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LAION eV 311

Nitrate electrochemical reduction to ammonia on Cu2O catalysts

10.26434/chemrxiv-2022-w6vr8

N.A.

N.A.

Dimitra Anastasiadou; Yvette van Beek; Wei Chen; Tim Wissink; Alexander Parastaev; Emiel Hensen; Marta Costa Figueiredo

This manuscript reports the electrosynthesis of ammonia from nitrate catalysed by Cu2O. Cu2O (111) and (100) preferential orientations were prepared through electrodeposition to investigate the effect of surface structure. Cu2O (111) is more active and selective for ammonia formation than Cu2O (100). The highest faradaic efficiency (FE) was achieved for both catalysts at -0.3 V vs RHE, with Cu2O (111) reaching up to 80%. Additional measurements with quasi-in situ X-ray photoelectron spectroscopy and in-situ Raman spectroscopy revealed that Cu0 is the active phase during the reaction. The stability of the catalysts was examined by ex-situ methods such as scanning electron microscopy, X-ray diffraction and inductively coupled plasma-optical emission spectrometry. The catalysts undergo severe morphological changes as a function of the applied potential and the reaction time, most likely due to the dissolution and redeposition of Cu. After three hours of reaction, the entire surface of the catalysts was reconstructed into nanoneedles. The final FE was still higher for the original Cu2O (111) electrode.

2022-12-01

chemRxiv

Physical Chemistry; Catalysis; Energy; Electrocatalysis; Heterogeneous Catalysis; Surface

CC BY NC ND 4.0

Vesicular Release Dynamics are Altered by Interaction between Chemical Cargo and Vesicle Membrane Lipids

10.26434/chemrxiv.14473377.v1

N.A.

N.A.

Farzaneh Asadpour; Xinwei Zhang; Mohammad Mazloum-Ardakani; Maysam Mirzaei; Soodabeh Majdi; Andrew Ewing

We used liposomes loaded with different monoamines, dopamine (DA) and serotonin (5-HT), to simulate vesicular release and to monitor the dynamics of chemical release from isolated vesicles during vesicle impact electrochemical cytometry (VIEC). The release of DA from liposomes presents a longer release time compared to 5-HT. Modelling the release time showed that DA filled vesicles had a higher percentage of events where the time for the peak fall was better fit to a double exponential (DblExp) decay function, suggesting multiple kinetic steps in the release. By fitting to a desorption-release model, where the transmitters adsorbed to the vesicle membrane, the dissociation rates of DA and 5-HT from liposome membrane were estimated. DA has a lower desorption rate constant, which leads to slower DA release than that observed for 5-HT, whereas there is little difference in pore size. The alteration of vesicular release dynamics due to the interaction between chemical cargo and vesicle membrane lipids provides an important mechanism to regulate vesicular release in chemical and physiological processes. It is highly possible that this introduces a fundamental chemical regulation difference between transmitters during exocytosis.

2021-04-26

chemRxiv

Biochemical Analysis; Electrochemical Analysis

CC BY 4.0

Rapid and scalable halosulfonylation of strain-release reagents

10.26434/chemrxiv-2022-6trwf

N.A.

N.A.

Helena Pickford; Vasyl Ripenko; Ryan McNamee; Serhii Holovchuk; Amber Thompson; Russell Smith; Pavel Mykhailiuk; Edward Anderson

Sulfonylated aromatics are commonplace motifs in drugs and agrochemicals. However, methods for the direct synthesis of sulfonylated non-classical arene bioisosteres, which could improve the physico-chemical properties of drug and agrochemical can-didates, are limited. Here we report a solution to this challenge: a one-pot halosulfonylation of [1.1.1]propellane, [3.1.1]propellane and bicy-clo[1.1.0]butanes that proceeds under practical, scalable and mild conditions. The sulfonyl halides used in this chemistry feature aryl, heteroaryl and alkyl substituents, and are conveniently generated in situ from readily available sulfinate salts and halogen atom sources. This methodology enables the syn-thesis of an array of pharmaceutically and agro-chemically relevant sulfonyl BCP, BCHep and cyclo-butyl halides, on milligram to decagram scales.

2022-09-07

chemRxiv

Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions

CC BY NC 4.0

Coupled-Cluster Treatment of Complex Open-Shell Systems: The Case of Single-Molecule Magnets

10.26434/chemrxiv-2024-plwn8

N.A.

N.A.

Maristella Alessio; Garrette Pauley Paran; Cansu Utku; Andreas Grueneis; Thomas-C. Jagau

We investigate the reliability of two cost-effective coupled-cluster methods for computing spin-state energetics and spin-related properties of a set of open-shell transition-metal complexes. Specifically, we employ the second-order approximate coupled-cluster singles and doubles (CC2) method and projection-based embedding that combines equation-of-motion coupled-cluster singles and doubles (EOM-CCSD) with density functional theory (DFT). The performance of CC2 and EOM-CCSD-in-DFT is assessed against EOM-CCSD. The chosen test set includes two hexaaqua transition-metal complexes containing Fe(II) and Fe(III), and a large Co(II)-based single-molecule magnet with a non-aufbau ground state. We find that CC2 describes the excited states more accurately, reproducing EOM-CCSD excitation energies within 0.05 eV. However, EOM-CCSD-in-DFT excels in describing transition orbital angular momenta and spin-orbit couplings. Moreover, for the Co(II) molecular magnet, using EOM-CCSD-in-DFT eigenstates and spin-orbit couplings, we compute spin-reversal energy barriers, as well as temperature-dependent and field-dependent magnetizations and magnetic susceptibilities that closely match experimental values within spectroscopic accuracy. These results underscore the efficiency of CC2 in computing state energies of multi-configurational, open-shell systems and highlight the utility of the more cost-efficient EOM-CCSD-in-DFT for computing spin-orbit couplings and magnetic properties of complex and large molecular magnets.

2024-03-15

chemRxiv

Theoretical and Computational Chemistry

CC BY NC ND 4.0

Modulating Enzyme’s Activity and Specificity through Pre-Installed Posttranslational Modifications (PTMs) on Substrate: The Role of PTM-induced Substrate-Assisted Stimulation

10.26434/chemrxiv-2023-cdqc6

N.A.

N.A.

Hong Guo; Ping Qian

Understanding the underlying principles for crosstalk involving posttranslational modifications (PTMs) is of fundamental importance. In this article, we review some of previous results which indicated that pre-installed PTMs on nucleosome substrates (or nucleosome peptides) may stimulate the activity and change the specificity of histone modifying enzymes for the next PTMs. Discussions are also made on the results showing that ubiquitin (Ub) within the M1-diUb substrate could remodel the active site of OTULIN, a human deubiquitinase (DUB), and stimulate its activity. We term such stimulation effects as PTM-induced substrate-assisted stimulation (PTM-induced SAS) and propose that it could be one of the general strategies in PTM crosstalk and may provide a unique way to relay signals. It is suggested that although PTM-induced SAS seems to offer an attractive mechanism, detailed studies are still necessary to fully understand how the stimulations are created and translated into the increased activities and how widely it may occur in biological systems.

2023-03-20

chemRxiv

Catalysis; Biocatalysis

CC BY NC ND 4.0

Nanospheres to Nanosheets: Unfolding the Morphological Influence of Microporous Organic Polymers on Micropollutants Removal

10.26434/chemrxiv.14333936.v1

N.A.

N.A.

ARKAPRABHA GIRI; Subha Biswas; Tapas Dutta; MD. WASEEM HUSSAIN; Abhijit Patra

<p>Nanoporous organic polymers with distinct morphologies are of immense interest for a broad spectrum of applications ranging from catalysis to molecular separation, energy storage, and energy conversion. However, developing facile and versatile methodologies to obtain well-orchestrated morphologies along with high specific surface area pertinent to a specific application is still a formidable challenge. The design of the task-specific networks can be benefitted through further analysis of subtle variations in the polymerization conditions. Herein, we have critically examined the fabrication of triptycene-based hypercrosslinked polymers (HCPs), exhibiting contrasting morphologies developed through three distinct polymerization routes. Astonishingly, a remarkable variation of nanostructured morphology of irregular aggregates, nanospheres, and nanosheets was noticeable in the resultant network polymers through Friedel-Crafts crosslinking using dimethoxymethane as an external crosslinker, Scholl coupling, and solvent knitting using dichloromethane as an external crosslinker and solvent, respectively. The dramatic role of reaction temperature, catalysts, and solvents driving the formation of specific nanostructured HCPs was elucidated. Mechanistic investigations coupled with spectroscopic and microscopic studies revealed that the 2D-nanosheets of highly porous solvent-knitted HCP (SKTP, S_BET: 2385 m² g^-1) evolved through the hierarchical self-assembly of rigid nanospheres into nanoribbons followed by the formation of nanosheets. We further demonstrated a structure-activity correlation of the pristine as well as post-synthetically sulfonated HCPs for the removal of a gamut of organic micropollutants from water. Solvent knitted triptycene polymer (SKTP) and its sulfonated derivative (SKTPS, S_BET: 1444 m² g^-1) owing to high specific surface areas, excellent dispersity in water, and better accessibility of analytes through 2D-sheet like morphology exhibited ultrafast sequestration (30 s to 5 min) of an extensive array of persistent organic micropollutants, including ionic dyes, plastic components, steroids, antibiotic drugs, and herbicides with excellent recyclability. The current study holds the promise that a delicate control over the morphologies of nanoporous polymers by tuning the fabrication conditions paves the way for the development of advanced porous materials for environmental remediation.</p>

2021-03-30

chemRxiv

Fibers; Materials Processing; Organic Polymers; Polymer morphology; Materials Chemistry

CC BY NC ND 4.0

Synthesis and Photochemical Properties of Re(I) Tricarbonyl Complexes Bound to Thione and Thiazole-2-ylidene Ligands

10.26434/chemrxiv.12324875.v1

N.A.

N.A.

Matthew Stout; Brian Skelton; Alexandre N. Sobolev; Paolo Raiteri; Massimiliano Massi; Peter Simpson

<p>Three Re(I) tricarbonyl complexes, with general formulation Re(N^L)(CO)₃X (where N^L is a bidentate ligand containing a pyridine functionalized in the position 2 with a thione or a thiazol-2-ylidene group and X is either chloro or bromo) were synthesized and their reactivity explored in terms of solvent-dependent ligand substitution, both in the ground and excited states. When dissolved in acetonitrile, the complexes bound to the thione ligand underwent ligand exchange with the solvent resulting in the formation of Re(NCMe)₂(CO)₃X. The exchange was found to be reversible, and the starting complex was reformed upon removal of the solvent. On the other hand, the complexes appeared inert in dichloromethane or acetone. Conversely, the complex bound to the thiazole-2-ylidene ligand did not display any ligand exchange reaction in the dark, but underwent photoactivated ligand substitution when excited to its lowest metal-to-ligand charge transfer manifold. Photolysis of this complex in acetonitrile generated multiple products, including Re(I) tricarbonyl and dicarbonyl solvato-complexes as well as free thiazole-2-ylidene ligand.</p>

2020-06-04

chemRxiv

Coordination Chemistry (Organomet.)

CC BY NC ND 4.0

A complete biomimetic iron-sulfur cubane redox series

10.26434/chemrxiv-2021-4qzlh-v2

10.1073/pnas.2122677119

https://doi.org/10.1073/pnas.2122677119

Liam Grunwald; Martin Clémancey; Daniel Klose; Lionel Dubois; Serge Gambarelli; Gunnar Jeschke; Michael Wörle; Geneviève Blondin; Victor Mougel

Synthetic iron-sulfur cubanes are essential models for biological cofactors in the more complex enzymatic environments. However, a complete series of [Fe4S4]n complexes spanning all biorelevant oxidation states (n = 0-3+) has never been prepared. Here, we demonstrate that the use of a bulky arylthiolate ligand promoting the encapsulation of alkali-metal cations in the vicinity of the cubane enables the synthesis of such a series. Characterization by EPR, 57Fe Mössbauer spectroscopy, UV-Vis electronic absorption and variable-temperature X-ray diffraction analysis reveals key trends for the Fe4S4 core’s geometry as well as for the Mössbauer isomer shift, which both correlate systematically with oxidation state. Furthermore, we confirm the S=4 electronic ground state of the most reduced member, [Fe4S4]0, in agreement with that proposed for the all-ferrous cubanes in Nature.

2021-12-09

chemRxiv

Inorganic Chemistry; Bioinorganic Chemistry; Coordination Chemistry (Inorg.)

CC BY NC ND 4.0

Modeling Ligand Binding Site Water Networks with Site-Identification by Ligand Competitive Saturation: Impact on Ligand Binding Orientations and Relative Binding Affinities

10.26434/chemrxiv-2024-sqhw9-v2

N.A.

N.A.

Anmol Kumar; Himanshu Goel; Wenbo Yu; Mingtian Zhao; Alexander D. MacKerell

Appropriate treatment of water contributions to protein-ligand interactions is a very challenging problem in the context of adequately determining the number of waters to investigate and undertaking the conformational sampling of the ligands, the waters, and the surrounding protein. In the present study, an extension of the Site Identification by Ligand Competitive Saturation-Monte Carlo (SILCS-MC) docking approach is presented that enables determination of the location of water molecules in the binding pocket and their impact on the predicted ligand binding orientation and affinities. The approach, termed SILCS-WATER, involves MC sampling of the ligand along with explicit water molecules in a binding site followed by selection of a subset of waters within specified energetic and distance cutoffs that contribute to ligand binding and orientation. To allow for convergence of both the water and ligand orientations, SILCS-WATER is based on just the overlap of the ligand and water with the SILCS FragMaps and the interaction energy between the waters and ligand. Results show that the SILCS-WATER methodology is able to capture important waters and improve ligand binding orientations. For 6 of 10 multiple-ligand protein systems the method improved relative binding affinity prediction against experimental results, with substantial improvements in three systems, when compared to standard SILCS-MC. Improved reproduction of crystallographic ligand binding orientations is shown to be an indicator of when SILCS-WATER will yield improved binding affinity correlations. The method also identifies waters interacting with ligands that occupy unfavorable locations with respect to the protein whose displacement through the appropriate ligands modifications should improve ligands binding affinity. Results are consistent with the binding affinity being modeled as a ligand-water complex interacting with the protein. The presented approach offers new possibilities in revealing water networks and their contributions to the binding orientation and affinity of a ligand to a protein and is anticipated to be of utility for computer-aided drug design.

2024-09-09

chemRxiv

Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational

CC BY NC ND 4.0

Unexpected reactivity related to support effects during xylose hydrogenation over ruthenium catalysts

10.26434/chemrxiv-2021-553zh

10.1039/D1RA08193D

https://doi.org/10.1039/D1RA08193D

Léa Vilcocq; Ana Maria Paez; Victoria Freitas; Laurent Veyre; Pascal Fongarland; Régis Philippe

Xylose is a major component of hemicelluloses. In this paper, its hydrogenation to xylitol in aqueous medium was investigated with two Ru/TiO2 catalysts prepared with two commercial TiO2 supports. A strong impact of support on catalytic performances was evidenced. Ru/TiO2-R led to fast and selective conversion of xylose (100 % conversion in 2 h at 120°C with 99 % selectivity) whereas Ru/TiO2-A gave a slower and much less selective transformation (58 % conversion in 4 h at 120°C with 17 % selectivity) with the formation of several by-products. Detailed characterization of catalysts with ICP, XRD, FTIR, TEM, H2 chemisorption, N2 porosimetry, TPR and acid-base titration were performed to elucidate the role of each support. TiO2-R has a small specific surface area with large ruthenium nanoparticles in weak interaction with TiO2 support and no acidity, whereas TiO2-A is a mesoporous material with a large specific surface area, mildly acidic, and bears small ruthenium particles in strong interaction with TiO2 support. The former was very active and selective for xylose hydrogenation to xylitol whereas the latter was less active and poorly selective. Moreover, careful analysis of reaction products also revealed that TiO2 anatase can catalyze undesired side-reactions such as xylose isomerisation to various pentoses, and therefore the corresponding unexpected polyols (arabitol, ribitol) were produced during xylose conversion by hydrogenation. In a first approach of the kinetics, a simplified kinetic model was built to compare quantitatively intrinsic reaction rates of both catalysts. The kinetic constant for hydrogenation was 20 times higher for Ru/TiO2-R at 120°C.

2021-11-09

chemRxiv

Catalysis; Heterogeneous Catalysis

CC BY NC ND 4.0

Multimaterial 3D Laser Printing of Cell-Adhesive and Cell-Repellent Hydrogels

10.26434/chemrxiv-2024-f94sf

N.A.

N.A.

Niklas Schwegler; Tanisha Gebert; Maria Villiou; Federico Colombo; Barbara Schamberger; Christine Selhuber-Unkel; Franziska Thomas; Eva Blasco

This study introduces a straightforward method for manufacturing 3D microstructured cell-adhesive and cell-repellent multimaterials using two-photon laser printing. Compared to existing strategies, this approach offers bottom-up molecular control, high customizability and rapid and precise 3D fabrication. The printable cell-adhesive PEG-based material includes an RGD-containing peptide synthesized through solid-phase peptide synthesis, allowing for precise control of the peptide design. Remarkably, minimal amounts of RGD peptide (< 0.1 wt%) suffice for imparting cell-adhesiveness, while maintaining identical mechanical properties in the 3D printed microstructures to those of the cell-repellent, PEG-based material. Fluorescent labeling of the RGD peptide facilitates visualization of its presence in cell-adhesive areas. To demonstrate the broad applicability of our system, we showcase the fabrication of cell-adhesive 2.5D and 3D structures, fostering the adhesion of fibroblast cells within these architectures. Thus, this approach allows for the printing of high-resolution, true 3D structures suitable for diverse applications, including cellular studies in complex environments.

2024-01-17

chemRxiv

Biological and Medicinal Chemistry; Materials Science

CC BY NC ND 4.0

Predicting the price of molecules using their predicted synthetic pathways

10.26434/chemrxiv-2024-8wcfp

N.A.

