id
stringlengths 24
24
| doi
stringlengths 28
32
| title
stringlengths 8
495
| abstract
stringlengths 17
5.7k
| authors
stringlengths 5
2.65k
| categories
stringlengths 4
700
| license
stringclasses 3
values | origin
stringclasses 1
value | date
stringdate 1970-01-01 00:00:00
2025-03-24 00:00:00
| url
stringlengths 119
367
⌀ |
|---|---|---|---|---|---|---|---|---|---|
667c1ab85101a2ffa88ec780 | 10.26434/chemrxiv-2024-t9pdh-v3 | Telomerase Reverse Transcriptase Degradation via a Rationally Designed Covalent Proteolysis Targeting Chimera | Expression of telomerase reverse transcriptase (TERT) is a hallmark of cancer, maintaining telomere length and integrity to enable replicative immortality. However, TERT also serves multiple enzyme-dependent and -independent functions to support cell growth and survival, including enhanced DNA damage response. Agents that inhibit TERT reverse transcriptase activity prevent telomere elongation but may fail to limit other TERT functions that mediate cancer therapy resistance. Thus, we applied structure-based design, modular synthesis, and biochemical assays toward developing a proteolysis targeting chimera (PROTAC) to drive proteasomal degradation of TERT in cancer cells. This yielded NU-PRO-1, a PROTAC linking the TERT active site-targeted covalent inhibitor NU-1 to the VHL E3-ligase ligand (S,R,S)-AHPC. Applied to cancer cells, NU-PRO-1 induced transient VHL- and proteasome-dependent TERT degradation. NU-PRO-1 did not induce DNA damage on its own but acted to further delay DNA repair after irradiation compared to NU-1. TERT-degrading PROTACs provide novel chemical probes of TERT's non-catalytic functions and may overcome the limitations of current telomerase inhibitors as cancer therapeutics. | Grant Frost; Yue Liu; Stephen Kron; Karl Scheidt | Biological and Medicinal Chemistry; Cell and Molecular Biology; Chemical Biology; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2024-06-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/667c1ab85101a2ffa88ec780/original/telomerase-reverse-transcriptase-degradation-via-a-rationally-designed-covalent-proteolysis-targeting-chimera.pdf |
64f09867dd1a73847fe3900a | 10.26434/chemrxiv-2023-ljnzz | Comparative techno-economic and life-cycle analysis of precious versus non-precious metal electrocatalysts: The case of PEM fuel cell cathodes | Sluggish kinetics in the oxygen reduction reaction (ORR) require significant quantities of expensive Pt-based nanoparticles on carbon (Pt/C) at the cathode of proton exchange membrane fuel cells (PEMFCs). This catalyst requirement hinders their large-scale implementation. Single atom Fe in N-doped C (Fe-N-C) electrocatalysts offer the best non-Pt-based ORR activities to date, but their environmental impacts have not been studied and their production costs are rarely quantified. Herein, we report a comparative life-cycle assessment and techno-economic analysis of replacing Pt/C with Fe-N-C at the cathode of an 80 kW PEMFC stack. In the baseline scenario (20 gPt/C vs. 690 gFe-N-C), we estimate that Fe-N-C could reduce damages on ecosystems and human health by 88-90% and 30-44%, respectively, while causing a comparable impact on resource depletion. The environmental impacts of Pt/C predominantly arise from the Pt precursor while those of Fe-N-C are presently dominated by the electricity consumption. The monetized costs of environmental externalities for both Fe-N-C and Pt/C catalysts exceed their respective direct production costs. Based on catalyst performance with learning curve analysis at 500,000 PEMFC stacks per annum, we estimate replacing Pt/C with Fe-N-C would increase PEMFC stack cost from 13.8 to 41.6 USD kW-1. The cost increases despite a reduction in cathode catalyst production cost from 3.41 to 0.79 USD kW-1 (excluding environmental externalities). To be cost-competitive with a Pt-based PEMFC stack delivering 2020 US Department of Energy target of 1,160 mW cm-2 (at 0.657 V), the same stack with an Fe-N-C cathode would need to reach 874 mW cm-2, equivalent to a 200% performance improvement. These findings demonstrate the need for continued Fe-N-C activity development with sustainable synthesis routes in mind to replace Pt-based cathode catalyst in PEMFCs. Based on forecasting scenarios of fuel cell vehicle deployment targets, we find that Pt consumption would be constrained by Pt supply. | Angus Pedersen; Jinil Pandya; Grazia Leonzio; Alexey Serov; Andrea Bernardi; Ifan Stephens; Maria-Magdalena Titirici; Camille Petit; Benoît Chachuat | Materials Science; Catalysis; Chemical Engineering and Industrial Chemistry; Electrocatalysis | CC BY NC 4.0 | CHEMRXIV | 2023-09-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64f09867dd1a73847fe3900a/original/comparative-techno-economic-and-life-cycle-analysis-of-precious-versus-non-precious-metal-electrocatalysts-the-case-of-pem-fuel-cell-cathodes.pdf |
61b3cdd8689c875d6adea959 | 10.26434/chemrxiv-2021-n4c1x | Capture of activated dioxygen intermediates at the copper-active site of a lytic polysaccharide monooxygenase | Metalloproteins perform a diverse array of redox-related reactions facilitated by the increased chemical functionality afforded by their metallocofactors. Lytic polysaccharide monooxygenases (LPMOs) are a class of copper-dependent enzymes that are responsible for the breakdown of recalcitrant polysaccharides via oxidative cleavage at the glycosidic bond. The activated copper-oxygen intermediates and their mechanism of formation remains to be established. Neutron protein crystallography which permits direct visualization of protonation states was used to investigate the initial steps of oxygen activation directly following active site copper reduction in Neurospora crassa LPMO9D. Herein, we cryo-trap an activated dioxygen intermediate in a mixture of superoxo and hydroperoxo states, and we identify the conserved second coordination shell residue His157 as the proton donor. Density functional theory (DFT) calculations indicate that both active site states are stable. The hydroperoxo formed is potentially an intermediate in the mechanism of hydrogen peroxide formation in the absence of substrate. We establish that the N-terminal amino group of the copper coordinating His1 remains doubly protonated directly following molecular oxygen reduction by copper. Aided by mining minima free energy calculations we establish His157 conformational flexibility in solution that is abolished by steric hindrance in the crystal. A neutron crystal structure of NcLPMO9D at low pH supports occlusion of the active site which prevents protonation of His157 at acidic conditions. | Gabriela C. Schröder; William B. O'Dell; Simon P. Webb; Pratul K. Agarwal; Flora Meilleur | Biological and Medicinal Chemistry; Catalysis; Biochemistry; Biocatalysis; Redox Catalysis | CC BY 4.0 | CHEMRXIV | 2021-12-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61b3cdd8689c875d6adea959/original/capture-of-activated-dioxygen-intermediates-at-the-copper-active-site-of-a-lytic-polysaccharide-monooxygenase.pdf |
