co2sb-o6.pdf
|
65c772fa66c1381729588fac
|
10.26434/chemrxiv-2024-thhvq
|
Enhancing the Performance of Natural Fiber Hybrid Green Composites through Coupling Agent modification
|
The search for sustainable resources has led to the use of biodegradable natural fibres in composites. As of now, no study has been performed on the fabrication of hybrid natural fiber green composite through coupling agent modification. Thus, this study investigates the fabrication of green composites using a hybrid blend of Empty Fruit Bunch (EFB) and Kenaf fibers utilizing coupling agent modification and hot compression method. The FTIR results indicates that the MAH was successfully reacted with the cellulose backbone of the fibers. The SEM result reveal that the surface morphology of green composite has been smooth after MAH modification. The coupling agent also improves fiber-PLA matrix bonding, improving the green composite's tensile strength, modulus, impact strength, and thermal stability. In addition, composites water absorption was shown to be decreased as a result of the treatment of MAH.
|
MD. ISLAM
|
Materials Science; Polymer Science; Composites; Fibers; Cellulosic materials; Materials Chemistry
|
CC BY 4.0
|
CHEMRXIV
|
2024-02-12
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65c772fa66c1381729588fac/original/enhancing-the-performance-of-natural-fiber-hybrid-green-composites-through-coupling-agent-modification.pdf
|
6186f5e78ac7a25bdd6ace4b
|
10.26434/chemrxiv-2021-3f1f9
|
Custom ML Module of AIDrugApp for Molecular Identification, Descriptor Calculation, and Building ML/DL QSAR Models
|
Computer-aided drug design (CADD) techniques continue to struggle to provide a useful advance in the area of drug development due to the difficulties in an efficient exploration of the vast drug-like chemical space to uncover new chemical compounds with desired biological properties. Other challenges that users must overcome in order to fully use the potential of CADD tools and techniques include a lack of completely autonomous methods, the necessity for retraining even after deployment, and their lack of interpretability. To solve this issue, we created the ‘Custom ML Tools’ integrated within the framework of ‘AIDrugAPP’. ‘Custom ML Tools’ includes four modules: ‘Mol Identifier’, ‘DesCal’, ‘AutoDL’, and ‘Auto-Multi-ML’ which give users free access to molecular identification using SMILES and compound names, similarity search, descriptor calculation, the building of ML/DL QSAR models, and their usage in predicting new data. The study demonstrates the potential of the novel tool for computational investigations in drug discovery research. The WebApp with its modules has therefore been made available for public use at: https://sars-covid-app.herokuapp.com/
|
Divya Karade
|
Theoretical and Computational Chemistry; Machine Learning; Quantum Computing; Chemoinformatics - Computational Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-11-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6186f5e78ac7a25bdd6ace4b/original/custom-ml-module-of-ai-drug-app-for-molecular-identification-descriptor-calculation-and-building-ml-dl-qsar-models.pdf
|
6660037f21291e5d1d1b7e7d
|
10.26434/chemrxiv-2024-17397
|
Image Analysis to Demonstrate Adsorption and Absorption Processes Through Image Brightness Using Copper(II) Ions and Fish Scales in Teabags: A Colorimetric-Based Analysis
|
We present a smartphone colorimetry activity designed to enhance students' understanding of adsorption and absorption processes through practical, hands-on experience. This activity utilized fish scale waste from Macolor niger as biosorbents for Cu(II) ions. Raw dried fish scales were enclosed in teabags and immersed in a known-amount copper(II) sulfate solution to observe their adsorption capabilities, with deionized water serving as a control. Students used their smartphones to capture images of the dried fish scales before and after adsorption and analyzed the R-values of the remaining solutions. They learned how to produce and use a calibration curve, determine average particle sizes, absorbance, and percentage Cu(II) ion removal through image analysis using ImageJ software. Statistical comparisons were conducted using the Mann-Whitney U Test via Jamovi software. The students tested their own hypotheses, reflected on their findings, and suggested improvements to the experiments. The overall activity not only demonstrates key chemical concepts but also integrates environmental science by showcasing the potential of using biosorbents for heavy metal ion removal. It is particularly suitable for high school and introductory chemistry courses, combining traditional laboratory skills with modern image analysis and statistical techniques.
|
Maribel Abigail Sofian; Laura Punsu; James Isaac Doloksaribu; Lie Miah; Norbertus Krisnu Prabowo
|
Chemical Education; Chemical Education - General
|
CC BY 4.0
|
CHEMRXIV
|
2024-06-05
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6660037f21291e5d1d1b7e7d/original/image-analysis-to-demonstrate-adsorption-and-absorption-processes-through-image-brightness-using-copper-ii-ions-and-fish-scales-in-teabags-a-colorimetric-based-analysis.pdf
|
6581655e66c13817298fcda7
|
10.26434/chemrxiv-2023-1xg8h
|
Ru(II)-Catalyzed C(sp2)–H Activation Annulation: Synthesis of Fluorescent Benzoisoquinolonyl Acetate/Peptides from N-Arylamides and Ethyne at Room Temperature
|
Benzoisoquinolones are aryl ring extended isoquinolinone derivatives, constituents of alkaloid natural products. This report describes the synthesis of benzoisoquinolones amino acids/peptides derivatives from respective N-aryl amino esters /peptides through Ru-catalyzed C(sp2)–H annulation at room temperature. Herein, the amino acid ester/amide residue acts as a directing group for annulation at the aryl ring, and then cyclization occurs at the amide NH. Importantly, these benzoisoquinolinones exhibit fluorescence in protic polar solvents. Hence, this methodology could be helpful to transform standard amino ac-ids/peptides into respective fluobenzoisoquinolinones conjugated fluorescent peptide derivatives at room temperature, which could be applicable for leveling amino acid/peptides effectively.
