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Ion mobility studies of Pyrroloquinoline Quinone Aza-Crown Ether-Lanthanide Complexes | 10.26434/chemrxiv-2022-n8lbf | N.A. | N.A. | Alexander Schäfer; Violeta Vetsova; Erik Schneider; Manfred Kappes; Michael Seitz; Lena Daumann; Patrick Weis | Lanthanide-dependent enzymes and their biomimetic complexes have arisen as an interesting target of research in the last decade. These enzymes, specifically, pyrroloquinoline quinone (PQQ)-bearing methanol dehydrogenases, efficiently turn over alcohols to the respective aldehydes. To rationally design bioinspired alcohol dehydrogenation catalysts, it is imperative to understand the species involved in catalysis. However, given the extremely flexible coordination sphere of lanthanides, it is often difficult to assess the number and nature of the active species. Here we show how such questions can be addressed by using a combination of ion mobility spectrometry, mass spectrometry and quantum chemical calculations to study the test systems PQQ and lanthanide-PQQ-crown ether ligand complexes. Specifically, we determine the gas phase structures of [PQQH2]-, [PQQH2+H2O]-, [PQQH2+MeOH]-, [PQQ-15c5+H]+ and [PQQ-15c5+Ln+NO3]+ (Ln=La to Lu, except Pm). In the latter case a trend to smaller collision cross sections across the lanthanide series is clearly observable, in line with the well-known lanthanide contraction. We hope that in future such investigations will help to guide the design and understanding of lanthanide based biomimetic complexes optimized for catalytic function. | 2022-01-20 | chemRxiv | Theoretical and Computational Chemistry; Physical Chemistry; Analytical Chemistry; Mass Spectrometry; Computational Chemistry and Modeling | null | CC BY NC ND 4.0 |
A Promising Strategy Against SARS-CoV-2 Infected Patients: Antisense Therapy | 10.26434/chemrxiv.12948746.v1 | N.A. | N.A. | Hasan Cubuk | <p></p><p>As of July 25-2020, 643,412 people in more than 215 countries
have been victims of the new type of coronavirus, SARS-CoV-2. Thereby, there is
a huge effort to develop a strategy to treat, and or prevent people from SARS-CoV-2
infection. Those efforts could be mainly categorized as drug repurposing,
anti-SARS-CoV-2 antibodies from people who recovered, and vaccines. However,
there is currently no specific treatment available against SARS-CoV-2 infected
patients. That`s why many new approaches and ideas are still studied every day
for the treatment of SARS-CoV-2 infected patients. Antisense therapy is one of
these promising approaches to target SARS-CoV-2 genomic RNA specifically and
inhibit its activity upon incorrect viral RNA processing. In
this study, antisense oligonucleotide (ASO) candidates targeting SARS-CoV-2
genomic RNA were designed. High-scored
ASOs with a high potential to inhibit SARS-CoV-2 replication and transcription
by inducing cleavage of the viral genomic were determined among ASO candidates.
For the future, those promising ASOs can be synthesized followed by required
modifications and test on SARS-CoV-2 infected Vero cells to
screen their efficacy for the treatment of SARS-CoV-2
infected patients.</p><br /><p></p> | 2020-09-15 | chemRxiv | Biochemistry; Bioinformatics and Computational Biology; Chemical Biology; Drug Discovery and Drug Delivery Systems | null | CC BY NC ND 4.0 |
Enzyme enhancement through computational stability design targeting NMR-determined catalytic hotspots | 10.26434/chemrxiv-2024-7xxzg | N.A. | N.A. | Luis I. Gutierrez-Rus; Eva Vos; David Pantoja-Uceda; Gyula Hoffka; Jose Gutierrez-Cardenas; Mariano Ortega-Muñoz; Valeria A. Risso; Maria Angeles Jimenez; Shina Caroline Lynn Kamerlin; Jose M. Sanchez Ruiz | Enzymes are the quintessential green catalysts, but realizing their full potential for biotechnology typically requires improvement of their biomolecular properties. Catalysis enhancement, however, is often accompanied by impaired stability. Here, we show how the interplay between activity and stability in enzyme optimization can be efficiently addressed by coupling two recently proposed methodologies for guiding directed evolution. We first identify catalytic hotspots from chemical shift perturbations induced by transition-state-analogue binding and then use computational/phylogenetic design (FuncLib) to predict stabilizing combinations of mutations at sets of such hotspots. We test this approach on a previously designed de novo Kemp eliminase, which is already highly optimized in terms of both activity and stability. Despite this, using our current approach, we were able to obtain 50-fold modulation in catalysis, with most variants displaying substantially increased denaturation temperatures and purification yields. Notably, our most efficient engineered variant (kcat 1700 s-1, kcat/KM 4.3·10^5 M-1s-1) is the most proficient proton-abstraction Kemp eliminase designed to date, with a catalytic efficiency on a par with naturally occurring enzymes. Molecular simulations pinpoint the origin of this catalytic enhancement as being due to the progressive elimination of a catalytically inefficient substrate conformation that is present in the original design. A large modulation in catalysis linked to substrate conformational selection illustrates the potential of our approach for the engineering of enzyme regio- and stereo-selectivity. Overall, our work showcases the power of dynamically guided enzyme engineering as a design principle for obtaining novel biocatalysts with tailored physicochemical properties, towards even anthropogenic reactions. | 2024-07-11 | chemRxiv | Biological and Medicinal Chemistry; Catalysis; Biochemistry; Bioengineering and Biotechnology; Bioinformatics and Computational Biology | null | CC BY 4.0 |
A Continuous Flow Process for the Defluorosilylation of HFC-23 and HFO-1234yf | 10.26434/chemrxiv-2024-mkm39 | N.A. | N.A. | Sarah Patrick; James Bull; Philip Miller; Mark Crimmin | A continuous flow process has been developed for the defluorosilylation of trifluoromethane (HFC-23) and 2,3,3,3-propene (HFO-1234yf) through reaction with lithium silanide reagents under inert conditions. Design of experiment optimization improved process conditions including productivity, yields, reduction of solvent use, and gas destruction. The small chain fluorinated organosilane products R3SiCF2H and R3SiCH2C(F)=CF2 were competent nucleophiles in the fluoride-catalyzed difluoromethylation of aldehydes, and trifluoroallylation of aldehydes, ketones, and imines. Stepwise treatment of R3SiCH2C(F)=CF2 with KHMDS and IPrCuCl gave IPrCuCC–CF2H, which reacted with allyl and acyl halides to transfer the fluorinated propyne motif. | 2024-08-30 | chemRxiv | Organic Chemistry; Inorganic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Main Group Chemistry (Inorg.) | null | CC BY 4.0 |
BuildAMol: A versatile Python toolkit for fragment-based molecular design | 10.26434/chemrxiv-2024-q90s4 | N.A. | N.A. | Noah Kleinschmidt; Thomas Lemmin | In recent years computational methods for molecular modeling have become a prime focus of computational biology and cheminformatics. Many dedicated systems exist for modeling specific classes of molecules such as proteins or small drug-like ligands. These are often heavily tailored toward the automated gen- eration of molecular structures based on some meta-input by the user and are not intended for expert-driven structure assembly. Dedicated manual or semi- automated assembly software tools exist for a variety of molecule classes but are limited in the scope of structures they can produce. In this work we present BuildAMol, a highly flexible and extendable, general-purpose fragment-based molecular assembly toolkit. Written in Python and featuring a well-documented, user-friendly API, BuildAMol empowers researchers with a framework for detailed manual or semi-automated construction of diverse molecular models. Unlike specialized software, BuildAMol caters to a broad range of applications. We demonstrate its versatility across various use cases, encompassing generating metal complexes or the modeling of dendrimers or integrated into a drug discov- ery pipeline. By providing a robust foundation for expert-driven model building, BuildAMol holds promise as a valuable tool for the continuous integration and advancement of powerful deep learning techniques. | 2024-07-01 | chemRxiv | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Chemoinformatics - Computational Chemistry | null | CC BY 4.0 |
A Simple and Cost-Effective Synthesis of Sulfated β-Cyclodextrin and Its Application as Chiral Mobile Phase Additive in the Separation of Cloperastine Enantiomers | 10.26434/chemrxiv.11907060.v1 | N.A. | N.A. | Krishna Deshpande; Pranav Pathak; Vishvas Joshi; Stephen barton; Krishnapriya Mohanraj | A new, simple and cost-effective
method for the synthesis of sulfated beta-cyclodextrin (S-β-CD), one of the
most widely used chiral mobile phase additive, using sulfamic acid as
sulfonating agent has been described. The method was optimized and the acquired
product was characterized and compared with a marketed Sigma Aldrich sulfated
beta-cyclodextrin (S-β-CD1). Beta cyclodextrin (β-CD), hydroxypropyl beta-cyclodextrin
(HP-β-CD), S-β-CD1 and S-β-CD2 were evaluated as chiral mobile phase additives
(CMPAs) for the enantiomeric separation of cloperastine, an antitussive agent,
using reversed-phase HPLC. Under the optimized conditions, a resolution of 3.14
was achieved within 15 minutes on an achiral Kromasil C<sub>8</sub> (150 x 4.6
mm, 5 µ) column with a mobile phase of 5mM monopotassium phosphate containing
10mM S-β-CD3 pH 3 and 45% methanol with a run time of 15 min. The method
utilizing S-β-CD3 as CMPA was validated as per ICH guidelines and applied for the
quantitative determination of cloperastine enantiomers in active pharmaceutical
ingredients and pharmaceutical formulations. The selectivity changes imparted
by S-β-CD were proven to be beneficial for chiral separation. The chiral recognition mechanism and elution order
of the reported enantiomers were determined by simulation studies. It was
observed that inclusion complex formation and hydrogen bonding are the major
forces for the chiral resolution. | 2022-11-22 | chemRxiv | Analytical Chemistry - General; Separation Science | null | CC BY NC ND 4.0 |
Investigation and Characterization of Flexible Polyurethane Foams from the use of Chicken Eggshells as Fillers. | 10.26434/chemrxiv-2022-mkc4d | N.A. | N.A. | Precious Ebereonwu ; Dayil Dashak; Chris Ogah | Chicken egg shells (ES) with 5%wt, 10%wt and 15%wt were incorporated and characterized as fillers in the production of flexible polyurethane foams. The results obtained were compared with conventional application of calcium carbonate (CaCO3). Physico-mechanical properties of the foam without fillers (unfilled), gave density of 20.87 kg/m3, compression set at room temperature (2.880C) and at higher temperature (70) had 3.960C, elongation at break (651.60%), tensile strength (112.10 KPa) and Indentation Force Deflection (hardness at 400C) was 187.20N. Subsequently, foams with 5% ES and 5% CaCO3 fillers depicted densities (21.72 and 21.50 kg/m3), compression set at room temperatures (3.66 and 3.450C), temperature at 700C (4.33 and 5.460C), elongation at break (312.70 and 328.50%), tensile strength (78.40 and 81.40 KPa) and Indentation Forces Deflections (Hardness at 400C) were 241.80 and 198N respectively. Foams with 10% CaCO3 and 10% ES also revealed densities of 21.68 and 21.80 kg/m3 respectively, Compression set at room temperature (6.96 and 4.120C), temperature at 700C (5.79 and 6.160C), elongation at break (359.50 and 362.40%), tensile strength (85.00 and 94.00 KPa) and Indentation Forces Deflections (Hardness at 400C) were 203.00 and 186.40N respectively. Consequently, 15% CaCO3 and 15% ES fillers depicted densities (22.14 and 22.39 kg/m3), compression set at room temperatures (5.24 and 3.030C), temperature at 700C (5.50 and 6.250C), elongation at break (383.10 and 397.50%), tensile strength (90.40 and 97.60 KPa) and Indentation Forces Deflections (Hardness at 400C) were 197.00 and 169.90N respectively. In all cases, the physcio-mechanical properties increased with increase in fillers weights. However, Eggshell-filled foams showed better quality in terms of density, compression set at room temperature, elongation at break and tensile strength than CaCO3-filled foams. Unfilled foams (foam without fillers) had the best compression set both at room temperature and intermediate temperature. All foam samples produced fell within the ASTM D-3574 set standard range of 1-10% for compression tests of polyurethane foams. | 2022-10-06 | chemRxiv | Polymer Science | null | CC BY NC ND 4.0 |
Synthesis of Cardiotonic Steroids Oleandrigenin and Rhodexin B | 10.26434/chemrxiv.14496015.v1 | N.A. | N.A. | Zachary Fejedelem; Nolan Carney; Pavel Nagorny | This article describes a concise synthesis of cardiotonic steroids oleandrigenin (7) and its subsequent
elaboration into the natural product rhodexin B (2) from the readily available intermediate (8) that could be derived from
the commercially available steroids testosterone or DHEA via 3 step sequences. These studies feature an expedient
installation of the β16-oxidation based on β14-hydroxyl directed epoxidation and subsequent epoxide rearrangement. The
following singlet oxygen oxidation of the C17 furan moiety provides access to oleandrigenin (7) in 12 steps (LLS) and 3.9%
overall yield from 8. The synthetic oleandrigenin (7) was successfully glycosylated with L-rhamnopyranoside-based donor
using Pd(II)-catalyst, and the subsequent deprotection under acidic conditions provided cytotoxic natural product rhodexin
B (2) in 68% yield (2 steps). <br /> | 2021-04-28 | chemRxiv | Bioorganic Chemistry; Natural Products; Organic Synthesis and Reactions; Stereochemistry | null | CC BY NC ND 4.0 |
Elucidating the Role of Isotopically Chiral Initiators in the Soai Asymmetric Autocatalytic Reaction | 10.26434/chemrxiv.5787984.v2 | N.A. | N.A. | Neil Hawbaker; Donna Blackmond | A mechanistic rationalization is given for how asymmetric amplification is induced with fidelity in the Soai autocatalytic reaction by chiral initiators that are enantiomeric only by virtue of an isotope, e.g. – CH3 vs.CD3. A transient <i>inhibition</i> of the autocatalytic pathway at the outset of the reaction implicates an interaction between initiator and product initially formed in the uncatalyzed background reaction. Selectivity in formation of the product-initiator complex ultimately induces a slight enantioenrichment in the active dimer catalysts that trigger and direct the autocatalytic pathway.<br /> | 2018-06-18 | chemRxiv | Organic Synthesis and Reactions | null | CC BY NC ND 4.0 |
Selecting Double Bond Positions with a Single Cation- Responsive Iridium Olefin Isomerization Catalyst | 10.26434/chemrxiv.13079603.v1 | N.A. | N.A. | Andrew M. Camp; Matthew
R. Kita; Thomas P. Blackburn; Henry M. Dodge; Chun-Hsing Chen; Alexander Miller | <div><div><div><p>The catalytic transposition of double bonds holds promise as an ideal route to alkenes with value as fragrances, commodity chemicals, and pharmaceuticals; yet, selective access to specific isomers is a challenge, requiring independent development of different catalysts for different products. In this work, a single cation-responsive iridium catalyst is developed for the selective production of either of two different internal alkene isomers. In the absence of salts, a single positional isomerization of 1-butene derivatives furnishes 2-alkenes with exceptional regioselectivity and stereoselectivity. The same catalyst, in the presence of Na+, mediates two positional isomerizations to produce 3-alkenes. The synthesis of new iridium pincer-crown ether catalysts based on an aza-18-crown-6 ether proved instrumental in achieving cation-controlled selectivity. Experimental and computational studies guided the development of a mechanistic model that explains the observed selectivity for various functionalized 1-butenes, providing insight into strategies for catalyst development based on non-covalent modifications.</p></div></div></div> | 2020-10-13 | chemRxiv | Supramolecular Chemistry (Inorg.); Homogeneous Catalysis; Catalysis; Ligand Design | null | CC BY NC ND 4.0 |
Suppressing Co-ion Generation via Cationic Proton Donors to Amplify Driving Forces for Electrochemical CO2 Reduction | 10.26434/chemrxiv-2023-12gkw | N.A. | N.A. | Wenxiao Guo; Beichen Liu; Matthew Gebbie | Interfacial microenvironments critically define reaction pathways for electrocatalytic processes through a combination of electric field gradients and proton activity. Non-aqueous ionic liquid electrolytes have been shown to sustain enhanced interfacial electric field gradients at intermediate ion concentration regimes of around 1 M, creating local environments that promote CO2 electroreduction. Notably, water at low concentrations absorbed by non-aqueous electrolytes is usually assumed to be the proton donor for CO2 reduction. Consumption of protons causes proton donors to become more negative by one unit charge, which significantly modifies the local concentration of charged species and hence should strongly impact local electric fields. Yet, how the coupling between proton donation and changing interfacial electric fields influences electrocatalytic processes in non-aqueous electrolytes remains largely unexplored. In this work, we show that the high activity of 1,3-dialkylimidazolium ionic liquids for CO2 reduction in acetonitrile-based electrolytes stems from the ability to act as cationic proton donors that release neutral conjugate bases. Using in situ electrochemical surface-enhanced Raman spectroscopy, we find that the formation of neutral conjugate bases from imidazolium cations preserves local electric field strengths at electrode-electrolyte interfaces, providing a powerful strategy to maintain an active local microenvironment for CO2 reduction. In contrast, conditions where water behaves as the primary proton donor generates [OH]- anions as negative “co-ions” in the electric double layer, which weakens the interfacial electric field and significantly compromises the steady-state CO2 reduction activity. Our study highlights that electrochemical driving forces are highly sensitive to the charge state of both reactant and product species and highlights the fact that the generation of interfacial co-ions plays a key role in determining electrochemical driving forces. | 2023-05-19 | chemRxiv | Catalysis; Chemical Engineering and Industrial Chemistry; Electrocatalysis | null | CC BY NC ND 4.0 |
Structure-based virtual screening for PDL1 dimerizers: evaluating generic scoring functions | 10.26434/chemrxiv-2022-52s4m | N.A. | N.A. | Viet-khoa Tran-nguyen; Saw Simeon; Muhammad Junaid; Pedro Ballester | An innovative mechanism to inhibit the PD1/PDL1 interaction is PDL1 dimerization induced by small-molecule PDL1 binders. Structure-based virtual screening is a promising approach to discovering such small-molecule PD1/PDL1 inhibitors. Here we investigate which type of generic scoring functions is most suitable to tackle this problem. We consider CNN-Score, an ensemble of convolutional neural networks, as the representative of machine-learning scoring functions. We also evaluate Smina, a commonly used classical scoring function, and IFP, a top structural fingerprint similarity scoring function. These three types of scoring functions were evaluated on two test sets sharing the same set of small-molecule PD1/PDL1 inhibitors, but using different types of inactives: either true inactives (molecules with no in vitro PD1/PDL1 inhibition activity) or assumed inactives (property-matched decoy molecules generated from each active). On both test sets, CNN-Score performed much better than Smina, which in turn strongly outperformed IFP. The fact that the latter was the case, despite precluding any possibility of exploiting decoy bias, demonstrates the predictive value of CNN-Score for PDL1. These results suggest that re-scoring Smina-docked molecules with CNN-Score is a promising structure-based virtual screening method to discover new small-molecule inhibitors of this important therapeutic target. | 2022-03-28 | chemRxiv | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Machine Learning; Artificial Intelligence | null | CC BY NC 4.0 |