N.A.

Massina Abderrahmane; Hamza Tajmouati; Vinicius Barros Ribeiro da Silva; Quentin Perron

Currently, numerous metrics allow chemists and computational chemists to refine and filter libraries of virtual molecules in order to prioritize their synthesis. Some of the most commonly used metrics and models are QSAR models, docking scores, diverse druggability metrics, and synthetic feasibility scores to name only a few. Among the known metrics, a function which estimates the price of a novel virtual molecule and which takes into account the availability and price of starting materials has never been considered before. Being able to make such a prediction could improve and accelerate the decision-making process related to the cost-of-goods. Taking advantage of recent advances in the field of Computer Aided Synthetic Planning (CASP), we decided to investigate if the predicted retrosynthetic pathways of a given molecule and the prices of its associated starting materials could be good features to predict the price of that compound. In this work, we present a deep learning model, RetroPriceNet, that predicts the price of molecules using their predicted synthetic pathways. On a holdout test set, the model achieves better performance than the state-of-the-art model. The developed approach takes into account the synthetic feasibility of molecules and the availability and prices of the starting materials.

2024-02-07

chemRxiv

Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Machine Learning; Artificial Intelligence; Chemoinformatics - Computational Chemistry

CC BY NC ND 4.0

Si-doped Polycyclic Aromatic Hydrocarbons: Synthesis and Opto-electronic Properties

10.26434/chemrxiv-2021-05g7k

N.A.

N.A.

Thomas Delouche; Ghizlene Taifour; Marie cordier; Thierry Roisnel; Denis Tondelier; Payal Manzhi; Bernard Geffroy; Boris Le Guennic; Denis Jacquemin; Muriel Hissler; Pierre-Antoine Bouit

We report the straightforward synthesis of Si-containing PAHs. The impact of pi-extension and exocyclic modifications on both the optical and redox properties is investigated using a joint experimental/theoretical approach. By taking advantage of the solid-state luminescence of these derivatives, electroluminescent devices are prepared. Such preliminary optoelectronic results highlight that these heteroatom-containing PAHs are promising building blocks for organic electronics.

2021-09-03

chemRxiv

Organic Chemistry; Physical Organic Chemistry

CC BY NC ND 4.0

Unmasked Primary Amines as C-Nucleophiles for Catalytic C–C Bond-Formation

10.26434/chemrxiv.11841489.v1

N.A.

N.A.

Alison Ryder; William Cunningham; George Ballantyne; Tom Mules; Anna Kinsella; Jacob Turner-Dore; Catherine Alder; Lee Edwards; Blandine McKay; Matthew Grayson; Alex Cresswell

A practical, catalytic entry to α,α,α‑trisubstituted (α‑tertiary) primary amines by C–H functionalisation has long been recognised as a critical gap in the synthetic toolbox. We report a simple and scalable solution to this problem that does not require any <i>in situ</i> protection of the amino group and proceeds with 100% atom-economy. Our strategy, which uses an organic photocatalyst in combination with azide ion as a hydrogen atom transfer (HAT) catalyst, provides a direct synthesis of <i>C</i>-alkylated amines or γ‑lactams, including valuable azaspirocycles. We anticipate that this methodology will inspire new retrosynthetic disconnections for substituted amine derivatives in organic synthesis, and particularly for challenging α‑tertiary primary amines.

2020-02-12

chemRxiv

Organic Synthesis and Reactions; Photochemistry (Org.); Photocatalysis

CC BY NC ND 4.0

A Live-Cell Epigenome Manipulation by Photo-stimuli-responsive Histone Methyltransferase Inhibitor

10.26434/chemrxiv-2024-c7vp2

N.A.

N.A.

Chuan-Shuo Wu; Xin Sun; Li Liu; Liang Cheng

Post-translational modifications (PTMs) on the histone H3 tail regulate chromatin structure and impact epigenetics and hence the gene expressions. Current chemical modulation tools, such as unnatural amino acid incorporation, protein splicing, and sortase-based editing, have allowed for the modification of histones with various PTMs in cellular contexts, but most of these methods are not applicable for editing native chromatin. The use of small organic molecules to manipulate histone-modifying enzymes alters endogenous histone PTMs but lacks precise temporal and spatial control. To date, there has been no achievement in modulating biologically significant histone methylation in living cells with spatiotemporal resolution. In this study, we present a new method for temporally editing dimethylation H3K9me2 using a photo-responsive inhibitor that specifically targets the histone methyltransferase G9a upon light irradiation. The photo-caged molecule was stable under physiological conditions and in cellular environments, but rapidly decomposed upon exposure to light, releasing the bioactive component that can immediately inhibit the catalytic ability of the G9a in vitro. Besides, this masked compound could also efficiently promote the inhibition of methyltransferase activity in living cells, subsequently suppress H3K9me2, a mark that regulates various chromatin functions. Therefore, our chemical system will be a valuable tool for manipulating the epigenome for therapeutic purposes and furthering the understanding of epigenetic mechanisms.

2024-02-07

chemRxiv

Biological and Medicinal Chemistry; Biochemistry; Chemical Biology

CC BY NC ND 4.0

CX-ASAP: A high throughput tool for the serial refinement and analysis of crystallographic data collected under varying conditions

10.26434/chemrxiv-2022-7c0cl

N.A.

N.A.

Amy Thompson; Kate Smith; Jack Clegg; Jason Price

Abstract CX-ASAP is a new open-source software project designed to greatly reduce the time required analysing crystallographic data collected under varying conditions. Scripted in Python3, CX-ASAP can automatically refine, finalise and analyse data collections with wide-ranging temperatures/pressures etc. This is done by use of a reference structure, allowing for quick identification of problems, phase changes and even model comparison. The modular design means that new features and custom scripts can be easily added, tailoring the capabilities to the specific needs of the user. It is envisioned that CX-ASAP will help close the growing gap between fast collection times and slow data finalisation.

2022-08-25

chemRxiv

Physical Chemistry; Organic Chemistry; Inorganic Chemistry; Crystallography; Crystallography – Inorganic; Crystallography – Organic

CC BY NC 4.0

Open-shell Magnetic States in Alternant and Non-alternant Nanographenes: Conceptions and Misconceptions

10.26434/chemrxiv-2023-mvvbx

N.A.

N.A.

Aristides Zdetsis

In contrast to alternant nanographenes (NGRs), in non-alternant NGRs no “sublattice structure” can be defined associated with significant conceptual and computational simplifications. This leads to some fundamental differences between the two. We uncover here the broken electron-hole symmetry in non-alternant NGRs as one fundamental difference closely related to distorted Dirac points (cones) and their diradical open-shell character. We also show by higher level calculations beyond common DFT that the alternant series of peri-acenes (bisanthene, peri-tetracene, peri-pentacene, … etc.), contrary to opposite reports in the literature, have clearly closed singlet ground states, in contrast to their non-alternant isomers based on Stone-Wales (SW) defects. This is experimentally supported by sub-molecularly resolved STM images. The misconceptions in the literature are due to insufficient correlation. For non-alternant NGRs/GNRs with antiaromatic rings the driving force for open-shell states and distorted Dirac points (involving localized electrons and delocalized holes) is antiaromaticity, which is a sufficient but not always necessary condition. This is in juxtaposition to the aromaticity of the alternant isomers with closed shell states. Thus, in both cases sublattice problems lead to open shell magnetic states; ferromagnetic in cases of sublattice imbalance (e.g. triangulenes), antiferromagnetic for non-sublattice cases (e.g. SW3x2, SW4x2), and non-magnetic (diamagnetic) for balanced sublattices (e.g. AGNRs). Obviously, similar results are expected for larger NGRs/GNRs obtained by concatenation of such SW-motifs.

2023-08-30

chemRxiv

Theoretical and Computational Chemistry; Physical Chemistry; Materials Chemistry

CC BY 4.0

Role of anionic backbone in NHC-stabilized coinage metal complexes: New precursors for atomic layer deposition

10.26434/chemrxiv-2021-0nrm1-v2

10.1002/chem.202103798

https://doi.org/10.1002/chem.202103798

Nils Boysen; Anish Philip; Detlef Rogalla; Maarit Karppinen; Anjana Devi

Cu and Ag precursors that are volatile, reactive, and thermally stable are currently of high interest for their application in atomic layer deposition (ALD) of thin metal films. In pursuit of new precursors for coinage metals namely Cu and Ag, a series of new N-heterocyclic carbene (NHC) based Cu(I) and Ag(I) complexes were synthesized. Modifications in the substitution pattern of diketonate-based anionic backbones led to five monomeric Cu complexes and four closely related Ag complexes with the general formula [M(tBuNHC)(R)] (M = Cu, Ag; tBuNHC = 1,3-di-tert-butyl-imidazolin-2-ylidene; R = diketonate). Thermal analysis indicated that most of the Cu complexes are thermally stable and volatile compared to the more fragile Ag analogs. One of the promising Cu precursors was evaluated for the ALD of nanoparticulate Cu metal films using hydroquinone as the reducing agent at appreciably low deposition temperatures (145–160 °C). This study highlights the considerable impact of the employed ligand sphere on the structural and thermal properties of metal complexes that are relevant for vapor phase processing of thin films.

2021-10-21

chemRxiv

Inorganic Chemistry; Organometallic Chemistry; Coordination Chemistry (Organomet.); Transition Metal Complexes (Organomet.); Materials Chemistry; Crystallography – Inorganic

CC BY NC ND 4.0

Synthesis of Bicyclo[1.1.0]butanes from Iodo-Bicyclo[1.1.1]pentanes

10.26434/chemrxiv-2023-z8jvt-v2

10.1021/acs.orglett.3c01417

https://doi.org/10.1021/acs.orglett.3c01417

Michael Mandler; James Mignone; Elizabeth Jurica; Maximilian Palkowitz; Darpandeep Aulakh; Anthony Cauley; Christopher Farley; Shasha Zhang; Sarah Traeger; Amy Sarjeant; Anthony Paiva; Heidi Perez; Bruce Ellsworth; Alicia Regueiro-Ren

We describe a two step process for the synthesis of substituted bicyclo[1.1.0]butanes. A photo-Hunsdiecker reaction generates iodo-bicyclo[1.1.1]pentanes under metal-free conditions at room temperature. These intermediates react with nitrogen and sulfur nucleophiles to afford substituted bicyclo[1.1.0]butane products.

2023-05-29

chemRxiv

Biological and Medicinal Chemistry; Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Crystallography – Organic

CC BY 4.0

Access to Fluoroalkylated Azoles and 2-Acylaminoketones via Anhydride-Mediated Cleavage of NH-1,2,3-Triazoles

10.26434/chemrxiv-2022-5m2t5

N.A.

N.A.

Vladimir Motornov; Petr Beier

NH-1,2,3-Triazoles undergo a ring cleavage in reactions with fluorinated acid anhydrides (trifluoroacetic, difluoroacetic chlorodifluoroacetic and pentafluoropropionic anhydrides) by nitrogen acylation and acid-mediated triazole ring opening. Structurally diverse fluoroalkylated oxazoles were prepared from 4,5-disubstituted-1,2,3-triazoles. Efficient synthesis of 2-acylaminoketones was achieved from 4-substituted-1,2,3-triazoles. Finally, easy access to fluoroalkylated imidazoles and 1,2,4-tetrazines was developed by one-pot two step routes from fluorinated anhydrides and NH-triazoles.

2022-02-17

chemRxiv

Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions

CC BY NC ND 4.0

A Broadly Applicable Strategy to Aminate Azines Enabled by Electronically Tuned Phosphine Reagents.

10.26434/chemrxiv-2024-f2vxg

N.A.

N.A.

Jeffrey N. Levy; Ren-Rong Liu; Andrew McNally

We describe a strategy for aminating pyridines and other azines via phosphonium salt intermediates. Precisely tuning the electronic properties of the phosphonium ion was key for C–N bond formation via an SNAr-halogenation, SNAr-amination sequence. The process accommodates a wide range of amine classes and pyridine coupling partners and is viable for applications such as late-stage amination of complex pharmaceuticals and fragment-fragment coupling reactions. The capacity to rapidly modify the structure of the phosphine reagent was decisive and is a valuable feature in pseudohalide design.

2024-08-09

chemRxiv

Biological and Medicinal Chemistry; Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions

CC BY NC ND 4.0

Observation and Analysis of Model Lipid Raft Deformation Dynamics Induced by Lipoprotein–Gold Nanorod-based Devices to Manipulate Phase Transition of Lipid Bilayer

10.26434/chemrxiv-2023-rq355

N.A.

N.A.

TOMOHIRO NOBEYAMA; Tatsuya Murakami

Lipid rafts, which are complexes that form on cholesterol-rich areas of cell membranes, play key roles as gates for the distribution of information between the inner and outer spaces of living cells. The physical and biological properties of lipid rafts have been investigated, but the engineering of lipid rafts remains a difficult subject. We developed a lipoprotein–gold nanorod nanodevice to control the formation/deformation of model lipid rafts. The nanodevice attached to the liquid order (Lo) phase region, selectively removed cholesterol from the Lo domain, and induced the Lo-to-solid order (So) phase transition. In this study, we analyzed the phase transition induced by the nanodevice. We found that the domain boundary gradually collapsed and that a local two-phase mixture was induced. Local instability resulted in domain incursion into other domains, and protrusions were torn to form small domains with the characteristics of two phases. The two different domains grouped together to form a non-circular So domain on giant unilamellar vesicles. Close observation of the non-equilibrium process of phase transition may lead to the design of strategies for external lipid raft manipulation methodology using biological macromolecules and/or nanoparticles.

2023-01-06

chemRxiv

Biological and Medicinal Chemistry; Nanoscience; Plasmonic and Photonic Structures and Devices; Bioengineering and Biotechnology; Biophysics

CC BY NC 4.0

Development of tailless homologue receptor (TLX) agonist chemical tools

10.26434/chemrxiv-2024-xkjhd

N.A.

N.A.

Emily C. Hank; Minh Sai; Till Kasch; Isabelle Meijer; Julian Marschner; Daniel Merk

The tailless homologue receptor (TLX) is a ligand-activated transcription factor acting as master regulator of neural stem cell homeostasis. Despite its promising potential in neurodegenerative disease treatment, TLX ligands are rare but required to explore phenotypic effects of TLX modulation and for target validation. We have systematically studied and optimized a TLX agonist scaffold obtained by fragment fusion. Structural modification enabled the development of two TLX agonists endowed with nanomolar potency and binding affinity. Both exhibited favorable chemical tool characteristics including high selectivity and low toxicity. Most notably, the TLX agonists comprise different scaffolds and display high chemical diversity enabling a use as set for target identification and validation studies.

2024-08-07

chemRxiv

Biological and Medicinal Chemistry

CC BY NC ND 4.0

Theoretical Approaches to Study Degradation in Li-ion Battery Cathodes: Crucial Role of Exchange and Correlation

10.26434/chemrxiv-2024-psjhk

N.A.

N.A.

Hrishit Banerjee; Andrew J Morris

Li-ion batteries have become essential in energy storage, with demand rising steadily. Cathodes, crucial for determining capacity and voltage, face challenges like degradation, thermal runaway, and battery failure. Understanding these degradation phenomena is vital for developing mitigation strategies. Experimental techniques such as XAS, XPS, PES, UV-Vis spectroscopy, RIXS, NMR, and OEMS are commonly used, but theoretical modelling, particularly atomistic modelling with density-functional theory (DFT), provides key insights into the microscopic electronic behaviours causing degradation. While DFT offers a precise formulation, its approximations in the exchange-correlation functional and its ground-state, 0K limitations necessitate additional methods like ab initio molecular dynamics. Recently, many-body electronic structure methods have been used alongside DFT to better explain electron-electron interactions and temperature effects. This review emphasizes material-specific methods and the importance of electron-electron interactions, highlighting the role of many-body methods in addressing key issues such as polaron formation and electron-phonon coupling in cathodes.

2024-07-10

chemRxiv

Theoretical and Computational Chemistry; Energy; Theory - Computational; Energy Storage; Materials Chemistry

CC BY NC ND 4.0

A Prelude to Biogermylene Chemistry

10.26434/chemrxiv.12515512.v1

10.1002/anie.202004551

https://doi.org/10.1002/anie.202004551

Pritam Mahawar,; Mishi Kaushal Wasson; Mahendra Kumar Sharma; Chandan Kumar Jha; Goutam Mukherjee; Perumal Vivekanandan; Selvarajan Nagendran

<p><b>Abstract:</b> The biological applications of germylenes remain an unconceivable domain owing to their unstable nature. We report the isolation of air, water, and culture-medium stable germylene DPMGeOH (<b>3</b>) and its potential biological application (DPM = dipyrromethene ligand). Compound <b>3 </b>exhibits antiproliferative effects comparable to that of cisplatin in human cancer cells. The cytotoxicity of compound <b>3 </b>on normal epithelial cells is minimal and is similar to that of the currently used anti-cancer drugs. These findings provide a framework for a plethora of biological studies using germylenes and have important implications for low-valent main group chemistry.</p>

2020-06-29

chemRxiv

Main Group Chemistry (Inorg.); Organometallic Compounds; Bioorganometallic Chemistry

CC BY NC ND 4.0

Inorganic Metal Thiocyanates

10.26434/chemrxiv-2024-tsqzh

N.A.

N.A.

Matthew Cliffe

Metal thiocyanates are some of the earliest reported molecular framework materials and adopta diverse range of structures. This review describes the structures, properties and syntheses ofthe known binary and ternary thiocyanates. It provides a categorization of their diverse structures,and connects them to the structures of atomic inorganic materials. In addition to this description ofcharacterized binary and ternary thiocyanates, the review summarizes the state of knowledge forall other binary metal thiocyanates. The review concludes by highlighting opportunities for futurematerials development.