|
Nagendra Sharma; Manish K Gupta; Ankita Panda
|
Biological and Medicinal Chemistry; Organic Chemistry; Catalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-12-20
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6581655e66c13817298fcda7/original/ru-ii-catalyzed-c-sp2-h-activation-annulation-synthesis-of-fluorescent-benzoisoquinolonyl-acetate-peptides-from-n-arylamides-and-ethyne-at-room-temperature.pdf
|
646ce69cccabde9f6e3be8de
|
10.26434/chemrxiv-2022-5p97s-v3
|
Chemical generation of checkpoint inhibitory T cell engagers (CiTEs) for the treatment of cancer
|
Bispecific antibodies (bsAbs) provide enticing therapeutic opportunities in the area of immunotherapy, especially in the field of immuno-oncology. These constructs can bind two separate antigenic epitopes and thus provide access to unique mechanisms of action (MoAs). A key MoA is unlocked by bispecific T cell engagers (BiTEs), which cause T cells to be cross-linked with a targeted cancer cell, ultimately leading to death of the targeted cell. It has been shown that the combination of a BiTE with checkpoint inhibition, such as blockade of the PD-1/PD-L1 pathway, can lead to a synergistic effect and greater efficacy. Constructs built from a BiTE core (anti-CD3/anti-cancer antigen) with an immunomodulatory protein added, have been dubbed checkpoint-inhibitory T cell-engagers (CiTEs). Both bsAbs and CiTEs have traditionally been generated via protein engineering. However, recently, improved chemical methods for the construction of bsAbs have been reported. This includes a strategy developed by the Chudasama and Baker groups to synthesize homogenous fragment-based bsAbs from antibodies’ fragments antigen binding (Fabs), utilising click-enabled pyridazinediones (PDs) for functional disulfide re-bridging, followed by strain-promoted inverse electron-demand Diels-Alder cycloaddition (SPIEDAC) click chemistry to attach the two Fabs to each other. In this paper, we describe a first-in-class chemical method to generate biotin-functionalized three-protein conjugates, building significantly on the previously described PD-method. The three-protein constructs generated here include two such CiTE molecules, one containing an anti-PD-1 Fab, the other containing an immunomodulatory enzyme Salmonella typhimurium sialidase; FabCD3-FabHER2-FabPD-1-Biotin and FabHER2-FabCD3-Sia-Biotin. These constructs (along with suitable controls) were tested for their biological activity, and each of their protein components were shown to retain their function. Their efficacy was also compared to a simpler BiTE scaffold and was shown to be superior, with the sialidase-containing CiTE especially showing significantly enhanced potency in vitro. The chemical method described here has the potential to enable the rapid generation of a plethora of multi-protein constructs, which we envisage would be especially useful in hit-identification screening but could also potentially be scaled up for drug-development after further optimization.
|
Peter A. Szijj; Melissa A. Gray; Mikaela K. Ribi; Calise Bahou; João C. F. Nogueira; Carolyn R. Bertozzi; Vijay Chudasama
|
Biological and Medicinal Chemistry; Organic Chemistry; Biochemistry; Bioengineering and Biotechnology; Chemical Biology
|
CC BY NC 4.0
|
CHEMRXIV
|
2023-05-24
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/646ce69cccabde9f6e3be8de/original/chemical-generation-of-checkpoint-inhibitory-t-cell-engagers-ci-t-es-for-the-treatment-of-cancer.pdf
|
64f7c9ec3fdae147fa9380b4
|
10.26434/chemrxiv-2023-cg61b-v2
|
Fate of ZnS:Mn quantum dots in Seine River water and seawater. Ecotoxicological effects on Chlorella Vulgaris microalgae
|
The release of engineered materials into the environment can have detrimental effects on living organisms in ground, rivers, and oceans. Despite the increasing use of nanomaterials, little research is conducted on their degradation. Understanding the biology and environmental consequences of manufactured materials is crucial for preserving the environment and developing more respectful chemistry protocols. Physicochemical studies are essential to understand material behavior and their uptake and distribution within microorganisms. II-VI semiconducting nanocrystals, like ZnS nanoparticles, have emerged due to their quantum confinement, allowing for customization of electronic and optical properties. To assess the toxicity of ZnS QDs doped with Mn2+ and perform ecotoxicological tests, a suitable natural environment and an aquatic model are needed. Microalgae, like Chlorella Vulgaris, offer advantages in ecotoxicology, including environmental relevance, sensitivity, experimental feasibility, ethical considerations, and comparative studies. This paper presents the synthesis of ZnS:Mn NPs with varying concentrations of Mn2+. These NPs induce an antioxidant defense system in algal cells, which may be toxic to Chlorella vulgaris via an oxidative stress mechanism. The toxicity of manganese-doped ZnS nanoparticles does exist but is lower than that induced by a Mn2+ ion concentration of 100 mg L-1.
|
Bingbing Deng; Rania Maaloul; Sophie Nowak; Yann Sivry; Claude Yéprémian; Souad Ammar; Fayna Mammeri; Roberta Brayner
|
Physical Chemistry; Materials Science; Nanoscience; Nanostructured Materials - Nanoscience; Physical and Chemical Properties
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-09-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64f7c9ec3fdae147fa9380b4/original/fate-of-zn-s-mn-quantum-dots-in-seine-river-water-and-seawater-ecotoxicological-effects-on-chlorella-vulgaris-microalgae.pdf
|
60c7494b4c8919305aad306d
|
10.26434/chemrxiv.12048876.v1
|
Objects Interacting with Solidification Fronts: Thermal and Solute Effects
|
In many materials processing routes, objects such as bubbles or particles interact with a moving solidification front. The output of this confrontation, from instantaneous encapsulation to complete rejection of objects, regulates the solidified microstructure and the spatial distribution of the objects, and thus the final properties of the materials. Here we investigate by in situ cryo-confocal microscopy how thermal conductivity and solute compete to control the interfacial curvature of the solidification front. We first validate the prediction of physical models in absence of solute, and then demonstrate the dominating effect of solute. In the case of cellular front morphology, we show that thermal effects depending on the particle conductivity induce a distortion of ice crystals thereby modifying the final microstructure of the solid. Overall our results show that to successfully predict and control solidification microstructure in the presence of objects, physical models that take into account both thermal and long-range solute effects are now required.