Interactions of Different Janus Particles with Passive Tracers | 10.26434/chemrxiv.9391925.v1 | N.A. | N.A. | Purnesh Chattopadhyay; Juliane Simmchen | In this manuscript we want to expand the strategies on tuneable phoretic interactions. Previously, we had kept the swimmer body fixed and varied fuel and light source. In this report we fix the fuel to hydrogen peroxide and change the species that favours its degradation, i.e. the 'catalytic' half on the Janus particles. Many materials are known to degrade hydrogen peroxide and our selection includes copper and silver, which present interesting effects besides the well known platinum. | 2019-08-09 | chemRxiv | Self-Assembly | null | CC BY NC ND 4.0 |
Elucidating the effects of temperature on nonaqueous redox flow cell cycling performance | 10.26434/chemrxiv-2023-r72sm-v2 | N.A. | N.A. | Alexander Quinn; Katelyn Ripley; Nicholas Matteucci; Bertrand Neyhouse; Chloe Brown; William Woltmann; Fikile Brushett | The impact of cell temperature is a relatively underexplored area within the burgeoning field of nonaqueous redox flow batteries (NAqRFBs). Here, we investigate the effect of elevated temperature on the performance of nonaqueous redox electrolytes and associated flow cells. Using a model compound, N-(2-(2-methoxyethoxy)-ethyl)phenothiazine (MEEPT), in a propylene-carbonate-based electrolyte, we experimentally measure the temperature dependence of relevant physicochemical properties (i.e., electrolyte conductivity, viscosity, diffusivity) and electrochemical characteristics (i.e., chemical and electrochemical reversibility) across a temperature range of 30 to 70 °C. We then perform flow cell studies, finding that while ohmic and mass transport resistances decrease significantly with increases in temperature for the MEEPT/MEEPT+● redox couple, accessible electrolyte capacity gradually reduces at temperatures >50 °C. Ex-situ, post-test characterization using microelectrode voltammetry suggests that this capacity fade is due to instability of the MEEPT radical cation. Finally, using MEEPT as a posolyte and a model viologen negolyte (bis(2-(2-methoxyethoxy)ethyl)viologen), we assemble a full cell and perform polarization analysis, observing a 2× increase in the peak power density when the operating temperature is increased from 30 to 70 °C. Broadly, this work highlights opportunities for systematic engineering of nonaqueous electrolytes and flow cells for higher power operation at elevated temperatures. | 2023-11-03 | chemRxiv | Energy; Energy Storage | null | CC BY NC ND 4.0 |
The Role of Al3+-Based Aqueous Electrolytes in the Charge Storage Mechanism of MnOx Cathodes | 10.26434/chemrxiv.13272980.v1 | 10.1002/smll.202101515 | https://doi.org/10.1002/smll.202101515 | Véronique Balland; Mickaël Mateos; Kenneth D. Harris; Benoit Limoges | <p>Rechargeable aqueous aluminium batteries
are the subject of growing interest, but the charge storage mechanisms at manganese
oxide-based cathodes remain poorly understood with as many mechanisms as
studies. Here, we use an original <i>in situ</i>
spectroelectrochemical methodology to unambiguously demonstrate that the reversible
proton-coupled MnO<sub>2</sub>-to-Mn<sup>2+</sup> conversion is the main charge
storage mechanism occurring at MnO<sub>2</sub> cathodes over a range of slightly
acidic Al<sup>3+</sup>-based aqueous electrolytes. In Zn/MnO<sub>2</sub> assemblies,
this mechanism is associated with high gravimetric capacity and discharge
potentials, up to 560 mAh·g<sup>-1</sup> and 1.76 V respectively, attractive
efficiencies (<i>CE</i> > 98.5 % and <i>EE</i> > 80%) and excellent cyclability (>
750 cycles at 10 A·g<sup>-1</sup>). Finally, we conducted a critical analysis of the
data previously published on MnO<sub>x</sub> cathodes in Al<sup>3+</sup>-based
aqueous electrolytes to conclude on a universal charge storage mechanism, <i>i.e.</i>, the reversible
electrodissolution/electrodeposition of MnO<sub>2</sub>.<i></i></p> | 2020-11-24 | chemRxiv | Energy Storage | null | CC BY NC ND 4.0 |
Defects in 3D Printing and Strategies to Enhance Quality of FFF Additive Manufacturing. A Review | 10.26434/chemrxiv-2023-lw1ns | 10.59761/RCR5103 | https://doi.org/10.59761/RCR5103 | Kirill Erokhin; Sergei Naumov; Valentine Ananikov | Additive manufacturing technologies (or 3D printing) have emerged as potent tools in the creation of a diverse array of objects, promising a paradigm shift in production methodologies across industries. However, the benefits of these technologies can be diminished by the use of suboptimal parameters or inferior materials, leading to defects that significantly degrade the quality and functionality of the resulting products. An incomplete understanding of defect formation keeps under the formulation of effective preventative strategies. In light of this, our review provides a comprehensive exploration of defects that arise during the Fused Filament Fabrication (FFF)—one of the most prevalent 3D printing methods. The defects are systematically classified according to several key characteristics, including size, type, mode of occurrence, and location. Each common defect is extensively discussed, detailing its external manifestation, root causes, the impact on the properties of printed parts, and potential preventative measures. Our findings unveil the complex interplay of material properties, printing parameters, and cooling dynamics in the defect formation process. This classification holds significant practical relevance, providing a solid foundation for the development of strategies for defect minimization and quality improvement in 3D printed products. It offers valuable insights for a broad audience, including researchers exploring additive manufacturing technologies, 3D printing engineers, 3D printer operators, and quality assurance (QA) engineers involved in production quality control. Furthermore, our review delineates the path for future research in this domain. There is a crucial need for the development of advanced machine learning and artificial intelligence models that can predict defect formation based on given printing parameters and material properties. Future investigations should also focus on the discovery of novel materials and refining of printing parameters to achieve superior quality of FFF 3D printed products. This review serves as a cornerstone for these future advancements, promoting a deeper understanding of defect formation and prevention in additive manufacturing. | 2023-10-03 | chemRxiv | Materials Science; Polymer Science; Chemical Engineering and Industrial Chemistry; Materials Processing; Industrial Manufacturing; Reaction Engineering | null | CC BY NC ND 4.0 |
Halide Anion Activated Reactions of Michael Acceptors with Tropylium Ion | 10.26434/chemrxiv.9639227.v1 | N.A. | N.A. | Mohanad A. Hussein; Uyen P. N. Tran; Vien T. Huynh; Junming Ho; Mohan Bhadbhade; Herbert Mayr; Thanh Vinh Nguyen | Tropylium bromide undergoes non-catalyzed,
regioselective additions to a large variety of Michael acceptors. In this way,
acrylic esters are converted into ß-bromo-α-cycloheptatrienyl-propionic esters.
The reactions are interpreted by nucleophilic attack of bromide ions at the
electron-deficient olefins and trapping of the incipient carbanion by the
tropylium ion. Quantum chemical calculations were performed to elucidate the
analogy to the amine or phosphine-catalyzed Rauhut-Currier reactions.
Subsequent synthetic transformations of the bromo-cycloheptatrienylated adducts
are reported. | 2019-08-19 | chemRxiv | Organic Compounds and Functional Groups; Organic Synthesis and Reactions | null | CC BY NC ND 4.0 |
Real-Time Video Imaging of Mechanical Motions of a Single Molecular Shuttle | 10.26434/chemrxiv.10029194.v1 | N.A. | N.A. | Toshiki Shimizu; Dominik Lungerich; Joshua Stuckner; Mitsuhiro Murayama; Koji Harano; Eiichi Nakamura | Miniatured machines has open up a new dimension of chemistry, studied
usually as an average over numerous molecules or for a single molecule bound on
a robust substrate. Mechanical motions at a single molecule level, however, are
under quantum control, strongly coupled with fluctuations of its environment --
a system rarely addressed because an efficient way of observing the
nanomechanical motions in real time is lacking. Here, we report sub-ms sub-Å
precision in situ video imaging of a single fullerene molecule shuttling,
rotating, and interacting with a vibrating carbon nanotube, using an electron
microscope, a fast camera, and a denoising algorithm. We have realized high
spatial precision of distance measurement with the standard error of the mean
as small as ± 0.01 nm, and revealed the rich molecular dynamics, where motions
are non-linear, stochastic and often non-repeatable, and a work and energy
relationship at a molecular level previously undetected by time-averaged
measurements or microscopy. | 2019-10-25 | chemRxiv | Microscopy | null | CC BY NC ND 4.0 |
Green Light Promoted Iridium(III)/Copper(I)-Catalyzed Addition of Alkynes to Aziridinoquinoxalines Through the Intermediacy of Azomethine Ylides | 10.26434/chemrxiv-2023-qx7tc | N.A. | N.A. | Oleksii Zhelavskyi; Seren Parikh; Richard Staples; Paul Zimmerman; Pavel Nagorny | This manuscript describes the development of alkyne addition to the aziridine moiety of aziridinoquinoxalines using dual Ir(III)/Cu(I) catalytic system under green LED photolysis (lmax = 525 nm). This mild method features high levels of chemo- and regioselectivity and was used to generate 29 highly functionalized substituted dihydroquinoxalines in 44-98% yield. This transformation was also carried asymmetrically using (S,R)-N-PINAP as the chiral ligand to provide 9 chiral addition products in 96:4 to 86:14 e.r. The experimental and quantum chemical explorations of this reaction suggest a mechanism that involves Ir(III)-catalyzed triplet energy transfer mechanism followed by a ring-opening reaction ultimately leading to the formation of azomethine ylide intermediates. These azomethine intermediates undergo sequential protonation/copper(I) acetelide addition to provide the products. | 2023-12-08 | chemRxiv | Theoretical and Computational Chemistry; Organic Chemistry; Catalysis; Organic Compounds and Functional Groups; Stereochemistry; Photocatalysis | null | CC BY NC ND 4.0 |
Structure and biosynthesis of desmamides A-C, lipoglycopeptides from the endophytic cyanobacterium Desmonostoc muscorum LEGE 12446 | 10.26434/chemrxiv-2022-q0692 | N.A. | N.A. | Sara Freitas; Raquel Castelo Branco; Arlette Wenzel-Storjohann; Vitor Vasconcelos; Deniz Tasdemir; Pedro Leão | Certain cyanobacteria of the secondary metabolite-rich order Nostocales can establish permanent symbioses with a large number of cycads, by accumulating in their coralloid roots and shifting their metabolism to dinitrogen fixa-tion. Here, we report the discovery of two novel lipoglycopeptides, desmamides A (1) and B (2), together with their aglycone desmamide C (3), from the nostocalean cyanobacterium Desmonostoc muscorum LEGE 12446 isolated from a cycad (Cycas revoluta) coralloid root. The chemical structures of the compounds were elucidated using a combination of 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy and Mass Spectrometry (MS). The desmamides are decapeptides, featuring O-glycosylation of tyrosine (in 1 and 2) and an unusual 3,5-dihydroxy-2-methyldecanoic acid residue. The biosynthesis of the desmamides was studied by substrate feeding experiments and bioinformatics. We describe herein the dsm biosynthetic gene cluster (BGC) and propose it to be associated with desmamide production. The discovery of this class of very abundant (>1.5% d.w.) bacterial lipoglycopeptides paves the way for exploration of their potential role in root endosymbiosis. | 2022-02-04 | chemRxiv | Biological and Medicinal Chemistry; Microbiology | null | CC BY NC ND 4.0 |
Zirconium Coordination Chemistry and its Role in Optimizing Hydroxymate Chelation: Insights from Molecular Dynamics | 10.26434/chemrxiv-2023-38t1v | N.A. | N.A. | Giulia Sormani; Aruna Korde; Alex Rodriguez; Melissa Denecke; Ali Hassanali | In the last decade, there has been a growth in using Zirconium-89 (89 Zr) as a radionuclide in nuclear medicine for cancer diagnostic imaging and drug discovery processes. One of the most popular chelators for 89 Zr, is desferrioxamine (DFO) which acts as a hexadentate ligand. The coordination structure of the Zr4+-DFO complex has primarily been informed by DFT-based calculations which typically ignore temperature and therefore entropic and dynamic solvent effects. In this work, free energy calculations using molecular dynamics simulations, where the conformational fluctuations of both the ligand and the solvent are explicitly included, are used to compare the binding of Zr4+ cation with two different chelators, DFO and 4HMS, the latter of which has been recently proposed as a better chelator. We find that thermal induced disorder leads an open hexadentate chelate structure of Zr4+-DFO complex, leaving the Zr4+ metal exposed to the solvent. A stable coordination of Zr4+ with 4HMS, however, is formed involving both hydroxamate groups and water molecules in a more closely packed structure. | 2023-06-05 | chemRxiv | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Theory - Computational; Physical and Chemical Processes | null | CC BY 4.0 |
Targeted photodynamic neutralization of SARS-CoV-2 mediated by singlet oxygen | 10.26434/chemrxiv-2022-2ws41 | N.A. | N.A. | Ruhui Yao; Jian Hou; Xin Zhang; Yi Li; Junhui Lai; Qinqin Wu; Qinglian Liu; Lei Zhou | The SARS-CoV-2 virus has been on a rampage for more than two years. Vaccines in combination with neutralizing antibodies (NAbs) against SARS-CoV-2 carry great hope in the treatment and final elimination of COVID-19. However, the relentless emergence of variants of concern (VOC), including the most recent Omicron variants, presses for novel measures to counter these variants that often show immune evasion. Hereby we developed a targeted photodynamic approach to neutralize SARS-CoV-2 by engineering a genetically encoded photosensitizer (SOPP3) to a diverse list of antibodies targeting the WT spike protein, including human antibodies isolated from a 2003 SARS patient, potent monomeric and multimeric nanobodies targeting RBD, and non-neutralizing antibodies (non-NAbs) targeting the more conserved NTD region. As confirmed by pseudovirus neutralization assay, this targeted photodynamic approach significantly increased the efficacy of these antibodies, especially that of non-NAbs, against not only the WT but also the Delta strain and the heavily immune escape Omicron strain (BA.1). Subsequent measurement of infrared phosphorescence at 1270 nm confirmed the generation of singlet oxygen (1O2) in the photodynamic process. Mass spectroscopy assay uncovered amino acids in the spike protein targeted by 1O2. Impressively, Y145 and H146 form an oxidization “hotspot”, which overlaps with the antigenic “supersite” in NTD. Taken together, our study established a targeted photodynamic approach against the SARS-CoV-2 virus and provided mechanistic insights into the photodynamic modification of protein molecules mediated by 1O2. | 2022-12-09 | chemRxiv | Biological and Medicinal Chemistry; Bioengineering and Biotechnology | null | CC BY NC ND 4.0 |
Universal Approach to Direct Spatiotemporal Dynamic in-situ Optical Visualization of On-Catalyst Water Splitting Electrochemical Processes | 10.26434/chemrxiv-2024-42v2r | N.A. | N.A. | Gaurav Bahuguna; Fernando Patolsky | Electrochemical reactions are the unrivaled backbone of next generation energy storage, energy conversion and healthcare devices. However, the in-situ real-time visualization of electrochemical reactions, which can shed light on various critical unknown insights on the electrochemical processes, still remains the bottleneck for fully exploiting their intrinsic potential. In this work, for the first time, a universal approach to the direct spatiotemporal-dynamic in-situ optical visualization of pH based as well as specific byproduct based electrochemical reactions is performed. As a highly relevant and impactful example, the in-operando optical visualization of on-catalyst water splitting processes is performed under neutral water/seawater conditions. pH based visualization are performed using a water-soluble fluorescent pH probe HPTS (8-hydroxypyrene-1,3,6-trisulfonicacid), known for its exceptional optical capability of detecting even the tiniest environment pH changes, thus allowing the unprecedented “spatiotemporal” real-time visualization at the cathode and anode. The successful experimental investigations embarked here, allowed us to reach several yet unveiled deeper insights into the spatiotemporal water splitting processes and their practical modulation for potentially improving the applicability and efficiency of water splitting devices. As a result, we were able to unprecedentedly reveal that at a critical cathode-to-anode distance, a continuous bulk-electrolyte “self-neutralization” phenomenon can be achieved during the water splitting process, leading to the practical realization of enhanced additive-free neutral water splitting. Furthermore, we experimentally unveiled that at increasing electrolyte flow rates, a swift and severe inhibition of the concomitantly forming acidic and basic ‘fronts’, developed at anode and cathode compartments is observed, thus acting as a continuous on-catalysts “buffering” mechanism that allows for a remarkably enhanced water splitting process. Furthermore, to demonstrate the universal applicability of this elegant strategy which is not limited to pH changes, the technique was extended to visualization of specific electrochemical process by the use of reaction product-specific fluorophore. For the purpose, N-(4-butanoic acid) dansylsulfonamide (BADS) fluorophore was successfully explored to in-situ visualize the formation of hypochlorite/ chlorine at the anode during electrolysis of sea water. Thus, a unique experimental tool that allow real-time spatiotemporal visualization and simultaneous mechanistic investigation of complex electrochemical processes in developed that can be universally extended to various fields of research. | 2024-01-23 | chemRxiv | Materials Science; Analytical Chemistry; Energy; Catalysts; Electrochemical Analysis; Spectroscopy (Anal. Chem.) | null | CC BY 4.0 |
A Sulfamate-Tethered Aza-Wacker Cyclization Strategy for the Syntheses of 2-Amino-2-Deoxyhexoses: Preparation of Orthogonally Protected D-Galactosamines | 10.26434/chemrxiv-2022-1nhbb | N.A. | N.A. | SHYAM SATHYAMOORTHI; Debobrata Paul; Joel Mague | We present a new strategy for the assembly of protected D-galactosamine synthons. Our route uses a
sulfamate-tethered aza-Wacker cyclization as a key step and commences from D-erythrono-1,4-lactone.