2024-01-18

chemRxiv

Inorganic Chemistry; Coordination Chemistry (Inorg.); Solid State Chemistry; Materials Chemistry; Crystallography – Inorganic

CC BY 4.0

Data-efficient modeling of catalytic reactions via enhanced sampling and on-the-fly learning of machine learning potentials

10.26434/chemrxiv-2024-nsp7n

N.A.

N.A.

Simone Perego; Luigi Bonati

Simulating catalytic reactivity under operative conditions poses a significant challenge due to the dynamic nature of the catalysts and the high computational cost of electronic structure calculations. Machine learning potentials offer a promising avenue to simulate dynamics at a fraction of the cost, but they require datasets containing all relevant configurations, particularly reactive ones. Here we present a scheme to construct reactive potentials in a data-efficient manner. This is achieved by combining enhanced sampling methods first with Gaussian processes to discover transition paths and then with graph neural networks to obtain a uniformly accurate description. The necessary configurations are extracted via an active learning procedure based on local environment uncertainty. We validated our approach by studying several reactions related to the decomposition of ammonia on iron-cobalt alloy catalysts. Our scheme proved efficient, requiring only ~1,000 DFT calculations per reaction, and robust, sampling reactive configurations from the different accessible pathways. Using this potential, we calculated free energy profiles and characterized reaction mechanisms, showing the ability to provide microscopic insights into complex processes under dynamic conditions.

2024-06-06

chemRxiv

Theoretical and Computational Chemistry; Physical Chemistry; Catalysis; Computational Chemistry and Modeling; Machine Learning

CC BY NC ND 4.0

Antiplasmodial diterpenoid alkaloid from Aconitum heterophyllum: Isolation, characterization, and UHPLC-DAD based quantification

10.26434/chemrxiv-2021-b2smg

N.A.

N.A.

Anmol -; Surekha Kumari; Rakesh Kumar; Raman Singh; Gaurav Aggarwal; Prakhar Agrawal; Dinkar Sahal; Upendra Sharma

Aconitum heterophyllum is a traditionally important medicinal plant having numerous therapeutic actions as documented in Ayurveda. This plant has been used alone as well as in combination with other plants for the preparation of different anti-malarial formulations. However, there is no report on the assessment of its anti-plasmodial activity, and the compound responsible for this activity. The main aim of this study was to conduct phytochemical investigation of A. heterophyllum roots for the preparation of extract, fractions and isolation of pure molecules to identify active fractions/molecules responsible for the anti-plasmodial activity, and development of UHPLC-DAD based analytical method which can be used for the quantification of marker compounds in the extracts and fractions. Hydro-alcoholic extract (1:1 v/v) and fractions (n-hexane, chloroform, ethyl acetate, n-butanol and water) were prepared from the dried powdered roots of A. heterophyllum. Fractions were further subjected to silica gel-based column chromatography to isolate pure specialized secondary metabolites from this plant. All extracts, fractions and pure molecules were evaluated against the chloroquine resistant Pf INDO and chloroquine sensitive Pf3D7 strains in culture for calculating their IC50 values. UHPLC-DAD based analytical method was also developed for the first time for the quantification and quality assessment of this commercially important Himalayan medicinal plant. Phytochemical investigation of A. heterophyllum root led to the isolation of six specialized metabolites named as 2-O-cinnamoyl hetisine (1), atisinium (2), 4-oxabicyclo [3.2.2] nona-1(7),5,8-triene (3), atisinium cinnamate (4), aconitic acid (5), and atisinium formate (6). Compound 1 is a new hetisine type diterpenoid alkaloid, compounds 4 and 6 are new counter ionic forms observed with atisinium ion, and compound 3 is being reported for the first time from this genus. Chloroform fraction was found to be the most active with IC50 (µg/mL) 1.01 (Pf INDO) and 1.32 (Pf3D7). The isolated molecule 2-O-cinnamoyl hetisine (1), a new diterpenoid alkaloid isolated from chloroform fraction, showed promising antiplasmodial activities with IC50 (µM) 1.92 (Pf INDO) and 10.8 (Pf 3D7). Activity of chloroform fraction was further validated by the developed UHPLC-DAD based method as the quantity of 2-O-cinnamoyl hetisine (1) was higher in the chloroform fraction (≅200 µg/mL) than in all other fractions (< 7µg/mL). Atisinium (2) and 2-O-cinnamoyl hetisine (1) were found to be the main marker compounds of this plant based on quantity and antiplasmodial activity, respectively. This study provides the scientific rational for the traditional use of this plant in treating malaria. Further, this study revealed that anti-malarial potential of this plant might be due to the presence of diterpenoid alkaloids.

2021-10-26

chemRxiv

Biological and Medicinal Chemistry; Organic Chemistry; Analytical Chemistry; Natural Products; Analytical Chemistry - General; Spectroscopy (Anal. Chem.)

CC BY NC ND 4.0

Vibrational transitions of H2Cl+: potential energy surface and anharmonic computations

10.26434/chemrxiv-2023-b4hhm-v2

N.A.

N.A.

Kokou M. Robert Afansounoudji; Rabiou Issa; Komi Sodoga; David Lauvergnat

A new three-dimensional potential energy surface of the electronic ground state of the chloronium ion, H2Cl+, based on the explicitly correlated coupled cluster method with a triple zeta basis set adapted to this method has been expanded in an analytical representation. This potential energy surface is later incorporated into our home-made Fortran code to compute variationally the vibrational levels, zero-point ground average structural parameters and the rotational constants of the chloronium ion and several isotopologues. Our results show a good agreement with experimental data and that our results will help to detect H2Cl+ isotopologues in the interstellar medium.

2023-10-26

chemRxiv

Theoretical and Computational Chemistry; Computational Chemistry and Modeling

CC BY 4.0

Controlling substrate selectivity in cross coupling with light

10.26434/chemrxiv-2021-8wqv0-v2

N.A.

N.A.

Pradipta Das; Eliot Woods; Jack Ly; Jack Olding; Kayla Presley; Brennan Romanoff; Tod Grusenmeyer; Emily Weiss; Julia Kalow

Substrate-selective reactions typically rely on differences in the ground-state reactivity of substrates or their interactions with supramolecular catalyst scaffolds. Here, we show that a photoinduced cross-coupling reaction provides high substrate selectivity that cannot be achieved under thermal conditions. We report a visible-light-promoted, Ni-catalyzed Suzuki–Miyaura cross-coupling of diiodo-boron-dipyrromethene (BODIPY) chromophores displaying high selectivity for mono-arylation, enabling the efficient sequential synthesis of unsymmetrically substituted BODIPYs. Substrate selectivity is maintained in mixtures containing non-absorbing aryl iodides or halogenated BODIPYs with similar absorption. This work demonstrates the potential of substrate photoexcitation-based reaction mechanisms for the selective functionalization of organic chromophores with desirable excited-state properties.

2022-04-19

chemRxiv

Organic Chemistry; Catalysis; Organometallic Chemistry; Photochemistry (Org.); Photocatalysis

CC BY NC ND 4.0

Discovery of a Two-Dimensional Type I Superionic Conductor

10.26434/chemrxiv.12753173.v2

N.A.

N.A.

Alex Rettie; Jingxuan Ding; Michael Johnson; Christos Malliakas; Naresh Osti; Duck Young Chung; Raymond Osborn; Olivier Delaire; Stephan Rosenkranz; Mercouri Kanatzidis

<div> <div> <div> <p>Type I superionic conductors (e.g., AgI, Ag₂Se, etc.) are defined by an abrupt transition to the superionic state and have so far been found exclusively in 3D crystal structures. Here, we reveal a new 2D type I superionic conductor, α-KAg₃Se₂ by total scattering techniques and complementary simulations. Quasi-elastic neutron scattering (QENS) from the high temperature superionic phase match a simple Fickian diffusion mechanism with a diffusion coefficient of ~10^-5 cm² s^-1 between 710 and 740 K. Ab initio molecular dynamics simulations confirm that the mobile Ag⁺ ions are confined to 4 Å thick layers, in addition to reproducing the experimental diffusion coefficient from QENS and the local structure obtained from X-ray powder pair-distribution-function analysis. Finally, chemical substitutions suggest that the nature of alkali metal ions comprising the charge-balancing layers can facilitate or inhibit the phase transition temperature. </p> </div> </div> </div>

2020-08-24

chemRxiv

Ceramics; Solid State Chemistry; Physical and Chemical Properties; Crystallography – Inorganic

CC BY NC ND 4.0

Scaffold Generator - A Java library implementing molecular scaffold functionalities in the Chemistry Development Kit (CDK)

10.26434/chemrxiv-2022-7tf0h-v2

N.A.

N.A.

Jonas Schaub; Julian Zander; Achim Zielesny; Christoph Steinbeck

The concept of molecular scaffolds as defining core structures of organic molecules is utilised in many areas of chemistry and cheminformatics, e.g. drug design, chemical classification, or the analysis of high-throughput screening data. Here, we present Scaffold Generator, a comprehensive open library for the generation, handling, and display of molecular scaffolds, scaffold trees and networks. The new library is based on the Chemistry Development Kit (CDK) and highly customisable through multiple settings, e.g. five different structural framework definitions are available. For display of scaffold hierarchies, the open GraphStream Java library is utilised. Performance snapshots with natural products (NP) from the COCONUT (COlleCtion of Open Natural prodUcTs) database and drug molecules from DrugBank are reported. The generation of a scaffold network from more than 450,000 NP can be achieved within a single day.

2022-10-26

chemRxiv

Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Organic Chemistry; Natural Products; Organic Compounds and Functional Groups; Chemoinformatics - Computational Chemistry

CC BY 4.0

Stereoretentive Decarboxylative C-3 Func-tionalization of Chromone-3-carboxylic Acids via Visible Light Irradiation

10.26434/chemrxiv-2023-7606k

N.A.

N.A.

Mohsen Monirialamdari; Ewelina Kowalska; Lesław Sieroń; Łukasz Albrecht; Anna Albrecht

ABSTRACT: Herein, we report a stereoretentive and decar-boxylative C-3 functionalization of chromone-3-carboxylic acids with optically active aziridines via visible light irradia-tion. This metal-free and operationally simple protocol utilizes a simple combination of stable and inexpensive tetrabu-tylammonium iodide and visible light irradiation. It enables a facile and direct access to chiral 3-substituted chromenones with maintaining the optical purity of starting aziri-dines.Cross-coupling reactions allowing for efficient carbon–carbon as well as carbon–heteroatom bond formations are of crucial importance in the modern organic chemistry.1 Among them transition-metal-catalyzed decarboxylative cross-couplings utilizing carboxylic acids as substrates occupy a prominent position.2 They offer several distinctive advantages related to availability and price of carboxylic acid derivatives, their stability and handling as well as generation of less-toxic carbon dioxide as the by-product that reduces the waste treatment costs. While these methods have proven particularly useful for C(sp2)-C(sp2) bond formations and were applied for the synthesis of numerous relevant products ranging from pharmaceuticals to organic materials, their application in the C(sp2)-C(sp3) remains limited. Consequently, there is a need for the development of alternative, transition-metal-free cross-coupling reactions allowing for C(sp2)-C(sp3) bond formations.

2023-12-13

chemRxiv

Organic Chemistry

CC BY 4.0

Synthesis and Characterization of Dense Carbon Films as Model Surfaces to Estimate Electron Transfer Kinetics on Redox Flow Battery Electrodes

10.26434/chemrxiv-2022-3f18q

N.A.

N.A.

Charles Wan; Akram Ismail; Alexander Quinn; Yet-Ming Chiang; Fikile Brushett

Redox flow batteries (RFBs) are a promising electrochemical technology for the efficient and reliable delivery of electricity, providing opportunities to integrate intermittent renewable resources and to support unreliable and/or aging grid infrastructure. Within the RFB, porous carbonaceous electrodes facilitate the electrochemical reactions, distribute the flowing electrolyte, and conduct electrons. Understanding electrode reaction kinetics is crucial for improving RFB performance and lowering costs. However, assessing reaction kinetics on porous electrodes is challenging as their complex structure frustrates canonical electroanalytical techniques used to quantify performance descriptors. Here, we outline a strategy to estimate electron transfer kinetics on planar electrode materials of similar surface chemistry to those used in RFBs. First, we describe a bottom-up synthetic process to produce flat, dense carbon films to enable evaluation of electron transfer kinetics using traditional electrochemical approaches. Next, we characterize physicochemical properties of the films using a suite of spectroscopic methods, confirming that their surface characteristics align with those of widely-used porous electrodes. Last, we study the electrochemical performance of the films in a custom-designed cell architecture, extracting intrinsic heterogeneous kinetic rate constants for two iron-based redox couples in aqueous electrolytes using standard electrochemical methods (i.e., cyclic voltammetry, electrochemical impedance spectroscopy). We anticipate that the synthetic methods and experimental protocols described here are applicable to a range of electrocatalysts and redox couples.

2022-08-05

chemRxiv

Materials Science; Energy; Chemical Engineering and Industrial Chemistry; Carbon-based Materials; Thin Films; Energy Storage

CC BY NC ND 4.0

Controlling superselectivity of multivalent interactions with cofactors and competitors

10.26434/chemrxiv-2022-tkxgk

10.1021/jacs.2c06942

https://doi.org/10.1021/jacs.2c06942

Tine Curk; Galina V. Dubacheva; Alain R. Brisson; Ralf P. Richter

Moieties that compete with multivalent interactions or act as cofactors are common in living systems, but their effect on multivalent binding remains poorly understood. We derive a theoretical model that shows how the superselectivity of multivalent interactions is modulated by the presence of cofactors or competitors. We find that the role of these participating moieties can be fully captured by a simple rescaling of the affinity constant of the individual ligand-receptor bonds. Theoretical predictions are supported by experimental data of the membrane repair protein annexin A5 binding to anionic lipid membranes in the presence of Ca2+ cofactors, and of the extracellular matrix polysaccharide hyaluronan (HA) binding to CD44 cell surface receptors in the presence of HA oligosaccharide competitors. The obtained findings should facilitate understanding of multivalent recognition in biological systems and open new routes for fine-tuning the selectivity of multivalent nanoprobes in medicinal chemistry.

2022-07-04

chemRxiv

Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Nanoscience

CC BY NC 4.0

A Strategy to Trap Oxygen and to Kill Cancer Cells by Photodynamic Therapy

10.26434/chemrxiv-2022-2gqfs

N.A.

N.A.

Marie Gaschard; Daniel L. Stares; Manuel Gallardo-Villagrán; David Yannick Leger; Bertrand Liagre; Christoph A. Schalley; Bruno Therrien

Low oxygen concentration in solid cancer tumors leads to resistance, especially when dealing with photodynamic therapy (PDT) treatments. In fact, the presence of oxygen is mandatory to obtain an efficient PDT treatment. The synthesis of new oxygen carriers, specifically targeting cancer cells, appears to be an elegant strategy to tackle this issue. With this in mind, we have synthetized 15 arene ruthenium(II) assemblies containing different anthracenyl-based ligands in which the anthracenyl moieties were used to capture O2. We present their synthesis and characterization, as well as their photo-oxygenation and their toxicity/phototoxicity behavior on DU145 prostatic cancer cells. The possibility to transport oxygen via the formation of endoperoxides was further confirmed by mass spectrometry.

2022-10-14

chemRxiv

Biological and Medicinal Chemistry; Organometallic Chemistry; Drug Discovery and Drug Delivery Systems; Bioorganometallic Chemistry

CC BY NC ND 4.0

Development and Application of a Single Neural Network Potential for IRMOF-n (n=1,4,6,7,10)

10.26434/chemrxiv-2021-25n6h

N.A.

N.A.

Omer Tayfuroglu; Abdul Kadir Kocak; Yunus Zorlu

Metal‑organic frameworks (MOFs) with their exceptional porous and organized structures have been subject of numerous applications. Predicting macroscopic properties from atomistic simulations require the most accurate force fields, which is still a major problem due to MOFs’ hybrid structures governed by covalent, ionic and dispersion forces. Application of ab‑initio molecular dynamics to such large periodic systems are thus beyond the current computational power. Therefore, alternative strategies must be developed to reduce computational cost without losing reliability. In this work, we describe the construction of a neural network potential (NNP) for IRMOF‑n series (n=1,4,7,10) trained by PBE-D4/def2-TZVP reference data of MOF fragments. We validated the resulting NNP on both fragments and bulk MOF structures by prediction of properties such as equilibrium lattice constants, phonon density of states and linker orientation. The energy and force RMSE values for the fragments are only 0.0017 eV/atom and 0.15 eV/Å, respectively. The NNP predicted equilibrium lattice constants of bulk structures, which are not included in training, are off by only 0.2-2.4% from experimental results. Moreover, our fragment trained NNP greatly predicts phenylene ring torsional energy barrier, equilibrium bond distances and vibrational density of states of bulk MOFs. Furthermore, NNP allows us to investigate unusual behaviors of selected MOFs such as the thermal expansion properties and the effect of mechanical strain on the adsorption of hydrogen and methane molecules. The NNP based molecular dynamics (MD) simulations suggest the IRMOF‑4 and IRMOF‑7 to have positive‑to‑negative thermal expansion coefficients while the rest to have only negative thermal expansion under the studied temperatures of 200 K to 400 K. The deformation of bulk structure by reduction of unit cell volume has shown to increase volumetric methane uptake in IRMOF‑1 but decrease in IRMOF‑7 due to the steric hindrance.

2021-12-07

chemRxiv

Theoretical and Computational Chemistry; Organometallic Chemistry; Computational Chemistry and Modeling; Machine Learning; Transition Metal Complexes (Organomet.); Materials Chemistry

CC BY NC ND 4.0

Tris-Azo Triangular Paraphenylenes: Synthesis and Reversible Interconversion into Radial π-Conjugated Macrocycles

10.26434/chemrxiv-2024-kpz68-v2

N.A.

N.A.