62c6f242fb6381e246cfff65 | 10.26434/chemrxiv-2022-ht3v5 | Rationalising the difference in crystallisability of two
Sulflowers using efficient in silico methods. | The molecular structures of the first and second generation Sulflowers, Sulflower and Persulfurated Coronene (PSC), are remarkably similar: carbon ring structures decorated with sulfur atoms, without any additional moiety. However, their crystallisability is starkly different, with Sulfower easily forming well-characterised crystals, but with PSC only resulting in amorphous forms, despite extensive experimental efforts. Here this phenomenon is investigated using Crystal Structure Prediction (CSP) methods to generate plausible structures on the lattice energy surface for both systems, followed by molecular dynamics and Well-Tempered metadynamics to investigate their persistence at finite temperature. Coherently with experimental observations, the Sulfower experimental form emerges as exceptionally stable under ambient conditions and persists in all dynamic simulations. However, all PSC structures transition to amorphous phases when subjected to a small amount of work. While CSP methods are commonly used to identify a shortlist of structures that a molecule could plausibly crystallise into, this work demonstrates, for the first time, the ability of in silico methods to predict whether a molecule can crystallise into any structure at all. | Isaac Sugden; Nicholas Francia; Torsten Jensen; Claire Adjiman; Matteo Salvalaglio | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Physical and Chemical Properties; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-07-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62c6f242fb6381e246cfff65/original/rationalising-the-difference-in-crystallisability-of-two-sulflowers-using-efficient-in-silico-methods.pdf |
60c74ec5469df4c68df44555 | 10.26434/chemrxiv.12800096.v1 | Valence Electrons in Lanthanide-Based Single-Atom Magnets: A Paradigm Shift in 4f-Magnetism Modeling and Design. | Detailed electronic structure of single atomic magnets is a crucial bit in the further understanding and design of a new generation of monoatomic magnetic elements on surfaces and in molecules. Control and manipulation of the single atomic state, as well as long relaxation of magnetization, have been demonstrated for lanthanide atoms on carefully chosen supporting substrates. However, these convincing experiments are puzzling by insufficient theoretical description, usually omitting the valence electrons of lanthanide atoms. In this work, starting with an idea of the inevitable need of local d- and p-shell electrons for a proper description of the magnetic states of lanthanide atoms, we rationalized the electronic structure and magnetic properties of Ho atom on the MgO substrate using ab initio multiconfigurational approaches. By doing so, we obtained the solution which complements experimental observations without any assumptions and has been able to pin-point the atomic state which most likely to be responsible for the exceptional magnetic properties of Ho on MgO. This study demonstrates that new paradigms are needed for understanding and interpretation of the lanthanide single-atomic magnets. | Vasilii Dubrovin; Alexey Popov; Stanislav Avdoshenko | Magnetic Materials; Nanostructured Materials - Materials; Magnetism; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2020-08-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74ec5469df4c68df44555/original/valence-electrons-in-lanthanide-based-single-atom-magnets-a-paradigm-shift-in-4f-magnetism-modeling-and-design.pdf |
65ba2fb2e9ebbb4db958efbb | 10.26434/chemrxiv-2024-fl90t | The role of quantum information in HEOM trajectories | Open quantum systems often operate in the non-Markovian regime where a finite history of a trajectory is intrinsic to its evolution. The degree of non-Markovianity for a trajectory may be measured in terms of the amount of information flowing from the bath back into the system. In this study we consider how information flows through the auxilary density operators (ADOs) in the hierarchical equations of motion (HEOM). We consider three cases for a range of baths,underdamped, intermediate and overdamped. By understanding how information flows, we are able to determine the relative importance of different ADOs within the hierarchy. We show that ADOs sharing a common Matsubara axis behave similarly while ADOs on different Matsubara axes behave differently. Using this knowledge we are able to truncate hierarchies significantly, thus reducing computation time, while obtaining qualitatively similar results. This is illustrated by comparing 2D electronic spectra for a molecule with an underdamped vibration subsumed into the bath spectral density. | Ben Humphries ; Joshua Kinslow; Dale Green; Garth Jones | Theoretical and Computational Chemistry; Physical Chemistry; Theory - Computational; Quantum Mechanics; Spectroscopy (Physical Chem.) | CC BY 4.0 | CHEMRXIV | 2024-02-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65ba2fb2e9ebbb4db958efbb/original/the-role-of-quantum-information-in-heom-trajectories.pdf |
60c7491e4c89199e13ad303c | 10.26434/chemrxiv.12030516.v1 | Liquid Metal Slingshot-a Self-Propelled and Controllable Motion | This manuscript reports a new self-propelled motion of
liquid metal droplet, which not rely on any external force, and we can change
the speed and direction by changing the shape of the surface. This self-propelled and
controllable motion is of great significance for the application of liquid
metals in nanomachines, robots, targeted therapy, and others. | Zhiping Yuan; Xudong Zhang; Huimin Hou; Zhifeng Hu; Xiaomin Wu; Jing Liu | Fluid Mechanics; Interfaces | CC BY NC ND 4.0 | CHEMRXIV | 2020-03-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7491e4c89199e13ad303c/original/liquid-metal-slingshot-a-self-propelled-and-controllable-motion.pdf |