This stands in contrast to most literature syntheses of 2-amino-2-deoxyhexose derivatives, as these
generally employ glycals or hexoses as starting materials. This strategy may serve as a template for the
assembly of many other 2-amino-2-deoxyhexoses with protection patterns difficult to access by
conventional methods. | 2022-09-30 | chemRxiv | Organic Chemistry | null | CC BY 4.0 |
Hexacyclotetradecenes as Polycyclic Fused exo-Norbornene Monomers: Synthesis of Cyclic Olefin Copolymers via Ti-Catalyzed Controlled Polymerization | 10.26434/chemrxiv-2024-bdl9p-v2 | N.A. | N.A. | Eri Funahashi; Yusuke Iwata; Shin-ichi Matsuoka | Polycyclic fused norbornenes (NBs) are important monomers for producing thermally stable cyclic olefin polymers and copolymers (COCs). However, the difficult addition polymerization of sterically demanding endo-substituted NBs limits the range of accessible COCs. Here, we explored the synthesis and polymerization of an isomeric mixture of hexacyclotetradecenes (1a and 1b) as new polycyclic fused exo-NB-based monomers. These monomers were readily prepared via a two-step catalysis process: norbornadiene dimerization followed by protic-acid-catalyzed isomerization. While ring-opening metathesis polymerization using conventional Ru carbene catalysts was not viable, addition polymerization and copolymerization with 1-octene, using a constrained geometry Ti catalyst, successfully proceeded in a controlled manner. Monomer 1 was consumed faster than 1-octene to form gradient copolymers. 13C nuclear magnetic resonance spectroscopies exhibited reasonable signals that indicated a 1,2-addition polymer structure. X-ray diffraction and thermogravimetry analysis confirmed the amorphous nature and thermal stability of poly1, which showed no weight loss below 400 °C. Thus, this study demonstrates the synthesis and polymerization of new promising polycyclic olefin monomers suitable for producing COC materials. | 2024-05-17 | chemRxiv | Organic Chemistry; Polymer Science; Polymerization (Polymers) | null | CC BY NC ND 4.0 |
Achieving a full-color palette with thickness, temperature, and humidity in cholesteric hydroxypropyl cellulose | 10.26434/chemrxiv-2023-06vk3 | N.A. | N.A. | Hongning Ren; Tadeusz Balcerowski; Ahu Gümrah DUMANLI | Hydroxypropyl cellulose (HPC) is a sustainable, cost-efficient, and bio-compatible cellulose derivative that forms cholesteric liquid crystalline phases in highly concentrated water solutions. While there have been studies exploiting HPC’s structural coloration and transferring the cholesteric order of the solutions into solid form via cross-linking and heat treatments, there is still a lack of understanding of the mechanisms that enable the transfer of the structural ordering of the HPC at high temperatures. In this work, we demonstrate the balance between temperature, humidity, and film thickness to achieve a full-color palette of pure HPC. While the cholesteric phase is trapped by water evaporation, the formation of a dense skin on the gels enables a thermal expansion of the encapsulated HPC gel during the heat treatment. Increasing the thickness, applying higher curing temperatures, and exposing the samples to higher humidity during the evaporation all result in increased pitch values that cause a red shift in coloration in the solid state. Our analysis of the HPC samples cured in controlled temperature and humidity conditions at a fixed thickness provided an understanding of the dominance of the thermal expansion which drives the final structural organization in the solid cholesteric phase. When the thickness of the films was varied against fixed temperature and humidity conditions, the color shift from red to violet follows the thickness gradient of the sample due to the change in the curing time required to reach the solid form. | 2023-01-12 | chemRxiv | Materials Science; Polymer Science; Liquid Crystals; Optical Materials; Cellulosic materials | null | CC BY NC ND 4.0 |
Rapid Biomolecular Trifluoromethylation Using Cationic Aromatic Sulfonate Esters as Visible Light-Triggered Radical Photocages | 10.26434/chemrxiv-2023-m9nsn-v2 | N.A. | N.A. | Nicholas Kuehl; Michael Taylor | Described here is a photo-decaging approach to radical trifluoromethylation of biomolecules. This was accomplished by designing a quinolinium sulfonate ester that, upon absorption of visible light, achieves decaging via photolysis of the sulfonate ester to ultimately liberate free trifluoromethyl radicals that are trapped by π-nucleophiles in biomolecules. This photo-decaging process enables protein and protein-interaction mapping experiments using trifluoromethyl radicals that require only one second reaction times and low photo-cage concentrations. In these experiments, aromatic side chains are labelled in an environmentally dependent fashion, with selectivity observed for tryptophan (Trp), followed by histidine (His) and tyrosine (Tyr). Scalable peptide trifluoromethylation through photo-decaging is also demonstrated, where bespoke peptides harboring trifluoromethyl groups at tryptophan residues can be synthesized with five to seven minute reaction times and good yields. | 2023-07-27 | chemRxiv | Biological and Medicinal Chemistry; Organic Chemistry; Organic Synthesis and Reactions; Photochemistry (Org.); Chemical Biology | null | CC BY NC ND 4.0 |
Chloro-silane vapor assisted in-plane delamination of liquid metal films for unconventional heterogeneous wettability | 10.26434/chemrxiv-2022-x0jml | 10.1039/d3sm00258f | https://doi.org/10.1039/d3sm00258f | Kazi Zihan Hossain ; Momena Monwar; M. Rashed Khan | Numerous complex methods have been reported to generate heterogeneously wettable surfaces in the literature. These surfaces are well-sought in energy, water, health care, separation science, self-cleaning, biology, and other lab-on-chip applications. While most of the demonstrations of heterogeneous wettability rely on a series of complex fabrication protocols, we reveal an unconventional approach to achieving heterogeneous wettability through three simple steps (i.e., patterning, silanizing, and rinsing). Here, we show heterogeneous wettability on a planar substrate harnessing (a) the wetting and dewetting behavior of nano-textured conductive surface patterns of Gallium alloys and (b) interfacial chemical reactivity of the native surface oxides of these alloys in the presence of chloro-silane vapor. Alloys of Gallium (eGaIn and others) have emerged as one of the most promising soft metals for the fabrication of soft functional devices harnessing their surface oxides, mostly Gallium Oxide (Ga2O3). These alloys can be 2D patterned utilizing the wetting behavior of the Ga2O3, which seems impossible due to the high surface tension of the bare metal. We utilized such 2D metal patterns on the planar glass surface and exposed the patterns in chloro-silane vapors to begin our study. Chloro-silanes can alter the surface energy of different substrates (i.e., glass, silicon wafer) to offer hydrophobicity and releases Chlorine vapors which etch Ga2O3 that induces the delamination. A simple DI water rinsing operation reveals a thin hydrophilic layer on the pre-patterned area that we utilized for an open-ended microfluidic demonstration, as well. We confirmed hydrophilicity through contact angle measurements; elemental compositions, and Chlorine's presence through energy dispersive spectroscopic (EDS) analyses. We believe such an unconventional approach of achieving heterogeneous wettability has the potential for fundamental studies related to bioinspired and biomimetic applications. | 2022-03-16 | chemRxiv | Materials Science; Thin Films; Materials Chemistry | null | CC BY NC ND 4.0 |
Chemical Potential Driven Reorganization of Anions between Stern and Diffuse Layers at the Air/Water Interface | 10.26434/chemrxiv-2021-f20gf-v2 | 10.1021/acs.jpcc.1c06925 | https://doi.org/10.1021/acs.jpcc.1c06925 | Raju Kumal; Srikanth Nayak; Wei Bu; Ahmet Uysal | Ion adsorption and transfer at charged interfaces play key roles in various industrial and environmental processes. Molecular scale details of ion-ion, ion-water, and ion-surface interactions and their dependence on the character of the ion (ion-specific effects) are still debated. Complex ions, such as SCN- and SeCN-, are particularly interesting due to their unexpected adsorption trends which are ascribed to their permanent dipole moment and non-spherical shape. Here, we combine vibrational sum frequency generation (VSFG) spectroscopy and surface sensitive synchrotron X-ray studies to provide a detailed description of SeCN- adsorption at a charged surfactant monolayer at the air/aqueous interface. The results show that the increasing chemical potential may lead to further reorganization of the adsorbed ions, even though the total interfacial ion population does not change. | 2021-08-05 | chemRxiv | Physical Chemistry; Interfaces | null | CC BY NC ND 4.0 |
A Small Molecule Inhibitor with Elongated Residence Time Blocking the Cytolytic Effects of the Pore-Forming Toxin Pneumolysin | 10.26434/chemrxiv-2022-fx0d2 | N.A. | N.A. | Umer Bin Abdul Aziz; Marcel Bermudez; Maren Mieth; Ali Saoud; Thomas Rudolf; Christoph Arkona; Christoph Böttcher; Kai Ludwig; Andreas Hocke; Gerhard Wolber; Jörg Rademann | Pneumolysin (PLY) is a pore-forming, cholesterol-dependent cytolysin (CDC) from Streptococcus pneumoniae, the main bacterial cause for community-acquired pneumonia. Liberation of PLY during host infection leads to strong immune activation and cytolytic cell death. Thus, inhibition of PLY could be a valuable approach to attenuate detrimental effects of hyper-inflammatory immune reactions during pneumococcal lung infection. Here, we report discovery, development, and validation of small molecule inhibitors of PLY, denominated as pore-blockers (PB). PB-1 was identified by combined screening inhibiting PLY-mediated hemolysis. PB-2 blocked pore formation with greatly improved potency as demonstrated by cryo-electron tomography. Scaffold-hopping delivered PB-3 with superior chemical stability, solubility, and a specific mode of action, characterized by an elongated residence time. It prevented human lung epithelial cells from PLY-mediated cytolysis and cell death, also during infection with Streptococcus pneumoniae. In conclusion, druglike PLY-inhibitors such as PB-3 might become valuable adjuvant options in the treatment of severe pneumococcal infections. | 2022-06-15 | chemRxiv | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Chemical Biology; Drug Discovery and Drug Delivery Systems | null | CC BY 4.0 |
The Role of Atomic Carbon in Directing Electrochemical CO(2) Reduction to Multicarbon Products | 10.26434/chemrxiv.11374785.v1 | 10.1039/D0EE02826F | https://doi.org/10.1039/D0EE02826F | Hongjie Peng; Michael Tang; Xinyan Liu; Philomena Schlexer Lamoureux; Michal Bajdich; Frank Abild-Pedersen | Electrochemical reduction of
carbon-dioxide/carbon-monoxide (CO<sub>(2)</sub>R) to fuels and chemicals
presents an attractive approach for sustainable chemical synthesis, but also
poses a serious challenge in catalysis. Understanding the key aspects that
guide CO<sub>(2)</sub>R towards value-added multicarbon (C<sub>2+</sub>)
products is imperative in designing an efficient catalyst. Herein, we identify
the critical steps toward C<sub>2</sub> products on copper through a
combination of energetics from density functional theory and micro-kinetic
modeling. We elucidate the importance of atomic carbon in directing C<sub>2+</sub>
selectivity and how it introduces surface structural sensitivity on copper
catalysts. This insight enables us to propose two simple thermodynamic
descriptors that effectively describe C<sub>2+</sub> selectivity on metal
catalysts beyond copper and hence it identifies an intelligible protocol to
screen for materials that selectively catalyze CO<sub>(2)</sub> to C<sub>2+</sub>
products. | 2019-12-31 | chemRxiv | Reaction Engineering; Electrocatalysis; Heterogeneous Catalysis | null | CC BY NC ND 4.0 |
Direct detection of molecular hydrogen upon p- and n- doping of organic semiconductors with complex oxidants or reductants | 10.26434/chemrxiv-2023-c4v46 | N.A. | N.A. | Francesca Pallini; Sara Mattiello; Norberto Manfredi; Sara Mecca; Alexey Fedorov; Mauro Sassi; Khaled Al Kurdi; Yi-Fan Ding; Chen-Kai Pan; Jian Pei; Stephen Barlow; Seth R. Marder; Thuc-Quyen Nguyen; Luca Beverina | Molecular doping enables increasing the conductivity of organic semiconductors and plays an increasingly important role in emerging and established plastic electronics applications. 1,3-Dimethyl-2-(4-(dimethylamino)phenyl)-2,4-dihydro-1H-benzoimidazole (N-DMBI-H) and tris(pentafluorophenyl)borane (BCF) are established n- and p-dopants, respectively, but neither functions as a simple one-electron redox agent. Molecular hydrogen has been proposed to be a byproduct of several mechanisms for doping using both DMBI-H and BCF. In this paper we show for the first time the direct detection of molecular hydrogen in the uncatalyzed doping of a variety of polymeric and molecular semiconductors using these dopants. Our results provide insight in the doping mechanism, providing information complementary to that obtained from more commonly applied methods such as optical, electron spin resonance, and electrical measurements. | 2023-01-11 | chemRxiv | Organic Chemistry; Polymer Science; Physical Organic Chemistry; Conducting polymers; Polymer blends; Materials Chemistry | null | CC BY NC ND 4.0 |
OOPS, the Ontology for Odor Perceptual Space: from molecular composition to sensory attributes of odor objects | 10.26434/chemrxiv-2022-lxdk2 | 10.3390/molecules27227888 | https://doi.org/10.3390/molecules27227888 | Alice Roche; Nathalie Mejean Perrot; Thierry Thomas-Danguin | When creating a flavor to elicit a specific odor object characterized by odor sensory attributes (OSA), expert perfumers or flavorists use mental combinations of odor qualities (OQ) such as Fruity, Green, Smoky. However, OSA and OQ are not directly related to the molecular composition in terms of odorants that constitute the chemical stimuli supporting odor object perception because of the complex non-linear integration of odor mixtures within the olfactory system. Indeed, single odorants are described with odor descriptors (OD), which can be found in various databases. Although classifications and aroma wheels studied the relationships between OD and OQ, the results are highly dependent of the studied products. Nevertheless, ontologies have proved to be very useful in sharing concepts across applications in a generic way but also to allow experts’ knowledge integration implying non-linear cognitive processes. In this paper we constructed the Ontology for Odor Perceptual Space (OOPS) to merge OD into a set of OQ best characterizing the odor further translated in a set of OSA thanks to expert knowledge integration. Results showed that OOPS can help to bridge molecular composition to odor perception and description as demonstrated in the case of wines. | 2022-05-10 | chemRxiv | Agriculture and Food Chemistry; Food | null | CC BY NC 4.0 |
Exploiting Electricity Market Dynamics using Flexible Electrolysis Units for Retrofitting Methanol Synthesis | 10.26434/chemrxiv-2023-fx947-v2 | N.A. | N.A. | jiaze ma; Michael Rebarchik; Saurabh Bhandari; Manos Mavrikakis; George Huber; Victor Zavala | We investigate the economic viability of integrating flexible electrolysis units to produce hydrogen in methanol synthesis processes. Specifically, we investigate whether this approach can help reduce methanol production costs by strategically exploiting dynamics of electricity markets. Our study integrates high-fidelity process simulations, optimization tools, and microkinetic modeling (informed by density functional theory) to conduct detailed techno-economic analyses and to compare performance against traditional processes that use hydrogen produced via steam-methane reforming (SMR). We also use this approach to estimate the levelized cost of hydrogen (LCOH) as a function of time-varying electricity prices (from day-ahead and real-time prices) and of key techno-economic parameters. Our results show that the proposed electrification framework is cost-competitive under certain electricity market conditions. Specifically, we find that, when the electrolysis system is operated in flexible mode (and can respond to dynamics of electricity markets), the associated electricity cost nearly collapses to zero. Conversely, when the unit is not flexible (and cannot respond to markets), the electricity cost comprises 60% of the total cost. Our results also reveal that the LCOH of the flexible electrolysis system participating in real-time electricity markets is 31% lower than the LCOH obtained from SMR. Overall, this indicates that exploiting the dynamics of electricity markets can make hydrogen production cost-competitive and this can lead to viable alternatives to electrify methanol production and other hydrogen-based processes. | 2023-03-15 | chemRxiv | Energy; Chemical Engineering and Industrial Chemistry; Industrial Manufacturing; Energy Storage | null | CC BY 4.0 |
Repurposing Therapeutics to Identify Novel Inhibitors Targeting 2'-O-Ribose Methyltransferase Nsp16 of SARS-CoV-2 | 10.26434/chemrxiv.12252965.v1 | N.A. | N.A. | Yuanyuan Jiang; Lanxin Liu; Morenci Manning; Madison Bonahoom; Aaron Lotvola; Zeng-Quan Yang | <p>Three
coronaviruses (CoVs): severe acute respiratory syndrome coronavirus
(SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and the
recently identified SARS-CoV-2 in December 2019, have caused deadly pneumonia
in humans since the beginning of the 21st century. The SARS-CoV-2 causes
coronavirus disease-19 (COVID-19) with influenza-like symptoms ranging from
mild discomfort to severe lung injury and multi-organ failure, eventually
leading to death. As of April 30, 2020, more than three million (3,175,207)
COVID-19 cases were reported worldwide, and more than 220,000 (224,172)
patients have died
(https://www.who.int/emergencies/diseases/novel-coronavirus-2019). Effective
treatments and vaccines for SARS-CoV-2 infection do not currently exist. Thus,
it will be of great benefit to identify and repurpose already
well-characterized compounds and approved drugs for use in combating COVID-19.</p>
<p> </p>
<p>CoVs are
positive-sense RNA viruses that replicate in the cytoplasm of infected cells.