Tomohito Ide; Wei-Ci Huang; Masaki Horie

We report the synthesis of cycloparaphenylene derivatives featuring tris-azo groups. The smaller derivative, [3]cycloazobenzene ([3]CAB-0), adopts a triangular all-cis form and exhibits thermally and photochemically stable characteristics due to significant ring strain, as well as symmetric Kagome-patterned crystal packing. In contrast, the as-synthesized [3]cycloazobenzene with three biphenylene bridges ([3]CAB-1) adopts a similar triangular all-cis form; however, it undergoes photoinduced isomerization, leading to a mixture of cis and trans forms at a photostationary state. Interestingly, the addition of an excess of acid selectively leads to the formation of the all-trans form. DFT calculations reveal that the interconversion from a triangular to a circular shape correlates with an increase in HOMO and a decrease in LUMO, characteristics intrinsic to radial π-conjugated systems.

2024-01-17

chemRxiv

Organic Chemistry; Organic Compounds and Functional Groups; Photochemistry (Org.); Materials Chemistry; Crystallography – Organic

CC BY NC ND 4.0

Accurate Rate Calculations for Hydrogen Atom Abstraction from Methane by Hydroxyl Radical: A Combination of RPMD, Machine Learning Potentials, and Active Learning

10.26434/chemrxiv-2023-bz2sr

N.A.

N.A.

Adrian Gordon; Jason Goodpaster

We employ an active learning scheme to train a neural network potential which is then utilized in RPMD simulations to calculate the thermal rate coefficients for a hydrogen atom abstraction from methane by hydroxyl radical. We use a active learning approach to determine which geometries from umbrella sampling trajectories, performed using our neural network potential, should be included in our CCSD(T) training data to improve the neural network potential. After sufficient accuracy of the neural network potential is achieved, we use this potential energy surface in RPMD trajectories to calculate the reaction rate using the Bennet-Chandler method. We find this approach to be exceptionally accurate, with errors in the rate less than 20% at 200K and decreasing to 10% at 1000K. Next, we examine the limit of how much data was required to obtain highly accurate neural network potentials and find that only 7,000 CCSD(T) are required to preserve the accuracy of the network. Finally, we examine a transfer learning approach for this reaction, and find that transfer learning does not provide sufficient accuracy for rate calculations.

2023-05-04

chemRxiv

Theoretical and Computational Chemistry; Theory - Computational; Machine Learning

CC BY NC 4.0

Different Nucleation Mechanisms during Atomic Layer Deposition of HfS2 on Cobalt Oxide Surfaces

10.26434/chemrxiv-2024-0qn5p

N.A.

N.A.

Georg Fickenscher; Nikolai Sidorenko; Kira Mikulinskaya; Joerg Libuda

We investigated the atomic layer deposition (ALD) of HfS2 on atomically defined CoO(100) and CoO(111) surfaces under ultrahigh-vacuum (UHV) conditions. The ALD process was performed by sequential dosing of the precursors tetrakis(dimethylamido)hafnium (TDMAH) and deuterium sulfide (D2S) separated by purging periods. The growth and nucleation reactions were monitored by in situ infrared reflection absorption spectroscopy (IRAS). HfS2 films nucleate and grow on both cobalt oxide surfaces, despite the fact that CoO(100) lacks acidic protons and CoO(111) exposes only very few OH groups at defects. On these OH- free or OH-lean surfaces, the nucleation step involves a Lewis acid-base reaction instead. The stoichiometry of the –Hf(NMe2)x nuclei changes during the first ALD half cycle. On CoO(100), the split-off ligands bind as –NMe2 to surface cobalt ions. The nucleation on CoO(111) is more complex and the split-off ligands undergo dehydrogenation to form various surface species with C=N double and C≡N triple bonds and surface OH. Our findings reveal a new nucleation mechanism for ALD in the absence of acidic protons and show that other factors such as Lewis acidity, surface structure, and surface reactivity must also be considered in the nucleation event.

2024-05-22

chemRxiv

Physical Chemistry; Interfaces; Physical and Chemical Processes; Spectroscopy (Physical Chem.); Materials Chemistry

CC BY 4.0

Visible Light-Mediated Oxidative Debenzylation

10.26434/chemrxiv.13135814.v1

N.A.

N.A.

Cristian Cavedon; Eric T. Sletten; Amiera Madani; Olaf Niemeyer; Peter H. Seeberger; Bartholomäus Pieber

Protecting groups are key in the synthesis of complex molecules such as carbohydrates to distinguish functional groups of similar reactivity. The harsh conditions required to cleave stable benzyl ether protective groups are not compatible with many other protective and functional groups. The mild, visible light-mediated debenzylation disclosed here renders benzyl ethers orthogonal protective groups. Key to success is the use of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as stoichiometric or catalytic photooxidant such that benzyl ethers can be cleaved in the presence of azides, alkenes, and alkynes. The reaction time for this transformation can be reduced from hours to minutes in continuous flow. <br />

2020-10-27

chemRxiv

Photocatalysis

CC BY NC ND 4.0

Tuning and Matching Error Compensated, Quantitative Solid-state NMR

10.26434/chemrxiv-2024-0l74f

N.A.

N.A.

Hector Javier Cortes Sanchez; Lukas Paul Rüthing; Jörn Schmedt auf der Günne

Abstract NMR spectroscopy has long been recognized as a powerful quantitative analytical tool. Quantification is commonly done against internal and external standards. A third approach is to quantify against an electronic reference which combines the advantages of the two methods. The implementation of this approach in solid-state NMR is more challenging due to the single-coil design of double resonance probes. In this study, a novel approach for implementing the electronic referencing method in solid-state NMR by injecting the reference signal using a broadband antenna installed near the NMR receiver coil is presented. This method demonstrates excellent accuracy and precision, as it remains robust to changes in the electronic conditions of the probe, including tuning and matching errors.

2024-04-12

chemRxiv

Analytical Chemistry; Spectroscopy (Anal. Chem.)

CC BY NC 4.0

Expressed Protein Ligation Without Intein

10.26434/chemrxiv.11559693.v1

10.1021/jacs.0c00252

https://doi.org/10.1021/jacs.0c00252

Yuchen Qiao; Ge Yu; Xiaoyan Wang; Kaci C. Kratch; Wesley Wei Wang; Jared S. Morse; Sunshine Z. Leeuwon; Wenshe Liu

Proteins with a functionalized <i>C</i>-terminus such as a <i>C</i>-terminal thioester are key to the synthesis of larger proteins via expressed protein ligation. They are usually made by recombinant fusion to intein. Although powerful, the intein fusion approach suffers from premature hydrolysis and low compatibility with denatured conditions. To totally bypass the involvement of an enzyme for expressed protein ligation, here we showed that a cysteine in a recombinant protein was chemically activated by a small molecule cyanylating reagent at its <i>N</i>-side amide for undergoing nucleophilic acyl substitution with amines including a number of L- and D-amino acids and hydrazine. The afforded protein hydrazides could be used further for expressed protein ligation. We demonstrated the versatility of this approach with the successful synthesis of ubiquitin conjugates, ubiquitin-like protein conjugates, histone H2A with a posttranslational modification, RNAse H that actively hydrolyzed RNA, and exenatide that is a commercial therapeutic peptide. The technique, which is exceedingly simple but highly useful, expands to a great extent the synthetic capacity of protein chemistry and will therefore make a large avenue of new research possible.

2020-01-10

chemRxiv

Chemical Biology

CC BY NC ND 4.0

Challenges in the direct detection of chirality-induced spin selectivity: investigation of foldamer-based donor/acceptor dyads

10.26434/chemrxiv-2022-dx58w

N.A.

N.A.

Alberto Privitera; Davide Faccio; Demetra Giuri; Damiano Genovese; Francesco Tassinari; Liviana Mummolo; Mario Chiesa; Claudio Fontanesi; Enrico Salvadori; Andrea Cornia; Claudia Tomasini; Roberta Sessoli

Over the past two decades, the chirality-induced spin selectivity (CISS) effect was reported in several experiments disclosing a unique connection between chirality and electron spin. Recent theoretical works have highlighted time-resolved Electron Paramagnetic Resonance (trEPR) as a powerful tool to directly detect the spin polarisation resulting from CISS. Because of the absence of interfaces with conducting electrodes, such spectroscopic evidence could provide a clear understanding of how CISS works at the intramolecular level. Experimental results have demonstrated the potential of this approach for detecting a spin-polarised photoinduced electron transfer (ET) in hybrid systems comprising a CdSe quantum dot as an electron donor (D) connected by a chiral linker (χ) to a fullerene derivative as an electron acceptor (A). However, the study of the ET process in fully organic D-χ-A dyads holds tremendous potential for the unambiguous detection of CISS. Here, we report a first attempt performed using novel D-χ-A dyads, comprising pyrene (D) and fullerene (A) connected by chiral saturated peptide bridges (χ) of different length and electric dipole moment. The dyads are investigated by an array of techniques, including cyclic voltammetry, optical spectroscopies, and trEPR. Despite the promising energy alignment of the electronic levels and the evidence of luminescence quenching, trEPR does not detect a significant ET highlighting the challenges of spectroscopic detection of CISS. However, the analysis allows the formulation of guidelines for the design of chiral organic model systems suitable to directly probe CISS-polarised ET.

2022-12-16

chemRxiv

Physical Chemistry; Organic Chemistry; Organic Synthesis and Reactions; Spectroscopy (Physical Chem.); Materials Chemistry

CC BY NC ND 4.0

Wastewater-Based Epidemiology for monitoring community derived antimicrobials and resistance genes: a one-year longitudinal study

10.26434/chemrxiv-2022-7cl0h

N.A.

N.A.

Natalie Sims; Andrew Kannan; Elizabeth Holton; Kishore Jagadeesan; Leonardos Mageiros; Richard Standerwick; Tim Craft; Ruth Barden; Edward Feil; Barbara Kasprzyk-Hordern

Increasing understanding and awareness of antimicrobial resistance (AMR) is critical in tackling this growing global crisis. Wastewater-based epidemiology (WBE) is a promising approach to monitoring a range of AMR targets in communities through analysis of wastewater. This longitudinal study provides insight into antimicrobial (AA) usage within two communities in the South West of the UK, one city (Bath) and one town (Keynsham). AAs, including metabolites, from a range of different classes were quantified over the study period. Average loads of AAs were higher in Bath than for Keynsham (difference on average was 88 ± 6%) which reflected the larger population. Several AAs experienced seasonal fluctuations, such as the macrolides erythromycin and clarithromycin that were found in higher loads in the winter, whilst other AA levels, including sulfamethoxazole and sulfapyridine, stayed consistent over the study period. Several antimicrobial resistant genes (ARGs) were also studied within the city area, in order to determine how closely the abundance of these genes correlates with the levels of relevant AAs. Several genes including ermB, sul1 and intI1 were not found at statistically significant different loads in winter 2018/19 when compared to summer 2019. Due to relatively stable AA and ARG levels across 13 months monitoring time, no clear correlation was observed between absolute loads of ARGs and total loads of associated AAs by class. Hospital effluent within the city catchment was also investigated for AAs and ARGs. Several AAs were more common in hospital wastewater than in community wastewater, including sulfamethoxazole and trimethoprim. This work can help establish baselines for AA usage in communities, providing community-wide surveillance and evidence for informing public health interventions.

2022-04-26

chemRxiv

Biological and Medicinal Chemistry; Analytical Chemistry; Earth, Space, and Environmental Chemistry; Hydrology and Water Chemistry; Mass Spectrometry; Microbiology

CC BY 4.0

Discovery of the Polyketide Lagriamide B by Integrated Genome Mining, Isotopic Labeling, and Untargeted Metabolomics

10.26434/chemrxiv-2023-zthnc

N.A.

N.A.

Claire H. Fergusson; Julia Saulog; Bruno S. Paulo; Darryl M. Wilson; Dennis Y. Liu; Nicholas J. Morehouse; Samantha Waterworth; John Barkei; Christopher A. Gray; Jason C. Kwan; Alessandra S. Eustaquio; Roger Linington

Microorganisms from the order Burkholderiales have been the source of a number of important classes of natural products in recent years. For example, study of the beetle-associated symbiont Burkholderia gladioli led to the discovery of the antifungal polyketide lagriamide; an important molecule from the perspectives of both biotechnology and chemical ecology. As part of a wider project to sequence Burkholderiales genomes from our in-house Burkholderiales library we identified a strain containing a biosynthetic gene cluster (BGC) similar to the original lagriamide BGC. Structure prediction failed to identify any candidate masses for the products of this BGC from untargeted metabolomics mass spectrometry data. However, genome mining from publicly available databases identified fragments of this BGC from a culture collection strain of Paraburkholderia. Whole genome sequencing of this strain revealed the presence of a homologue of this BGC with very high sequence identity. Stable isotope feeding of the two strains in parallel using our newly developed IsoAnalyst platform identified the product of this lagriamide-like BGC directly from the crude fermentation extracts, affording a culturable supply of this important class of antifungal agents. Using a combination of bioinformatic, computational and spectroscopic methods we defined the absolute configurations for all 11 chiral centers in this new metabolite, which we named lagriamide B. Biological testing of lagriamide B against a panel of 21 bacterial and fungal pathogens revealed selective antifungal activity against the opportunistic human pathogen Aspergillus niger.

2023-10-31

chemRxiv

Biological and Medicinal Chemistry; Organic Chemistry; Analytical Chemistry; Natural Products; Chemoinformatics; Bioinformatics and Computational Biology

CC BY NC ND 4.0

Accelerating Alchemical Free Energy Prediction Using a Multistate Method: Application to Multiple Kinases

10.26434/chemrxiv-2023-kfh2s-v2

10.1021/acs.jcim.3c01469

https://doi.org/10.1021/acs.jcim.3c01469

Candide Champion; René Gall; Benjamin Ries; Salomé R. Rieder; Emilia P. Barros; Sereina Riniker

Alchemical free-energy methods based on molecular dynamics (MD) simulations have become important tools to identify modifications of small organic molecules that improve their protein binding affinity during lead optimization. The routine application of pairwise free-energy methods to rank potential binders from best to worst is impacted by the combinatorial increase of calculations to perform when the number of molecules to assess grows. To address this fundamental limitation, our group has developed replica-exchange enveloping distribution sampling (RE-EDS), a pathway-independent multistate method, enabling the calculation of alchemical free-energy differences between multiple ligands (N > 2) from a single MD simulation. In this work, we apply the method to a set of four kinases with diverse binding pockets, and their corresponding inhibitors (42 in total), chosen to showcase the general applicability of RE-EDS in prospective drug design campaigns. We show that for the targets studied, RE-EDS is able to model up to 13 ligands simultaneously with high sampling efficiency, leading to a substantial decrease in computational cost when compared to pairwise methods.

2023-09-14

chemRxiv

Theoretical and Computational Chemistry; Computational Chemistry and Modeling

CC BY NC ND 4.0

Metal-Free Aryl Cross-Coupling Directed by Traceless Linkers

10.26434/chemrxiv.8792117.v1

10.1002/chem.201903582

https://doi.org/10.1002/chem.201903582

Veit G. Haensch; Toni Neuwirth; Johannes Steinmetzer; Florian Kloss; Rainer Beckert; Stefanie Gräfe; Stephan Kupfer; Christian Hertweck

<div>The metal-free, highly selective synthesis of biaryls poses a major challenge in organic synthesis. We report the scope and mechanism of a promising new approach to (hetero)biaryls by the photochemical fusion of aryl substituents tethered to a traceless linker (photosplicing). Interrogating photosplicing with varying reaction conditions and comparison of diverse synthetic probes (40 examples, including a suite of heterocycles) showed that the reaction has a surprisingly broad scope and involves neither metals nor radicals. Quantum chemical calculations revealed that the C–C bond is formed by an intramolecular photochemical process that involves an excited singlet state and the traverse of a five-membered transition state, thus warranting consistent <i>ipso</i>‑<i>ipso</i>‑coupling fidelity. These results demonstrate that photosplicing is a unique aryl cross-coupling method in the excited state that can be applied to synthesize a broad range of biaryls. </div>

2019-07-08

chemRxiv

Organic Synthesis and Reactions; Photochemistry (Org.); Computational Chemistry and Modeling

CC BY NC ND 4.0

Synthesis, Characterization and Study of DC Electrical Conductivity of Poly[MWCNT/Imidoselenium] Composite

10.26434/chemrxiv.11441313.v1

N.A.

N.A.

Abeer O. Obeid; Fatma Al-Yusufy; Sama A Al-Aghbari; omar alshujaa; Yassin Gaber; Zinab A. Al-Washal

<p>The chemical functionalization of amino multi-walled carbon nanotubes (MWCNT-NH₂) by selenium dioxide (SeO₂) was used to produce Poly [MWCNT/Imidoselenium] composite. The prepared poly-composite was characterized by FTIR, SEM, TEM, XRD, UV, DSC and TGA. The DC electrical conductivity of poly-composite was 4.3×10^-4 S/cm due to the interaction between the nanotubes. </p>

2019-12-24

chemRxiv

Organic Synthesis and Reactions

CC BY NC ND 4.0

Where is the Hidden Intramolecular H-bonding Vibrational Signal in the Proline Matrix IR Spectrum?

10.26434/chemrxiv-2023-tp95r-v2

N.A.

N.A.

James Langford; Yuzhe Zhang; Zehua Chen; Yang Yang

The assignment of the hydrogen bonded O-H stretch vibration in the proline matrix IR spectrum has sparked controversy. Employing constrained nuclear electronic orbital methods, we provide a clear assignment that the vibrational frequency drops to near 3000 cm-1 as a result of the interplay between electronic effects, nuclear quantum effects, and matrix effects.

2024-09-04

chemRxiv

Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Spectroscopy (Physical Chem.)

CC BY 4.0

Building a Shp: A New Rare-Earth Metal-Organic Framework and Its Application in a Catalytic Photo-Oxidation Reaction

10.26434/chemrxiv.12355406.v1

N.A.

N.A.