60c74a719abda2551cf8ce52 | 10.26434/chemrxiv.12148524.v2 | How ATP-Competitive Inhibitors Allosterically Modulate Tyrosine Kinases That Contain a Src-like Regulatory Architecture | <p>Small molecule kinase inhibitors that stabilize distinct ATP-binding site conformations can differentially modulate the glob-al conformation of Src-family kinases (SFKs). However, it is unclear which specific ATP-binding site contacts are responsible for modulating the global conformation of SFKs and whether these inhibitor-mediated allosteric effects are general to other tyrosine kinases. Here, we describe the development of chemical probes that allow us to deconvolute which features in the ATP-binding site are responsible for the allosteric modulation of the global conformation of Src. We find that the ability of an inhibitor to modulate the global conformation of Src’s regulatory domain-catalytic domain module relies mainly on the influence it has on the conformation of a structural element called helix aC. Furthermore, by developing a set of orthogonal probes that target a drug-sensitized Src variant, we show that stabilizing Src’s helix aC in an active conformation is sufficient to promote a Src-mediated, phosphotransferase-independent alteration in cell morphology. Finally, we report that ATP-competitive, conformation-selective inhibitors can influence the global conformation of tyrosine kinases beyond the SFKs, suggesting that the allosteric networks we observe in Src are conserved in kinases that have a similar regulatory architecture. Taken together, our study highlights that an ATP-competitive inhibitor’s interactions with helix aC can have a major influence on the global conformation of some tyrosine kinases in vitro and in cells.</p> | Linglan Fang; Jessica Vilas-Boas; sujata chakraborty; zachary potter; Ames Register; Markus Seeliger; Dustin J. Maly | Organic Compounds and Functional Groups; Biochemistry; Biophysics; Cell and Molecular Biology; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2020-04-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74a719abda2551cf8ce52/original/how-atp-competitive-inhibitors-allosterically-modulate-tyrosine-kinases-that-contain-a-src-like-regulatory-architecture.pdf |
678444b7fa469535b9b5c2e2 | 10.26434/chemrxiv-2025-n5v68 | Design and Optimization of an N-Pt-N Coordinated Phenalene Model for Enhanced Photocatalytic Hydrogen Evolution | Charge recombination, limited selectivity, and stability remain major challenges in the scaling of photocatalytic materials for hydrogen evolution reactions (HER). In this study, we address these issues by designing the N-Pt-N coordinated phenalene model, engineered to enhance photocatalytic efficiency through improved selectivity, reduced recombination, and broadened absorption peaks. Using ChemDraw for material modeling, DMOL3 in Material Studio for optical, electronic, and catalytic property calculations, and MATLAB for overpotential analysis, we investigate the model’s potential for hydrogen production. The observed HOMO-LUMO gap values are -0.02376, -0.02146, and 0.13246 eV, and the N-Pt-N phenalene derivative shows a spin range of -0.165 to 0.342. The nitrogen component exhibits a range of -0.003 to 0.171, with three distinct oscillation domes within the absorption ranges of 420-515 nm, 515-575 nm, and 575-625 nm. The Gibbs free energy difference between H⁺ and H (ΔG ≈ -0.082 eV) and the HER overpotential of 0.08 J demonstrate the material’s efficient reaction pathway. While the N-Pt-N model exhibits remarkable selectivity and stability, positioning it as a highly efficient photocatalyst for sustainable hydrogen production, challenges associated with charge recombination still require attention. These non-recombinant charge properties must be further studied and optimized to maximize the material’s photocatalytic potential and achieve scalable solutions for renewable energy applications. | Chidi Daniel Chukwu | Catalysis; Energy; Photocatalysis; Fuels - Energy Science; Fuel Cells; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2025-01-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/678444b7fa469535b9b5c2e2/original/design-and-optimization-of-an-n-pt-n-coordinated-phenalene-model-for-enhanced-photocatalytic-hydrogen-evolution.pdf |
66d24fef20ac769e5f672ad0 | 10.26434/chemrxiv-2024-z5b8m | A multi-species benchmark for training and validating mass spectrometry proteomics machine learning models | Training machine learning models for tasks such as de novo sequencing or spectral clustering requires large collections of confidently identified spectra. Here we describe a dataset of 2.8 million high-confidence peptide-spectrum matches derived from nine different species. The dataset is based on a previously described benchmark but has been re-processed to ensure consistent data quality and enforce separation of training and test peptides. | Bo Wen; William Noble | Analytical Chemistry; Mass Spectrometry | CC BY 4.0 | CHEMRXIV | 2024-09-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66d24fef20ac769e5f672ad0/original/a-multi-species-benchmark-for-training-and-validating-mass-spectrometry-proteomics-machine-learning-models.pdf |
66b212ddc9c6a5c07a27cd59 | 10.26434/chemrxiv-2024-tzfrk | Coiled double amyloid-like fibrils allosterically catalyze hydrolysis of beta-lactam antibiotics | The release of antibiotic compounds into wastewater constitutes a significant and growing health and environmental hazard, particularly contributing to the spread of antibiotic resistant bacterial strains. Here, we demonstrate that amyloid fibrils, consisting of an alternating lysine/phenylalanine -sheet forming short peptide, catalyze hydrolysis of β-lactam antibiotics, the most prominent family of antibiotic compounds, which is further widespread in wastewater. Peptide variant analysis, molecular dynamics (MD) simulations, and cryogenic electron microscopy (cryo-EM) reveal that the β-lactam molecules dock onto the fibrils’ surface via electrostatic interactions with the lysine sidechains. Importantly, catalytic hydrolysis occurs via an allosteric mechanism mediated by a unique coiled double fibril structure in which the anchored β-lactam molecules are embedded within twisted fiber strands, facilitating nucleophilic attacks by the lysine sidechains. Utilization of the catalytic lysine-displaying amyloid fibrils for hydrolytic degradation and removal of β-lactam antibiotics from water was accomplished through display of the fibrils on silica beads placed in a conventional column filtration setup. Amyloid fibrils displaying lysine arrays may furnish a versatile platform for hydrolysis and removal of β-lactam antibiotics in water, underscoring new avenues for addressing the considerable threat of antibiotics water contamination. | raz jelinek; sisira Mambram Kunnath; elad arad; ran zalk; itamar kass; albert Batushansky; hanna rapaport | Catalysis; Biocatalysis | CC BY 4.0 | CHEMRXIV | 2024-08-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66b212ddc9c6a5c07a27cd59/original/coiled-double-amyloid-like-fibrils-allosterically-catalyze-hydrolysis-of-beta-lactam-antibiotics.pdf |