|
Sidhanth Tyagi; Hélène Huynh; Cécile Monteux; Sylvain Deville
|
Materials Processing
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-03-31
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7494b4c8919305aad306d/original/objects-interacting-with-solidification-fronts-thermal-and-solute-effects.pdf
|
6696ae9d01103d79c52f0169
|
10.26434/chemrxiv-2024-4xr79-v2
|
Efficient synthesis of (±)-de-O-methyllasiodiplodin
|
Resorcinolic macrolides are a large class of fungal natural products with conserved resorcinolic ester cores within highly variable ten- to fourteen-membered macrocycles. They exhibit a broad range of biological activities, depending largely on the size and substitution on the macrocycle bridge. Here, we report a protecting group-free synthesis of (±)-de-O-methyllasiodiplodin, a minimal resorcinolic macrolide derived from the fungus Lasiodiplodia theobromae. The route proceeds in 42% yield over 5 steps (longest linear sequence) from 9-decenoic acid, a cheap and abundant starting material. Given the broad commercial availability of a variety of similar (terminal)-enoic acids, this route provides an entry to libraries of resorcinolic macrolides with highly variable macrocycle bridges.
|
Jesus M. Madrigal Lombera; Ian B. Seiple
|
Organic Chemistry; Natural Products; Organic Synthesis and Reactions
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2024-07-17
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6696ae9d01103d79c52f0169/original/efficient-synthesis-of-de-o-methyllasiodiplodin.pdf
|
678d13176dde43c908305007
|
10.26434/chemrxiv-2025-f009l
|
Unveiling Interactions of Peptide-bound Monolayer Protected Metal Nanocluster with Lipid Bilayer
|
Monolayer-protected atomically precise nanoclusters (MPCs) are potential candidates for drug delivery because of their unique, versatile, and tunable physiochemical properties. The rational design of nano-sized drug carriers relies on a deep understanding of their molecular-level interactions with cell membranes and other biological entities. Here, we applied coarse-grained molecular dynamics and umbrella sampling simulations to investigate the interactions between the Magainin 2 (MG2)-loaded $Au_{144}(MPA)_{60}$ nanocluster (MG2-MPC) and model anionic tumor cell membrane. Electrostatic interactions between MPC ligands and MG2's positively charged residues with the polar head groups of lipids play a crucial role in the adhesion of the MG2-MPC complex to the membrane surface. Furthermore, MG2-MPCs self-assemble in the linear trimeric supramolecular aggregate on the bilayer surface indicating a possible mechanism of MPC's action in peptide delivery to the membrane.
|
Soumya Mondal; Dr. Tarak Karmakar
|
Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational; Chemoinformatics - Computational Chemistry
|
CC BY NC 4.0
|
CHEMRXIV
|
2025-01-21
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/678d13176dde43c908305007/original/unveiling-interactions-of-peptide-bound-monolayer-protected-metal-nanocluster-with-lipid-bilayer.pdf
|
60c74a27842e657dd7db2eb5
|
10.26434/chemrxiv.12115359.v2
|
IN Silico Approach of Some Selected Honey Constituents as SARS-CoV-2 Main Protease (COVID-19) Inhibitors
|
<p>The huge attack of coronavirus
disease 2019 (COVID-19) over all the world forces the researcher around the
world to study the crystal structure of the main protease M<sup>pro</sup> (
3-chymotrypsin-like cysteine enzyme) which is the essential enzyme for
coronavirus processing the polyproteins and its life cycles. And by the way,
the inhibition of this enzyme active site becomes the target of all scientists of
drug discovery in order to overcome this disease. In this study, we have used
the molecular modeling approach to evaluate the activity of different active
compounds from honeybee and propolis to inhibit the presented sars-cov-2 main
protease via Schrödinger Maestro
v10.1. the presented study resulted in six main compounds possess high
binding energy with the receptor active site of COVID-19 main protease. we hope
this study being the way for honeybee constitution as an effective ligand for
sars-cov-2 main protease inhibition and be in the medicinal study of
anti-COVID-19 therapeutic drugs.</p>
|
Heba Hashem
|
Drug Discovery and Drug Delivery Systems
|
CC BY NC 4.0
|
CHEMRXIV
|
2020-04-16
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74a27842e657dd7db2eb5/original/in-silico-approach-of-some-selected-honey-constituents-as-sars-co-v-2-main-protease-covid-19-inhibitors.pdf
|
60c75246469df4bb19f44b39
|
10.26434/chemrxiv.13217774.v2
|
Design, Synthesis, and Evaluation of Transition-State Analogs as Inhibitors of the Bacterial Quorum Sensing Autoinducer Synthase CepI
|
<p></p><p>Quorum
sensing is a bacterial signaling system that involves the synthesis and detection of small signal molecules called autoinducers. A main class of autoinducers in Gram-negative bacteria are acylated homoserine lactones,
produced by the LuxI family of autoinducer synthase enzymes and detected by the
LuxR family of autoinducer receptors. Quorum sensing allows for changes in gene
expression and bacterial behaviors in a coordinated, cell density dependent manner.