Victor Quezada-Novoa; Hatem M. Titi; Amy Sarjeant; Ashlee J Howarth

The design and synthesis of new metal–organic frameworks (MOFs) is important from both a fundamental and application standpoint. In this work, a novel, highly‐connected rare‐earth (RE) MOF with shp topology is reported, named RE‐CU‐10 (RE = rare‐earth, CU = Concordia University), comprised of nonanuclear RE(III)‐cluster nodes and tetratopic pyrene‐based linkers. This represents the first time that the 1,3,6,8‐tetrakis(p‐benzoic acid)pyrene (H4TBAPy) linker is integrated in the shp topology. Y‐CU‐10 was explored as a heterogeneous photocatalyst for the selective oxidation and detoxification of a sulfur mustard simulant, 2‐chloroethyl ethyl sulfide (2‐CEES), showing a halflife for conversion to the less toxic 2‐chloroethyl ethyl sulfoxide (2‐CEESO) of 6.0 min.<br />

2020-05-22

chemRxiv

Hybrid Organic-Inorganic Materials; Coordination Chemistry (Inorg.); Crystallography – Inorganic

CC BY NC ND 4.0

A Marcus-Hush Perspective on Adiabatic Singlet Fission

10.26434/chemrxiv.8038892.v1

10.1063/1.5108669

https://doi.org/10.1063/1.5108669

Timothy Schmidt

<div>Singlet fission is a process whereby a bichromophoric system crosses from an excitonically coupled singlet state to a singlet-coupled triplet pair state. If the electronic structure is described locally, then the process may be described by a formal exchange of electrons. As such, it lends itself to a treatment rooted in the Marcus-Hush description of electron transfer. Here we use ab initio and density functional electronic structure theories to reveal a Marcus-Hush perspective on singlet fission and propose experiments to probe singlet fission in the spirit of photo-induced electron transfer.</div>

2019-04-25

chemRxiv

Computational Chemistry and Modeling; Theory - Computational; Photochemistry (Physical Chem.); Physical and Chemical Processes; Quantum Mechanics; Spectroscopy (Physical Chem.)

CC BY NC ND 4.0

Control of Heparin Surface Density in Multilayers of Partially Hydrolyzed Poly(2-ethyl-2-oxazoline) by Degree of Hydrolysis

10.26434/chemrxiv-2024-q4tws

N.A.

N.A.

Ghazaleh Azizi Saadatlou; Pinar Tatar Guner; A. Levent Demirel

Controlling the surface density of heparin in active anticoagulant coatings is important in applications where an optimum is required. An approach based on tuning the degree of hydrolysis of poly(2-ethyl-2-oxazoline) (PEOX) is presented to control the surface density of heparin in layer-by-layer (LbL) assembled films. Multilayers are prepared at pH5 in 0.5M aqueous NaCl solutions by electrostatic interactions between negatively charged heparin and the positively charged amine groups in hydrolyzed PEOX. Characterization of the multilayers by QCM-D, TBO assay and XPS all show that the amount of heparin deposited increases with the degree of hydrolysis. While non-hydrolyzed PEOX/Heparin multilayers do not grow, the average deposited mass per area per bilayer, as determined by QCM-D measurements, increases with the degree of hydrolysis. At 50% hydrolysis, ITC measurements exhibit an exothermic enthalpy below -500 kJ/mol, TBO assay gives a heparin surface density of 1.03 ug/cm2 and atomic % of sulfur as determined by XPS leveled off at ~14%. These results show the potential of acidic hydrolysis of PEOX combined with LbL assembly of heparin as a reproducible method for controlling the surface density of heparin in anticoagulant coatings.

2024-03-27

chemRxiv

Materials Science; Polymer Science; Coating Materials; Multilayers; Thin Films; Materials Chemistry

CC BY NC ND 4.0

Chemistry of Cyclo-[2n]-Carbon: A Many-Particle Quantum Mechanics Investigation

10.26434/chemrxiv-2023-plj1t-v2

N.A.

N.A.

Xi Chen; Xueyuan Yan; Zihan Liu; Tao Yuan; Caijie Bu; Yunlong Shang; Han Xiao; Yong Wu; Haiyan Wei; Jiawei Xu

Direct observations of cyclo-[2n]-carbon molecules (C10, C14, C16 and C18) experimentally prepared by atom manipulation technique raised immense attraction in the general chemistry society. The cyclic π-conjugated systems, namely in-plane and out-plane, construct dual aromaticity for odd n while dual anti-aromaticity for even n. In this work, we performed electronic structure investigation into cyclo-[2n]-carbon with n = 3 ~ 9 by comparing results obtained by density functional theory (DFT) and density matrix renormalization group (DMRG) method. By using Huckel molecular orbital (HMO) theory and the particle in a ring model, the electronic feature of such innovative carbon allotrope was clearly and chemically presented. Comparison showed that DFT results are considered to be incorrect for C6, which has a unique bonding structure among all cyclo-[2n]-carbon. The bond length alternating (BLA) phenomenon results from difference in electron correlation intensity and spatial distribution observed in pairs of bonding and anti-bonding orbitals. Therefore, results suggested that the dual anti-aromaticity in cyclo-[2n]-carbon with even n should be attributed to electron correlation effect, instead of decreased geometric symmetry, which actually exists in all cyclo-[2n]-carbon molecules and does not point out the essence.

2023-11-08

chemRxiv

Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Clusters; Quantum Mechanics

CC BY 4.0

A Flat-bottom Elastic Network Model for Generating Improved Plausible Reaction Paths

10.26434/chemrxiv-2024-h15dh

N.A.

N.A.

Shin-ichi Koda; Shinji Saito

Rapid generation of a plausible reaction path connecting a given reactant and product in advance is crucial for the efficient computation of precise reaction paths or transition states. We propose a computationally efficient potential energy based on molecular structure to generate such paths. This potential energy has a flat bottom consisting of structures without atomic collisions while preserving non-reactive chemical bonds, bond angles, and partial planar structures. By combining this potential energy with the direct MaxFlux method, a recently developed reaction path/transition state search method, we can find the shortest plausible path passing within the bottom. Numerical results show that this combination yields lower-energy paths compared to the paths obtained by the well-known image-dependent pair potential. We also theoretically investigate the differences between these two potential energies. The proposed potential energy and path generation routine are implemented in our Python version of the direct MaxFlux method, available on GitHub.

2024-06-18

chemRxiv

Theoretical and Computational Chemistry

CC BY 4.0

Thermochromic behavior of polydiacetylene nanomaterials driven by charged peptide amphiphiles

10.26434/chemrxiv-2023-4mh7l

10.1021/acs.biomac.3c00422

https://doi.org/10.1021/acs.biomac.3c00422

Sujeung Lim; Dmitri Leo Cordova; Alicia Robang; Yuyao Kuang; Anant Paravastu; Maxx Arguilla; Herdeline Ann Ardoña

The stimuli-responsive chromogenic transitions in polydiacetylenes (PDA) result from the conformational changes that directly alter the electronic structure of the π-conjugated backbone. In this work, we studied the ability of electrostatic interactions to modulate the chromatic phases afforded by charged, amphiphilic peptide-PDA nanostructures and their coassembly under pH-neutral, aqueous environments. Two oppositely charged, diacetylene-bearing peptide sequences were used as model monomers in this study. Based on solid-state nuclear magnetic resonance (ssNMR) analyses, the positively charged, trilysine-containing sequence (K3GV) forms a β-sheet-like assembly with higher structural order than the disordered, negatively charged triaspartic acid-containing sequence (D3GV). The equimolar mixture of the two charged monomers results in a more ordered coassembly structure than D3GV, as evidenced by ssNMR, which still fulfills the geometric requirement to topochemically polymerize diacetylenes. At various temperatures tested, single component assemblies and coassembled peptide-PDAs all demonstrate a thermochromic response, with the hysteresis of the blue phase (planar conformation) spectral features being much larger than that of the red phase (twisted conformation). Resonance Raman spectroscopy of thin films revealed that the coexistence of blue and red phase chains is more stabilized in coassemblies that have electrostatic complementarity compared to their single component counterparts. Both the characterization of the solution and film samples at 20–80°C suggest that the red phase PDA with twisted conformation is more favored by the charge-coassembled material. In summary, this work shows the important role of the attractive electrostatic interactions arising from the peptidic side chains in controlling the adaptive properties of amphiphilic PDAs. Furthermore, this work sheds light on the nature of structural changes responsible for the thermally responsive chromatic transitions of a biomolecule-functionalized polymeric material and how this process can be directed by design-tunable electrostatic interactions.

2023-04-17

chemRxiv

Materials Science; Polymer Science; Materials Chemistry

CC BY NC ND 4.0

Three-Dimensional sp2 Carbon-Linked Covalent Organic Frameworks for Bioresponsive Fluorescence Imaging

10.26434/chemrxiv.14189060.v1

N.A.

N.A.

Li Liao; Zerong Zhang; Xinyu Guan; Hui Li; Yaozu Liu; Minghao Zhang; Liangkui Zhu; Bin Tang; Valentin Valtchev; Yushan Yan; Shilun Qiu; Xiangdong Yao; Qianrong Fang

<a>Three-dimensional (3D) covalent organic frameworks (COFs) are crystalline porous polymers with potential in numerous high-tech applications, but the linkages involved in their synthesis are still rather limited. Herein we report the first </a><a>case of 3D sp² carbon-linked COFs</a> fabricated by the formation reaction of C=C bonds and their application in bioresponsive fluorescence imaging. These new COFs, namely JUC-580 and JUC-581, showed high stability and excellent light-emitting properties in solid state and dispersed in various solvents. <a>Furthermore, we investigated </a>the potential application of JUC-581 for a drug carrier combined with bioresponsive fluorescence imaging. The results indicated that 3D sp² carbon-linked COFs are not only potential drug-loaded and sustained release materials but also promising cell fluorescent stains. This study expands the structural categories of 3D COFs based on different linkages, and promotes their prospective applications for biomedicine and fluorescent materials.

2021-03-10

chemRxiv

Materials Chemistry

CC BY NC ND 4.0

A Single and Two-Stage, Closed-Tube, Molecular Test for the 2019 Novel Coronavirus (COVID-19) at Home, Clinic, and Points of Entry

10.26434/chemrxiv.11860137.v1

10.1021/acs.analchem.1c03016

https://doi.org/10.1021/acs.analchem.1c03016

Mohamed El-Tholoth; Haim H. Bau; Jinzhao Song

<p>The 2019 novel coronavirus (COVID-19) is a newly emerged strain that has never been found in humans before. At present, the laboratory-based reverse transcription-polymerase chain reaction (RT-PCR) is the main method to confirm COVID-19 infection. The intensification of the COVID-19 epidemic overwhelms limited clinical resources in particular, but not only, in developing countries, resulting in many patients not being tested for the infection and in large queues of potentially infected individuals waiting to be tested while providing a breeding ground for the disease. We describe here a rapid, highly sensitive, point-of-care, molecular test amenable for use at home, in the clinic, and at points of entry by minimally trained individuals and with minimal instrumentation. Our test is based on loop mediated isothermal amplification (COVID-19 LAMP) and for higher sensitivity on nested nucleic acid, two stage isothermal amplification (COVID-19 Penn-RAMP). Both tests can be carried out in closed tubes with either fluorescence or colorimetric (e.g., leuco crystal violet LCV) detection. COVID-19 LAMP performs on par with COVID-19 RT-PCR. COVID-19 RAMP has 10 fold better sensitivity than COVID-19 LAMP and COVID-19 RT-PCR when testing purified targets and 100 times better sensitivity than COVID-19 LAMP and COVID-19 RT-PCR when testing rapidly prepared sample mimics. Due to fortunate scarcity of COVID-19 infections in the USA, we were not able to test our assays and methods with patient samples. We hope that such tests will be carried out by colleagues in impacted countries. Our Closed-Tube Penn-RAMP has the potential to significantly reduce false negatives while being amenable to use with minimal instrumentation and training. </p>

2020-02-19

chemRxiv

Biochemical Analysis

CC BY NC ND 4.0

Metal Ions Turn on a Stereoselective Nonenzymatic Reduction of Keto Acids by the Coenzyme NADH

10.26434/chemrxiv-2023-jdhxk

N.A.

N.A.

Robert Mayer; Joseph Moran

The relationship between genetic molecules and metabolism is one of the longest standing problems for the origin of life. A central molecule within early metabolism is the coenzyme nicotinamide adenine dinucleotide (NAD(H)), a modified ribonucleotide and reducing agent. Yet, without enzymes, NADH does not reduce carbonyl compounds, its primary metabolic substrates, leading to an apparent paradox regarding its role in the evolution of metabolism. We now report that abundant metal ions turn on a nonenzymatic, stereoselective, and potentially primordial reduction reaction of keto acids by NADH. Kinetic, mechanistic, and computational studies elucidate the reaction mechanism and the way stereochemistry is transferred. Complexes of metals with RNA-derived coenzymes could have mediated the transition from inorganic to organic reducing agents and the propagation of chirality in early metabolism.

2023-10-10

chemRxiv

Biological and Medicinal Chemistry; Organic Chemistry; Bioorganic Chemistry; Stereochemistry; Biochemistry

CC BY NC ND 4.0

Ortho-substituted aryldiazonium design for defect configuration-controlled photoluminescent functionalization of chiral single-walled carbon nanotubes

10.26434/chemrxiv-2022-3hspc

N.A.

N.A.

Boda Yu; Sadahito Naka; Haruka Aoki; Koichiro Kato; Tsuyohiko Fujigaya; Tomohiro Shiraki

Defect functionalization using chemical modification of single-walled carbon nanotubes (SWCNTs) is promising, especially for near-infrared photoluminescence (NIR PL) over 1000 nm in advanced telecom and bio/medical applications. The covalent attachment of modifier molecules is utilized to create sp3 carbon defects in the sp2 carbon lattice for bright, red-shifted PL generation. The positional difference in proximal sp3 carbons, known as the defect binding configuration, can dominate NIR PL properties; however, the defect arrangement chemistry remains unelucidated. We developed aryldiazonium modifiers with -conjugated ortho-substituents (phenyl and acetylene groups) to introduce molecular interactions with nanotube sidewalls into the chemical reaction process for defect formation. Single defect emissions of ~1230–1270 nm selectively appeared in the functionalized chiral SWCNTs, showing a different binding configuration from those observed for typical aryl- or alkyl- functionalized chiral tubes emitting approximately 1150-nm PL. Moreover, the acetylene-based substituent design allows PL brightening and subsequent molecular modification using click chemistry.

2022-05-09

chemRxiv

Nanoscience; Nanostructured Materials - Nanoscience

CC BY NC ND 4.0

A Biopolymer Based 3D Printable Hydrogel for Toxic Metal Adsorption from Water

10.26434/chemrxiv.7137680.v1

10.1002/pi.5787

https://doi.org/10.1002/pi.5787

Gayan A. Appuhamillage; Danielle Berry; Candace Benjamin; Michael A. Luzuriaga; John C. Reagan; Jeremiah J. Gassensmith; Ron Smaldone

<div><div><div><p>Herein, we describe a 3D<br />printable hydrogel that is capable of<br />removing toxic metal pollutants from water<br />solutions. To achieve this, shear-thinning<br />hydrogels were prepared by blending<br />chitosan with diacrylated Pluronic F-127 (F127-DA) which allows for UV curing after printing. Several hydrogel compositions were tested for their ability to absorb common metal pollutants such as lead, copper, cadmium and mercury, as well as for their printability. These hydrogels displayed excellent metal adsorption with some examples capable of up to 95% metal removal within 30 min. We show that 3D printed hydrogel structures that would be difficult to fabricate by conventional manufacturing methods, can adsorb metal ions significantly faster than solid objects, owing to their higher accessible surface areas.</p></div></div></div>

2018-09-28

chemRxiv

Composites; Materials Processing; Biopolymers; Hydrology and Water Chemistry

CC BY NC ND 4.0

Cationic Biphotonic Lanthanide Luminescent Bioprobes Based on Functionalized Cross-Bridged Cyclam Macrocycles

10.26434/chemrxiv.11591835.v1

10.1002/cphc.202000085

https://doi.org/10.1002/cphc.202000085

Jonathan Mendy; Amandine Roux; Jean-Christophe Mulatier; Alain Duperray; Alexei Grichine; Yannick Guyot; Sophie Brasselet; François Riobé; Chantal Andraud; Boris Le Guennic; Véronique Patinec; Raphael Tripier; Maryline Beyler; Olivier MAURY; Anh Thy Bui; Damien Curton

<p>Cationic lanthanide complexes are generally able to spontaneously internalize into living cells. Following our previous works based on diMe-cyclen framework, a second generation of cationic water-soluble lanthanide complexes based on a constrained cross-bridged cyclam macrocycle functionalized with donor-p-conjugated picolinate antennas has been prepared with europium(III) and ytterbium(III). Their spectroscopic properties were thoroughly investigated in various solvents and rationalized with the help of DFT calculations. A significant improvement is observed in the case of the Eu³⁺ complex, while the Yb³⁺ analogous conserve an excellent brightness in aqueous solvent. Two-photon (2P) microscopy imaging experiments on living T24 human cancer cells confirmed the spontaneous internalization of the probes and images with good signal-to-noise have been obtained in the classical NIR-to-visible configuration with Eu³⁺ luminescent bioprobe and in the NIR-to-NIR with the Yb³⁺ one.</p>

2020-01-22

chemRxiv

Biophysical Chemistry; Spectroscopy (Physical Chem.)

CC BY NC ND 4.0

Facile collisional dissociation of N2 on a Si(111)-7x7 surface at room temperature

10.26434/chemrxiv-2022-rjcvc

N.A.

N.A.

Elie GEAGEA; Judicael JEANNOUTOT; Frank PALMINO; Nicolas BREAULT; Alain ROCHEFORT; Samar HAJJAR; Carmelo PIRRI; Christophe THOMAS; Frederic CHERIOUX

We demonstrate that the strong N2 bond can be efficiently dissociated at low pressure and ambient temperature on a Si(111)-7x7 surface. The reaction was experimentally investigated by scanning tunnelling microscopy and X-ray photoemission spectroscopy. Experimental and density functional theory results suggest that relatively low thermal energy collision of N2 with the surface can facilitate electron transfer from the Si(111)-7x7 surface to the p*-antibonding orbitals of N2 that significantly weaken the N2 bond. This facile N2 triple bond dissociation on the surface leads to the formation of a Si3N interface.