Replication and transcription of the CoV RNA genome are achieved by a complex
RNA replication/transcription machinery, consisting of at least 16 viral
nonstructural proteins (nsp). Previous studies demonstrated that nsp16 proteins
of SARS-CoV-1 and MERS-CoV have methyltransferase (MTase) activities that
catalyze methylation of the first transcribed nucleotide at the ribose 2’-O
position (2’-O-Me). The 2’-O-Me of virus cap RNAs protects itself from
degradation by 5′-3′ exoribonucleases, ensures efficient translation, and helps
to prevent recognition by the host innate immune system. The importance of
nsp16 2'-O-MTase activity for CoV infection and pathogenesis was previously
documented by in vitro and in vivo studies. For SARS-CoV-1, the absence of
nsp16 2′-O-MTase activity results in significant attenuation characterized by
decreased viral replication, reduced weight loss, and limited breathing dysfunction
in mice. In addition, nsp16 down-regulates the activities of innate immune
sensing factors: retinoic acid-inducible gene I (RIG-I) and melanoma
differentiation-associated gene 5 protein (MDA5). Thus, inhibition of nsp16
2’-O-MTase activities should restrain viral replication and enable recognition
by the host innate immune system, making the nsp16-MTase a promising target for
the identification of new anti-SARS-CoV-2 drugs. </p>
<p> </p>
<p>In the
present study, we employed structural analysis, virtual screening, and
systematic drug repurposing approaches to identify “approved” drugs which can
act as promising inhibitors against nsp16 2′-O-MTase of SARS-CoV-2. We first
performed comparative analysis of primary amino acid sequences and crystal
structures of seven human CoVs and defined the key residues for nsp16
2-O’-MTase functions. From the virtual screening against nsp16 2′-O-MTase of
SARS-CoV-2, we provide a ranking of the predicted binding affinities of 1,380
top hit compounds corresponding to 967 “approved” drugs. Furthermore, we have
calculated various structural parameters of our top-ranking drugs. Our studies
provided the foundation to further test and repurpose these candidate drugs
experimentally and clinically for COVID-19 treatment. </p><br /> | 2020-05-11 | chemRxiv | Chemical Biology | null | CC BY NC ND 4.0 |
Nonadiabatic Excited State Molecular Dynamics with explicit solvent: NEXMD-SANDER implementation | 10.26434/chemrxiv-2024-tgbjq | N.A. | N.A. | Dustin Tracy; Sebastian Fernandez-Alberti; Johan Fabian Galindo; Sergei Tretiak; Adrian Roitberg | In this article, the Nonadiabatic Excited-state Molecular dynamics (NEXMD) package is linked with the SANDER package, provided by AMBERTOOLS. The combination of these software packages enables the simulation of photoinduced dynamics of large multichromophoric conjugated molecules involving several coupled electronic excited states embedded in an explicit solvent by using Quantum/Mechanics/Molecular Mechanics (QM/MM) methodology. The fewest switches surface hopping algorithm, as implemented in NEXMD, is used to account for quantum transitions among the adiabatic excited-states Simulations of the photoexcitation and subsequent nonadiabatic electronic transitions and vibrational energy relaxation of a substituted polyphenylene vinylene oligomer (PPV3-NO2) in vacuum and methanol as explicit solvent has been used as a test case. The impact of including specific solvent molecules in the QM region is also analysed. Our NEXMD-SANDER QM/MM implementation provides a useful computational tool to simulate qualitatively solvent-dependent effects, like electron transfer, stabilization of charge separated excited states, the role of solvent reorganization in the molecular optical properties, observed in solution-based spectroscopic experiments. | 2024-08-27 | chemRxiv | Physical Chemistry; Spectroscopy (Physical Chem.) | null | CC BY NC ND 4.0 |
An In Vivo Biocatalytic Cascade Featuring an Artificial Enzyme Catalyzed New-to-Nature Reaction | 10.26434/chemrxiv-2021-nppzq | N.A. | N.A. | Linda Ofori Atta; Zhi Zhou; Gerard Roelfes | Artificial enzymes utilizing the genetically encoded non-proteinogenic amino acid p-aminophenylalanine (pAF) as catalytic residue are able to react with carbonyl compounds through an iminium ion mechanism, making reactions possible that have no equivalent in nature. Here, we report an in vivo biocatalytic cascade that is augmented with such an artificial enzyme catalyzed new-to-nature reaction. The artificial enzyme in this study is a pAF containing evolved variant of the Lactococcal multidrug resistance Regulator, designated LmrR_V15pAF_RMH, which efficiently converts in vivo produced benzaldehyde derivatives into the corresponding hydrazone products inside E. coli cells. These in vivo biocatalytic cascades comprising an artificial enzyme catalyzed reactions are an important step towards achieving a hybrid metabolism. | 2021-11-11 | chemRxiv | Catalysis; Biocatalysis; Organocatalysis | null | CC BY NC ND 4.0 |
Synergistic Photoredox/Palladium Catalysis Enables Enantioconvergent Cross-Electrophile Esterification with CO2 | 10.26434/chemrxiv-2024-s9wwt | N.A. | N.A. | Jiawang Liu; Bihai Ye; Lei Su; kaiting Zheng; Shen Gao | Herein, we presented a synergistic catalytic system that utilizes 4CzIPN and (R)-L1/Pd(acac)2 as catalysts for an efficient and enantioconvergent synthesis of axially chiral esters from racemic heterobiaryl bromides and alkyl bromides with CO2 under mild conditions. A wide range of axially chiral esters, featuring various functional groups, were obtained through this novel methodology in good to high yields with excellent enantioselectivities. Detailed mechanistic studies unveiled that the ratio of 4CzIPN/[Pd/(R)-L1] significantly influences the chemo- and enantioselectivity of the reaction. Kinetic studies and control experiments supported the proposed mechanism involving cascade asymmetric carboxylation followed by SN2 substitution. Achieving high enantioselectivities relies not only on the choice of synergistic metallaphotoredox catalysts but also on the utilization of alkyl bromides, which trap the generated chiral carboxylic anions in situ, preventing their immediate racemization. | 2024-04-22 | chemRxiv | Organic Chemistry; Catalysis | null | CC BY NC 4.0 |
Negative swelling hydrogel enabled by osmotic pressure induced dehydration | 10.26434/chemrxiv-2023-gmjjr | N.A. | N.A. | Zhi Zhao; Xuan Yao; Xiaotong Zheng; Yurong Li; Haibin Wang; Xuemei Liu; Tielong Han; Xiaoyan Song | Swelling positively in water is a common behavior of hydrogels, which may lead to reduced mechanical performance and stability. Enabling negative swelling represents a promising way to address those issues, but is extremely challenging to realize. Here real negative swelling hydrogels had been successfully prepared for the first time through a unique double network design. A transformable network confined by a rigid network was prone to self-assembly under osmotic pressure, which eventually caused dehydration of the entire hydrogel. Such gels could lose up to 35% of their weight underwater, and featured water-strengthened mechanical properties, enhanced structural responsiveness, underwater repair ability, resistance to deformation and swelling turn-off effect. Those unique properties allow future material development and applications to be carried out in much broader dimensions. | 2023-12-05 | chemRxiv | Materials Science; Polymer Science; Metamaterials; Hydrogels; Polymer chains; Materials Chemistry | null | CC BY NC 4.0 |
Multiphoton Excitation of Organic Molecules in a Cavity – Superradiance as a Measure of Coherence | 10.26434/chemrxiv.13130228.v1 | N.A. | N.A. | Inga Ulusoy; Johana A. Gomez; Oriol Vendrell | <div>Coherent excitation of a molecular ensemble coupled to a common radiation mode can lead to the collective emission of radiation known as superradiance. This collective emission only occurs if there is an entanglement between the molecules in their ground and excited state and can therefore serve as a macroscopic measure of coherence in the ensemble. Reported here are wave packet propagations for various pyrazine models of increasing complexity and molecular ensembles thereof. We show that ensemble coherence upon photoexcitation can prevail up to relatively long time scales, although the effect can diminish quickly with increasing ensemble size. Coherence can also build up over time and even reemerge after the molecules have passed through a conical intersection. The effect of the pump-pulse characteristics on the collective response of the molecular ensemble is also studied. A broad-band pulse imprints a large amount of initial coherence to the system, as compared to a longer pulse with a smaller spread in the frequency domain. However, the differential effects arising from a different pulse duration and coherent bandwidth become less prominent if the emission of light from the ensemble takes place after a non-adiabatic decay process.</div> | 2020-10-23 | chemRxiv | Theory - Computational; Photochemistry (Physical Chem.); Physical and Chemical Processes; Quantum Mechanics | null | CC BY NC ND 4.0 |
Side Area-Assisted 3D Evaporator with Antibiofouling Function for Ultra-Efficient Solar Steam Generation | 10.26434/chemrxiv.14185643.v1 | N.A. | N.A. | Haoxuan Li; wei zhu; Meng Li; Ying Li; Jacky W. Y. Lam; Lei Wang; Dong Wang; Ben Zhong Tang | <p><a></a></p><p>Solar-driven interfacial steam generation (SISG) has been recognized as the most promising strategy to solve water shortages in an eco-friendly and low-cost way. However, the practical application of SISG is vitally restricted by some inherent limits, especially for finite evaporation rate and insufficient working life of evaporator. Herein, we explore a novel SISG system involving an all-fiber porous cylinder-like foam (AFPCF) 3D evaporator, side area-assisted evaporation protocol, and aggregation-induced emission (AIE)-active molecules with “one stone two birds” function. The AIE-featured solar absorber exhibits highly efficient sunlight absorption and photothermal conversion, endowing the side area-assisted evaporator with as high as 3.6 kg
m-2
h
-1 of solar evaporation rate under 1 sun of irradiation. Moerover, the evaporator is capable of powerfully producing reactive oxygen species (ROS) upon sunlight irradiation benefiting the prominent photosensitizing property of the AIE molecules, which results in extraordinary photodynamic killing of bacteria nearby the fiber to prevent biofouling, consequently improving the working life of evaporator</p><br /><p></p> | 2021-03-10 | chemRxiv | Water Purification | null | CC BY NC ND 4.0 |
Molybdenum Sulfide Clusters as Molecular Co-Catalyst on Antimony Selenide Photocathodes for Photoelectrochemical Hydrogen Evolution | 10.26434/chemrxiv-2024-v4h15 | 10.1021/acsenergylett.4c01570 | https://doi.org/10.1021/acsenergylett.4c01570 | Pardis Adams; Jan Bühler; Iva Walz; Thomas Moehl; Helena Roithmeyer; Olivier Blacque; Nicolò Comini; Trey Diulus; Roger Alberto; Sebastian Siol; Mirjana Dimitrievska; Zbynek Novotny; David Tilley | Molybdenum sulfide serves as an effective non-precious metal catalyst for hydrogen evolution, primarily active at edge sites with unsaturated molybdenum sites or terminal disulphides. To improve the activity at low loading density, two molybdenum sulfide clusters, [Mo3S4]4+ and [Mo3S13]2–, were investigated. The Mo3Sx molecular catalysts were heterogenized on Sb2Se3 with a simple soaking treatment, resulting in a thin catalyst layer of only a few nanometers that gave up to 20 mA cm–2 under one sun illumination. Both [Mo3S4]4+ and [Mo3S13]2– exhibit catalytic activities on Sb2Se3 through a simple soaking process, with [Mo3S13]2– emerging as the superior catalyst, demonstrating enhanced photovoltage and average faradaic efficiency of 100% for hydrogen evolution. This superiority is attributed to the effective loading and higher catalytic activity of [Mo3S13]2– on the Sb2Se3 surface, validated by X-ray photoelectron and Raman spectroscopy. | 2024-06-12 | chemRxiv | Catalysis; Electrocatalysis | null | CC BY 4.0 |
Rapid Characterization of Structural and Behavioral Changes of Therapeutic Proteins by Relaxation and Diffusion 1H-SOFAST NMR Experiments | 10.26434/chemrxiv-2024-nj5cc | N.A. | N.A. | Xingjian Xu; Guilherme Dal Poggetto; Mark McCoy; Mikhail Reibarkh; Pablo Trigo Mourino | Biologic drugs have emerged as a rapidly expanding and important modality, offering promising therapeutic solutions by interacting with previously 'undruggable' targets, thus significantly expanding the range of modern pharmaceutical applications. However, the inherent complexity of these drugs also introduces liabilities and poses challenges in their development, necessitates efficient screening methods to evaluate the structural stability and behavior. Although NMR spectroscopy is well-suited for detecting weak interactions, changes in dynamics, high-order structure, and association states of macromolecules in fully formulated samples, the inherent low sensitivity limits its utility as a fast screening and characterization tool. In this study, we present two fast pulsing NMR experiments, namely the SOFAIR (band-Selective Optimized Flip-Angle Internally-encoded Relaxation) and the SOFIT (band-Selective Optimized Flip-angle Internally-encoded Translational diffusion), which enable rapid and reliable measurements of transverse relaxation rates and diffusion coefficients with more than 10-fold higher sensitivity compared to commonly used methods, like CPMG (Carr-Purcell-Meiboom-Gill) and DOSY (Diffusion-Ordered Spectroscopy), allowing the rapid assessment of biologics even at low concentrations. We demonstrated the effectiveness and versatility of these experiments by evaluating several examples, including thermally stressed proteins, proteins at different concentrations, and a therapeutic protein in various formulations. We anticipate that these novel approaches will greatly facilitate the analysis and characterization of biologics during drug discovery. | 2024-08-08 | chemRxiv | Analytical Chemistry; Spectroscopy (Anal. Chem.) | null | CC BY NC ND 4.0 |
Poly(2-ethyl-2-oxazoline-co-N-propylethylene imine)s by controlled partial reduction of poly(2-ethyl-2-oxazoline) | 10.26434/chemrxiv.5786853.v1 | N.A. | N.A. | Maria Pfister; Annemarie Ringhand; Corinna Fetsch; Robert Luxenhofer | The partial reduction of poly(2-ethyl-2-oxazoline) was investigated. A series of poly(2-ethyl-2-oxazoline-co-N-propylethylene imine)s were synthesized by direct reduction using lithium aluminum hydride or borane/dimethylsulfide (BH<sub>3</sub>/DMS), respectively. It is shown that the degree of reduction can be readily controlled either by the reaction time when using an excess of LiAlH<sub>4</sub> or by the stoichiometry of BH<sub>3</sub>/DMS as was demonstrated by 1H-NMR spectroscopy. Differential scanning calorimetry revealed that the glass transition temperature of the products decreased with increasing degree of reduction up to 25% of reduction, above which no glass transition could be detected. This control over the reduction allows the tailor synthesis of partially cationic polymers, which, in combination over the hydrophilic/lipophilic balance through the side chain length allows a tight control over materials properties. Such materials may be interesting, <i>inter alia</i>, for biomaterials or organic electronics. | 2018-01-16 | chemRxiv | Drug delivery systems; Polyelectrolytes - Polymers | null | CC BY NC ND 4.0 |
Aza-Yang Cyclization—Buchner Aromatic Ring Expansion: Collective Synthesis of Cycloheptatriene-containing Azetidine Lactones | 10.26434/chemrxiv-2021-z4w2d | N.A. | N.A. | Manvendra Singh; Bryce Gaskins; Daniel Johnson; Christopher Elles; Zarko Boskovic | We prepared a collection of complex cycloheptatriene-containing azetidine lactones by ap- plying two key photochemical reactions: “aza-Yang” cyclization and Buchner carbene insertion into aromatic rings. While photolysis of phenacyl amines leads to a rapid charge transfer and elimination, we found that a simple protonation of the amine enables the formation of azetidinols as single diastereomers. We provide evidence, through ultrafast spectroscopy, for the electron transfer from free amines in the excited state. Further, we characterize aza-Yang re- action by establishing the dependence of initial reaction rates on rates of photon absorption. Unanticipated change in reactivity in morpholine analogs is explained through interactions with the tosylate anion. Buchner reaction proceeds with slight preference for one diastereomer over the other, and successful reaction requires electron-donating carbene-stabilizing substituents. Overall, sixteen compounds were prepared over seven steps. Guided by an increase in structural complexity, efforts such as this one extend reach of chemists into unexplored chemical space and provide useful quantities of new compounds for studies focused on their properties. | 2021-12-29 | chemRxiv | Organic Chemistry; Organic Synthesis and Reactions; Photochemistry (Org.); Physical Organic Chemistry | null | CC BY NC ND 4.0 |
From Theory to Experiment: Transformer-Based Generation Enables Rapid Discovery of Novel Reactions | 10.26434/chemrxiv-2021-c192z-v2 | N.A. | N.A. | Xinqiao Wang; Chuansheng Yao; Yun Zhang; Jiahui Yu; Haoran Qiao; Chengyun Zhang; Yejian Wu; Renren Bai; Hongliang Duan | Deep learning methods have been proven their potential roles in the chemical field, such as reaction prediction and retrosynthesis analysis. However, the de novo generation of unreported reactions using artificial intelligence technology remains not be completely explored. Inspired by molecular generation, we proposed the task of novel reaction generation. In this work, we applied the Heck reactions to train the transformer model, state-of-art natural language process model and obtained 4717 generated reactions after sampling and processing. We then confirmed that 2253 novel Heck reactions by organizing chemists to judge the generated reactions, and adopted organic synthesis experiment to verify the feasibility of unreported reactions. In this process, it only took 15 days from Heck reaction generation to experimental verification, proving that our model learns reaction rules in-depth and can make great contributions in the novel reaction discovery. | 2021-08-10 | chemRxiv | Theoretical and Computational Chemistry; Organic Chemistry | null | CC BY NC ND 4.0 |
Development and Application of ReaxFF Methodology for Understanding the Chemical Dynamics of Metal Carbonates in Aqueous Solutions | 10.26434/chemrxiv-2021-v2rcx | 10.1039/D1CP04790F | https://doi.org/10.1039/D1CP04790F | Nabankur Dasgupta; Chen Chen; Adri van Duin | A new ReaxFF reactive force field has been developed for metal carbonate systems including Na+, Ca2+, and Mg2+ cations and the CO32- anion. This force field is fully transferable with previous ReaxFF water and water/electrolyte descriptions. The Me-O-C three-body valence angle parameters and Me-C non-reactive parameters of the force field have been optimized against quantum mechanical calculations including equations of states, heats of formation, heats of reaction, angle distortions and vibrational frequencies. The new metal carbonate force field has been validated using molecular dynamics simulations to study solvation and reactivity of metal and carbonate ions in water at 300 K and 700 K. The coordination radius and self-diffusion coefficient show good consistency with existing experiments and simulations results. The angular distribution analysis explains the structural preference of carbonate ions to form carbonates and bicarbonates, where Na+ predominantly forms carbonates due to lesser angular strain, while Ca2+ and Mg2+ prefer to form bicarbonates monodentate in nature. Residence time distribution analyses on different systems reveal the role of ions in accelerating and decelerating dynamics of water and carbonate ions under different thermodynamic conditions. The formation and dissolution of bicarbonates and carbonates in the solution were explored on the basis of protonation capability in different systems. The nucleation phenomenon of metal carbonates at ambient and supercritical conditions is explained from the perspective of clusters formation over time: Ca2+ ions can form prenucleation clusters at ambient temperature but shows a saturation with temperature, whereas Na+ and Mg2+ ions show rapid increase in cluster size and amount upon increasing time and temperature. | 2021-10-21 | chemRxiv | Theoretical and Computational Chemistry; Physical Chemistry; Earth, Space, and Environmental Chemistry; Computational Chemistry and Modeling; Electrochemistry - Mechanisms, Theory & Study; Statistical Mechanics | null | CC BY NC 4.0 |