Quorum sensing controls the expression of virulence factors in some human
pathogens, making quorum sensing an antibacterial drug target. Here we describe
the design and synthesis of transition-state analogs of the autoinducer
synthase enzymatic reaction and evaluation of these compounds as inhibitors
of the synthase CepI. One such compound potently inhibits CepI and constitutes
a new type of inhibitor against this underdeveloped antibacterial target.</p><br /><p></p>
|
Erin Higgins; Julian Kellner-Rogers; Alexandra Estanislau; Alec Esposito; Nora R. Vail; Sterling Payne; Julia Stockwell; Scott Ulrich
|
Drug Discovery and Drug Delivery Systems
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-12-07
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75246469df4bb19f44b39/original/design-synthesis-and-evaluation-of-transition-state-analogs-as-inhibitors-of-the-bacterial-quorum-sensing-autoinducer-synthase-cep-i.pdf
|
66701e6dc9c6a5c07aa79c9d
|
10.26434/chemrxiv-2024-p6r6d
|
Energy exchange between Nd3+ and Er3+ centers within molecular complexes
|
The controlled and reproducible molecular assemblies incorporating lanthanide centers represents a crucial step in driving forward up- and down-conversion processes. This challenge calls for the development of strategies to facilitate the efficient in-situ segregation of different Ln metal ions into distinct positions within the molecule. The unique family of pure [LnLn′Ln] heterometallic coordination compounds previously developed by us represents an ideal platform for studying the desired Ln-to-Ln′ energy transfer (ET). In this context, we report here the new pure one-step synthetically produced [ErNdEr] (3) complex, which allows for the first time at the molecular level to study the mechanisms behind Nd-to-Er energy transfer. To further assess the photophysical properties of this complex, the analogous [LuNdLu] (1) and [ErLaEr] (2) complexes have been also prepared and photophysically studied. Efficient sensitization via the two β-diketones employed as main ligands was proben for both Nd3+ and Er3+ ions, resulting in highly resolved emission spectra and sufficiently long excited state lifetimes, which allowed to further assess the Ln-to-Ln′ ET. This intermetallic transfer was first detected by comparing the emission spectra of iso-absorbant solutions and demonstrated by comparing the lifetime values with or without the lanthanide quencher (Er3+), as well as with a deep analysis of the excitation spectrum of the three complexes. Thus, a very unique phenomenon was discovered, consisting in a mutual Nd-to-Er and Er-to-Nd ET with no net increase of brightness by any metal ; while Nd3+ transfers the energy received from the antena to Er3+, the sensitization of the latter results into back-transfer to Nd3+ to a non-emissive, thus silent state.
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Diamantoula Maniaki; Annika Sickinger; Leoní A. Barrios; David Aguilá; Olivier Roubeau; Yannick Guyot; François Riobé; Olivier Maury; Laura Abad Galán; Guillem Aromi
|
Inorganic Chemistry; Lanthanides and Actinides; Spectroscopy (Inorg.)
|
CC BY NC 4.0
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CHEMRXIV
|
2024-06-18
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66701e6dc9c6a5c07aa79c9d/original/energy-exchange-between-nd3-and-er3-centers-within-molecular-complexes.pdf
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67cfc58d81d2151a02f5d1e1
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10.26434/chemrxiv-2025-0mx20
|
Cooperative Free Energy: Induced Protein–Protein Interactions and Cooperative Solvation in Ternary Complexes
|
Protein-protein interactions (PPIs) play an essential role in biological processes. Molecules that stabilize or induce PPIs in ternary complexes have received growing attention for their therapeutic potential in engaging ’undruggable’ targets and their high selectivity. Here, we investigate the kinetics and thermody- namics of the cooperative phenomenon in ternary complexes. The thermodynamics of cooperativity are characterized by cooperative free energy, which comprises induced PPIs, cooperative solvation free energy, ligand-associated geometric free-energy costs, and gas-phase correlation. Importantly, the induced PPIs only account for the binding affinity between stabilized conformations of the protein partners, i.e. the free-energy change associated with the conformational transition during protein-ligand binding is not accounted for. By introducing an approximated expression for the cooperative free energy, we developed a rapid computational method, which allowed us to predict cooperativity in eight ternary complexes (Kendall τ = 0.79). We highlight that the term cooperativity used in protein-protein stabilization does not represent the cooperativity phenomenon in three-body systems. We also critically discuss the counter-intuitive interpretation of cooperative free energy due to its asymmetric nature. Our study shows how cooperativity stabilizes ternary complexes, and provides a thermodynamic basis of cooperativity in protein-ligand-protein complexes.
|
Shu-Yu Chen; Riccardo Solazzo; Marianne Fouché; Hans-Jörg Roth; Birger Dittrich; Sereina Riniker
|
Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Biophysics; Computational Chemistry and Modeling
|
CC BY 4.0
|
CHEMRXIV
|
2025-03-13
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67cfc58d81d2151a02f5d1e1/original/cooperative-free-energy-induced-protein-protein-interactions-and-cooperative-solvation-in-ternary-complexes.pdf
|
620b1e80bd05a023a807383e
|
10.26434/chemrxiv-2022-cn9hw
|
Assessment of Predicting Frontier Orbital Energies for Small Organic Molecules Using Knowledge-Based and Structural Information
|
A systematic comparison is demonstrated for the predictions of frontier orbital energies – HOMO (EH), LUMO (EL), and energy gap (ΔEHL) of the molecules in QM9 dataset, where it contains 120k-plus three-dimensional organic molecule structures determined by first-principle simulations. The target molecular properties (EH, EL, and ΔEHL) are predicted using the linear regression (LR), machine learning (random forest, RF), and continuous-filter convolutional neural network (SchNET) approaches. LR and RF models built upon various knowledge-based descriptors, being derived from SMILES of the molecules, can provide predictivity of the target properties with the mean-absolute-errors (MAEs) at 4-6 times of chemical accuracy (0.043 eV). The best approach – SchNET, using the graph representation derived from molecular Cartesian coordinates, is confirmed to provide MAEs of EH, EL, and ΔEHL at 0.051, 0.041, and 0.076 eV, respectively. With the introduction of bond-step matrix representation with SchNET model, the computational cost of dataset preparation can be substantially reduced, and the corresponding MAEs increases moderately to 2-3 times of chemical accuracy. The chemical interpretation of the important descriptors identified in the LR and RF models appear to align with the chemical knowledge of describing these molecular electronic properties, however, being accompanied with tolerable prediction errors. The combination of bond-step representation and SchNET model can provide an assessable-and-balanced option for the high-throughput screening of organic molecules and the preparation of data science approach.