2022-04-04

chemRxiv

Nanoscience; Nanostructured Materials - Nanoscience

CC BY 4.0

Deep Learning Models for the Estimation of Free Energy of Permeation of Small Molecules across Lipid Membranes

10.26434/chemrxiv-2022-h2rw7

N.A.

N.A.

Prantar Dutta; Deepak Jain; Rakesh Gupta; Beena Rai

Calculating the free energy of drug permeation across membranes carries great importance in pharmaceutical and related applications. Traditional methods, including experiments and molecular simulations, are expensive and time-consuming, and existing statistical methods suffer from low accuracy. In this work, we propose a hybrid approach that combines molecular dynamics simulations and deep learning techniques to predict the free energy of permeation of small drug-like molecules across lipid membranes with high accuracy and at a fraction of the computational cost of advanced sampling methods like umbrella sampling. We have performed several molecular dynamics simulations of molecules in water and lipid bilayers to obtain multidimensional time-series data of features. Deep learning architectures based on Long Short-Term Memory networks, attention mechanisms, and dense layers are built to estimate free energy from the time series data. The prediction errors for the test set and an external validation set are much lower than that of existing data-driven approaches, with R2 of the best model around 0.99 and 0.82 for the two cases. Our approach reduces the time required for free energy calculations by an order of magnitude. This work presents an attractive option for high-throughput virtual screening of molecules based on their membrane permeabilities, demonstrates the applicability of language processing techniques in biochemical problems, and suggests a novel way of integrating physics with statistical learning to great success

2022-03-25

chemRxiv

Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Machine Learning; Artificial Intelligence

CC BY NC ND 4.0

Discovery of red-shifting mutations in firefly luciferase using high-throughput biochemistry

10.26434/chemrxiv-2023-px3t6-v2

10.1021/acs.biochem.3c00708

https://doi.org/10.1021/acs.biochem.3c00708

Clair M. Colee; Nicole M. Oberlag; Marcell Simon; Owen S. Chapman; Lyndsey C. Flanagan; Edison S. Reid-McLaughlin; Jordan A. Gewing-Mullins; Synaida Maiche; Devi F. Patel; Andre R.O. Cavalcanti; Aaron M. Leconte

The Photinus pyralis luciferase (FLuc) has proven a valuable tool for bioluminescence imaging, but much of the light emitted from the native enzyme is absorbed by endogenous biomolecules. Thus, luciferases displaying red-shifted emission enable higher resolution during deep-tissue imaging. A robust model of how protein structure determines emission color would greatly aid the engineering of red-shifted mutants, but no consensus has been reached to date. In this work, we apply deep mutational scanning to systematically assess twenty functionally important amino acid positions on FLuc for red-shifting mutations, predicting that an unbiased approach would enable novel contributions to this debate. We report dozens of red-shifting mutations as a result, a large majority of which have not been previously identified. Further characterization revealed that mutations L286V and T352M, in particular, cause pure red emission with much of the light being >600 nm. The red-shifting mutations identified by this high-throughput approach provide strong biochemical evidence for the multiple-emitter mechanism of color determination, and point to the importance of a water network in the enzyme binding pocket for altering the emitter ratio. This work provides a broadly applicable mutational data set tying FLuc structure to emission color that informs our mechanistic understanding of emission color determination and should facilitate the further engineering of improved probes for deep-tissue imaging.

2023-12-11

chemRxiv

Biological and Medicinal Chemistry; Biochemistry; Bioengineering and Biotechnology; Chemical Biology

CC BY NC ND 4.0

MOLECULAR DOCKING STUDY TO IDENTIFY POTENTIAL INHIBITOR OF COVID-19 MAIN PROTEASE ENZYME: AN IN-SILICO APPROACH

10.26434/chemrxiv.12170904.v1

N.A.

N.A.

Anurag Agrawal; Nem Kumar Jain; Neeraj Kumar; Giriraj T Kulkarni

This study belongs to identification of suitable COVID-19 inhibitors<br /><div><br /></div><div>Coronavirus became pandemic very soon and is a potential threat to human lives across the globe. No approved drug is currently available therefore an urgent need has been developed for any antiviral therapy for COVID-19. For the molecular docking study, ten herbal molecules have been included in the current study. The three-dimensional chemical structures of molecules were prepared through ChemSketch 2015 freeware. Molecular docking study was performed using AutoDock 4.2 simulator and Discovery studio 4.5 was employed to predict the active site of target enzyme. Result indicated that all-natural molecules found in the active site of enzyme after molecular docking. Oxyacanthine and Hypericin (-10.990 and -9.05 and kcal/mol respectively) have shown good binding efficacy among others but Oxyacanthine was the only natural product which made some of necessary interactions with residues in the enzyme require for target inhibition. Therefore Oxyacanthine may be considered to be potential inhibitor of main protease enzyme of virus but need to be explored for further drug development process. <br /></div>

2020-04-23

chemRxiv

Bioinformatics and Computational Biology

CC BY NC ND 4.0

Ring Mechanism of Fast Na+Ion Transport in Na2LiFeTeO6: Insight from MolecularDynamics Simulation

10.26434/chemrxiv-2021-s79hz

N.A.

N.A.

Kartik Sau; Tamio Ikeshoji

Honeycomb layered oxides have attracted recent attention because of their rich crystal chemistry. However, the atomistic mechanisms of cationic transport in these structures remain vastly unexplored. Herein, we perform an extensive, systematic molecular dynamics study on Na2LiFeTeO6 using combined force-field and first-principles-based molecular dynamics simulations. We use are fined set of inter-atomic potential parameters of a previously reported potential model that represents various structural and transport properties of this recently reported promising material for all-solid-state battery applications. The present simulation study elucidates the roles of octahedral ordering and entropic contributions in Na+-ion distribution in the ab-plane. Our theoretical simulation also develops a ring-like atomistic diffusion mechanism and relevant atomistic energy barriers that help to understand the origin of fast ion conduction in honeycomb layered oxides.

2021-11-16

chemRxiv

Materials Science; Energy; Energy Storage; Materials Chemistry

CC BY 4.0

Bonding character, electron delocalization, and aromaticity of cyclo[18]carbon (C18) precursors, C18-(CO)n (n = 6, 4, and 2): Focusing on the effect of -CO groups

10.26434/chemrxiv-2021-01pw7-v2

10.1002/chem.202103815

https://dx.doi.org/10.1002/chem.202103815

Xia Wang; Zeyu Liu; Xiufen Yan; Tian Lu; Weiwei Xiong

Although the unique cyclo[18]carbon (C18) realized by recent experiments has been greatly concerned, it has so far remained elusive. In contrast, its precursors C18-(CO)n (n = 6, 4, and 2), which can be separated stably, are of more practical significance. In this paper, the bonding character, electron delocalization, and aromaticity of the C18-(CO)n (n = 6, 4, and 2) with out-of-plane and in-plane dual π systems (πout and πin) perpendicular to each other are studied by combining quantum chemical calculations and wavefunction analyses. These cyclocarbon oxides exhibit alternating long and short C-C bonds and extensive electron delocalization, and a significant diatropic induced ring current under the action of external magnetic field is therefore observed, which reveals the aromatic characteristic in the molecules. The global electron delocalization and significant influence of the number of intramolecular carbonyl (-CO) on the two sets of π conjugated systems have been focused on, and the essential reason for the distinct difference in the overall aromaticity of the molecules was also clarified. It seems that the substituent -CO groups hinders the electron delocalization of the πin system but has relatively small effect on the πout system, resulting in the molecules with less -CO group showing greater aromaticity.

2021-08-10

chemRxiv

Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Theory - Computational; Physical and Chemical Properties; Materials Chemistry

CC BY 4.0

Sign Inversion in Photopharmacology: Incorporation of Cyclic Azobenzenes in Photoswitchable Potassium Channel Blockers and Openers

10.26434/chemrxiv.8014580.v1

10.1002/anie.201905790

https://doi.org/10.1002/anie.201905790

Julie Trads; Katharina Hüll; Bryan Matsuura; Laura Laprell; Timm Fehrentz; Nicole Görldt; Krystian A. Kozek; David Weaver; Nikolaj Klöcker; David Barber; Dirk Trauner

Photopharmacology relies on ligands that change their pharmacodynamics upon photoisomerization. Many of these ligands are azobenzenes that are thermodynamically more stable in their elongated <i>trans</i>configuration, which predominates in the dark. Often, they are biologically active in this form and lose activity upon irradiation and photoisomerization to their <i>cis</i>-isomer. Recently, cyclic azobenzenes, so-called diazocines, have emerged. They are thermodynamically more stable in their bent <i>cis</i>­‑form than in their elongated <i>trans</i>-form. Incorporation of these switches into a variety of photopharmaceuticals could convert dark-active ligands into dark-inactive ligands, which is preferred in most biological applications. This “pharmacological sign-inversion” is demonstrated for a photochromic blocker of voltage-gated potassium channels, termed <b>CAL</b>, and a photochromic opener of G-protein-coupled inwardly rectifying potassium (GIRK) channels, termed <b>CLOGO</b>.<br />

2019-04-19

chemRxiv

Bioorganic Chemistry; Photochemistry (Org.); Chemical Biology

CC BY NC ND 4.0

A Generalized Kirkwood Implicit Solvent for the Polarizable AMOEBA Protein Model

10.26434/chemrxiv-2023-cbb38-v2

10.1063/5.0158914

https://doi.org/10.1063/5.0158914

Rae Corrigan; Andrew Thiel; Jack Lynn; Thomas Casavant; Pengyu Ren; Jay Ponder; Michael Schnieders

Computational simulation of biomolecules can provide important insights into protein design, protein-ligand binding calculations, and ab initio biomolecular folding, among other applications. Accurate treatment of the solvent environment is essential in such applications, but use of explicit solvent can add considerable cost. Implicit treatment of solvent effects using a dielectric continuum model is an attractive alternative to explicit solvation since it is able to describe solvation effects without the inclusion of solvent degrees of freedom. Previously, we described the development and parameterization of implicit solvent models for small molecules. Here, we extend the parameterization of the generalized Kirkwood (GK) implicit solvent model for use with biomolecules described by the AMOEBA force field via the addition of interstitial space corrections to account for biomolecular geometry. These corrections include updating pairwise descreening scale factors to be element-specific and adding neck and tanh corrections to the calculation of effective radii. We then apply the AMOEBA/GK implicit solvent to a set of nine proteins and achieve an average RMSD of 2.1 Å across 500 ns simulations. Overall, the continued development of implicit solvent models will help to facilitate simulation of arbitrary biomolecules on biologically relevant timescales.

2023-05-26

chemRxiv

Theoretical and Computational Chemistry; Physical Chemistry; Biological and Medicinal Chemistry; Computational Chemistry and Modeling; Statistical Mechanics; Thermodynamics (Physical Chem.)

CC BY NC ND 4.0

Calibrate Ligand-ligand Interaction on Nanocrystals via the Dynamic Volume of Chain Segments

10.26434/chemrxiv-2022-f3lks-v3

N.A.

N.A.

Weicheng Cao; Zhenfeng Pang; Xiaoqi Zhou; Zhenming Cao; Jiachen Li; Qi Wang; Xiaogang Peng; Xueqian Kong

The intermolecular ligand-ligand interaction is crucial for the surface chemistry, solution properties, and self-assembly processes of colloidal nanocrystals (NCs). The studies on the ligand-ligand interaction are hampered by the disordered and dynamic nature of the surface, the low electron contrast of organic moieties, and the non-characteristic weak intermolecular forces. Solid-state nuclear magnetic resonance (NMR) can provide site-specific information on organic ligands and especially the motional behavior of chain segments. In this work, we develop an advanced solid-state NMR measurement and modelling strategy to quantify the “dynamic volume” of chain segments. The dynamic volume depicts the accessible space of a chain segment under the confinement of neighboring molecules, and is inversely proportional to the intermolecular interaction energy. The ligand-ligand interaction energies have been obtained for NCs with alkanoate ligands of different lengths. We show that the calculated ligand-ligand interaction energy determines solution dispersity and the melting transitions of NCs. This dynamic volume concept can be extended beyond experimental NMR measurements and offer semi-empirical predictions of the interaction energies for arbitrary selections of alkanoate ligands. Our study not only advances the quantitative understanding of ligand-ligand interaction on NCs but also establishes novel tactics to calibrate weak intermolecular interactions.

2022-06-14

chemRxiv

Materials Science; Nanoscience; Nanostructured Materials - Materials; Nanostructured Materials - Nanoscience; Materials Chemistry

CC BY 4.0

High Energy Density Picoliter Zn-Air Batteries for Colloidal Robots and State Machines

10.26434/chemrxiv-2022-20jjz-v2

N.A.

N.A.

Ge Zhang; Jingfan Yang; David Gonzalez-Medrano; Marc Z. Miskin; Sungyun Yang; Volodymyr B. Koman; Yuwen Zeng; Sylvia Xin Li; Matthias Kuehne; Albert Tianxiang Liu; Allan M. Brooks; Michael S. Strano

The recent interest in microscopic autonomous systems, including microrobots, colloidal state machines and smart dust has created a need for microscale energy storage and harvesting. However, macroscopic materials for energy storage have noted incompatibilities with micro-fabrication techniques, creating significant challenges to realizing microscale energy systems. Herein, we photolithographically pattern a microscale Zn/Pt/SU-8 system to generate the highest energy density microbattery at the picoliter (10^-12 L) scale. The device scavenges ambient or solution dissolved oxygen for a Zn oxidation reaction, achieving an energy density ranging from 760 to 1070 Wh L-1 at scales below 100 μm lateral and 2 μm thickness in size. More than 10,000 devices per wafer can be released into solution as functional colloids with energy stored onboard. Within a volume of only 2 pL each, these microbatteries can deliver open circuit voltages of 1.16 V with total energies ranging from 5.5 ± 0.3 to 7.7 ± 1.0 μJ and a maximum power near 2.7 nW. We demonstrate that such systems can reliably power a micron-sized memristor circuit, providing access to non-volatile memory. We also cycle power to drive the reversible bending of microscale bimorph actuators at 0.05 Hz for mechanical functions of colloidal robots. Additional capabilities such as powering two distinct nanosensor types and a clock circuit are also demonstrated. The high energy density, low volume and simple configuration promise the mass fabrication and adoption of such picoliter Zn-air batteries for micron-scale, colloidal robotics with autonomous functions.

2022-08-11

chemRxiv

Nanoscience; Energy; Energy Storage

CC BY NC 4.0

A Dual-Fluorophore Sensor Approach for Ratiometric Fluorescence Imaging of Potassium in Living Cells

10.26434/chemrxiv.12649730.v1

N.A.

N.A.

Zeming Wang; Tyler C. Detomasi; Christopher Chang

Potassium is the most abundant intracellular metal in the body, playing vital roles in regulating intracellular fluid volume, nutrient transport, and cell-to-cell communication through nerve and muscle contraction. On the other hand, aberrant alterations in K⁺ homeostasis contribute to a diverse array of diseases spanning cardiovascular and neurological disorders to diabetes to kidney disease to cancer. Owing to the large differences in intracellular versus extracellular K⁺ concentrations ([K⁺]_intra = 150 mM, [K⁺]_extra = 3-5 mM), an unmet need for studies of K⁺ physiology and pathology remains a relative dearth of methods to reliably measure dynamic changes in intracellular K⁺ in biological specimens that meet the dual challenges of low affinity and high selectivity for K⁺, particularly over Na⁺, as currently available fluorescent K⁺ sensors are largely optimized with high-affinity receptors that are more amenable for extracellular K⁺ detection. We report the design, synthesis, and biological evaluation of Ratiometric Potassium Sensor 1 (<b>RPS-1</b>), a dual-fluorophore sensor that enables ratiometric fluorescence imaging of intracellular potassium in living systems. <b>RPS-1</b> links a potassium-responsive fluorescent sensor fragment (<b>PS525</b>) with a low-affinity, high-selectivity crown ether receptor for K⁺ to a potassium-insensitive reference fluorophore (<b>Coumarin 343</b>) as an internal calibration standard through ester bonds. Upon intracellular delivery, esterase-directed cleavage splits these two dyes into separate fragments to enable ratiometric detection of K⁺. <b>RPS-1</b> responds to K⁺ in aqueous buffer with high selectivity over competing metal ions and is sensitive to potassium ions at steady-state intracellular levels and can respond to decreases or increases from that basal set point. Moreover, <b>RPS-1</b> was applied for comparative screening of K⁺ pools across a panel of different cancer cell lines, revealing elevations in basal intracellular K⁺ in metastatic breast cancer cell lines vs normal breast cells. This work provides a unique chemical tool for the study of intracellular potassium dynamics and a starting point for the design of other ratiometric fluorescent sensors based on two-fluorophore approaches that do not rely on FRET or related energy transfer designs.

2020-07-15

chemRxiv

Organic Synthesis and Reactions; Analytical Chemistry - General; Imaging; Chemical Biology

CC BY NC ND 4.0

Rh2(II)-Catalyzed Intermolecular N-Aryl Aziridination of Olefins using Nonactivated N-Atom Precursors

10.26434/chemrxiv.14622462.v1

N.A.

N.A.

Wrickban Mazumdar; Tianning Deng; Yuki Yoshinaga; Pooja B. Patel; Dana Malo; Tala Malo; Donald Wink; Tom Driver

The development of the first intermolecular Rh₂(II)-catalyzed aziridination of di-, tri-, or tetraubstituted olefins using aryl- or heteroaryl amines as nonactivated N-atom precursors and an iodine(III) reagent as the stoichiometric oxidant is reported. The Rh₂(II)-catalyzed N-atom transfer to the olefin is stereospecific, chemo- and diastereoselective to produce the <i>N</i>-aryl aziridine as the only amination product.