60c740e4bdbb894266a38224 | 10.26434/chemrxiv.7211942.v3 | A New and Efficient Equation-of-Motion Coupled-Cluster Framework for Core-Excited and Core-Ionized States | We present a fully analytical implementation of the core-valence separation (CVS) scheme for the equation-of-motion (EOM) coupled-cluster singles and doubles (CCSD) method for calculations of core-level states. In the spirit of the original CVS approximation proposed by Cederbaum, Domcke and Schirmer, pure valence excitations are excluded from the EOM target space and the frozen-core approximation is imposed on the reference-state amplitudes and multipliers. This yields an efficient, robust, and accurate EOM-CCSD framework for calculations of excitation and ionization energies as well as state and transition properties (e.g., spectral intensities, natural transition and Dyson orbitals). The accuracy of the new scheme is improved relative to the results obtained applying the CVS only during the solution of the EOM eigenvalue equations. The errors in absolute excitation/ionization energies relative to the experimental reference data are of the order of 0.2{3.0 eV, depending on the K-edge considered and on the basis set used, and the shifts are systematic for each edge.<br /> | Marta L. Vidal; Xintian Feng; Evgeny Epifanovsky; Anna Krylov; Sonia Coriani | Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2019-02-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c740e4bdbb894266a38224/original/a-new-and-efficient-equation-of-motion-coupled-cluster-framework-for-core-excited-and-core-ionized-states.pdf |
65946f8566c138172991f846 | 10.26434/chemrxiv-2024-1gl4r | Attenuating N-oxyl Decomposition for Improved Hydrogen Atom Transfer Catalysts Design | The design of N-oxyl hydrogen atom transfer catalysts has proven challenging to date. Previous efforts have focused on the functionalization of the archetype phthalimide-N-oxyl. Driven in part by the limited options for modification of this structure, this strategy has provided only modest improvement in reactivity and/or solubility. Our previous mechanistic efforts have suggested that while the electron-withdrawing carbonyls of the phthalimide are necessary to maximize the O-H bond dissociation enthalpy of the HAT product hydroxylamine and thus overall reaction thermodynamics, they can undergo nucleophilic substitution leading to catalyst decomposition. In an attempt to minimize this vulnerability, this work replaces the aryl ring in PINO with the combination of a substituted heteroatom and quaternary carbon. By rendering one carbonyl carbon less electrophilic and the other less sterically accessible, the corresponding N1-aryl-hydantoin-N3-oxyl showed significantly higher stability than PINO as well as a modest improvement in reactivity. This proof-of-principle in new scaffold design may accelerate future HAT catalyst discovery and development. | Cheng Yang; Luke Farmer; Elvis McFee; Rahul Jha; Stephen Maldonado; Derek Pratt; Corey Stephenson | Organic Chemistry; Catalysis; Electrocatalysis; Organocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-01-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65946f8566c138172991f846/original/attenuating-n-oxyl-decomposition-for-improved-hydrogen-atom-transfer-catalysts-design.pdf |
6630ee5821291e5d1d1696a6 | 10.26434/chemrxiv-2024-7mk1c | C1-4 Alkylation of Aryl Bromides with Light Alkanes enabled by Metallaphotocatalysis in Flow | The homologous series of gaseous C1-4 alkanes represents one of the most abundant sources of short alkyl fragments. However, their application in synthetic organic chemistry is exceedingly rare due to the challenging C–H bond cleavage, which typically demands high temperatures and pressures, thereby limiting their utility in the construction of complex organic molecules. In particular, the formation of C(sp2)–C(sp3) bonds is crucial for constructing biologically active molecules, including pharmaceuticals and agrochemicals. In this study, we present the previously elusive coupling between gaseous alkanes and (hetero)aryl bromides, achieved through a combination of Hydrogen Atom Transfer (HAT) photocatalysis and nickel-catalyzed cross coupling at room temperature. Utilizing flow technology allowed us to conduct this novel coupling reaction with reduced reaction times and in a scalable fashion, rendering it practical for widespread adoption in both academia and industry. Density Functional Theory (DFT) calculations unveiled that the oxidative addition constitutes the rate-determining step, with the activation energy barrier increasing with smaller alkyl radicals. Furthermore, radical isomerization observed in propane and butane analogues could be attributed to the electronic properties of the bromoarene coupling partner, highlighting the crucial role of oxidative addition in the observed selectivity of this transformation. | Antonio Pulcinella; Prakash Tiwari; Alberto Luridiana; Ken Yamazaki; Daniele Mazzarella; Akshay Sadhoe; Antonella Alfano; Eveline Tiekink; Trevor Hamlin; Timothy Noel | Organic Chemistry; Catalysis; Organometallic Chemistry; Organic Synthesis and Reactions; Homogeneous Catalysis; Photocatalysis | CC BY 4.0 | CHEMRXIV | 2024-05-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6630ee5821291e5d1d1696a6/original/c1-4-alkylation-of-aryl-bromides-with-light-alkanes-enabled-by-metallaphotocatalysis-in-flow.pdf |
60c75833f96a00424d288da2 | 10.26434/chemrxiv.14165951.v2 | Mediated Inner-Sphere Electron Transfer Induces Homogeneous Reduction of CO2 via Through-Space Electronic Conjugation | The electrocatalytic reduction of CO<sub>2</sub> is an appealing method for converting renewable energy sources into value-added chemical feedstocks. We report a co-electrocatalytic system for the reduction of CO<sub>2</sub> to CO comprised of a molecular Cr complex and dibenzothiophene-5,5-dioxide (DBTD) as a redox mediator which achieves high activity (TOF = 1.51-2.84 x 10<sup>5</sup> s<sup>–1</sup>) and quantitative selectivity. Under aprotic or protic conditions, DBTD produces a co-electrocatalytic response with <b>1</b> by coordinating <i>trans</i> to the site of CO<sub>2</sub> binding and mediating electron transfer from the electrode with quantitative efficiency for CO. This assembly is reliant on through-space electronic conjugation between the <i>π</i> frameworks of DBTD and the bpy fragment of the catalyst ligand, with contributions from dispersive interactions and weak sulfone coordination. The resulting interaction stabilizes a key intermediate in a new aprotic catalytic pathway and lowers the energy of the rate-determining transition state under protic conditions. To the best of our knowledge through-space electronic conjugation has not been explored in molecular electrocatalytic systems.<br /> | Shelby L. Hooe; Juan Moreno; Amelia Reid; Emma Cook; Charles Machan | Coordination Chemistry (Inorg.); Electrochemistry; Supramolecular Chemistry (Inorg.); Electrocatalysis; Homogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2021-04-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75833f96a00424d288da2/original/mediated-inner-sphere-electron-transfer-induces-homogeneous-reduction-of-co2-via-through-space-electronic-conjugation.pdf |