Distinct RNA N-Demethylation Pathways Catalyzed by Non-Heme Iron ALKBH5 and FTO Enzymes Enable Regulation of Formaldehyde Release Rates | 10.26434/chemrxiv.12816224.v1 | N.A. | N.A. | Joel D.W. Toh; Steven W. M. Crossley; Kevin Bruemmer; Eva J. Ge; Dan He; Diana Iovan; Christopher Chang | <p>Abstract</p><p><br /></p><p>The AlkB family of non-heme-Fe(II)/2-oxoglutarate(2OG)-dependent oxygenases are essential regulators of RNA epigenetics by serving as erasers of one-carbon marks on RNA with release of formaldehyde (FA). Two major human AlkB family members, FTO and ALKBH5, both act as oxidative demethylases of N6 methyladenosine (m6A) but furnish different major products, N6 hydroxymethyladenosine (hm6A) and adenosine (A), respectively. Here we identify foundational mechanistic differences between FTO and ALKBH5 that promote these distinct biochemical outcomes. In contrast to FTO, which follows a traditional oxidative N-demethylation pathway to catalyze conversion of m6A to hm6A with subsequent slow release of A and FA, we find that ALKBH5 catalyzes a direct</p><p>m6A-to-A transformation with rapid FA release. We identify a catalytic R130/K132/Y139 triad within ALKBH5 that facilitates release of FA via an unprecedented covalent-based demethylation mechanism with direct detection of a covalent intermediate. Importantly, a K132Q mutant furnishes an ALKBH5 enzyme with an m6A demethylation profile that resembles that of FTO, establishing the importance of this residue in the proposed covalent mechanism. Finally, we show that ALKBH5 is an endogenous source of FA in the cell by activity-based sensing of FA fluxes perturbed via ALKBH5 knockdown. This work provides a fundamental biochemical rationale for non-redundant roles of these RNA demethylases beyond different substrate preferences and cellular localization, where m6A demethylation by ALKBH5 versus FTO results in release of FA, an endogenous one-carbon unit but potential genotoxin, at different rates in living systems.</p><p><br /></p><p><br /></p><p>Significance Statement</p><p><br /></p><p>Non-heme iron enzymes FTO and ALKBH5 play central roles in epigenetic RNA regulation by catalyzing the oxidation of N6-methyladenosine (m6A) to produce N6-hydroxymethyladenosine (hm6A) and adenosine (A), respectively. Here, we provide a mechanistic rationale for these distinct biochemical outcomes by identifying that ALKBH5 performs m6A demethylation via an unprecedented covalent-based mechanism with concomitant and rapid release of A and formaldehyde (FA), whereas FTO liberates hm6A to release A and FA over longer timescales. This work reveals foundational biochemical differences between these closely related but non-redundant epigenetic enzymes and identifies ALKBH5 as an endogenous source of rapid formaldehyde generation in cells.</p> | 2020-08-18 | chemRxiv | Biochemistry; Cell and Molecular Biology; Chemical Biology | null | CC BY NC ND 4.0 |
E Pluribus Unum: Functional Aggregation of Cell-Free Proteins Enables Fungal Ice Nucleation | 10.26434/chemrxiv-2023-63qfl-v2 | 10.1073/pnas.2303243120 | https://doi.org/10.1073/pnas.2303243120 | Ralph Schwidetzky; Ingrid de Almeida Ribeiro; Nadine Bothen ; Anna Backes; Arthur L. DeVries; Mischa Bonn; Janine Frhlich-Nowoisky; Valeria Molinero; Konrad Meister | Biological ice nucleation plays a key role in the survival of cold-adapted organisms. Several species of bacteria, fungi, and insects produce ice nucleators (INs) that enable ice formation at temperatures above -10 oC. Bacteria and fungi produce particularly potent INs that can promote water crystallization above -5 oC. Bacterial INs consist of extended protein units that aggregate to achieve superior functionality. Despite decades of research, the nature and identity of fungal INs remain elusive. Here we combine ice nucleation measurements, physicochemical characterization, numerical modeling and nucleation theory to shed light on the size and nature of the INs from the fungus Fusarium acuminatum. We find ice-binding and ice-shaping activity of Fusarium IN, suggesting a potential connection between ice growth promotion and inhibition. We demonstrate that fungal INs are composed of small 5.3 kDa protein subunits which assemble into ice nucleating complexes that can contain more than 100 subunits. Fusarium INs retain high ice-nucleation activity even when only the ~12 kDa fraction of size-excluded proteins are initially present, suggesting robust pathways for their functional aggregation in cell-free aqueous environments. We conclude that the use of small proteins to build large assemblies is a common strategy among organisms to create potent biological INs. | 2023-09-11 | chemRxiv | Physical Chemistry; Earth, Space, and Environmental Chemistry; Atmospheric Chemistry; Biophysical Chemistry; Self-Assembly | null | CC BY NC ND 4.0 |
Does Tyrosine Protect S. Coelicolor Laccase from Oxidative Degradation? | 10.26434/chemrxiv.12671612.v1 | N.A. | N.A. | Patrycja Kielb; Harry B. Gray; Jay R. Winkler | We have investigated the roles of tyrosine (Tyr) and
tryptophan (Trp) residues in the four-electron reduction of oxygen catalyzed by
<i>Streptomyces coelicolor</i> laccase
(SLAC). During normal enzymatic turnover in laccases, reducing equivalents are
delivered to a type 1 Cu center (Cu<sub>T1</sub>) and then are transferred over
13 Å to a trinuclear Cu site (TNC: (Cu<sub>T3</sub>)<sub>2</sub>Cu<sub>T2</sub>)
where O<sub>2</sub> reduction occurs. The TNC in SLAC is surrounded by a large
cluster of Tyr and Trp residues that can provide reducing equivalents when the
normal flow of electrons is disrupted. Canters and coworkers have shown that
when O<sub>2</sub> reacts with a reduced SLAC variant lacking the Cu<sub>T1</sub>
center, a Tyr108<sup>·</sup>
radical near the TNC forms rapidly. We have found that ascorbate reduces the
Tyr108<sup>·</sup><sup> </sup>radical
in wild-type SLAC about 10 times faster than it reacts with the Cu<sub>T1</sub><sup>2+</sup>
center, possibly owing to radical transfer along a Tyr/Trp chain. Aerobic
oxidation of two reduced SLAC mutants (Y108F and W132F) leads to the formation
of a long-lived (~15 min) Tyr<sup>·</sup><sup> </sup>radical with distinct
absorption at 408 nm. The diffusion of redox equivalents away from the primary
enzymatic pathway in SLAC may indicate a poorly optimized enzyme or a mechanism
to protect against protein damage. | 2020-07-20 | chemRxiv | Biocatalysis; Redox Catalysis; Biophysical Chemistry | null | CC BY NC ND 4.0 |
Side Chain Dispersity Matters: Topologically Precise and Discrete Bottlebrush Polymers | 10.26434/chemrxiv-2021-0vjfg | N.A. | N.A. | Nduka Ogbonna; Michael Dearman; Cheng-Ta Cho; Bhuvnesh Bharti; Andrew J. Peters; Jimmy Lawrence | The synthesis of bottlebrush polymers with topologically precise and fully discrete structures is reported. Key features of the synthesis include the combination of scalable synthesis and separation strategies to access discrete macromonomer libraries, followed by their polymerization and further separation into topologically uniform and discrete bottlebrushes. Discrete macromonomers prove crucial for regulating the structural heterogeneity of bottlebrushes and their macroscopic properties. When assembled as a monolayer at the air-water interface, bottlebrushes with discrete side chains display high packing density and distinct three-phase Langmuir-Blodgett isotherms. The impact of precisely regulating side chain dispersity and sequence on polymer properties was further demonstrated through tailoring the interbrush interactions and thermomechanical properties of well-defined block bottlebrushes. | 2021-12-16 | chemRxiv | Materials Science; Polymer Science; Polymer brushes; Polymerization (Polymers); Polymerization kinetics; Materials Chemistry | null | CC BY NC ND 4.0 |
Efficient Synthesis of Azido Sugars using Fluorosulfuryl Azide Diazotransfer Reagent | 10.26434/chemrxiv-2021-jdmn0 | N.A. | N.A. | Chantelle J. Capicciotti; Joshua M. Kofsky; Gour C. Daskhan; Matthew S. Macauley | Azide-containing sugars are important tools for the synthesis of biologically relevant 1,2-cis-glycosides and for bioconjugation chemistry. Previous strategies for the installation of a non-participating C2-azido functionality use harsh conditions and long reaction times. Herein, we report the synthesis of azido sugars using fluorosulfuryl azide (FSO2N3; 1) with a Cu(II) catalyst as a safe and efficient diazotransfer reagent. Common hexosamine substrates were converted to 2-azido-2-deoxy sugars in less than 5 minutes in quantitative yield. Glycosyl donors with orthogonal protecting groups were readily prepared from these azido sugars with good overall yield and a single column purification. The diazotransfer protocol was also efficiently used on other amino sugar derivatives, including aminoglycosides and substrates with amine-containing linkers. This optimized method will expand access to important non-participating C2-azido protecting groups and other azido sugar derivatives. | 2021-10-22 | chemRxiv | Organic Chemistry | null | CC BY NC ND 4.0 |
An introduction to digital microfluidic concepts in chemistry using a macroscopic droplet generator | 10.26434/chemrxiv.7450898.v1 | N.A. | N.A. | Clotilde Vié; Jacques Fattaccioli; philippe jacq | <div><div><div><div><div><div><p>This activity introduces digital microfluidics and the usage of aqueous droplets as independent chemical microreactors for reaction kinetics studies. Students build their own droplet generator from common macroscopic glassware and connecting parts, to create trains of millimetric droplets in which a redox reaction takes place. The activity allows working on reaction kinetics, hydrodynamics at low Reynolds number and image analysis at a macroscopic scale.</p></div></div></div></div></div></div> | 2018-12-13 | chemRxiv | Chemical Education - General | null | CC BY NC ND 4.0 |
Excited-State Geometry Optimization of Small Molecules with Many-Body Green's Functions Theory | 10.26434/chemrxiv.13106813.v1 | 10.1021/acs.jctc.0c01099 | https://doi.org/10.1021/acs.jctc.0c01099 | Onur Çaylak; Björn Baumeier | We present a benchmark study of gas phase geometry optimizations in the excited states of carbon monoxide, acetone, acrolein, and methylenecyclopropene using many-body Green's functions theory within the <i>GW</i> approximation and the Bethe-Salpeter Equation (BSE). We scrutinize the influence of several typical approximations in the <i>GW</i>-BSE framework: using of one-shot <i>G<sub>0</sub>W<sub>0</sub></i> or eigenvalue self-consistent ev<i>GW</i>, employing a fully-analytic approach or plasmon-pole model for the frequency dependence of the electron self-energy, or performing the BSE step within the Tamm--Dancoff approximation. The obtained geometries are compared to reference results from multireference perturbation theory (CASPT2), variational Monte Carlo (VMC), second-order approximate coupled cluster (CC2), and time-dependent density-functional theory (TDDFT). We find overall a good agreement of the structural parameters optimized with the <i>GW</i>-BSE calculations with CASPT2, with an average relative error of around 1% for the <i>G<sub>0</sub>W<sub>0</sub></i> and 1.5% for the ev<i>GW</i> variants, respectively, while the other approximations have negligible influence. The relative errors are also smaller than those for CC2 and TDDFT with different functionals and only larger than VMC, indicating that the <i>GW</i>-BSE method does not only yield reliable excitation energies but also geometries. | 2020-10-19 | chemRxiv | Computational Chemistry and Modeling; Theory - Computational | null | CC BY NC ND 4.0 |
A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19 | 10.26434/chemrxiv.12579137.v1 | 10.1371/journal.pbio.3000970 | https://doi.org/10.1371/journal.pbio.3000970 | Yadi Zhou; Yuan Hou; Jiayu Shen; Asha Kalianpur; Joe Zein; Daniel A. Culver; Samar Farha; Suzy Comhair; Claudio Fiocchi; Michaela U. Gack; Reena Mehra; Thaddeus S Stappenbeck; Timothy Chan; Charis Eng; Jae U. Jung; Lara Jehi; Serpil Erzurum; Feixiong Cheng | The global Coronavirus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of co-existing medical conditions while the underlying mechanisms remain unclear. Furthermore, there are no proven effective therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, diseases manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations. We incorporate SARS-CoV-2 virus-host protein-protein interactions, transcriptomics, and proteomics into the human interactome. Network proximity measure revealed underlying pathogenesis for broad COVID-19-associated manifestations. Multi-modal analyses of single-cell RNA-sequencing data showed that co-expression of <i>ACE2 </i>and <i>TMPRSS2 </i>was elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn's disease patients compared to uninflamed tissues, revealing shared pathobiology by COVID-19 and inflammatory bowel disease. Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma patients indicated that COVID-19 shared intermediate inflammatory endophenotypes with asthma (including<i>IRAK3</i> and <i>ADRB2</i>). To prioritize potential treatment, we combined network-based prediction and propensity score (PS) matching observational study of 18,118 patients from a COVID-19 registry. We identified that melatonin (odds ratio (OR) = 0.36, 95% confidence interval (CI) 0.22-0.59) was associated with 64% reduced likelihood of a positive laboratory test result for SARS-CoV-2. Using PS-matching user active comparator design, melatonin was associated with 54% reduced likelihood of SARS-CoV-2 positive test result compared to angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (OR = 0.46, 95% CI 0.24-0.86). | 2020-07-02 | chemRxiv | Biochemistry; Bioinformatics and Computational Biology; Cell and Molecular Biology; Chemical Biology; Drug Discovery and Drug Delivery Systems; Microbiology | null | CC BY NC ND 4.0 |
Real-time label-free imaging of living crystallization-driven self-assembly | 10.26434/chemrxiv-2024-d1gd3-v2 | N.A. | N.A. | Yujie Guo; Tianlai Xia; Vivien Walter; Yujie Xie; Julia Rho; Laihui Xiao; Rachel O'Reilly; Mark Wallace | Living crystallization-driven self-assembly (CDSA) of semicrystalline block copolymers is a powerful method for the bottom-up construction of uniform polymer microstructures with complex hierarchies. Improving our ability to engineer such complex particles demands a better understanding of how to precisely control the self-assembly process. Here, we apply interferometric scattering (iSCAT) microscopy to observe the real-time growth of individual poly(caprolactone)-based fibers and platelets. This label-free method enables us to map the role of key reaction parameters on platelet growth rate, size, and morphology. Furthermore, iSCAT provides a contrast mechanism for studying multi-annulus platelets formed via the sequential addition of different unimers, offering new insights into the spatial distribution of polymer compositions within a single platelet. | 2024-07-10 | chemRxiv | Physical Chemistry; Materials Science; Polymer Science | null | CC BY 4.0 |
In Silico Analysis of Sea Urchin Pigments as Potential Therapeutic Agents Against SARS-CoV-2: Main Protease (Mpro) as a Target. | 10.26434/chemrxiv.12598487.v1 | N.A. | N.A. | Tamara Rubilar; Elena Susana Barbieri; Ayelén Gázquez; Marisa Avaro; Mercedes Vera-Piombo; Agustín Gittardi; Erina Noé Seiler; Jimena Pía Fernandez; Lucas Sepulveda; Florencia Chaar | The SARS-CoV-2 outbreak has spread rapidly and globally generating a new coronavirus disease (COVID-19) since December 2019 that turned into a pandemic. Effective drugs are urgently needed and drug repurposing strategies offer a promising alternative to dramatically shorten the process of traditional de novo development. Based on their antiviral uses, the potential affinity of sea urchin pigments to bind main protease (Mpro) of SARS-CoV-2 was evaluated in silico. Docking analysis was used to test the potential of these sea urchin pigments as therapeutic and antiviral agents. All pigment compounds presented high molecular affinity to Mpro protein. However, the 1,4-naphtoquinones polihydroxilate (Spinochrome A and Echinochrome A) showed high affinity to bind around the Mpro´s pocket target by interfering with proper folding of the protein mainly through an H-bond with Glu166 residue. This interaction represents a potential blockage of this protease´s activity. All these results provide novel information regarding the uses of sea urchin pigments as antiviral drugs and suggest the need for further in vitro and in vivo analysis to expand all therapeutic uses against SARS-CoV-2. <br /> | 2020-07-03 | chemRxiv | Chemoinformatics - Computational Chemistry | null | CC BY NC ND 4.0 |
Functionalized graphene-based biosensors for early detection of subclinical ketosis in dairy cows | 10.26434/chemrxiv-2024-zj1j2 | N.A. | N.A. | Md Azahar Ali; Shannon Chick; Matin Ataei Kachouei; Katharine Knowlton | Precision livestock farming utilizing advanced diagnostic tools including biosensors can play a key role in the management of livestock operations to improve the productivity, health, and well-being of animals. . Detection of ketosis, a metabolic disease that occurs in early lactation dairy cows due to the negative energy balance, is one potential on-farm use of biosensors. Beta–hydroxybutyrate (βHB) is an excellent biomarker for monitoring ketosis in dairy cows because βHB is one of the main ketones produced during this metabolic state. In this report, we develop a low-cost, Keto-sensor (graphene-based sensor) for the detection and quantification of βHB concentrations in less than a minute. In this device, graphene nanosheets were layered onto a screen–printed electrode (SPE), and then a stabilized enzyme (Beta–hydroxybutyrate dehydrogenase, NADH, and glycerol) was used to functionalize the graphene surface enabled by EDC–NHS conjugation chemistry. The Keto-sensor offers an analytical sensitivity of 10 nM and a limit-of-detection (LoD) of 0.24 nM within a detection range of 0.00001-3.0 mM. Spike testing indicates that the Keto-sensor can detect βHB in serum samples from bovines with subclinical ketosis. The Keto-sensor developed in this study shows promising results for early detection of subclinical ketosis on farms. | 2024-07-17 | chemRxiv | Analytical Chemistry; Nanoscience; Agriculture and Food Chemistry; Nanodevices; Nanostructured Materials - Nanoscience; Food | null | CC BY NC 4.0 |
Machine Learning Seams of Conical Intersection: A Characteristic Polynomial Approach | 10.26434/chemrxiv-2023-53k0m | N.A. | N.A. | Tzu Yu Wang; Simon Neville; Michael Schuurman | The machine learning of potential energy surfaces (PESs) has undergone rapid progress in recent years. The vast majority of this work, however, has been focused on the learning of ground state PESs. To reliably extend machine learning protocols to excited state PESs, the occurrence of seams of conical intersections between adiabatic electronic states must be correctly accounted for. This introduces a serious problem, for at such points the adiabatic potentials are not differentiable to any order, complicating the application of standard machine learning methods. We show that this issue may be overcome by instead learning the coordinate-dependent coefficients of the characteristic polynomial of a simple decomposition of the potential matrix. We demonstrate that, through this approach, quantitatively accurate machine learning models of seams of conical intersection may be constructed. | 2023-06-20 | chemRxiv | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational; Machine Learning | null | CC BY NC ND 4.0 |
Temperature and curvature-dependent thermal interface conductance between nanoscale-gold and water from molecular simulation | 10.26434/chemrxiv-2022-30jv2 | N.A. | N.A. | Blake Wilson; Steven Nielsen; Jaona Randrianalisoa; Zhenpeng Qin | Plasmonic gold nanoparticles (AuNPs) can convert laser irradiation into thermal energy and act as nano heaters in avariety of applications. Although the AuNP-water interface is an essential part of the plasmonic heating process,there is a lack of mechanistic understanding of how interface curvature and the heating itself impact interfacial heattransfer. Here, we report atomistic molecular dynamics simulations that investigate heat transfer through nanoscalegold-water interfaces. We confirmed that interfacial heat transfer is an important part of AuNP heat dissipation inAuNPs with diameter less than 100 nm, particularly for small particles with diameter≤10 nm. To account forvariations in the gold-water interaction strength reported in the literature, and to implicitly account for differentsurface functionalizations, we modeled a moderate and a poor AuNP-water wetting scenario. We found that thethermal interface conductance increases linearly with interface curvature regardless of the gold wettability, while itincreases non-linearly, or remains constant, with the applied heat flux under different wetting conditions. Our analysissuggests the curvature dependence of the interface conductance is due to the changes in interfacial water adsorption,while the temperature dependence is caused by heat-induced shifts in the distribution of water vibrational states.Our study advances the current understanding of interface thermal conductance for a broad range of applications. | 2022-01-11 | chemRxiv | Theoretical and Computational Chemistry; Physical Chemistry; Nanoscience; Interfaces; Transport phenomena (Physical Chem.) | null | CC BY 4.0 |