2021-05-24

chemRxiv

Organic Synthesis and Reactions

CC BY NC ND 4.0

Transferable diversity – a data-driven representation of chemical space

10.26434/chemrxiv-2023-5075x-v3

N.A.

N.A.

Tim Gould; Bun Chang; Stephen Dale; Stefan Vuckovic

Transferability, especially in the context of model generalization, is a paradigm of all scientific disciplines. However, the rapid advancement of machine learned model development threatens this paradigm, as it can be difficult to understand how transferability is embedded (or missed) in complex models. While transferability in general chemistry machine learning should benefit from diverse training data, a rigorous understanding of transferability together with its interplay with chemical representation remains an open problem. We introduce a transferability framework and apply it to a controllable data-driven model for developing density functional approximations (DFAs), an indispensable tool in everyday chemistry research. We reveal that human intuition introduces chemical biases that can hamper the transferability of data-driven DFAs, and we identify strategies for their elimination. We then show that uncritical use of large training sets can actually hinder the transferability of DFAs, in contradiction to typical “more is more” expectations. Finally, our transferability framework yields transferable diversity, a cornerstone principle for data curation for developing general-purpose machine learning models in chemistry

2024-04-29

chemRxiv

Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational

CC BY NC ND 4.0

The internal structure of the velvet worm projectile slime: A small-angle scattering study

10.26434/chemrxiv-2022-qggs2

N.A.

N.A.

Alexander Baer; Ingo Hoffmann; Najet Mahmoudi; Alexandre Poulhazan; Matthew J. Harrington; Georg Mayer; Stephan Schmidt; Emanuel Schneck

Velvet worms capture prey and defend themselves by ejecting an adhesive slime which has been established as a model system for recyclable complex liquids. Triggered by mechanical agitation, the sticky fluid rapidly transitions into solid fibers. The assembly of slime proteins into stiff polymers is fully reversible and recyclable enabling the recovery of the soluble precursors. In order to understand the rapid and reversible mechanoresponsive behavior of this material, here, we study the nanostructural organization of slime components using small-angle scattering with neutrons and x-rays under physiological native conditions, after drying and re-hydration, and mechanical agitation. The scattering intensities are successfully described with a three-component model accounting for proteins of two dominant molecular weight fractions and for protein-based nanoglobules with a radius of ~40-45 nm, which is in line with the literature. However, in contrast to the previous assumption that high molecular weight (HMW) proteins -- the presumed building blocks of the fiber core -- are contained in the nanoglobules, we find that the majority of slime proteins exist as free proteins in solution, including the HMW fiber core precursors. Only less than 10 % of the slime proteins are contained in the nanoglobules, necessitating a reassessment of the previously proposed function of nanoglobules in fiber formation. Exploiting distinct differences in the x-ray and neutron scattering contrast of slime re-hydrated with light and heavy water (D2O) indicates that the majority of lipids available in the slime are contained in the nanoglobules, where they are homogeneously distributed. Surprisingly, mechanical agitation of slime in a completely filled container causes gelification; however, this neither leads to fiber formation nor alters the bulk structure of the slime significantly, suggesting that interfacial phenomena and directional shearing are required for the formation of stiff fibers in velvet worm slime.

2022-11-07

chemRxiv

Physical Chemistry; Materials Science; Nanoscience; Biological Materials; Nanostructured Materials - Nanoscience; Biophysical Chemistry

CC BY NC ND 4.0

Efficiency and suitability when exploring the conformational space of phase transfer catalysts

10.26434/chemrxiv-2022-nrmf0-v2

N.A.

N.A.

Iñigo Iribarren; Cristina Trujillo

In this study, a complete exploration of the conformational space of phase transfer catalysts by means of computational methods benchmarking is presented. For this particular research work, only the most significant and relevant conformational analysis approaches have been chosen to characterise the main Cinchona alkaloid-based phase transfer catalysts. This particular guiding study aims to rigorously compare the performance of different conformational methods, determining the strengths of each method and providing recommendations regarding suitable and efficient choices of methods for analysis.

2022-07-27

chemRxiv

Theoretical and Computational Chemistry; Organic Chemistry; Catalysis; Computational Chemistry and Modeling; Chemoinformatics - Computational Chemistry; Organocatalysis

CC BY NC ND 4.0

Water in Hydration Shell of an Azide Ion: Structure and Dynamics of Solute-water Hydrogen Bonds and Vibrational Spectral Diffusion from First Principles Simulations At Supercritical Condition

10.26434/chemrxiv.9808391.v1

N.A.

N.A.

Anwesa Karmakar

<p>A series of ab initio MD simulations has been carried out for aqueous azide (N₃^-) ion solutions at three different densities and at supercritical condition (673 K) using Car-Parrinello molecular dynamics simulation. The time dependent trajectories at three different densities have been used to analyze the hydrogen bond dynamics, residence dynamics, dangling OD bond dynamics and spectral diffusion and underlying connections between them. The time dependent frequency of both the OD and NN stretching mode has been calculated using the time series analysis of the wavelet method. The population correlation function approach has been used to compute the hydrogen bond dynamics, dangling OD bond and residence dynamics of the Sc-water both inside and outside the solvation shell of the ion. The faster hydrogen bond dynamics has been observed in the vicinity of the azide ion, however the calculated OD stretching frequency is found to show red shift in the vicinity of the azide ion indicative to the formation of stronger ion-water hydrogen bond even at the supercritical condition. The overall hydrogen bond dynamics at the supercritical condition was faster with respect to the aqueous azide ion solutions at the ambient condition.</p>

2019-09-13

chemRxiv

Theory - Computational

CC BY NC ND 4.0

Molecular Surface Quantification of Multi-Functionalized Gold Nanoparticles Using UV-Vis Spectroscopy Deconvolution

10.26434/chemrxiv-2022-8rdkt-v2

N.A.

N.A.

Jordan Potts; Akhil Jain; David Brian Amabilino; Frankie Rawson; Lluïsa Pérez-García

ABSTRACT: Multi-functional gold nanoparticles (AuNPs) are of great interest, owing to their vast potential for use in many areas including sensing, imaging, delivery, and medicine. A key factor in determining the biological activity of multi-functional AuNPs is the quantification of surface conjugated molecules. There has been a lack of accurate methods to determine this for multi-functionalized AuNPs. In this work, we address this limitation by using a new method based on deconvolution and Levenberg-Marquardt algorithm fitting of UV-Vis spectrum to calculate the precise concentration and number of cytochrome C (Cyt C) and Zinc Porphyrin (Zn Porph) bound to each multi-functional AuNP. Dynamic light scattering (DLS), Zeta potential measurements, and Transmission Electron Microscopy (TEM) were used to confirm the functionalization of AuNPs with Cyt C and Zn Porph. Despite the overlapping absorption bands of Cyt C and Zn Porph this method was able to reveal the accurate concentration and number of Cyt C and Zn Porph molecules attached per AuNP. Furthermore, using this method we were able to identify unconjugated molecules, suggesting the need for further purification of the sample. This guide provides a simple and effective method to quickly quantify molecules bound to AuNPs, giving users accurate and valuable information, especially for applications in drug delivery and biosensors.

2022-09-26

chemRxiv

Analytical Chemistry; Analytical Chemistry - General

CC BY 4.0

Predicting stable lithium iron oxysulphides for battery cathodes

10.26434/chemrxiv-2021-fbffd-v2

N.A.

N.A.

Bonan Zhu; David O. Scanlon

Cathode materials that have high specific energies and low manufacturing costs are vital for the scaling up of lithium-ion batteries (LIBs) as energy storage solutions. We perform an extensive computational search for iron-based oxysulphides using ab initio random structure searching (AIRSS). Several new oxysulphide phases have been discovered which are predicted to be less than 50 meV/atom from the convex hull. Among the predicted phases, two anti-Ruddlesden-Popper structured materials Li2Fe2S2O and Li4Fe3S3O2 have been found to be attractive as they have high theoretical capacities. With band gaps as low as about 2.0 eV, they are expected to exhibit good electronic conductivities. Climbing-image NEB calculations show that the Li-ion transport in these materials has low activation barriers between 0.3 eV and 0.5 eV. The richness of new materials in the Li-Fe-S-O phase field illustrate the great opportunity in these mixed anion systems for energy storage applications and beyond.

2021-06-22

chemRxiv

Theoretical and Computational Chemistry; Materials Science; Energy; Computational Chemistry and Modeling; Theory - Computational; Energy Storage

CC BY 4.0

Anti-Selective Cyclopropanation of Non-Conjugated Alkenes with Diverse Pronucleophiles via Directed Nucleopalladation

10.26434/chemrxiv-2023-b1bdb

N.A.

N.A.

Hui-Qi Ni; Warabhorn Rodphon; Nicholas Scherschel; Shouliang Yang; Fen Wang; Indrawan McAlpine; Davin Piercey; Keary Engle

A facile approach to densely functionalized cyclopropanes is described. The reaction proceeds under mild conditions via the directed nucleopalladation of non-conjugated alkenes with readily available pronucleophiles and gives excellent yields and good anti-selectivity using I2 and TBHP as oxidants. Pronucleophiles bearing a diverse collection electron-withdrawing groups, including–CN, –CO2R, –COR, –SO2Ph, -CONHR and –NO2, are well tolerated. Internal alkenes, which are generally challenging substrates in other cyclopropanation methods, provide excellent yields and good diastereoselectivity in this methodology, allowing for controlled access to cyclopropanes substituted at all three C-atoms.

2023-03-22

chemRxiv

Organic Chemistry; Catalysis; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Homogeneous Catalysis

CC BY NC ND 4.0

Effect of Ethanol Treatment on Lycopene Extraction yield

10.26434/chemrxiv.5924140.v1

N.A.

N.A.

Nam Kyong-il; KIM rak-chon; Kang chang-hyok; Lee song-nam; Ryom sok-hun

In order to extract lycopene more effectively, this experiment focused on the optimization of ethanol pretreatment method to study the effects of ethanol treatment on the extraction rate of lycopene and its antioxidant activity. The test results show that 2 times ethanol treatment is very effective for improving lycopene yield. The optimum conditions of ethanol treatment are temperature 50 ℃, treatment time 1 time 2h, 2 times 2h, solid to liquid ratio is 1:12. The lycopene yield can be reached 20mg / 100g above.

1970-01-01

chemRxiv

Natural Products; Food

CC BY NC ND 4.0

Quantum-Induced Symmetry-Breaking in the Deuterated Dihydroanthracenyl Radical

10.26434/chemrxiv.8123648.v1

10.1021/acs.jpca.9b04561

https://doi.org/10.1021/acs.jpca.9b04561

Olha Krechkivska; Callan Wilcox; Klaas Nauta; Scott Kable; Timothy Schmidt

The hydrogen-atom adduct with anthracene, 9-dihydroanthracenyl radical (C₁₄H₁₁), and its deuterated analogue, have been identified by laser spectroscopy coupled to time-of-flight mass spectrometry, supported by time-dependent density functional theory calculations. The electronic spectrum of 9-dihydroanthracenyl radical exhibits an origin band at 19115 cm^-1 and its ionization energy was determined to be 6.346(1) eV. The spectra reveal a low-frequency vibrational progression corresponding to a mode described by a butterfly-inversion. In the deuterated analogue, a zero-point-energy imbalance along this coordinate is found to lead to a doubling of the observed spectral lines in the progression. This is attributed to quantum-induced symmetry breaking as previously observed in isotopologues of CH₅⁺.

2019-05-15

chemRxiv

Space Chemistry; Theory - Computational; Quantum Mechanics; Spectroscopy (Physical Chem.)

CC BY NC ND 4.0

Multi-task ADME/PK Prediction at Industrial Scale: Leveraging Large and Diverse Experimental Datasets

10.26434/chemrxiv-2024-pf4w9

10.1002/minf.202400079

https://doi.org/10.1002/minf.202400079

Moritz Walter; Jens Markus Borghardt; Lina Humbeck; Miha Skalic

ADME (Absorption, Distribution, Metabolism, Excretion) properties are key parameters to judge whether a drug candidate exhibits a desired pharmacokinetic (PK) profile. In this study, we tested multi-task machine learning (ML) models to predict ADME and animal PK endpoints trained on in-house data generated at Boehringer Ingelheim. Models were evaluated both at the design stage of a compound (i.e., no experimental data of test compounds available) and at testing stage when a particular assay would be conducted (i.e., experimental data of earlier conducted assays may be available). Using realistic time-splits, we found a clear benefit in performance of multi-task graph-based neural network models over single-task models, which was even stronger when experimental data of earlier assays is available. In an attempt to explain the success of multi-task models, we found that especially endpoints with the largest numbers of data points (physicochemical endpoints, clearance in microsomes) are responsible for increased predictivity in more complex ADME and PK endpoints. In summary, our study provides insight into how data for multiple ADME/PK endpoints in a pharmaceutical company can be best leveraged to optimize predictivity of ML models.

2024-01-12

chemRxiv

Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems; Machine Learning; Chemoinformatics - Computational Chemistry

CC BY NC ND 4.0

Revolutionizing Diagnostic Frontiers: The Emergence of Graphene-Based Nanobiosensors

10.26434/chemrxiv-2024-36t1s

N.A.

N.A.

Fathima Shadin P

The integration of graphene into the realm of biosensing has marked a transformative era in diagnostic methodologies, particularly in the detection of health-related biomarkers. This review paper delves into the multifaceted applications of graphene and its derivatives in the development of advanced nanobiosensors, underscoring their role in revolutionizing clinical diagnostics. Graphene’s unique chemical structure and its exceptional electrical, optical, and mechanical properties have been pivotal in enhancing the performance of biosensors. These advancements are characterized by their high sensitivity, selectivity, rapid response, and low detection limits, coupled with long-term stability. The paper explores various fabrication methods and functionalization techniques of graphene-based materials, highlighting their successful application in detecting a wide array of chemical and biological molecules for disease diagnosis, pathogen identification, and biomarker analysis. In the context of point-of-care devices, the review emphasizes the growing popularity of graphene in oral bioelectronics, particularly for salivary biomarker detection. The ease of access to human saliva and its rich composition of analytes positions it as an ideal medium for non-invasive health monitoring. The review provides a comprehensive overview of the structural designs of graphene electronics, their performance in health monitoring applications, and the challenges and future directions in this field. Furthermore, the review assesses the suitability of graphene in creating wearable diagnostic and prognostic devices, considering its biocompatibility, ease of functionalization, and flexibility. The potential of graphene-based biosensors in early disease detection and real-time health monitoring is critically analyzed, offering insights into their current status toward commercialization and the challenges ahead. This paper aims to provide a holistic view of graphene’s impact on clinical diagnostics, envisioning a future where nanotechnology and biosensing converge to offer advanced healthcare solutions.

2024-08-09

chemRxiv

Nanoscience; Nanodevices; Nanostructured Materials - Nanoscience; Materials Chemistry

CC BY NC 4.0

Berkelium–Carbon Bonding in a Tetravalent Berkelocene

10.26434/chemrxiv-2024-h7njh

N.A.

N.A.

Dominic Russo; Alyssa Gaiser; Amy Price; Dumitru-Claudiu Sergentu; Jennifer Wacker; Nicholas Katzer; Appie Peterson; Jacob Branson; Xiaojuan Yu; Sheridon Kelly; Erik Ouellette; John Arnold; Jeffrey Long; Wayne Lukens; Simon Teat; Rebecca Abergel; Polly Arnold; Jochen Autschbach; Stefan Minasian

Interest in actinide–carbon bonds has persisted since actinide organometallics were first targeted for isotope separation during the Manhattan Project. Sandwich complexes with cyclooctatetraenide ligands have been used extensively to form tetravalent actinide compounds, “actinocenes,” from thorium through plutonium. These complexes have been pivotal in the development of electronic structure models used throughout inorganic chemistry. The isolation and structural characterization of transplutonium organometallics is extremely challenging due to limited isotope inventories, a scarcity of suitable laboratory infrastructure, and intrinsic difficulties with the anaerobic conditions required. Herein, we show that berkelium–carbon bonds can be stabilized in an organometallic “berkelocene” complex. Metal–ligand bonding involves the berkelium 5f orbitals in covalent overlap; however, charge transfer from the ligands is reduced to maximize contributions from the stable, half-filled 5f^7 configuration of tetravalent berkelium.

2024-07-17

chemRxiv

Physical Chemistry; Inorganic Chemistry; Organometallic Chemistry; Lanthanides and Actinides; Coordination Chemistry (Organomet.); Theory - Organometallic

CC BY NC ND 4.0

A computational study of APTES surface functionalization of diatom-like amorphous SiO2 surfaces for heavy metal adsorption

10.26434/chemrxiv.11473080.v1

10.1021/acs.langmuir.9b03755

https://doi.org/10.1021/acs.langmuir.9b03755

Jose Julio Gutierrez Moreno; Ke Pan; Yu Wang; Wenjin Li

The amorphous silica (SiO₂) shell on diatom frustules is a highly attractive biomaterial for removing pollutants from aquatic ecosystems. The surface activity of silica can be enhanced by modification with organosilanes. In this work, we present an atomic-level theoretical study based on Molecular Dynamics (MD) and dispersion-corrected Density Functional Theory (DFT-D3BJ) calculations on the surface stability and adsorption of heavy metal compounds on silane and APTES covered SiO₂ surfaces. Our simulations show that at low APTES coverage, molecular adsorption of Cd(OH)₂ and HgCl₂ is more favourable near the modifier, compared to As(OH)₃ that binds at the hydroxylated region on silica. At higher coverages, the metallic compounds are preferentially adsorbed by the terminating amino group on the surface, whereas the adsorption in the region between APTES and the oxide surface is also spontaneous. The adsorption is strongly driven by van der Waals interactions at the highly-covered surface, where the consideration of dispersion corrections reduces the modifier-adsorbate interatomic distances and increases the adsorption energy by c.a. 0.4-0.7 eV. The adsorption of water is favourable, although it is generally weaker than for the heavy metal compounds. Based on our results, we conclude that the addition of APTES modifiers on silica increases the adsorption strength and provides extra binding sites for the adsorption of heavy metal pollutants. These outcomes can be used for the design more efficient biomaterials’ structures for heavy metals depollution. <br />

2020-03-23

chemRxiv

Biocompatible Materials; Biological Materials; Coating Materials; Nanostructured Materials - Materials; Computational Chemistry and Modeling; Theory - Computational; Water Purification; Interfaces; Self-Assembly; Surface

CC BY NC ND 4.0

A FOXC2 inhibitor, MC-1-F2, as a therapeutic candidate for targeting EMT in castration-resistant prostate cancer

10.26434/chemrxiv-2022-3wg9m

N.A.