67579417f9980725cf8eaff6 | 10.26434/chemrxiv-2024-k99r6-v3 | Eight-Membered-Ring-Forming Chain-Growth Cyclopolymerization of 2,2'-Diisocyano-1,1'-binaphthalenes for the Synthesis of Helical Poly([1,4]diazocine-2,3-diyl)s | Novel helical macromolecules, poly([1,4]diazocine-2,3-diyl)s (PDACs), are synthesized by living cyclopolymerization of 2,2'-diisocyano-1,1'-
binaphthalenes in the presence of organonickel or organopalladium complexes as initiators. The conformation of the main PDAC chain
obtained from (R)-monomer is deduced from experimental results as (M)-helix and depends on the optical purity of the monomer. | Yukako Yoshinaga; Ryo Nishimaru; Michinori Suginome | Polymer Science; Organic Polymers; Polymerization (Polymers); Polymer scaffolds | CC BY NC ND 4.0 | CHEMRXIV | 2024-12-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67579417f9980725cf8eaff6/original/eight-membered-ring-forming-chain-growth-cyclopolymerization-of-2-2-diisocyano-1-1-binaphthalenes-for-the-synthesis-of-helical-poly-1-4-diazocine-2-3-diyl-s.pdf |
65712d4a5bc9fcb5c937952b | 10.26434/chemrxiv-2023-05gjp | Structure-Function Relationships in Pure Archaeal Bipolar Tetraether Lipids | Archaea, the third fundamental domain of life are distinguished from bacteria and eukaryotes due to the presence of unique lipids in their cell membranes. Archaeal bipolar lipids are among the most unusual lipids occurring in nature because of their presumed ability to span the entire membrane. They are challenging to extract in pure form from natural sources or synthesize chemically, and as a result, prior studies on pure lipids have been limited. Here we have utilized synthesis to enable in-depth biophysical investigations on a series of archaeal glycerol dialkyl glycerol tetraether (GDGT) lipids having symmetric or unsymmetric combinations of polar head groups. We showed that these lipids self-assemble to form membrane-bound vesicles in aqueous media, encapsulate polar molecules, and reconstitute a functional integral membrane protein. Membrane thicknesses and electron density profiles were investigated by performing small-angle X-ray scattering (SAXS) studies and cryogenic electron microscopy (cryo-EM) imaging on unilamellar vesicles of GDGT lipids. SAXS studies on bulk aqueous dispersions of GDGT lipids over a large temperature range (10-90 °C) allowed us to identify lamellar and non-lamellar phases and their interconversions under various buffer conditions. We also studied how the propensity to form various mesophases is reflected in the functional behavior of the GDGT membranes. Specifically, we asked whether vesicles overwhelmingly composed of GDGTs can undergo fusion as it is difficult to conceptualize such behavior with the assumption that such membranes have a monolayer structure. Interestingly, we observed that GDGT vesicles undergo fusion with influenza virus with lipid mixing kinetics comparable to that with vesicles composed of typical monopolar phospholipids. Our results suggest that GDGT membranes may consist of regions with a bilayer structure which facilitates fusion and thus offer insight into how archaea may perform important physiological functions that require dynamical membrane behavior. | Ahanjit Bhattacharya; Isaac D. Falk; Frank R. Moss III; Thomas M. Weiss; Khoi N. Tran; Noah Z. Burns; Steven G. Boxer | Physical Chemistry; Biological and Medicinal Chemistry; Organic Chemistry; Organic Synthesis and Reactions; Biophysical Chemistry; Self-Assembly | CC BY 4.0 | CHEMRXIV | 2023-12-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65712d4a5bc9fcb5c937952b/original/structure-function-relationships-in-pure-archaeal-bipolar-tetraether-lipids.pdf |
6394e5e692f08443c83029d4 | 10.26434/chemrxiv-2022-pq21j | Direct CO2 Activation and Conversion to Ethanol via Reactive Oxygen Species | The growing demand for energy and the excessive use of fossil fuels represents one of the main challenges for humanity. Storing solar energy in the form of chemical bonds to generate solar fuels or value-added chemicals without creating additional environmental burdens is a key requirement for a sustainable future. Here we use biomimetic artificial photosynthesis and present a dPCN-224(H) MOF-based photocatalytic system, which uses reactive oxygen species (ROS) to activate and convert CO2 to ethanol under atmospheric conditions, at room temperature and in 2-5 h reaction time without the use of sacrificial donors. The system provides a CO2-to-ethanol conversion efficiency (CTE) of 92%, while attaining a selectivity for EtOH formation. Furthermore, this method also allows the conversion of CO2 through direct air capture (DAC), making it an incredibly fast and versatile method for both dissolved and gaseous CO2. | Alina Meindl; Mathias Senge | Physical Chemistry; Materials Science; Energy; Hybrid Organic-Inorganic Materials; Photosensitizers; Fuels - Energy Science | CC BY NC ND 4.0 | CHEMRXIV | 2022-12-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6394e5e692f08443c83029d4/original/direct-co2-activation-and-conversion-to-ethanol-via-reactive-oxygen-species.pdf |
67af3359fa469535b94cb24d | 10.26434/chemrxiv-2025-9t0z9 | New heptazines bearing strongly electron-donating substituents with quasi-degenerate singlet and triplet excited states: an experimental and computational study
| New compounds based on heptazine core bearing phenoxazines substituent were synthesized, starting from the easily accessible 2,5,8-tri(3,5-diethyl-1H-pyrazolyl-1-yl)heptazine. The pyrazolyl groups were substituted by one, two, or three phenoxazines, yielding compounds H1, H2, H3. Heptazine (Hz) being an exceptionally strong electron acceptor and the phenoxazines being strong electron donors, these novel compounds are expected to exhibit low-lying singlet and triplet states of pronounced charge-transfer (CT) character. The excited-state electronic structures of these chromophores were investigated with electronic absorption and emission spectroscopies, electrochemical methods, and ab initio electronic-structure calculations. The UV-Vis absorption spectra in the solution were assigned by comparison with computed vertical electronic excitation energies. The absorption spectra exhibit strong transitions to the bright locally-excited 1ππ* state of the Hz core as well as to bright low-lying singlet CT states. The calculations predict that the vertical excitation spectra of all three compounds exhibit singlet-triplet inversion, that is, the lowest singlet state of the Hz core is lower in energy than the lowest triplet states of CT character, albeit the S1 and T1 states are nearly degenerate in H3. When the 0-0 transition energies are considered, on the other hand, the CT states are lowest in energy in all three compounds, and singlet and triplet CT states are nearly degenerate, which is confirmed by stationary and time-resolved spectroscopy in thin solid films. Remarkably, clear emission from the bright locally-excited singlet state of the Hz core is observed in solution in violation of Kasha’s rule. Conversely, luminescence is predicted to occur in thin solid films from the lowest quasi-degenerate singlet and triplet states of CT character. | Maggiore Antonio; Daniele Conelli; Roberto Grisorio; Gian Paolo Suranna; Vincenzo Maiorano; Andrzej Sobolewski; Wolfgang Domcke; Fabien Miomandre; Pierre Audebert | Physical Chemistry; Organic Chemistry; Organic Synthesis and Reactions; Quantum Mechanics; Spectroscopy (Physical Chem.); Materials Chemistry | CC BY NC 4.0 | CHEMRXIV | 2025-02-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67af3359fa469535b94cb24d/original/new-heptazines-bearing-strongly-electron-donating-substituents-with-quasi-degenerate-singlet-and-triplet-excited-states-an-experimental-and-computational-study.pdf |