|
Zong-Rong Ye; Sheng-Hsuan Hung; Berlin Chen; Ming-Kang Tsai
|
Theoretical and Computational Chemistry; Machine Learning; Artificial Intelligence; Chemoinformatics - Computational Chemistry
|
CC BY 4.0
|
CHEMRXIV
|
2022-02-16
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/620b1e80bd05a023a807383e/original/assessment-of-predicting-frontier-orbital-energies-for-small-organic-molecules-using-knowledge-based-and-structural-information.pdf
|
67c0ea95fa469535b93b1f29
|
10.26434/chemrxiv-2025-07zmn
|
Directed Evolution of APOX for Proximity Labeling Using Phenols with High Redox Potentials
|
Proximity labeling (PL) identifies endogenous proteins in specific subcellular regions. APEX2 is a peroxidase that enables PL with high temporal resolution by oxidizing biotin phenol (BP) into a radical that tags nearby proteins. However, the BP radical has a relatively large diffusion radius, limiting spatial resolution. Replacing the phenol in BP with nitrophenol (NP) could potentially increase spatial resolution by generating shorter-lived radicals, but APEX2 cannot efficiently oxidize phenols with high redox potentials. Here, we report the directed evolution of APOX, a quadruple mutant of APEX2 with a higher reduction potential that exhibits 6-fold and 2.5-fold faster oxidation of NPs and BP, respectively. Using APOX with a membrane-permeable alkyne-NP probe, we demonstrate PL in living mammalian cells, including proteomic mapping with excellent subcellular compartment specificity. APOX expands peroxidase PL by accessing high redox potential probes, opening opportunities to further tune the diffusion radius and enhance the tagging of biomolecules beyond proteins.
|
Sifei Fang; Leslie D. Acevedo; Alexander J. Solivais; Xu Zhou; Elliot S. Delfosse; Brian L. Frey; Lloyd M. Smith; Jeffrey D. Martell
|
Biological and Medicinal Chemistry; Catalysis; Chemical Biology; Biocatalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2025-03-03
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67c0ea95fa469535b93b1f29/original/directed-evolution-of-apox-for-proximity-labeling-using-phenols-with-high-redox-potentials.pdf
|
60c7470abb8c1a72e73da9c2
|
10.26434/chemrxiv.11516544.v1
|
Metal-like Ductility in Organic Plastic Crystals: Role of Molecular Shape and Dihydrogen Bonding Interactions in Aminoboranes
|
Ductility, which is a common phenomenon in most
metals and metal-based alloys, is hard to achieve in molecular crystals. Organic
crystals have been recently shown to deform plastically, but only on one or two
faces, and fracture when stressed in any other arbitrary direction. Here, we
report an exceptional metal-like ductility in crystals of two globular
molecules, BH<sub>3</sub>NMe<sub>3</sub> and BF<sub>3</sub>NMe<sub>3</sub>,
with characteristic stretching, necking and thinning with deformations as large
as ~ 500%. Surprisingly, the mechanically deformed samples not only retained good
long range order, but also allowed structure determination by single crystal
X-ray diffraction. Molecules in these high symmetry crystals interact predominantly
via electrostatic forces (B<sup>–</sup>–N<sup>+</sup>) and form columnar
structures, thus forming multiple slip planes with weak dispersive forces among
columns. While the former interactions hold molecules together, the latter
facilitate exceptional malleability. On the other hand, the limited number of
facile slip planes and strong dihydrogen
bonding in BH<sub>3</sub>NHMe<sub>2</sub> negates ductility. We show the possibility
to simultaneously achieve both exceptional ductility and crystallinity in solids
of certain globular molecules, which may enable designing highly modular,
easy-to-cast crystalline functional organics, for applications in
barocalorimetry, ferroelectrics and soft-robotics.
|
Amit Mondal; Biswajit Bhattacharya; SUSOBHAN DAS; Surojit Bhunia; Rituparno Chowdhury; Somnath Dey; MALLA REDDY CHILLA
|
Supramolecular Chemistry (Org.); Crystallography – Organic
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-01-08
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7470abb8c1a72e73da9c2/original/metal-like-ductility-in-organic-plastic-crystals-role-of-molecular-shape-and-dihydrogen-bonding-interactions-in-aminoboranes.pdf
|
67adf79781d2151a0249b18f
|
10.26434/chemrxiv-2025-lb3q6
|
Near-zero Thermal Expansion in Coordination Polymer Cd(1,2,4-triazole)2(H2PO4)2
|
Zero thermal expansion is a rare but desirable physical property for materials. Here, we report an unprecedented near-zero thermal expansion (nZTE) behavior in a two-dimensional coordination polymer (CP) Cd(1,2,4-triazole)2 (H2PO4)2 (Cd-Tz) across a broad temperature range of 25 K - 400 K. Using multi-temperature high-resolution single-crystal X-ray diffraction, we investigated the structural dynamics of the wine-rack-like framework of Cd-Tz and compared it with that of positive thermal expansion (PTE) CPs Zn-Tz and Mn-Tz with similar framework topology. We show that nZTE in Cd-Tz is a consequence of two monotonic and opposing trends with PTE (a, c ~ 22 MK-1) in the ac plane and negative thermal expansion (NTE) in the b direction (b ~ -47 MK-1). A new mechanism for the uniaxial NTE is established based on concerted out-of-plane single atom libration of similarly oriented adjacent triazole rings in the wine-rack motifs. X-ray electron density analysis and modelling of low-temperature vibrational anharmonicity reveals the role of Cd-triazole bonds and hydrogen bonds in promoting the single atom libration. Tuning the metal−ligand bonding strength through minor doping of Zn/Mn (~8/12 %) in the Cd-Tz lattice results in a prominent shift from nZTE to NTE behavior in the solid solution phases.