Breaking the Access to Education Barrier: Enhancing HPLC Learning with Virtual Reality Digital Twins | 10.26434/chemrxiv-2023-c28km | N.A. | N.A. | Nazrul Bin Abdullah; Mae Taylor; Ayah Al-Dargazelli; Mireia Benito Montaner; Fatma Kareem; Amy Locks; Zijing Cao; Benjamin Bowles; Sophie Schafhauser; Jean-Charles Sarraf; Tamara Fajinmi; Zaid Muwaffak; Cory Beckwith; Gary N. Parkinson; Zoe Waller; Blanka R. Szulc; Stephen Hilton | This research focuses on an innovative approach to High Performance Liquid Chromatography (HPLC) practical teaching, specifically exploring the application of Virtual Reality (VR) digital twin models to revolutionize undergraduate education. Traditionally, the exposure to HPLC instrumentation for undergraduates has been severely limited due to the substantial student population and the prohibitively high costs of these systems. To surmount these constraints, we designed and developed custom in-house multi-user VR software and created a VR digital twin model of the HPLC instrument in a training environment containing multiple HPLCs, aiming to simulate a realistic, interactive, and immersive learning environment. The investigation included a group of undergraduates with no previous HPLC experience, assessing the effectiveness of the VR digital twin model juxtaposed with conventional teaching methods. Results exhibited a marked improvement in student comprehension of HPLC and their engagement levels, with the VR digital twin model serving as a significant enhancer. Notably, students reported a heightened confidence in their operational understanding of the instrument and exhibited a more profound grasp of the underlying theoretical concepts. In light of these findings, we propose that VR digital twin models can revolutionize practical teaching, particularly in areas constrained by equipment accessibility. This paper, therefore, offers compelling insights into the transformative potential of VR digital twin models in reshaping HPLC practical teaching in undergraduate education. | 2023-08-04 | chemRxiv | Chemical Engineering and Industrial Chemistry; Chemical Education; Chemical Education - General; Industrial Manufacturing; Pharmaceutical Industry | null | CC BY NC ND 4.0 |
Effect of buffers and pH in antenna sensitized Eu(III) luminescence | 10.26434/chemrxiv-2022-71mvq | N.A. | N.A. | Lea Gundorff Nielsen; Thomas Just Sørensen | The photophysics of a europium(III) complex of 1,4,7,10-tetraazacycododecane-1,4,7-triacetic acid-10-(2-methylene)-1-azathioxanthone is investigated in three buffer systems and at three pH values. The buffers—phosphate buffered saline (PBS), HEPES, and universal buffer—had no effect on the europium luminescence, but a lower overall emission intensity is determined in HEPES. It is found that this is due to quenching of the 1-azathioxanthone first excited singlet state by HEPES. The effect of pH on the photophysics of the complex is found to be minimal, and protonation of the pyridine nitrogen was found to be irrelevant. Even so, pH is shown to change the intensity ratio between 1-azathioxanthone fluorescence and europium luminescence. It is concluded that the full photophysics of a potential molecular probe should be investigated to achieve the best possible results in any application. For instance moving from HEPES to PBS improves the signal of the investigated europium(III) complex significantly. | 2022-11-16 | chemRxiv | Physical Chemistry; Inorganic Chemistry; Lanthanides and Actinides; Spectroscopy (Inorg.); Spectroscopy (Physical Chem.) | null | CC BY NC ND 4.0 |
Experimental and computational studies of the production of 1,3-butadiene from 2,3-butanediol using SiO2-supported H3PO4 derivatives | 10.26434/chemrxiv-2023-fd9kr | N.A. | N.A. | Juan Vicente Alegre Requena; Glenn R. Hafenstine; Xiangchen Huo; Yanfei Guan; Jim Stunkel; Frederick G. Baddour; Kinga A. Unocic; Bruno C. Klein; Ryan E. Davis; Robert S. Paton; Derek R. Vardon; Seonah Kim | Silica-supported phosphoric acid and metal phosphate catalyzed 1,3-butadiene (BDE) production from 2,3-butanediol (2,3-BDO) was studied using experimental and computational techniques. The catalyst was initially tested in a continuous flow reactor using commercially available 2,3-BDO, leading to maximum BDE yields of 63 C%. Quantum chemical mechanistic studies revealed 1,2-epoxybutane is a kinetically viable and thermodynamically stable intermediate, supported by experimental demonstration that this epoxide can be converted to BDE under standard reaction conditions. Newly proposed E2 and SN2’ elementary steps were studied to rationalize the formation of BDE and all detected side-products. Additionally, using QM/MM (ONIOM) calculations, we modeled silica-supported phosphate catalysts to study the effect of the alkali metal center. Natural population analysis showed that phosphate oxygen atoms are more negatively charged in CsH2PO4/SiO2 than in H3PO4/SiO2. In combination with temperature-programmed desorption experiments using CO2, the results of this study suggest that the improved selectivity achieved when adding the metal center is related to an increase in the basicity of the catalyst. | 2023-01-04 | chemRxiv | Theoretical and Computational Chemistry; Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Computational Chemistry and Modeling; Heterogeneous Catalysis | null | CC BY NC ND 4.0 |
Phase Separation and Gelation in Solutions and Blends of Hetero-Associative Polymers | 10.26434/chemrxiv-2023-1hz22 | 10.1021/acs.macromol.3c00854 | https://doi.org/10.1021/acs.macromol.3c00854 | Scott Danielsen; Alexander Semenov; Michael Rubinstein | An equilibrium statistical mechanical theory for the formation of reversible networks in two-component solutions of associative polymers is presented to account for the phase behavior due to hydrogen bonding, metal–ligand, electrostatic, or other pairwise heterotypic associative interactions. We derive explicit analytical expressions for the binding statistics, gelation condition, and free energy, in which we consider polymers of types A and B with many associating groups per chain and consider only A–B association between the groups. The free energy is approximated at the mean-field level, considering overlapping polymer chains with an ideal gas of "stickers" capable of intermolecular association. It is shown that the number of associations is maximized at stoichiometric conditions between A and B associative groups. Accordingly, homogeneous networks are most easily formed near stoichiometric conditions between A and B associative groups, resulting in a re-entrant sol–gel–sol transition as the overall composition is altered. Association and reversible network formation are found to be accompanied by a tendency for phase separation. These results demonstrate that reversibly associating polymers have a large parameter space in terms of molecular design, binding energy, and mixture compositions. Our predictions are expected to be useful in the rational design of interacting polymer mixtures and the formation of reversible networks. | 2023-05-03 | chemRxiv | Materials Science; Polymer Science | null | CC BY NC ND 4.0 |
A Practical Approach to Large Scale Electronic Structure Calculations in Electrolyte Solutions via Continuum-Embedded Linear-Scaling DFT | 10.26434/chemrxiv.11743071.v1 | 10.1021/acs.jpcc.0c00762 | https://doi.org/10.1021/acs.jpcc.0c00762 | Jacek Dziedzic; Arihant Bhandari; Lucian Anton; Chao Peng; James Womack; marjan famili; Denis Kramer; Chris-Kriton Skylaris | We present the implementation of a hybrid continuum-atomistic model for including the effects of surrounding electrolyte in large-scale density functional theory (DFT) calculations within the ONETEP linear-scaling DFT code, which allows the simulation of large complex systems such as electrochemical interfaces. The model represents the electrolyte ions as a scalar field and the solvent as a polarisable dielectric continuum, both surrounding the quantum solute. The overall energy expression is a grand canonical functional incorporating the electron kinetic and exchange correlation energies, the total electrostatic energy, entropy and chemical potentials of surrounding electrolyte, osmotic pressure, and the effects of cavitation, dispersion and repulsion. The DFT calculation is performed fully self-consistently in the electrolyte model, allowing the quantum mechanical system and the surrounding continuum environment to interact and mutually polarize. A bespoke parallel Poisson-Boltzmann solver library, DL_MG, deals with the electrostatic problem, solving a generalized Poisson-Boltzmann equation. Our model supports open boundary conditions, which allows the treatment of molecules, entire biomolecules or larger nanoparticle assemblies in electrolyte. We have also implemented the model for periodic boundary conditions, allowing the treatment of extended systems such as electrode surfaces in contact with electrolyte. A key feature of the model is the use of solute-size and solvation-shell-aware accessibility functions that prevent the unphysical accumulation of electrolyte charge near the quantum solute boundary. The model has a small number of parameters: here we demonstrate their calibration against experimental mean activity coefficients. We also present an exemplar simulation of a 1634-atom model of the interface between a graphite anode and LiPF<sub>6</sub> electrolyte in ethylene carbonate solvent. We compare the cases where Li atoms are intercalated at opposite edges of the graphite slab and in solution, demonstrating a potential application of the model in simulations of fundamental processes in Li-ion batteries. | 2020-01-29 | chemRxiv | Theory - Computational | null | CC BY NC ND 4.0 |
Chiral Counteranion-Controlled Chemoselectivity in Gold-Catalysed Hydroamination/Enantioselective Formal 1,3-Allylic Alcohol Isomerisation of -Amino-1,4-enynols | 10.26434/chemrxiv-2022-n5sm7 | N.A. | N.A. | Lorenzo Carli; Anyawan Tapdara; Jianwen Jin; Yichao Zhao; Philip Wai Hong Chan | A synthetic method for the preparation of 1,8-dihydroindeno[2,1-b]pyrroles and pyrrol-2-yl methanols in an enantioselective manner that relies on the chiral gold(I)-catalysed reactions of -amino-1,4-enynols is described. A divergence in product selectivity was achieved by exploiting the electrostatic interactions between the chiral counteranion of the metal catalyst and the substrate. With a gold(I) complex containing a chiral triflylamide-based counteranion, tandem dehydrative Nazarov-type electrocyclization/hydroamination of the substrate was found to selectively occur to afford the indeno-fused pyrrole adduct. In contrast, changing to a chiral phosphate-based counteranion was observed to result in a hydroamination/1,3-allylic alcohol isomerisation cascade pathway to give the 1H-pyrrole derivative. | 2022-11-14 | chemRxiv | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Homogeneous Catalysis | null | CC BY NC ND 4.0 |
Efficient Co-Harvesting of Solar Energy and Low-Grade Heat by Molecular Photoswitches for High Energy Density, Long-Term Stable Solar Thermal Battery | 10.26434/chemrxiv.9730694.v1 | N.A. | N.A. | Zhao-Yang Zhang; Tao LI | Solar
energy and ambient heat are two inexhaustible energy sources for addressing the
global challenge of energy and sustainability. Solar thermal battery based on molecular
switches that can store solar energy and release it as heat has recently attracted
great interest, but its development is severely limited by both low energy
density and short storage stability. On the other hand, the efficient recovery
and upgrading of low-grade heat, especially that of the ambient heat, has been
a great challenge. Here we report that solar energy and ambient heat can be
simultaneously harvested and stored, which is enabled by room-temperature
photochemical crystal-to-liquid transitions of small-molecule photoswitches.
The two forms of energy are released together to produce high-temperature heat during
the reverse photochemical phase change. This strategy, combined with molecular
design, provides high energy density of 320-370 J/g and long-term storage
stability (half-life of about 3 months). On this basis, we fabricate
high-performance, flexible film devices of solar thermal battery, which can be
readily recharged at room temperature with good cycling ability, show fast rate
of heat release, and produce high-temperature heat that is >20<sup> o</sup>C
higher than the ambient temperature. Our work opens up a new avenue to harvest ambient
heat, and demonstrate a feasible strategy to develop high-performance solar
thermal battery. | 2019-08-27 | chemRxiv | Fuel Cells | null | CC BY NC ND 4.0 |
InFrag: Using Attribution-based Explainability to Guide Deep Molecular Optimization | 10.26434/chemrxiv-2021-qtq8d | N.A. | N.A. | Pierre Wüthrich; Jun Jin Choong; Shinya Yuki | The recently proposed Genetic expert guided learning (GEGL) framework has demonstrated impressive performances on several \textit{de novo} molecular design tasks. Despite the displayed state-of-the art results, the proposed system relies on an expert-designed Genetic expert. Although hand-crafted experts allow to navigate the chemical space efficiently, designing such experts requires a significant amount of effort and might contain inherent biases which can potentially slow down convergence or even lead to sub-optimal solutions. In this research, we propose a novel genetic expert named \textit{InFrag} which is free of design rules and can generate new molecules by combining promising molecular fragments. Fragments are obtained by using an additional graph convolutional neural network which computes attributions for each atom for a given molecule. Molecular substructures which contribute positively to the task score are kept and combined to propose novel molecules. We experimentally demonstrate that, within the GEGL framework, our proposed attribution-based genetic expert is either competitive or outperforms the original expert-designed genetic expert on goal-directed optimization tasks. When limiting the number of optimization rounds to one and three rounds, a performance increase of approximately 43% and 20% respectively is observed compared to the baseline genetic expert. Furthermore, we empirically show that combining several experts that share a fixed sampling budget at each optimization round generally improves or maintains the overall performance of the framework. | 2021-09-13 | chemRxiv | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Machine Learning; Artificial Intelligence | null | CC BY NC ND 4.0 |
Combined Gas Electron Diffraction and Mass Spectrometric Experimental Setup at Bielefeld University | 10.26434/chemrxiv.12236942.v1 | N.A. | N.A. | Yury Vishnevskiy; Sebastian Blomeyer; Christian G. Reuter; Oleg A. Pimenov; Sergey A. Shlykov | We have designed and constructed a combined experimental setup for synchronous measurements of electron diffraction patterns and mass-spectra of gas samples. Test measurements have been performed for acetic acid at two temperatures, 296 and 457 K, respectively. Electron diffraction data have been analysed taking into account mass spectra measured in the same experiments. From the diffraction intensities molecular structures and mole fractions of the acetic acid monomer and dimer have been refined. The obtained results demonstrate the importance of measuring mass spectra in gas electron diffraction experiments. In particular, it is possible to detect the sample decomposition, which can be used for the optimization of experimental conditions and for the data interpretation. The determined in this work length of the hydrogen bond in the acetic acid dimer, re(O<sup>...</sup>H) = 1.657(9) Å, is in good agreement with modern theoretical predictions. We recommend to measure diffraction patterns of acetic acid for the calibration of the sample pressure in the diffraction point.<br /> | 2020-05-06 | chemRxiv | Spectroscopy (Physical Chem.); Structure | null | CC BY NC ND 4.0 |
Current Vortices in Aromatic Carbon Molecules | 10.26434/chemrxiv.8251076.v1 | 10.1103/PhysRevB.102.075405 | https://doi.org/10.1103/PhysRevB.102.075405 | Thomas Stegmann; John A. Franco-Villafañe; Yenni P. Ortiz; Michael Deffner; Carmen Herrmann; Ulrich Kuhl; Fabrice Mortessagne; Francois Leyvraz; Thomas H. Seligman | <div><div><div><p>The local current flow through three small aromatic carbon molecules, namely benzene, naphthalene and anthracene, is studied. Applying density functional theory and the non-equilibrium Green’s function method for transport, we demonstrate that pronounced current vortices exist at certain electron energies for these molecules. The intensity of these circular currents, which appear not only at the anti-resonances of the transmission but also in vicinity of its maxima, can exceed the total current flowing through the molecular junction and generate considerable magnetic fields. The π electron system of the molecular junctions is emulated experimentally by a network of macroscopic microwave resonators. The local current flows in these experiments confirm the existence of current vortices as a robust property of ring structures. The circular currents can be understood in terms of a simple nearest-neighbor tight-binding Hückel model. Current vortices are caused by the interplay of the complex eigenstates of the open system which have energies close-by the considered electron energy. Degeneracies, as observed in benzene and anthracene, can thus generate strong circular currents, but also non-degenerate systems like naphthalene exhibit current vortices. Small imperfections and perturbations can couple otherwise uncoupled states and induce circular currents.</p></div></div></div> | 2019-06-12 | chemRxiv | Nanodevices; Nanostructured Materials - Nanoscience; Computational Chemistry and Modeling; Quantum Mechanics; Transport phenomena (Physical Chem.) | null | CC BY NC ND 4.0 |
MOFganic Chemistry: Challenges and Opportunities for Metal-Organic Frameworks in Synthetic Organic Chemistry | 10.26434/chemrxiv-2023-w67kp | N.A. | N.A. | Bayu Ahmad; Kaitlyn Keasler; Emily Stacy; Sijing Meng; Thomas Hicks; Phillip Milner | Metal-organic frameworks (MOFs) are porous, crystalline solids constructed from organic linkers and inorganic nodes that have been widely studied for applications in gas storage, chemical separations, and drug delivery. Owing to their highly modular structures and tunable pore environments, we propose that MOFs have significant untapped potential as catalysts and reagents relevant to the synthesis of next-generation therapeutics. Herein, we outline the properties of MOFs that make them promising for applications in synthetic and organic chemistry, including new reactivity and selectivity, enhanced robustness, and user-friendly preparation. In addition, we outline the challenges facing the field and propose new directions to maximize the utility of MOFs for drug synthesis. This perspective aims to bring together the organic and MOF communities to develop new heterogeneous platforms capable of achieving synthetic transformations that can-not be replicated by homogeneous systems. | 2023-03-30 | chemRxiv | Organic Chemistry; Materials Science | null | CC BY NC ND 4.0 |
Organic Photovoltaic Behaviour with Centimeter-long Lateral Junctions | 10.26434/chemrxiv.14345318.v1 | N.A. | N.A. | Jaseela Palassery Ithikkal; Adrien Girault; Mitsuru Kikuchi; Yusuke Yabara; Seiichiro Izawa; Masahiro Hiramoto | In the field of organic solar cells, lateral junction is a new concept. Moreover, the photovoltaic behavior is firstly observed for surprising long organic lateral junctions reaching 1.8 cm and the new operation mechanism dominated by trap-assisted recombination is proposed. <div><br /></div> | 2021-04-01 | chemRxiv | Thin Films | null | CC BY NC ND 4.0 |
A Bio-inspired Dendritic MoOx Electrocatalyst for Efficient Electrochemical Nitrate Reduction to Ammonia | 10.26434/chemrxiv-2024-4gxn8 | 10.1002/aenm.202402294 | https://doi.org/10.1002/aenm.202402294 | Yuan-Zi Xu; Daniel Abbott; Robin Dürr; Tran Ngoc Huan; Victor Mougel | Drawing inspiration from the nitrate reductase enzymes, which catalyze nitrate to nitrite in nature, here we introduce a bio-inspired, reduced molybdenum oxide (MoOx) shell that is grown on top of a dendritic nickel foam core (NiNF). The resulting MoOx/NiNF material is prepared via a facile, two-step electrodeposition strategy using commercially available, low-cost precursors. This catalytic material displays a remarkable faradaic efficiency (FE) of 99% at −0.5 V vs. RHE and a high ammonia (NH3) yield rate of up to 4.29 mmol h−1 cm−2 at −1.0 V vs. RHE in neutral media. Most importantly, MoOx/NiNF exhibits exceptional stability for the nitrate reduction reaction (NO3RR), maintaining operation for over 3,100 hours at a high current density of −650 mA cm−2, with a yield rate of 2.6 mmol h−1 cm−2 and a stable average NH3 FE of ~83%. We show, through combined XPS and in-situ Raman spectroscopy, that the pronounced affinity of MoOx/NiNF for nitrate is associated with a substantial presence of oxygen vacancies within the material. | 2024-05-29 | chemRxiv | Catalysis; Electrocatalysis; Materials Chemistry | null | CC BY NC ND 4.0 |