673391c4f9980725cff88e2f | 10.26434/chemrxiv-2024-b2wss | Site-selective Aryne Formation from Aryl Sulfonium Salts En-abled by Intramolecular Functional Group Translocation. | Recent advantages in the field of aryl sulfonium salts made these salts readily avaible in one chemical step from common functional groups. A new class of aryl sulfonium salts was developed to improve the site-selectivity of the aryne formation via deprotonation/elimination sequence. Mechanism study revealed an intramolecular aryne translaoction pathway enabled by the reversible proton transfer. Current method could enable late stage (hetero)aryne formation on the pharmaceuticals and greatly reduce the synthetic effort to access structurally highly diversed (hetero)aryne. Mild condition and broad scope pro-vide orthogonal reactivity compared with Kobayashi aryne precursors. | Lu Deng ; Bo Xiao; Meng Zhou; hairong cao; Tian-Yu Sun; zhe dong | Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2024-11-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/673391c4f9980725cff88e2f/original/site-selective-aryne-formation-from-aryl-sulfonium-salts-en-abled-by-intramolecular-functional-group-translocation.pdf |
64644764a32ceeff2dc48869 | 10.26434/chemrxiv-2023-mxdcf | Solvation enthalpy determination for aqueous-phase reaction adsorbates from first principles ab initio molecular dynamics | The interplay between covalent and non-covalent interactions at the solid-liquid interface strongly influences electrocatalytic reactions. Although methods to determine the former interactions have been rigorously developed, the latter are often described with static bilayer models or similarly approximate methods. In this study, we account for disorder and dynamics at complex electrochemical interfaces by proposing a simple theory to estimate the enthalpy of solvation for adsorbed intermediates. In a strategy reminiscent of Born-Haber cycles, the enthalpy of solvation is expressed in terms of two sub-processes: vacancy creation by water reorganization, and adsorbate interaction with solvent molecules. The magnitude of the solvation enthalpy is then determined as a mean value from statistical sampling of hydrated adsorbate-catalyst configurations obtained from simulated annealing with ab initio molecular dynamic (AIMD) simulations. This theory is generalizable for many combinations of surfaces and adsorbates. Its application improves treatment of energetics at electrified solid-liquid interfaces, as well as corresponding structure-activity-stability predictions, as demonstrated for electrochemical oxygen reduction on Pt(111) and on Fe-N-C catalysts and for ethanol electrooxidation on Pt(111). | Hee-Joon Chun; Ankita Morankar; Zhenhua Zeng; Jeffrey Greeley | Theoretical and Computational Chemistry; Physical Chemistry; Materials Science; Interfaces; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-05-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64644764a32ceeff2dc48869/original/solvation-enthalpy-determination-for-aqueous-phase-reaction-adsorbates-from-first-principles-ab-initio-molecular-dynamics.pdf |
673e10d4f9980725cf016907 | 10.26434/chemrxiv-2024-w4h8s | Transient Colloidal Crystals Fueled by Electrochemical Reaction Products | Conventional directed colloidal assembly enables fabricating complex hierarchical structures using external stimuli like electric fields, but lacks control over the assembly state in time. Chemical reaction networks have been discovered that transiently assemble colloids; however, they have slow dynamics (hrs – days) and poor temporal tunability, utilize complex reagents, and produce kinetically trapped states. Here we demonstrate transient colloidal crystals that autonomously form, breakup, and reconstitute in response to an electrochemical reaction network driven by a time invariant electrical stimulus. Aqueous mixtures of micron sized colloids and para-benzoquinone (BQ) were subject to superimposed oscillatory and steady electric potentials, i.e., multimode potentials, that induced electrokinetic flows around colloids and proton-coupled BQ redox reactions. We demonstrate wide tunability of transient assembly state lifetimes over nearly two orders of magnitude from 1 - 500 s by modifying the steady component of the multimode potential and electrode separation. Transient assembly states coincided with electrochemically generated pH spikes near the cathode. An electrochemical transport model showed that interaction of advancing acidic and alkaline pH fronts from anodic BQ oxidation and cathodic BQ reduction caused pH transients. We present theoretical and experimental evidence that indicates transient colloidal crystals were mediated by competition between opposing colloidal scale electrohydrodynamic and electroosmotic flows, the latter of which is pH dependent. | Medha Rath; Satyam Srivastava; Eric Carmona; Sarangua Battumur; Shakti Arumugam; Paul Albertus; Taylor Woehl | Physical Chemistry; Materials Science; Chemical Engineering and Industrial Chemistry; Aggregates and Assemblies; Transport Phenomena (Chem. Eng.); Electrochemistry - Mechanisms, Theory & Study | CC BY 4.0 | CHEMRXIV | 2024-11-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/673e10d4f9980725cf016907/original/transient-colloidal-crystals-fueled-by-electrochemical-reaction-products.pdf |