|
Sounak Sarkar; Bo Brummerstedt Iversen
|
Materials Science; Hybrid Organic-Inorganic Materials; Materials Chemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2025-02-18
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67adf79781d2151a0249b18f/original/near-zero-thermal-expansion-in-coordination-polymer-cd-1-2-4-triazole-2-h2po4-2.pdf
|
63ab84e0b9c5f682f3e1e84e
|
10.26434/chemrxiv-2022-4mtw9
|
Probing Edge/Support Electronic Cooperativity in Single Edge Fe/Co6Se8 Clusters
|
This study provides insights into the electronic structure of an atomically precise Fe/Co6Se8 cluster and the extent of redox cooperativity between the Fe active site and the non-innocent Co6Se8 support. Chemical oxidation studies enable the isolation of two types of oxidized Fe/Co6Se8 clusters, in which the counterion is either directly coordinated to the Fe, or completely dissociated. Experimental characterization by single crystal X-ray diffraction, 57Fe Mössbauer spectroscopy, and 31P NMR spectroscopy is complemented by computational analysis. In aggregate, the study reveals that upon oxidation, the charge is shared between the Fe edge site and the Co6Se8 core, and that anion coordination perturbs the density of unpaired electrons on Co6Se8.
|
Benjamin S. Mitchell; Andrei Chirila; Kevin Anderton; Werner Kaminsky; Alexandra Velian
|
Inorganic Chemistry; Bonding; Coordination Chemistry (Inorg.); Ligands (Inorg.)
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2022-12-30
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63ab84e0b9c5f682f3e1e84e/original/probing-edge-support-electronic-cooperativity-in-single-edge-fe-co6se8-clusters.pdf
|
60c750e34c89198b6bad3e53
|
10.26434/chemrxiv.13090265.v1
|
Punching Above its Weight: Life Cycle Energy Accounting and Environmental Assessment of Vanadium Microalloying in Reinforcement Bar Steel
|
<p>The manuscript presents a detailed analysis of embodied
energy and carbon footprint reduction enabled by microalloying of steel,
thereby providing a rich global perspective of the (outsized) role of chemical
elements added in trace concentrations on the overall footprint of the construction
industry. As such, the manuscript addresses an important and timely topic at
the intersection of materials criticality, structural performance, life cycle
assessment, and policy interventions.</p><p><br /></p>
<p>The United Nations estimates that the worldwide energy
consumption of buildings accounts for 30—40% of global energy production,
underlining the importance of the judicious selection of construction
materials. Much effort has focused on the use of high-strength low-alloy steels
in reinforcement bars whose economy of materials use is predicated upon
improved yield strengths in comparison to low-carbon steels. While
microalloying is known to allow for reduced steel consumption, a sustainability
analysis in terms of embodied energy and CO 2 has not thus far been performed.
Here we calculate the impact of supplanting lower grade reinforcement bars with
higher strength vanadium microalloyed steels on embodied energy and carbon
footprint. We find that the increased strength of vanadium microalloyed steel
translates into substantial material savings over mild steel thus reducing the
total global fossil carbon footprint by as much as 0.385%. A more granular analysis
pegs savings for China and the European Union at 1.01 and 0.19%, respectively,
of their respective emissions.</p>
|
Pranav Pradeep Kumar; David A. Santos; Erick J. Braham; Diane G. Sellers; Sarbajit Banerjee; Manish K. Dixit
|
Alloys; Environmental Science; Industrial Manufacturing
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2020-10-15
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c750e34c89198b6bad3e53/original/punching-above-its-weight-life-cycle-energy-accounting-and-environmental-assessment-of-vanadium-microalloying-in-reinforcement-bar-steel.pdf
|
60d388a167d49119a0959c4f
|
10.26434/chemrxiv-2021-z10sw
|
Enhancing thermally activated delayed fluorescence
by fine-tuning the dendron donor strength
|
Thermally activated delayed fluorescence (TADF) relies on a small energy gap between the emissive singlet and the non-emissive triplet state, obtained by reducing the wavefunction overlap between donor and acceptor moieties. Efficient emission, however, requires maintaining a good oscillator strength, which is itself based on sufficient overlap of the wavefunctions between donor and acceptor moieties. We demonstrate an approach to subtly fine-tune the required wavefunction overlap by employing donor-dendrons of changing functionality. We use a carbazolyl-phthalonitrile based donor-acceptor core, 2CzPN, as a reference emitter, and progressively localize the hole density through substitution at the 3,6-positions of the carbazole donors (Cz) with further carbazole, (4-tert-butylphenyl)amine (tBuDPA) and phenoxazine (PXZ). Using detailed photoluminescence studies, complemented with Density Functional Theory (DFT) calculations, we show that this approach permits a gradual decrease of the singlet-triplet gap, ΔEST, from 300 meV to around 10 meV in toluene, yet we also demonstrate why a small ΔEST alone is not enough. While sufficient oscillator strength is maintained with the Cz- and tBuDPA-based donor dendrons, this is not the case for the PXZ-based donor dendron, where the wavefunction overlap is reduced too strongly. Overall, we find the donor-dendron extension approach allows successful fine-tuning of the emitter photoluminescence properties.