Machine Learned Potentials by Active Learning from Organic Crystal Structure Prediction Landscapes | 10.26434/chemrxiv-2023-97rmb | N.A. | N.A. | Patrick W. V. Butler; Roohollah Hafizi; Graeme Day | A primary challenge in organic molecular crystal structure prediction (CSP) is accurately ranking the energies of potential structures. While high-level solid-state density functional theory (DFT) methods allow for mostly reliable discrimination of the low energy structures, their high computational cost is problematic because of the need to evaluate tens to hundreds of thousands of trial crystal structures to fully explore typical crystal energy landscapes. Consequently, lower-cost but less accurate empirical force fields are often used, sometimes as the first stage of a hierarchical scheme involving multiple stages of increasingly accurate energy calculations. Machine learned potentials (MLPs), trained to reproduce the results of ab initio methods with computational cost close to that of force fields, can improve the efficiency of CSP by reducing or eliminating the need for costly DFT calculations at the final stages of CSP. Here, we investigate active learning methods for training MLPs with CSP datasets. The combination of active learning with the well-developed sampling methods from CSP yields potentials in a highly automated workflow that are relevant over a wide range of the crystal packing space. To demonstrate these potentials, we illustrate efficiently re-ranking large, diverse crystal structure landscapes to near-DFT accuracy from force field-based CSP, improving the reliability of the final energy ranking. Furthermore, we demonstrate how these potentials can be extended to more accurately model structures far from lattice energy minima through additional on-the-fly training within Monte Carlo simulations. | 2023-10-27 | chemRxiv | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Machine Learning; Materials Chemistry | null | CC BY 4.0 |
Engineering transient dynamics of artificial cells by stochastic distribution of enzymes | 10.26434/chemrxiv-2021-02c1d | N.A. | N.A. | Jan C. van Hest; Shidong Song; Alexander Mason; Richard Post; Marco de Corato; Rafael Mestre; Amy Yewdall; Shoupeng Cao; Remco van der Hofstad; Samuel Sanchez; Loai Abdelmohsen | Random fluctuations are inherent to all complex molecular systems. Although nature has evolved mechanisms to control stochastic events to achieve the desired biological output, reproducing this in synthetic systems represents a significant challenge. Here we present an artificial platform that enables us to exploit stochasticity to direct motile behavior. We found that enzymes, when confined to the fluidic polymer membrane of a core-shell coacervate, were distributed stochastically in time and space. This resulted in a transient, asymmetric configuration of propulsive units, which imparted motility to such coacervates in presence of substrate. This mechanism was confirmed by stochastic modelling and simulations in silico. Furthermore, we showed that a deeper understanding of the mechanism of stochasticity could be utilized to modulate the motion output. Conceptually, this work represents a leap in design philosophy in the construction of synthetic systems with life-like behaviors. | 2021-08-25 | chemRxiv | Nanoscience; Nanostructured Materials - Nanoscience | null | CC BY NC ND 4.0 |
Efficient automatic construction of atom-economical QM regions with point-charge variation analysis | 10.26434/chemrxiv-2023-4p00l-v2 | 10.1039/D3CP01263H | https://doi.org/10.1039/D3CP01263H | Felix Brandt; Christoph Jacob | The setup of QM/MM calculations is not trivial since many decisions have to be made by the simulation scientist to achieve reasonable and consistent results. The main challenge to be tackled is the construction of the QM region to make sure to take into account all important parts of the adjacent environment and exclude less important ones. In our previous work [J. Chem. Theory Comput. 65, 18, 2584–2596 (2022)], we introduced the point charge variation analysis (PCVA) as a simple and reliable tool to systematically construct QM regions based on the sensitivity of the reaction energy with respect to variations of the MM point charges. Here, we assess several simplified variants of this PCVA approach for the example of catechol O-methyltransferase and apply PCVA for another system, the triosephosphate isomerase. Furthermore, we extend its scope by applying it to a DNA system. Our results indicate that PCVA offers an efficient and versatile approach of the automatic construction of atom-economical QM regions, but also identify possible pitfalls and limitations. | 2023-04-24 | chemRxiv | Theoretical and Computational Chemistry; Theory - Computational | null | CC BY 4.0 |
Real-time Voltammetric Anion Sensing Under Flow | 10.26434/chemrxiv-2021-2nqwc | 10.1002/chem.202103249 | https://dx.doi.org/10.1002/chem.202103249 | Sophie C. Patrick; Robert Hein; Mohamed Sharafeldin; Xiaoxiong Li; Paul D. Beer; Jason J. Davis | The development of real-life applicable ion sensors, in particular those capable of repeat use and long-term monitoring, remains a formidable challenge. Herein, we demonstrate, in a proof-of-concept, the real-time voltammetric sensing of anions under continuous flow at electroactive anion receptive halogen bonding (XB) and hydrogen bonding (HB) ferrocene-isophthalamide-(iodo)triazole interfaces. Upon exposure to anions, the cathodic perturbations of the ferrocene redox-transducer are monitored by repeat square-wave voltammetry (SWV) cycling and peak fitting of the voltammograms by a custom-written MATLAB script. This enables the facile and automated data processing of thousands of SW scans and is associated with an over one order-of-magnitude improvement in LODs. In addition, this improved analysis enables tuning of the measurement parameters such that high temporal resolution can be achieved. More generally, this novel flow methodology is extendable to a variety of other analytes, including cations, and presents an important step towards translation of voltammetric ion sensors from laboratory to real-world applications. | 2021-08-30 | chemRxiv | Inorganic Chemistry; Analytical Chemistry; Electrochemical Analysis; Sensors; Supramolecular Chemistry (Inorg.) | null | CC BY NC ND 4.0 |
Expedient Synthesis of a Library of Heparan Sulfate Like “Head to Tail” Linked Multimers for Structure and Activity Relationship Studies | 10.26434/chemrxiv-2022-m03tb-v2 | N.A. | N.A. | Jicheng Zhang; Li Liang; Weizhun Yang; Sherif Ramadan; Kedar Baryal; Chang-xin Huo; Jamie Bernard; Jian Liu; Linda Hsieh-wilson; Fuming Zhang; Robert Linhardt; Xuefei Huang | Heparan sulfate (HS) plays significant roles in various biological processes such as inflammation, cell proliferation, and bacterial and viral infection. The inherent complexity of naturally existing HS has severely hindered the thorough understanding of the relationship between their diverse structures and biological functions. While HS syntheses have advanced significantly in recent years, preparation of HS libraries remains a tremendous challenge due to the difficulties in achieving high yields in glycosylation and sulfation reactions especially with longer glycans and the need to prepare multiple compounds. A new strategy to synthesize a library of HS-like pseudo-hexasaccharides has been developed to expedite library preparation. HS disaccharides were linked in a “head-to-tail” fashion from the reducing end of a module to the non-reducing end of a neighboring module to mimic native HS. Three differentially sulfated HS disaccharides were designed and prepared from a common intermediate. Conjugation of these modules using amide chemistry bypassed the need for challenging glycosylation reactions to extend the HS backbone. Combinatorial syntheses of 27 HS-like pseudo-hexasaccharides were achieved using these three HS modules. This new class of compounds mimicked well the native HS with their binding to fibroblast growth factor 2 (FGF-2) exhibiting similar structure-activity relationship trends as HS hexasaccharides. The ease of synthesis and the ability to mimic natural HS suggest the new head-to-tail linked pseudo-hexasaccharides could be an exciting tool to facilitate the understanding of HS biology. | 2022-07-01 | chemRxiv | Organic Chemistry | null | CC BY NC ND 4.0 |
Resolving the Quadruple Bonding Conundrum in C2 Using Insights Derived from Excited State Potential Energy Surfaces: A Molecular Orbital Perspective | 10.26434/chemrxiv.11446224.v1 | N.A. | N.A. | Ishita Bhattacharjee; Debashree Ghosh; Ankan Paul | The question of quadruple bonding in C<sub>2</sub> has emerged as a hot button issue, with opinions sharply divided between the practitioners of Valence Bond (VB) and Molecular Orbital (MO) theory. Here, we have systematically studied the Potential Energy Curves (PECs) of low lying high spin sigma states of C<sub>2</sub>, N<sub>2</sub> and Be<sub>2</sub> and HC≡CH using several MO based techniques such as CASSCF, RASSCF and MRCI. The analyses of the PECs for the<sup> 2S+1</sup>Σ<sub>g/u</sub> (with 2S+1=1,3,5,7,9) states of C<sub>2</sub> and comparisons with those of relevant dimers and the respective wavefunctions were conducted. We contend that unlike in the case of N<sub>2</sub> and HC≡CH, the presence of a deep minimum in the <sup>7</sup>Σ state of C<sub>2</sub> and CN<sup>+</sup> suggest a latent quadruple bonding nature in these two dimers. Hence, we have struck a reconciliatory note between the MO and VB approaches. The evidence provided by us can be experimentally verified, thus providing the window so that the narrative can move beyond theoretical conjectures. | 2019-12-26 | chemRxiv | Theory - Computational | null | CC BY NC 4.0 |
Evaluation of an Internal Standard for Qualitative DART-MS Analysis of Seized Drugs | 10.26434/chemrxiv-2021-5q4mb | 10.1016/j.forc.2021.100392 | https://dx.doi.org/10.1016/j.forc.2021.100392 | Edward Sisco; Amber Burns; Elizabeth Schneider; Ikenna Ikpeama | Rapid and accurate screening tools for seized drug analysis continue to be needed due to the complexities associated with the emerging drug landscape. Direct analysis in real-time mass spectrometry (DART-MS) is one technique that has been used for this purpose and is seeing increased implementation due to its ability to provide high-fidelity information rapidly. As with any analytical technique, ensuring data integrity with DART-MS results is critical. To further enhance data integrity and eliminate some of the challenges associated with qualitative analysis of seized drugs using DART-MS, the incorporation of an internal standard was investigated. After evaluating a number of candidate compounds, tetracaine was chosen because of its desirable characteristics. An appropriate concentration of tetracaine was established that provided similar sensitivity to GC-MS for a panel of drugs. The presence of tetracaine in a drug extract was found to cause a reduction in signal for some common drugs due to competitive ionization but did not cause complete suppression of signal at relevant concentrations. Evaluation of a set of 60 representative case samples with and without internal standard found that the presence of internal standard did not negatively impact the results and that its presence eliminated the false identification of noise peaks in negative samples. The use of an internal standard also provided within-sample mass calibration and analyte concentration checks. It also allowed for automated mass drift compensation, removing a time-consuming process for high resolution DART-MS data processing. | 2021-07-26 | chemRxiv | Analytical Chemistry; Mass Spectrometry | null | CC BY NC ND 4.0 |
Machine Learning of Atomic Dynamics and Statistical Surface Identities in Gold Nanoparticles | 10.26434/chemrxiv-2022-7wfm9-v2 | N.A. | N.A. | Daniele Rapetti; Massimo Delle Piane; Matteo Cioni; Daniela Polino; Riccardo Ferrando; Giovanni M. Pavan | It is known that metal nanoparticles (NPs) may be dynamic and atoms may move within them even at fairly low temperatures. Characterizing such complex dynamics is key for understanding NPs’ properties in realistic regimes, but detailed information on, e.g., the stability, survival, and interconversion rates of the atomic environments (AEs) populating them are non-trivial to attain. Here we show a machine learning approach that allows us to reconstruct the complex atomic dynamics of metal NPs from high-dimensional data extracted from molecular dynamics simulations. Using different-shape gold NPs as a representative example, an AEs’ dictionary allows us to label step-by-step the individual atoms in the NPs, identifying the native and non-native AEs and populating them along the MD simulations at various temperatures. Tracking the emergence, annihilation, lifetime, and dynamic interconversion of the AEs, our approach permits estimating a “statistical equivalent identity” for metal NPs based on the intrinsic atomic dynamics present within them. | 2022-11-04 | chemRxiv | Theoretical and Computational Chemistry; Physical Chemistry; Materials Science; Computational Chemistry and Modeling; Machine Learning; Statistical Mechanics | null | CC BY 4.0 |
ColorLab: Visualizing Color from Absorbance Spectra | 10.26434/chemrxiv-2022-g5v90 | N.A. | N.A. | Spencer M. Yeager; Michael A. Anderson; Priscilla Babiak; Bryon W. Larson; Erin L. Ratcliff | We present here the first public release of ColorLab, a Python-based program that can convert absorbance spectra into color images. It was designed for use with organic photovoltaic (OPV) materials and blends, which represent a myriad of colors based on molecular design and material blending that can exhibit persistent color or evolve over time via degradation or morphology changes. However, ColorLab is not limited to this application, and can generate color images from a single spectrum or an evolving color bar on a time axis from multiple time-stamped spectra. Using internationally defined illuminants, ColorLab can display colors that are representative of a variety of lighting situations, from indoor to outdoor. The development of this program aims to aid with the visualization of semitransparent materials and to connect researchers with designers, through conversion of spectra to color. | 2022-06-08 | chemRxiv | Materials Science | null | CC BY NC 4.0 |
In Silico Study on Spice-Derived Antiviral Phytochemicals Against SARS-CoV-2 TMPRSS2 Target | 10.26434/chemrxiv.12753539.v1 | N.A. | N.A. | Pradeep Kumar Yadav; Amit Jaiswal; Rajiv Kumar Singh | We predicted the structure of TMPRSS2 (transmembrane protease serine 2), a host protein that truncates spike protein of SARS-CoV-2. Then we docked 18 anti-viral compounds found in Indian spices against the catalytic domain of TMPRSS2. We then performed rigorous molecular simulation dynamics simulation to screen the best natural phytochemical which could act as a potential inhibitor of TMPRSS2 activation. <br /> | 2020-08-04 | chemRxiv | Bioinformatics and Computational Biology; Biophysics; Drug Discovery and Drug Delivery Systems; Computational Chemistry and Modeling | null | CC BY NC ND 4.0 |
eFluorination using cheap and readily available tetrafluoroborate salts | 10.26434/chemrxiv-2022-b1v2c | N.A. | N.A. | Kevin Lam; Matthew Leech; Dmitrii Nagornii; Jamie Walsh; Cyrille Kiaku; Darren Poole; Joseph Mason; Iain Goodall; Perry Devo | A new practical electrochemical method for the rapid, safe, and mild synthesis of tertiary hindered alkyl fluorides from easily accessed carboxylic acids has been developed without the need for hydrofluoric acid derivatives or non-glass reactors. In this anodic fluorination, collidinium tetrafluoroborate (Coll·HBF4) is advantageous as a supporting electrolyte and fluoride donor. A wide range of functional groups has been shown to be compatible with this new methodology. The possibility of scale-up using flow electrochemistry has also been demonstrated, thus representing a viable procedure for tertiary fluorination on a larger scale. | 2022-11-25 | chemRxiv | Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions | null | CC BY NC ND 4.0 |
α-Methylene-β-Lactone Probe for Measuring Live-Cell Reactions of Small Molecules | 10.26434/chemrxiv.12078582.v2 | N.A. | N.A. | Lei Wang; Louis Riel; Bekim Bajrami; Bin Deng; Amy Howell; Xudong Yao | The novel use of the α-methylene-β-lactone (MeLac) moiety as a warhead of multiple electrophilic sites is reported. In this study, we demonstrate that a MeLac-alkyne is a competent covalent probe and reacts with diverse proteins in live cells. Proteomics analysis of affinity-enriched samples identifies probe-reacted proteins, resolves their modified peptides/residues, and thus characterizes probe-protein reactions. Unique methods are developed to evaluate confidence in the identification of the reacted proteins and modified peptides. Tandem mass spectra of the peptides reveal that MeLac reacts with nucleophilic cysteine, serine, lysine, threonine, and tyrosine residues, through either Michael addition or acyl addition. A peptide-centric proteomics platform, using MeLac-alkyne as the measurement probe, successfully analyzes the Orlistat selectivity in live HT-29 cells. MeLac is a versatile warhead demonstrating enormous potential to expedite the development of covalent probes and inhibitors in interrogating protein (re)activity. MeLac-empowered platforms in chemical proteomics are widely adaptable for measuring the live-cell action of reactive molecules. | 2020-04-13 | chemRxiv | Bioorganic Chemistry; Organic Synthesis and Reactions; Mass Spectrometry; Separation Science; Bioinformatics and Computational Biology; Chemical Biology; Drug Discovery and Drug Delivery Systems | null | CC BY NC ND 4.0 |
Contact resistance of carbon-Li𝑥(Ni,Mn,Co)O2 interfaces | 10.26434/chemrxiv-2022-1m2wh | 10.1002/aenm.202201114 | https://doi.org/10.1002/aenm.202201114 | Jimmy Jiahong Kuo; Stephen Dongmin Kang; William C. Chueh | Electronic resistance in lithium-ion battery positive electrodes is typically attributed to the bulk resistance of the active material and the network resistance of the carbon additive. Expected overpotentials from these bulk components are minimal relative to that from charge-transfer resistance. However, literature reports show that cell overpotentials are often much more sensitive to conductive additives than the expected level from bulk or
percolating-network transport. This discrepancy motivates a detailed examination of the contact resistance between the active material and conductive additive. We simultaneously
measure contact and bulk resistances using dense bar samples of lithium layered oxides (LixNi1/3Mn1/3Co1/3O2 and LixNi0.5Mn0.3Co0.2O2) in contact with carbon black. We find that the contact resistance dominates the overall electronic resistance when the length scale is smaller than millimeters; after correcting for contact effects, bulk conductivity of layered oxides is determined to be orders-of-magnitude higher than previously reported. In porous
electrodes, we find from three-electrode electrochemical impedance spectroscopy that the carbon content most heavily influences the low-frequency regime (around 0.01 Hz), as opposed to the high frequency (>10^3 Hz) regime expected from electronic percolating properties. We identify constriction effects within the layered oxide as the dominant mechanism for contact resistance and investigate its implication for porous electrodes. | 2022-04-19 | chemRxiv | Physical Chemistry; Materials Science; Energy; Energy Storage; Electrochemistry - Mechanisms, Theory & Study; Transport phenomena (Physical Chem.) | null | CC BY NC 4.0 |
Asymmetric Polymerization-Induced Crystallization-Driven Self-Assembly of Helical, Rod-Coil Poly(Aryl Isocyanide) Block Copolymers | 10.26434/chemrxiv-2022-qvrsd | 10.1021/jacs.2c13354 | https://doi.org/10.1021/jacs.2c13354 | Randall Scanga; Ali Shahrokhinia; Jake Borges; Michael Ross; James Reuther | The helical motif is ubiquitous in naturally occurring chemical systems where it confers numerous useful and distinct material properties. Accordingly, a great many synthetic materials have been produced in efforts to mimic biological systems. As an inherently chiral structural feature, the helix provides a modular platform for the creation of chiral nanomaterials exhibiting a diverse range of capabilities. Nonetheless, the development of rapid, scalable methods for production of chiral nanomaterials presents a formidable challenge. However, recent advances in both amphiphilic block copolymer (BCP) synthesis and self-assembly provide tractable means to do just that. In this work, polymerization induced crystallization-driven self-assembly (PI-CDSA) is combined, for the first time, with helical, rod-coil BCP self-assembly to enable scalable and controllable in situ synthesis of chiral nanostructures with variable shape, size, and dimensionality. Herein, we detail the use of newly developed Asymmetric PI-CDSA methodologies in the synthesis and in situ self-assembly of chiral, rod-coil BCPs comprised of poly(aryl isocyanide) (PAIC) rigid-rod and poly(ethylene glycol) (PEG) random-coil components. Using PEG-based Ni(II) macroinitiators, chiral PAIC-BCP nanostructures are constructed in a controlled, scalable fashion forming variable chiral morphologies including 1D twisted nanofibers, 2D hexagonal nanosheets and 3D twisted spirangles (i.e., spirally arranged hexagonal nanosheet stacks). Using seeded, living asymmetric PI-CDSA, the lengths and heights of 1D nanofiber and 3D spirangle nanostructures, respectively, can be selectively tuned via alterations in unimer-to-seed ratios. The formation of these nanostructures is dictated by the liquid crystalline nature of PAIC blocks and the hierarchical assembly of these BCPs, with chirality translated across length scales and in multiple dimensions (i.e., spirangles), led to large amplifications in chiroptical activity with high Kuhn’s dissymmetry factors reaching 0.029. | 2023-10-05 | chemRxiv | Polymer Science; Nanoscience; Organic Polymers; Polymerization (Polymers); Nanofabrication; Materials Chemistry | null | CC BY NC ND 4.0 |