6169e9597d3da5ff02f96022 | 10.26434/chemrxiv-2021-9hk6q | Using machine learning to estimate wildfire PM2.5 at California ZIP codes (2006-2020) | Epidemiological studies on the detrimental health impacts of exposure to fine particulate matter (PM2.5) from different sources of emission can inform regulatory policy and identify vulnerable communities. Though PM2.5 has decreased in the U.S. in the two past decades, the increasing frequency and severity of wildfires contribute to episodically impair air quality in wildfire-prone regions and beyond. Monitoring air quality extensively is challenging. Since government-operated monitors are sparsely located across California and the U.S., several regions and populations remain unmonitored. Current approaches to estimate PM2.5 concentrations in unmonitored areas often rely on gathering large amounts of data, such as satellite-derived aerosol properties and meteorological variables. and direct use of low-cost air sensor measurements that may be associated with substantial uncertainty Furthermore, modelling wildfire-specific PM2.5 is often based on chemical transport model predictions, which results in highly computationally intensive efforts. Our study used an ensemble model that integrated multiple machine learning algorithms and a large set of predictor variables to estimate daily PM2.5 at the ZIP code level, a relevant spatio-temporal resolution for epidemiological and public health studies. Our models achieved comparable results to previous machine learning studies for PM2.5 prediction, but avoided processing larger, computationally intensive datasets. In addition, we use machine learning to estimate the wildfire-specific PM2.5 concentrations through a novel multiple imputation approach. | Rosana Aguilera; Nana Luo; Rupa Basu; Jun Wu; Alexander Gershunov; Tarik Benmarhnia | Earth, Space, and Environmental Chemistry; Atmospheric Chemistry; Environmental Science | CC BY NC ND 4.0 | CHEMRXIV | 2021-10-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6169e9597d3da5ff02f96022/original/using-machine-learning-to-estimate-wildfire-pm2-5-at-california-zip-codes-2006-2020.pdf |
6273ed06d55550e7ad8e9bd5 | 10.26434/chemrxiv-2022-4sdvl | A Photo-triggered Wittig-Cyclization for Detecting and Sequencing 5-Formylcytidine in RNA | The simultaneous detection of a specific post-transcriptional modification that decorates the natural RNA can provide comprehensive information to better understand cellular and molecular functions of this variation. 5-Formylcytidine f5C is one of the natural nucleotides that was discovered in the tRNA of many species during the oxidative demethylation of 5-methylcytidine m5C. Despite the evident importance of f5C in playing an important role in gene expression regulation, little is known about the exact amount and positions of this modified cytidine in RNAs, as well as its exact functions. To capture this type of information, we performed a site-specific dual functionalization of f5C with semi-stabilized ylide cyanomethylene triphenylphosphorane that can simultaneously seizure the C5-formyl and N4-amino groups in the cytidine residue under light irradiation. The photochemical labelling with f5C-containing oligonucleotides imparts a high selectivity towards f5C and allows distinction from structurally similar 5-formyluridine f5U. We implemented a detection strategy of f5C modification in RNA based on the fluorescence signal of the cyclization product 4,5-pyridin-2-amine-cytidine paC, which exhibited a relatively high fluorescence quantum yield. The results could clearly identify f5C with a limit of detection LOD at 0.58 nM. The chemical labelling was capable of altering the hydrogen bonding activity of the parent cytidine and enabled the modulation of the reverse transcription signature of f5C in sequencing profile. We showed that using this Pan-Seq strategy, f5C can be detected from tRNA segments with a single-base resolution. Taken together, this approach represents a sensitive, robust, antibody-free and applicable detection ad sequencing to f5C RNA. | Liang Cheng; Xiao-Yang Jin; Zu-Rui Huang; Da-Li Han; Li-Jun Xie; Li Liu | Biological and Medicinal Chemistry; Organic Chemistry; Biochemistry; Bioengineering and Biotechnology; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2022-05-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6273ed06d55550e7ad8e9bd5/original/a-photo-triggered-wittig-cyclization-for-detecting-and-sequencing-5-formylcytidine-in-rna.pdf |
67c25f6e6dde43c908f40e5a | 10.26434/chemrxiv-2025-jn8wb | A Concise Proof of the Triangle Inequality for the Tanimoto Distance and its Equality Conditions | The Tanimoto distance is a widely used distance metric in cheminformatics that satisfies the triangle inequality. Several methods have been proposed to prove this inequality; however, we note that there has been no discussion regarding the conditions under which equality holds, which can be crucial in specific contexts. In this paper, we provide a concise and intuitive proof of the triangle inequality for the Tanimoto distance and, based on this proof, derive the corresponding equality conditions. | Xiuyuan Hu; Yang Zhao; Hao Zhang | Theoretical and Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2025-03-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67c25f6e6dde43c908f40e5a/original/a-concise-proof-of-the-triangle-inequality-for-the-tanimoto-distance-and-its-equality-conditions.pdf |
649d7e956e1c4c986b8a3466 | 10.26434/chemrxiv-2023-926vf | Practical synthetic method for amino acids derived diazo-ketones – shelf-stable reagents for organic synthesis. | A novel approach for a safe generation of the diazomethane-contained organic solution has been proposed using a serial flow reactor. The productivity of the diazomethane generation has reached 0.45 mol/h. Several chiral diazoketones have been prepared in quantities up to 150 g through the reaction of diazomethane with mixed anhydrides, generated in situ by treatment of Boc-protected α-amino-acids with ethyl chloroformate. The synthesized diazoketones are crystalline sub-stances stable up to 110-142 °C and can easily be purified on silica gel and stored for a long term. The overall stability and availability on a large scale allow considering such diazoketones as promising bench-stable regents for the broad scope of applications. The quantum chemical studies show that the stability of diazoketones is probably connected with conjugation of the carbonyl group with diazo moiety. As an example of applicability: the reaction of diazoketones with concentrated HBr gives corresponding pure chiral α-bromoketones without additional purification was demonstrated. | Viacheslav Pendiukh; Hanna Yakovleva; Ivan Stadniy; Alexander Pashenko; Eduard Rusanov; Natalia Grabovaya; Sergey Kolotilov; Alexander Rozhenko; Sergey Ryabukhin; Dmitriy Volochnyuk | Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Process Chemistry | CC BY NC 4.0 | CHEMRXIV | 2023-06-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/649d7e956e1c4c986b8a3466/original/practical-synthetic-method-for-amino-acids-derived-diazo-ketones-shelf-stable-reagents-for-organic-synthesis.pdf |
60c744bd337d6c534ee26e8b | 10.26434/chemrxiv.9906194.v1 | Fulgazepam: A Fulgimide-Based Potentiator of GABAA Receptors | The <i>γ</i>-aminobutyric acid gated chloride channel