|
Eimantas Duda; David Hall; Sergey Bagnich; Cameron L. Carpenter-Warren; Rishabh Saxena; Michael Y. Wong; David B. Cordes; Alexandra M. Z. Slawin; David Beljonne; Yoann Olivier; Eli Zysman-Colman; Anna Köhler
|
Physical Chemistry; Organic Chemistry; Physical Organic Chemistry; Physical and Chemical Properties; Spectroscopy (Physical Chem.)
|
CC BY NC 4.0
|
CHEMRXIV
|
2021-06-28
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60d388a167d49119a0959c4f/original/enhancing-thermally-activated-delayed-fluorescence-by-fine-tuning-the-dendron-donor-strength.pdf
|
60c740a1469df4f124f42c77
|
10.26434/chemrxiv.7773611.v1
|
Facilitating the Transmetalation Step with Aryl-Zincates in Nickel-Catalyzed Enantioselective Arylation of Secondary Benzylic Halides
|
<div>
<div>
<div>
<p>A method for the highly enantioselective construction of fluoroalkyl-substituted stereogenic center by a nickel-catalyzed asymmetric Suzuki-Miyaura coupling of a-bromobenzyl trifluoro-/difluoro-/monofluoromethanes with a variety of lithium organoborate in the presence of 1.0 equivalent of ZnBr2 was described. Preliminary mechanistic studies disclosed that reaction of lithium organoborate with ZnBr2 generated a zincate [Ph2ZnBr]Li, which facilitates the transmetallation step of the nickel-catalyzed cross-coupling reaction to enable high enantioselectivity. <br /></p>
</div>
</div>
</div>
|
Weichen Wan; Mei Hu; Xiaolong Wan; Qilong Shen
|
Organic Synthesis and Reactions; Stereochemistry
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2019-02-27
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c740a1469df4f124f42c77/original/facilitating-the-transmetalation-step-with-aryl-zincates-in-nickel-catalyzed-enantioselective-arylation-of-secondary-benzylic-halides.pdf
|
615c76ae7d3da5aa28edb9fb
|
10.26434/chemrxiv-2021-bkdfv
|
Coarse-Grained Density Functional Theory Predictions via Deep Kernel Learning
|
Scalable electronic predictions are critical for soft materials design. Recently, the Electronic Coarse-Graining (ECG) method was introduced to renormalize all-atom quantum chemical (QC) predictions to coarse-grained (CG) molecular representations using deep neural networks (DNN). While DNN can learn complex representations that prove challenging for traditional kernel-based methods, they are susceptible to overfitting and the overconfidence of uncertainty estimations. Here, we develop ECG within the GPU-accelerated Deep Kernel Learning (DKL) framework to enable CG QC predictions of a conjugated oligomer using range-separated hybrid density functional theory. DKL-ECG provides accurate reproduction of QC electronic properties in conjunction with prediction uncertainties that facilitate efficient training over multiple temperature data sets via active learning. We show that while active learning algorithms enable efficient sampling of a more diverse configurational space relative to random sampling, the predictive accuracy of DKL-ECG models is effectively identical across all active learning methodologies employed. We attribute this result to the low conformational barriers of our test molecule and the redundant sampling of configurations induced by Boltzmann sampling, even for distinct temperature ensembles.
|
Nicholas Jackson; Ganesh Sivaraman
|
Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Machine Learning
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-10-06
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/615c76ae7d3da5aa28edb9fb/original/coarse-grained-density-functional-theory-predictions-via-deep-kernel-learning.pdf
|
6486e385e64f843f41ac0e9c
|
10.26434/chemrxiv-2023-bd7r6
|
How Orange Carotenoid Protein controls the excited state dynamics of Canthaxanthin
|
Orange Carotenoid Protein (OCP) is a ketocarotenoid-binding protein essential for photoprotection in cyanobacteria. The main steps of the photoactivated conversion which converts OCP from its resting state to the active one have been extensively investigated. However, the initial photochemical event in the ketocarotenoid which triggers the large structural changes finally leading to the active state is still not understood. Here we employ QM/MM surface hopping nonadiabatic dynamics to investigate the excited-state decay of canthaxanthin in OCP, both in the ultrafast S2 to S1 internal and the slower decay leading back to the ground state. For the former step we show the involvement of an additional excited state, which has been often named SX state, and we characterize its nature. For the latter step, we reveal an excited state decay characterized by multiple timescales, which are related to the ground-state conformational het- erogeneity of the carotenoid. We assigned the slowly decaying population to the so-called S∗ state.Finally, we identify a minor decay pathway involving the photoisomerization which could be the initial trigger to photoactivation of OCP.
|
Amanda Arcidiacono; Davide Accomasso; Lorenzo Cupellini; Benedetta Mennucci
|
Theoretical and Computational Chemistry; Physical Chemistry; Biological and Medicinal Chemistry; Biophysics; Computational Chemistry and Modeling; Photochemistry (Physical Chem.)