Unravelling Irreversible Adsorbate Thermodynamics through Adsorption Assisted Desorption | 10.26434/chemrxiv-2023-5kzdk-v2 | N.A. | N.A. | Omar Abdelrahman; Ajibola Lawal | Strongly bound surface species like alkylamines adsorbed on the Brønsted acid site of aluminosilicate zeolites exhibit negligible rates of molecular desorption, preventing them from achieving an equilibrated state on experimentally relevant timescales that limit the measurement of their adsorption thermodynamics. Through adsorption-assisted desorption, whereby distinct alkylamines facilitate desorption from Brønsted acid sites, we demonstrate that equilibrated states are achieved. Breakthrough adsorption measurements reveal that while 2-butylammonium on a Brønsted acid site is irreversibly adsorbed, it readily undergoes molecular desorption when exposed to a distinct alkylamine like 2-propylamine. As a result, two-adsorbate equilibrium was achieved when exposing Brønsted acid sites of aluminosilicate zeolites to a binary vapor phase alkylamine mixture. By varying relative vapor phase partial pressures and temperatures, we demonstrate the ability to experimentally measure the adsorption enthalpy and entropy of alkylammonium adsorbates on mostly isolated Brønsted acid sites in H-ZSM-5 (Si/Al = 140). A multi-adsorbate Langmuir isotherm was found to quantitatively describe the co-adsorption of alkylamines varying in size and basicity over a wide range of conditions, through which the relative adsorption enthalpy and entropy of alkylamines were measured. Across a homologous family of sec-alkylamines (C3-C5) adsorbed on isolated Brønsted acid sites, a fixed contribution to the enthalpy (19 ± 4 kJ mol CH2-1) and entropy (25 ± 4 J mol CH2-1 K-1) of adsorption per methylene unit of was found to exist, likely resulting from electrostatic interactions between the alkyl chain and surrounding pore environment. | 2023-08-22 | chemRxiv | Catalysis; Materials Chemistry | null | CC BY NC ND 4.0 |
tert-Butyl as a Functional Group: Non-Directed Catalytic Hydroxylation of Sterically Congested Primary C−H Bonds | 10.26434/chemrxiv-2024-0cprf | N.A. | N.A. | Siu-Chung Chan; Andrea Palone; Massimo Bietti; Miquel costas | The tert-butyl group is a common aliphatic motif extensively employed to implement steric congestion and conformational rigidity in organic and organometallic molecules. Because of the combination of a high bond dissociation energy (~ 100 kcal mol-1) and limited accessibility, in the absence of directing groups, neither radical nor organometallic approaches are effective for the chemical modification of tert-butyl CH bonds. Herein we overcome these limits by employing an electron-poor manganese catalyst that operates in the strong hydrogen bond donor solvent nonafluoro-tert-butyl alcohol (NFTBA) and catalytically activates hydrogen peroxide to generate a powerful manganese-oxo species that effectively oxidizes tert-butyl C−H bonds. Leveraging on the interplay of steric, electronic, medium and torsional effects, site-selective and product chemoselective hydroxylation of the tert-butyl group is accomplished with broad reaction scope, delivering primary alcohols as largely dominant products in preparative yields. Late-stage hydroxylation at tert-butyl sites is demonstrated on 6 densely functionalized molecules of pharmaceutical interest. This work uncovers a novel disconnection approach, harnessing tert-butyl as a potential functional group in strategic synthetic planning for complex molecular architectures. | 2024-01-17 | chemRxiv | Organic Chemistry; Organic Synthesis and Reactions | null | CC BY NC 4.0 |
BF3.Et2O Promoted Electrophilic Sulfinylation and Spirocyclization of Biaryl Ynones: Access to SOAr-Containing Spiro[5.5]trienones | 10.26434/chemrxiv-2023-fcw92 | N.A. | N.A. | Barnali Roy; Puspendu Kuila; Sangam Jha; Debayan Sarkar | A simple sulfinylated cascade transformation has remained largely underexplored. Herein, we disclose a detail and unified strategy of BF3.Et2O promoted cascade addition/dearomatization spiro-cyclization of biaryl ynones with aryl sulfinic acid. This approach provides a wide variety of functionalized spirotrienones in mild conditions and moderate to high yield at room temperature. A detailed mechanistic study has been carried out to prove cationic process. | 2023-03-06 | chemRxiv | Organic Chemistry; Organic Synthesis and Reactions; Process Chemistry | null | CC BY NC ND 4.0 |
The Energetics of Electron Transfer in Redox-DNA Layers Mimics that of Redox Proteins | 10.26434/chemrxiv-2024-k51xn | N.A. | N.A. | Zhiyong Zheng; Simon Grall; Soo Hyeon Kim; Arnaud Chovin; Nicolas Clément; Christophe Demaille | Redox-DNA layers have recently demonstrated unique properties, such as reorganization energy of electron transfer that can be tuned with DNA length or hybridization, and completely suppressed under nanoconfinement. These dis-coveries, attributed to the changes in the solvation of the redox marker and/or fast chain dynamics, provide a unique opportunity to use electrochemical measurements as a tool to address open questions in ion solvation and to clarify the origin of low reorganization energies reported in protein electron transfer. Here, high-scan-rate, variable-temperature cyclic voltammetry, analyzed using the Marcus formalism and molecular dynamics simulations, reveals that the total free energy barrier of electron transfer consists of two additive elements: the reorganization energy of the partially desolvated redox marker and the energy cost for solvation changes of the redox marker at the solid/liquid interface. These results may have profound implications for our understanding of electron transfer and solvation effects in fast-moving molecules, providing opportunities for better design of artificial photosynthetic systems, biosensing, and ener-gy conversion devices. | 2024-09-05 | chemRxiv | Analytical Chemistry | null | CC BY NC ND 4.0 |
Block chemistry for accurate modeling of epoxy resins | 10.26434/chemrxiv-2022-d5cwr | 10.1021/acs.jpcb.3c04724 | https://doi.org/10.1021/acs.jpcb.3c04724 | Mattia Livraghi; Sampanna Pahi; Piotr Nowakowski; David M. Smith; Christian R. Wick; Ana-Sunčana Smith | Accurate molecular modelling of the physical and chemical behavior of highly cross-linked epoxy resins at the atomistic scale is important for the design of new property-optimized materials. However, a systematic approach to parametrizing and characterizing these systems in molecular dynamics is missing. We, therefore, present a unified scheme to derive atomic charges for amine- based epoxy resins, in agreement with the AMBER force field, based on defining reactive fragments – blocks – building the network. The approach is applicable to all stages of curing, from pure liquid, to gelation, to fully cured glass. We utilize this approach to study DGEBA/DDS epoxy systems, incorporating dynamic topology changes into atomistic Molecular Dynamics simulations of the curing reaction with 127,000 atoms. We study size effects in our simulations and predict the gel point utilizing rigorous percolation theory to accurately recover the experimental data. Furthermore, we observe excellent agreement between the estimated and the experimentally determined glass transition temperatures as a function of curing rate. Finally, we demonstrate the quality of our model by the prediction of the elastic modulus, based on uniaxial tensile tests. The presented scheme paves the way for a broadly consistent approach for modelling and characterizing all amine-based epoxy resins. | 2022-09-14 | chemRxiv | Theoretical and Computational Chemistry; Polymer Science; Polymerization (Polymers); Computational Chemistry and Modeling; Materials Chemistry | null | CC BY 4.0 |
Quantum vs Thermal Effects in Formic Acid Adsorption on (101) TiO2 Anatase Surfaces | 10.26434/chemrxiv.7797719.v2 | N.A. | N.A. | gloria tabacchi; Ettore Fois; Marco Fabbiani; Lorenzo Mino; Gianmario Martra | <p>Carboxylic acids adsorption on
anatase TiO<sub>2</sub> is a key process in circular economy and
sustainability. Yet, in spite of several decades of investigations, its
intimate working mechanisms still remain elusive. In particular, the behavior
of the acid proton and its localization – either on the molecule or on the
surface – are still open issues. By modeling the adsorption of formic acid on
top of regular (101) anatase TiO<sub>2</sub> surfaces, we found that, in the 0
K limit, the acid proton is shared between a carboxylic oxygen and a surface oxygen.
In this regime, the proton behavior is mainly governed by quantum
delocalization effects in a single potential well. Nonetheless, as temperature
is raised to room conditions, simulations evidenced a rapid “classical”
shuttling of the proton due to the onset of a two-wells free energy profile
separated by a free energy barrier of the order of <i>kT</i>. This picture, supported by the agreement between simulated and
experimental IR spectra, shows that the titania surface acts like a protecting
group for the carboxylic acid functionality. Such a conceptual insight might
help rationalize the chemical processes of carboxylic species on TiO<sub>2</sub>
surfaces.</p><div>
<div>
<div><a></a>
<p> </p>
</div>
</div>
</div> | 2019-04-10 | chemRxiv | Theory - Computational; Interfaces; Quantum Mechanics; Spectroscopy (Physical Chem.); Surface | null | CC BY NC ND 4.0 |
Photosensitization Enables Pauson-Khand-type Reactions with Nitrenes | 10.26434/chemrxiv-2023-jj6ln | N.A. | N.A. | Fang Li; W. Felix Zhu; Claire Empel; Oleksandr Datsenko; Adarsh Kumar; Yameng Xu; Johanna H. M. Ehrler; Iuliana Atodiresei; Stefan Knapp; Pavel K. Mykhailiuk; Ewgenij Proschak; Rene M. Koenigs | The Pauson-Khand reaction was invented in 1971, and is one of the most common pericyclic reactions in chemistry featuring the reaction of two unsaturated bonds and carbon monoxide. Even 50 years after its discovery, it remains limited to carbon monoxide as a C1 building block. Herein we report pericyclic reactions with nitrenes as a N1 unit. The reaction that comprises a non-conjugated diene and a nitrene precursor allows the rapid synthesis of bicyclic bioisosteres for common saturated heterocycles such as piperidine, morpholine, piperazine. This is achieved by relaying the diradical nature of triplet nitrene as shown experimentally and computationally. We exemplified this approach in two protocols, late-stage functionalization of drugs, and the application in drug discovery for inhibitors of soluble epoxide hydrolase. | 2023-10-31 | chemRxiv | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Photochemistry (Org.) | null | CC BY NC ND 4.0 |
Nonacethrene Unchained: A Cascade to Chiral Contorted Conjugated Hydrocarbon with Two sp3-Defects | 10.26434/chemrxiv-2022-p6kp9 | 10.1021/jacsau.2c00190 | https://doi.org/10.1021/jacsau.2c00190 | Daniel Čavlović; Daniel Häussinger; Olivier Blacque; Prince Ravat; Michal Juríček | A dihydro precursor of helical diradicaloid nonacethrene undergoes a reaction cascade triggered by an oxidant to a chiral contorted polycyclic aromatic hydrocarbon named hypercethrene. In this ten-electron-oxidation process, four σ bonds, one π bond, and three six-membered rings are formed in a reaction sequence of up to nine steps to yield a 72-carbon-atom warped framework, comprising two configurationally locked [7]helicene units, fluorescent peropyrene unit, and two precisely installed sp3-defects.The key intermediate in this cascade is a closed nonacethrene derivative with one quaternary center, presumably formed via an electrocyclic ring closure of nonacethrene, which—
when activated by oxidation—undergoes an oxidative dimerization of phenalenyl to peropyrene. By controlling the amount oxidant used, two intermediates and one side product could be isolated and fully characterized, including single-crystal X-ray diffraction analysis, and one intermediate was detected by electron paramagnetic resonance spectroscopy. In concert with density functional theory calculations, these intermediates support the proposed reaction mechanism. Compared to peropyrene, the absorption and emission of hypercethrene are slightly red-shifted on account of extended conjugation and the fluorescence quantum yield of 0.45 is decreased by a factor of ~2. Enantiomerically enriched hypercethrene displays circularly polarized luminescence with a CPL brightness value of 8.3 M–1cm–1. This unexpected reaction cascade demonstrates that the reactivity of “unchained”diradicaloid compounds, which is typically considered an undesired feature, can be well-defined and employed as a useful, step-economic synthetic tool toward novel carbon nanostructures. | 2022-03-17 | chemRxiv | Organic Chemistry; Organic Synthesis and Reactions; Physical Organic Chemistry; Stereochemistry | null | CC BY NC ND 4.0 |
AutoParams: An Automated Web-Based Tool To Generate Force Field Parameters for Molecular Dynamics Simulations | 10.26434/chemrxiv-2023-4cbwb-v2 | N.A. | N.A. | Mark A. Hix; Alice R. Walker | The growth of machine learning as a predictive tool in biochemical research has led to an increased need for large-scale datasets. Certain research questions benefit from molecular dynamics simulations to observe the motions and conformations of molecules over time, however contemporary methods rely on forcefields which describe sets of common biomolecules. Unusual molecules, such as nucleotide analogues, functionalized carbohydrates, and modified amino acids are often ill-described in standard forcefields, requiring the development of custom parameters for each unique molecule. While these parameters may be created by individual users, the process is time-consuming and can introduce errors that may not be immediately apparent. We present an open-source automated parameter generation service, AutoParams, which requires minimal input from the user and creates useful forcefield parameter sets for most molecules, particularly those that combine molecular types (ex: a carbohydrate functionalized with a benzene). It can be straightforwardly linked to any charge generation program, and currently has interfaces to PsiRESP and TeraChem, and is available via GitHub and as a Docker container. It includes error checking and testing protocols to ensure the parameters will be sufficient for subsequent molecular dynamics simulations, and streamlines the creation of force field databases. | 2023-07-14 | chemRxiv | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Chemoinformatics - Computational Chemistry | null | CC BY NC ND 4.0 |
Finding non-fluorinated alternatives to fluorinated gases used as refrigerants | 10.26434/chemrxiv-2024-kkjwj | N.A. | N.A. | Juliane Glüge; Katharina Breuer; Armin Hafner; Christian Vering; Dirk Müller; Ian T. Cousins; Rainer Lohmann; Gretta Goldenman; Martin Scheringer | Hydrofluorocarbons (HFCs) and so-called hydrofluoroolefins (HFOs) are used as refrigerants in air conditioning, refrigeration, chillers, heat pumps and devices for dehumidification and drying. However, many HFCs, including R-134a and R-125, have a high global warming potential and some of the HFCs and HFOs degrade atmospherically and form persistent degradation products. Thus, there is an urgent need to replace fluorinated refrigerants with non-fluorinated working fluids to avoid direct emissions due to leakage, incorrect loading or removal. It is important, however, also to select refrigerants with high efficiencies to avoid indirect CO2 emissions due to a (too) high energy consumption during the use phase. The present study investigates the available non-fluorinated alternatives to fluorinated refrigerants and shows that a transition to non-fluorinated refrigerants, in general, is possible and has happened in many sectors already. Technically, there are only slight barriers to overcome to replace fluorinated refrigerants in almost all newly developed systems conforming to existing standards. Additionally, we show that alternatives are available even for some use cases for which derogations have been proposed in the PFAS restriction proposal and suggest making these derogations more specific to support bringing the use of non-fluorinated refrigerants into practice. | 2024-07-24 | chemRxiv | Earth, Space, and Environmental Chemistry; Chemical Engineering and Industrial Chemistry; Environmental Science | null | CC BY NC ND 4.0 |
Kinetics-Constrained Neural Ordinary Differential Equations: Artificial Neural Network Models tailored for Small Data to boost Kinetic Model Development | 10.26434/chemrxiv-2023-x39xt | N.A. | N.A. | Aleksandr Fedorov; Anna Perechodjuk; David Linke | Artificial neural networks (ANNs) are powerful tools for solving a wide range of tasks in fundamental and applied science. However, training and building reliable ANN models requires a lot of data which so far hinders their wider application in kinetic modelling where typically only small (experimental) datasets are available. In the present work we propose a method to design ANN models for kinetic modelling that can be trained even with small data sets as are typically available. The key idea is to constrain the architecture of the ANN models by integrating kinetic and thermodynamic knowledge leading to what we call Kinetics-Constrained Neural Ordinary Differential Equations (KCNODE). The feasibility and effectiveness of the approach is first demonstrated in a numerical experiment using the catalytic hydrogenation of CO2 to methane as example. Next, we demonstrate the approach for real experimental data of a more complex reaction, the hydrogenation of CO2 to higher hydrocarbons (CO2-FT). Finally, the ANN trained for CO2-FT is used to derive an improved mechanistic model for the reverse water gas shift reaction which is a key reaction in the CO2-FT reaction network. This last step exemplifies how the opportunity to obtain reliable ANN models from small data opens new ways to approach kinetic model development. | 2023-05-15 | chemRxiv | Theoretical and Computational Chemistry; Catalysis; Chemical Engineering and Industrial Chemistry; Machine Learning; Reaction Engineering; Heterogeneous Catalysis | null | CC BY 4.0 |
The Source of Proton in the Noyori−Ikariya Reaction | 10.26434/chemrxiv-2022-dbc0n | N.A. | N.A. | Nikolay V. Tkachenko; Pavel Rublev; Pavel A. Dub | The study of the mechanism of the Noyori‒Ikariya asymmetric transfer hydrogenation of ketones spans nearly three decades of investigations. Whereas the early part of the catalytic cycle being the hydride transfer is now well-understood, the late part being the proton transfer is still ambiguous. Specifically, the source of the proton can be the N‒H functionality of the catalyst and/or the O‒H functionality of the reagent/solvent leading to two conceptually different catalytic cycles or even their combination. For three popular reagents/solvents typically used in the method, namely propan-2-ol, 5:2 HCO2H‒NEt3 and water, the source of the proton is presently either unknown, or the evidence is presented partially by only one approach ‒ experimental or computational. This work eliminates this ambiguity by means of various state-of-the-art molecular dynamics simulation methods (ab initio, quantum mechanics/molecular mechanics and path integral to include quantum tunneling effects). Here we show that the source of proton in propan-2-ol is catalyst’s N‒H functionality, whereas in more acidic water, binary 5:2 HCO2H‒NEt3 or neat formic acid the source of proton is reagent/solvent. Thus, depending on the source of reagent/solvent the catalyst’s ligand can be either chemically non-innocent or chemically innocent in the Noyori‒Ikariya reaction, which opens new opportunities for the outer-sphere homogeneous catalysts design. | 2022-07-22 | chemRxiv | Theoretical and Computational Chemistry; Catalysis; Computational Chemistry and Modeling; Homogeneous Catalysis | null | CC BY NC ND 4.0 |
Assessing the Calculation of Exchange Coupling Constants and Spin Crossover Gaps Using the Approximate Projection Model to Improve Density Functional Calculations | 10.26434/chemrxiv.7976474.v4 | 10.1021/acs.jctc.9b00387 | https://doi.org/10.1021/acs.jctc.9b00387 | Xianghai Sheng; Lee Thompson; Hrant Hratchian | This work evaluates the quality of exchange coupling constant and spin crossover gap calculations using density functional theory corrected by the Approximate Projection model. Results show that improvements using the Approximate Projection model range from modest to significant. This study demonstrates that, at least for the class of systems examined here, spin-projection generally improves the quality of density functional theory calculations of $J$-coupling constants and spin crossover gaps. Furthermore, it is shown that spin-projection can be important for both geometry optimization and energy evaluations. The Approximate Projection model provides an affordable and practical approach for effectively correcting spin-contamination errors in such calculations. | 2019-11-27 | chemRxiv | Theory - Computational; Transition Metal Complexes (Organomet.) | null | CC BY 4.0 |