N.A.

Maria Castaneda; Liandra Rodriguez; Jihyun Oh; Hanna Suh; Jiyong Lee

Androgen deprivation therapy (ADT) is the major treatment option for advanced prostate cancer. However, prostate cancer can develop into androgen-independent castration-resistant prostate cancer (CRPC) which is resistant to ADT. Alternative treatments for CRPC have focused on targeting the epithelial-mesenchymal transition (EMT). EMT is governed by a series of transcription factors of which FOXC2 is a central mediator. Our previous research into the inhibition of FOXC2 in breast cancer cells lead to the discovery of MC-1-F2, the first direct inhibitor of FOXC2. During our current study on CRPC, MC-1-F2 has shown a decrease in mesenchymal markers, inhibition of caner stem cell (CSC) properties and decrease in invasive capabilities of CRPC cell lines. We have also demonstrated a synergistic effect between MC-1-F2 and docetaxel treatments, leading to a decrease in docetaxel dosage, suggesting the possible combination therapy of MC-1-F2 and chemotherapeutic drugs for the effective treatment of CRPC.

2022-11-03

chemRxiv

Biological and Medicinal Chemistry; Biochemistry; Chemical Biology; Drug Discovery and Drug Delivery Systems

CC BY NC ND 4.0

Sensitive Mechanocontrolled Luminescence in Cross-Linked Polymer Films

10.26434/chemrxiv.9943943.v1

N.A.

N.A.

Ayumu Karimata; Pradnya Patil; Eugene Khaskin; Sébastien Lapointe; Robert R. Fayzullin; Pavlos Stampoulis; Julia Khusnutdinova

Direct translation of mechanical force into changes in chemical behavior on a molecular level has important implication not only for the fundamental understanding of mechanochemical processes, but also for the development of new stimuli-responsive materials. In particular, detection of mechanical stress in polymers via non-destructive methods is important in order to prevent material failure and to study the mechanical properties of soft matter. Herein, we report that highly sensitive changes in photoluminescence intensity can be observed in response to the mechanical stretching of cross-linked polymer films when using stable, (pyridinophane)Cu-based dynamic mechanophores. Upon stretching, the luminescence intensity increases in a fast and reversible manner even at small strain (< 50%) and applied stress (< 0.1 MPa) values. Such sensitivity is unprecedented when compared to previously reported systems based on organic mechanophores. The system also allows for the detection of weak mechanical stress by spectroscopic measurements or by direct visual methods.<br />

2019-10-10

chemRxiv

Organic Polymers; Coordination Chemistry (Organomet.); Ligand Design

CC BY NC ND 4.0

The role of excited-state character, structural relaxation, and symmetry breaking in enabling delayed fluorescence activity in push-pull chromophores

10.26434/chemrxiv-2021-b3jfg

10.1039/D1CP03792G

https://dx.doi.org/10.1039/D1CP03792G

Patrick Kimber; Pooja Goddard; Iain Wright; Felix Plasser

Thermally activated delayed fluorescence (TADF) is a current promising route for generating highly efficient light-emitting devices. However, the design process of new chromophores is hampered by the complicated underlying photophysics that requires a number of different pathways to be optimised simultaneously. In this work, four closely related donor-pi-acceptor-pi-donor systems have been investigated, two of which were synthesised previously, with the aim of elucidating their varying effectiveness for TADF. We, first, outline that neither the frontier orbitals nor the singlet-triplet gaps are sufficient in discriminating between the molecules. Subsequently, a detailed analysis of the excited states, performed at a correlated ab initio level, is shown highlighting the presence of a number of closely spaced singlet and triplet states of varying character. Five density functionals are benchmarked against this reference revealing dramatic changes in, both, excited state energies and wavefunctions following variations in the amount of Hartree-Fock exchange included. Excited-state minima are optimised in solution showing the crucial role of structural variations for stabilising locally excited and CT states and of symmetry breaking for producing a strongly emissive S1 state. More generally, this work shows how a detailed analysis of excited-state wavefunctions can provide critical new insight into excited-state electronic structure, helping to reveal the photophysics of existing push-pull chromophores and ultimately guiding the design of new ones.

2021-08-19

chemRxiv

Theoretical and Computational Chemistry; Physical Chemistry; Theory - Computational; Photochemistry (Physical Chem.); Quantum Mechanics

CC BY 4.0

Online Acoustic Emission Sensing of Rechargeable Batteries: Technology, Status and Prospects

10.26434/chemrxiv-2024-m4wtw

10.1039/D4TA04571H

https://doi.org/10.1039/D4TA04571H

Inti Espinoza Ramos; Amina Coric; Boyang Su; Qi Zhao; Lars Eriksson; Mattias Krysander; Annika Ahlberg Tidblad; Leiting Zhang

Online acoustic emission (AE) sensing is a nondestructive method that has the potential to be an indicator of battery health and performance. Rechargeable batteries exhibit complex mechano-electrochemical behaviors during operation, such as electrode expansion/contraction, phase transition, gas evolution, film formation, and crack propagation. These events emit transient elastic waves, which may be detected by a piezoelectric-based sensor attached to the battery cell casing. Research in this field is active and new findings are generated continuously, highlighting its potential and importance of further research and development. This Review provides a comprehensive analysis of AE sensing in rechargeable batteries, aiming to describe the underlying mechanisms and potential applications in battery monitoring and diagnostics.

2024-07-03

chemRxiv

Materials Science; Energy; Energy Storage

CC BY NC ND 4.0

Molecular Mechanism of Autodissociation in Liquid Water: Density Functional Theory Molecular Dynamics Simulations

10.26434/chemrxiv-2022-9t6vf-v2

N.A.

N.A.

Tatsuya Joutsuka

Autodissociation in liquid water is one of the most important processes in various topics of physical chemistry, such as acid-base chemistry. Molecular simulations have elucidated most of the molecular mechanisms at the atomic level, yet quantitative analysis to compare with experiments using the potential of mean force (PMF) remains a hurdle, including the definition of reaction coordinates and accuracy of liquid structures by ab initio molecular dynamics (AIMD) simulations with density functional theory (DFT) methods. Here, we perform AIMD simulations with the revPBE-D3 exchange-correlation functional to compute the PMF profiles of autoionization, or proton transfer (PT), in liquid water. For the quantitative analysis with physically meaningful reaction coordinates, we employ a PT coordinate, donor-acceptor (OH--H3O+) distance, and hydrogen (H)-bond number. The one-dimensional (1D) PMF profile along the PT coordinate shows no local minimum in the product state of PT (OH- and H3O+), which is necessary to accurately compute acid dissociation constant (or pKa). On the other hand, the 2D PMF profiles along the PT coordinate and donor-acceptor distance show local minima in the product state and reaction barriers, and the computed pKw is comparable to the experiment. In addition, the 2D PMF profiles along the PT coordinate and the H-bond number reveal the molecular mechanism of the H-bond rearrangement concomitant with PT, in which the H-bond breaking before PT is slightly preferable. These findings indicate that accurate evaluation of pKa by MD simulations requires the donor-acceptor distance in addition to the conventional PT coordinate.

2022-05-26

chemRxiv

Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Theory - Computational; Solution Chemistry

CC BY NC ND 4.0

Predictive Machine Learning Models Trained on Experimental Datasets for Electrochemical Nitrogen Reduction

10.26434/chemrxiv-2023-x81t3

N.A.

N.A.

Darik Rosser; Brianna Farris; Kevin Leonard

Obtaining useful insights from machine learning models trained on experimental datasets collected across different groups to improve the sustainability of chemical processes can be challenging due to the small size and heterogeneity of the dataset. Here we show that shallow learning models such as decision trees and random forest algorithms can be an effective tool for guiding experimental research in the sustainable chemistry field. This study trained three different machine learning algorithms (decision tree, random forest, and multilayer perceptron) using 254 unique reaction conditions for the nitrogen reduction reaction (NRR) on heterogeneous electrocatalysts. Using the catalyst properties and experimental conditions as the features, we determined the ability of each model to regress the ammonia rate and the faradaic efficiency. We observed that the shallow learning decision tree and random forest models performed equal to or better than the deep learning multilayer perceptron models. Analysis of the models showed that the complex interaction between the applied potential and catalysts on the effective rate for the NRR. In addition, our model uncovered some underexplored catalysts-electrolyte combinations that give guidance to experimental researchers looking to improve both the rate and efficiency of the NRR reaction.

2023-07-25

chemRxiv

Catalysis; Electrocatalysis

CC BY NC ND 4.0

Low-Valent Tungsten Redox Catalysis Enables Controlled Isomerization and Carbonylative Functionalization of Alkenes

10.26434/chemrxiv.14362238.v1

N.A.

N.A.

Tanner Jankins; William Bell; Yu Zhang; Zi-Yang Qin; Milan Gembicky; Peng Liu; Keary Engle

Tungsten catalysis has played an instrumental role in the history of organometallic chemistry, with electrophilic, fully oxidized W(VI) catalysts featuring prominently in olefin polymerization and metathesis reactions. Here, we report that the simple W(0) precatalyst, W(CO)₆, catalyzes the isomerization and hydrocarbonylation of alkenes via a W(0)/W(II) redox couple. The 6- to 7-coordinate geometry changes associated with this redox process are key in allowing isomerization to take place over multiple positions and stop at a defined unactivated internal site that is primed for <i>in situ</i> functionalization. DFT studies and crystallographic characterization of multiple directing-group-bound W(II) model complexes illuminate potential intermediates of this redox cycle and showcase the capabilities of the 7-coordinate W(II) geometry to facilitate challenging alkene functionalizations.

2021-04-05

chemRxiv

Organic Synthesis and Reactions; Homogeneous Catalysis; Theory - Organometallic; Transition Metal Complexes (Organomet.)

CC BY NC ND 4.0

Disentangling Viral Entry Kinetics Using Lipid Bilayers Coating Silica Nanoparticles

10.26434/chemrxiv.12123126.v1

N.A.

N.A.

Ana M. Villamil Giraldo; Peter Kasson

<div> <div> <div> <p>Enveloped viruses infect cells via fusion between the viral envelope and a cellular membrane. This membrane fusion process is driven by viral proteins, but slow stochastic protein activation dominates fusion kinetics, making it challenging to probe the role of membrane mechanics in viral entry directly. We have used bilayer-coated silica nanoparticles to restrict the deformability of lipid membranes in a controllable manner. These bilayer-coated nanoparticles are then used in a single-particle fusion assay with infectious influenza virus. We observe that as we vary the free energy of membrane deformation by changing nanoparticle size, we obtain a corresponding response in fusion kinetics and apparent fusion protein stoichiometry. We thus directly measure the effect of membrane deformability on the free-energy barrier to membrane fusion by influenza, overcoming the masking effect of slow protein activation kinetics. </p> </div> </div> </div>

2020-04-17

chemRxiv

Nanostructured Materials - Nanoscience; Biophysics; Microbiology; Biophysical Chemistry

CC BY NC ND 4.0

Pulsed Photothermal Heterogeneous Catalysis

10.26434/chemrxiv-2022-c6jll

10.1021/acscatal.2c05435

https://doi.org/10.1021/acscatal.2c05435

Andrea Baldi; Sven Askes

Anthropogenic climate change urgently calls for the greening and intensification of the chemical industry. Most chemical reactors make use of catalysts to increase their conversion yields, but their operation at steady-state temperatures limits rate, selectivity, and energy efficiency. Here, we show how to break such steady-state paradigm using ultrashort light-pulses and photothermal nanoparticle arrays to modulate the temperature of catalytic sites at timescales typical of chemical processes. By using heat dissipation and time-dependent microkinetic modelling for a number of catalytic landscapes, we numerically demonstrate that pulsed photothermal catalysis can result in a favorable, dynamic mode of operation with higher energy efficiency, higher catalyst activity than for any steady-state temperature, reactor operation at room temperature, resilience against catalyst poisons, and access to adsorbed reagent distributions that are normally out of reach. Our work identifies the key experimental parameters controlling reaction rates in pulsed heterogeneous catalysis and provides specific recommendations to explore its potential in real experiments, paving the way to a more sustainable and process-intense operation of catalytic reactors.

2022-10-25

chemRxiv

Physical Chemistry; Catalysis; Nanoscience; Plasmonic and Photonic Structures and Devices; Heterogeneous Catalysis; Photocatalysis

CC BY NC 4.0

High-Throughput Assessment of Hypothetical Zeolite Materials for Their Synthesizability and Industrial Deployability

10.26434/chemrxiv.7770758.v1

N.A.

N.A.

Nils Zimmermann; Jose Luis Salcedo Perez; Maciej Haranczyk

<div>Zeolites are important microporous framework materials, where 200+ structures are known to exist and many millions so-called hypothetical materials can be computationally created. Here, we screen the “Deem” database of hypothetical zeolite structures to find experimentally feasible and industrially relevant materials. We use established and existing criteria and structure descriptors (lattice energy, local interatomic distances, TTT angles), and we develop new criteria which are based on 5-th neighbor distances to T-atoms, tetrahedral order parameters (or, tetrahedrality), and porosity and channel dimensionality. Our filter funnel for screening the most attractive zeolite materials that we construct consists of 9 different types of criteria and a total of 53 subcriteria. The funnel reduces the pool of candidate materials from initially >300,000 to 24 and 11, respectively, depending on the channel dimensionality constraint applied (2- and 3-dimensional vs only 3-dimensional channels). </div><div>We find that it is critically important to define longer range and more stringent criteria such as the new 5-th neighbor distances to T-atoms and the tetrahedrality descriptor in order to succeed in reducing the huge pool of candidates to a manageable number. Apart from one experimentally achieved structure (SSF), all other candidates are hypothetical frameworks, thus, representing most valuable targets for synthesis and application. Detailed analysis of the screening data allowed us to also propose an exciting future direction how such screening studies as ours could be improved and how framework generating algorithms could be competitively optimized.</div>

2019-02-26

chemRxiv

Catalysts; Nanostructured Materials - Materials; Nanocatalysis - Catalysts & Materials; Minerals; Computational Chemistry and Modeling

CC BY NC ND 4.0

The Use of Zeolite-Based Geopolymers as Adsorbent for Copper Removal from Aqueous Media

10.26434/chemrxiv.14368982.v1

N.A.

N.A.

Haci Baykara; Maria de Lourdes Mendoza Solorzano; Jose Javier Delgado Echeverria; Mauricio H. Cornejo; Clotario V. Tapia-Bastidas

In this study the use of a natural zeolite-based geopolymer use in removal of copper from aqueous media has been presented for the first time. <div>Additionally, kinetics and isotherms of the adsorption have also been demonstrated. </div>

2021-04-05

chemRxiv

Inorganic Polymers; Separation Science; Chemical Kinetics; Structure

CC BY NC ND 4.0

Polarizable Embedding without Artificial Boundary Polarization

10.26434/chemrxiv-2023-fc0gk-v2

10.1021/acs.jctc.3c00434

https://doi.org/10.1021/acs.jctc.3c00434

Sonata Kvedaravičiūtė; David Carrasco-Busturia; Klaus B. Møller; Jógvan Magnus Haugaard Olsen

We present a fully self-consistent polarizable embedding (PE) model that does not suffer from unphysical boundary polarization. This is achieved through the use of the minimum-image convention (MIC) in the induced electrostatics. It is a simple yet effective approach that includes a more physically accurate description of the polarization throughout the molecular system. Using PE with MIC (PE-MIC), we shed new light on the limitations of commonly employed cutoff models, such as the droplet model, when used in PE calculations. Specifically, we investigate the effects of the unphysical polarization at the outer boundary by comparing induced dipoles and the associated electrostatic potentials, as well as some optical properties of solute-solvent and biomolecular systems. We show that the magnitude of the inaccuracies caused by the unphysical polarization depends on multiple parameters: the nature of the quantum subsystem and of the environment, the cutoff model and distance, and the calculated property.

2023-06-15

chemRxiv

Theoretical and Computational Chemistry

CC BY 4.0

Highly Regio-, Enantio-, and Exo-selective Diels–Alder Reactions Enabled by a Bispyrrolidine Diboronate

10.26434/chemrxiv-2021-4jqls

N.A.

N.A.

Yuan-He Li; Su-Lei Zhang; Bo Xiao; Tian-Yu Sun; Jia-Hua Chen; Yun-Dong Wu; Zhen Yang

Catalytic asymmetric Diels−Alder reaction is one of the most powerful reactions in organic chemistry. It is still a challenge to achieve high and general exo-selectivity. A novel bispyrrolidine diboronate compound has been derived from the reaction of two molecules of oxazaborolidine with one molecule of water. Upon activation, it effectively catalyzes (0.4-5 mol % loading) the Diels–Alder reaction between a variety of mono- and di-carbonyl activated dienophiles and dienes with better than 20:1 regioselectivity, up to >99:1 enantioselectivity, and better than 20:1 exo/endo selectivity. Mechanistic studies show a remarkable nonlinearity in enantioselectivity, and a second-order kinetics with respect to the catalyst concentration. A model is proposed to rationalize the above observations. The reaction is expected to find wide applications in organic synthesis.

2021-08-24

chemRxiv

Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Stereochemistry

CC BY NC ND 4.0