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2023-06-13
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6486e385e64f843f41ac0e9c/original/how-orange-carotenoid-protein-controls-the-excited-state-dynamics-of-canthaxanthin.pdf
|
60c743294c89199f97ad25ba
|
10.26434/chemrxiv.8944970.v1
|
Commercially Available Tin(II) Halides as Catalysts for the Dihydroboration of Carbodiimides
|
<div>Dihydroboration of a variety of carbodiimides using pinacolborane (HBpin) is achieved through commercially available tin(II) halides [SnBr2 (1) and SnCl2 (2)] as catalysts at room temperature (21 °C) with short reaction times (0.13 to 6 h).</div>
|
Pritam Mahawar,; Dhirendra Yadav; Dharmendra Singh; Mahendra Kumar Sharma; Selvarajan Nagendran
|
Heterogeneous Catalysis
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2019-07-18
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c743294c89199f97ad25ba/original/commercially-available-tin-ii-halides-as-catalysts-for-the-dihydroboration-of-carbodiimides.pdf
|
60e855288a469bd9c378c8f1
|
10.26434/chemrxiv-2021-q9rcr
|
Asymmetric Total Synthesis of Clionastatins A and B
|
Herein we report the first total synthesis of polychlorinated steroids clionastatins A and B, which was accomplished asymmetrically by means of a convergent, radical fragment coupling approach. Key features of the synthesis include an Ireland–Claisen rearrangement to introduce the C5 stereocenter (which was ultimately transferred to the C10 quaternary stereocenter of the clionastatins via a traceless stereochemical relay), a regioselective acyl radical conjugate addition to join the two fragments, an intramolecular Heck reaction to install the C10 quaternary stereocenter, and a diastereoselective olefin dichlorination to establish the synthetically challenging pseudoequatorial dichlorides. This work also enabled us to determine that the true structures of clionastatins A and B are in fact C14 epimers of the originally proposed structures.
|
Wei Ju; Xudong Wang; Hailong Tian; Jinghan Gui
|
Organic Chemistry; Natural Products
|
CC BY NC ND 4.0
|
CHEMRXIV
|
2021-07-12
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60e855288a469bd9c378c8f1/original/asymmetric-total-synthesis-of-clionastatins-a-and-b.pdf
|
67d30334fa469535b9187bd8
|
10.26434/chemrxiv-2025-cjxfm
|
Tailings as a Source for Generating valuable Magnesium and Calcium Carbonates by Leaching and Carbonization
|
Mining produces a lot of disposable mineral waste after the ore has been removed. This waste with added CO2 can be used as a feedstock for carbonate production. The advantage of this production process would be the recycling of a waste product with additional carbon capture. However, the processing challenge is a feed with a fluctuating composition of the mining waste, which makes classical engineering and control with fixed process parameters difficult. For characterization, model particles and tailings are studied for their behavior with fluctuating acid and mass concentrations as a function of leaching time. The results confirm the possibility of leaching calcium (max 7g/L) and magnesium (max 0.7 g/L) using hydrochloric acid. The amount varies depending on the particle, concentration and pH. Mathematically, the leaching over time can be described by a power law, which is applied to both investigated cases for the leaching of calcium and magnesium ions. Finally, a pH shift process is used to precipitate solid CaCO3 from the ion-enriched solution obtained, thus demonstrating the successful production of CaCO3 and carbon capture from mine waste.
|
Volker Bächle; Chinmay Hegde; Andreas Voigt; Kai Sundmacher; Marco Gleiß
|
Chemical Engineering and Industrial Chemistry; Industrial Manufacturing; Process Control; Reaction Engineering
|
CC BY 4.0
|
CHEMRXIV
|
2025-03-14
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67d30334fa469535b9187bd8/original/tailings-as-a-source-for-generating-valuable-magnesium-and-calcium-carbonates-by-leaching-and-carbonization.pdf
|
631ef55703e27d4c50d1aa3d
|
10.26434/chemrxiv-2022-9scm5-v2
|
Bridging the Catalyst Reactivity Gap Between Au and Cu for the Reverse Water Gas Shift Reaction
|
The reverse water gas shift reaction (rWGSR) is highly relevant for CO2 utilization in sustainable fuel and chemical production. Both Au and Cu are interesting for rWGSR catalysis, but it turns out that the reactivities of Au and Cu are very different. In this study, we consider alloys made from Au, Ag, Cu, Pt, and Pd to identify surfaces with reactivities for CO2 dissociation in between Cu(111) and Au(111). Additionally, interesting alloy surfaces should have activation energies for CO2 dissociation that are only a little higher than the endothermic reaction energy. We find that certain Cu based alloys with Ag and Au meet these criteria, whereas alloys containing Pt or Pd do not. The low additional cost in activation energy occurs when the transition state and final state configurations are made to look very similar due to the placement of the different metal elements in the surface. Finally, we construct a kinetic model that compares the rate of the rWGSR to the estimated rate of unwanted side reactions (i.e. methane formation or coking) on Ag-Cu alloy surfaces with varying composition and random placement of the Ag and Cu atoms. The thermodynamics favor methane formation over rWGSR, but the model suggests that Ag-Cu alloy surfaces are highly selective for the rWGSR.
|
Dengxin Yan; Henrik H. Kristoffersen; Ivano E. Castelli; Jan Rossmeisl
|
Catalysis; Heterogeneous Catalysis
|
CC BY NC 4.0
|
CHEMRXIV
|
2022-09-13
|
https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/631ef55703e27d4c50d1aa3d/original/bridging-the-catalyst-reactivity-gap-between-au-and-cu-for-the-reverse-water-gas-shift-reaction.pdf
|
60c73d7c842e654ce1db179c
|
10.26434/chemrxiv.5831865.v1
|
Rhombic Fe3+ at the unpolished surface of single crystals SrTiO3
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EPR measurements show an isotropic asymmetrical line in SrTiO<sub>3</sub> ranging from g = 3.9 to 4.1. This line is attributed to the presence of rhombic impurity Fe<sup>3+</sup> ions at the unpolished surfaces of single crystals of SrTiO<sub>3</sub>.<br />
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Thomas (Tom) Kool
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Optical Materials
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CC BY NC ND 4.0
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CHEMRXIV
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2018-01-30
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https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d7c842e654ce1db179c/original/rhombic-fe3-at-the-unpolished-surface-of-single-crystals-sr-ti-o3.pdf
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