represents the major mediator of inhibitory neurotransmission in the mammalian
central nervous system and its dysfunction is related to severe diseases like
epilepsy and depression, which can be relieved by the application of allosteric
modulators. However, the drugs’ potential side-effects limit their application
for long-term treatment. Applying light as external stimulus to modify the
pharmacophore’s activity, as emerged in the field of photopharmacology, provides
a non-invasive tool with high spatial and temporal resolution for the
modulation of protein function. Herein, we report the design, synthesis, and
biological evaluation of photochromic fulgimide-based benzodiazepine
derivatives as light-controllable potentiators of GABA<sub>A</sub> receptors
(GABA<sub>A</sub>Rs). A photocontrolled potentiator of GABA<sub>A</sub>Rs
(Fulgazepam) has been identified that does not display agonist or antagonist
activity and allows manipulating zebrafish larvae swimming. | Karin Rustler; Galyna Maleeva; Alexandre M. J. Gomila; Pau Gorostiza; Piotr Bregestovski; Burkhard Koenig | Photochemistry (Org.) | CC BY NC ND 4.0 | CHEMRXIV | 1970-01-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c744bd337d6c534ee26e8b/original/fulgazepam-a-fulgimide-based-potentiator-of-gabaa-receptors.pdf |
65a933499138d2316136be5b | 10.26434/chemrxiv-2024-w5sxn | Impact of Symmetry and Donor Set on the Electronic Energy Levels in Nine-coordinated Eu(III) and Sm(III) Crystals Structures Determined from Single Crystal Luminescence Spectra | Lanthanide luminescence is characterised by “forbidden” 4f-4f transitions and a complicated electronic structure. Our understanding of trivalent lanthanide(III) ions luminescence is centered on Eu3+ because absorbing and emitting transition in Eu3+ occur from a single electronic energy levels. In Sm3+ both absorpbing and emitting multiplets have a larger multiplicity. A transition from the first emitting state multiplet to the ground state multiplet will result in nine lines for a Sm3+ complex. In this study, high resolution emission and excitation spectra were used to determine the electronic energy levels for the ground state multiplet and first excited state multiplet in four Sm3+ compounds with varying donor set and site symmetry. This was achieved by the use of Boltzmann distribution population analysis and experimentally determined transition probabilities from emission and excitation spectra. Using this analysis it was possible to show the effect of changing three oxygen atoms with three nitrogen atoms in the tricapping donor set for compounds with the same Trigonal Tricapped Prism (TTP) site symmetry on the crystal field splitting in both Eu3+ and Sm3+ crystals. This work celebrates the 40 year annivesary for the first report of [Eu(ODA)3]3- luminescence by Kirby and Richardson. | Sabina Svava Mortensen; Villads R. M. Nielsen; Thomas Just Sørensen | Physical Chemistry; Inorganic Chemistry; Coordination Chemistry (Inorg.); Lanthanides and Actinides; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2024-01-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65a933499138d2316136be5b/original/impact-of-symmetry-and-donor-set-on-the-electronic-energy-levels-in-nine-coordinated-eu-iii-and-sm-iii-crystals-structures-determined-from-single-crystal-luminescence-spectra.pdf |
65dc25f366c13817299005ef | 10.26434/chemrxiv-2024-wlx21 | High-throughput Quantum Theory of Atoms in Molecules (QTAIM) for Geometric Deep Learning of Molecular and Reaction Properties | We present a package, Generator, for geometric molecular property prediction based on topological features of quantum mechanical electron density. Generator computes Quantum Theory of Atoms in Molecules (QTAIM) features, at density functional theory (DFT) level, for sets of molecules or reac- tions in a high-throughput manner, and compiles features into a single data structure for processing, analysis, and geometric machine learning. An accompanying graph neural network package can be used for property prediction and allows users to readily use computed features for learning tasks. To test the efficacy of electron density-based data for machine learning, we benchmark several datasets including QM8, QM9, LIBE, Tox21, and a Green 2022 Reaction dataset. This wide dataset diversity underscores the flexibility of QTAIM descriptors and our package. In addition, we made our code high-throughput methods compatible with new versions of BondNet and Chemprop architectures to allow for both reaction and molecular property prediction out-of-the-box. To motivate the use of QTAIM features for varied prediction tasks we also perform extensive benchmarking of our new mod- els to existing benchmark models as well as to our own models without QTAIM features. We show that almost universally, QTAIM features improve model performance on our algorithms, ChemProp, and BondNet. We also determine that QTAIM can aid in generalizing model performance to out-of- domain (OOD) datasets and improve learning at smaller data regimes. Combined, we hope that this framework could enable QTAIM-enhanced structure-to-property predictions - especially in domains with less data, including experimental or reaction-level datasets with complex underlying chemistries | Santiago Vargas; Winston Gee; Anastassia Alexandrova | Theoretical and Computational Chemistry; Theory - Computational; Artificial Intelligence; Chemoinformatics - Computational Chemistry | CC BY 4.0 | CHEMRXIV | 2024-02-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65dc25f366c13817299005ef/original/high-throughput-quantum-theory-of-atoms-in-molecules-qtaim-for-geometric-deep-learning-of-molecular-and-reaction-properties.pdf |
60e97c1eb95bdd5c9f60c0ee | 10.26434/chemrxiv-2021-w7rss-v2 | Profiling the proteome-wide selectivity of diverse electrophiles | Targeted covalent inhibitors are powerful entities in drug discovery, but their application has so far mainly been limited to addressing cysteine residues. The development of cysteine-directed covalent inhibitors has largely profited from determining their proteome-wide selectivity using competitive residue-specific proteomics. Several probes have recently been described to monitor other amino acids using this technology and many more electrophiles exist to modify proteins. Nevertheless, a direct, proteome-wide comparison of the selectivity of diverse probes is still entirely missing. Here, we developed a completely unbiased workflow to analyse electrophile selectivity proteome-wide and applied it to directly compare 54 alkyne probes containing diverse reactive groups. In this way, we verified and newly identified probes to monitor a total of nine different amino acids as well as the N-terminus proteome-wide. This selection includes the first probes to globally monitor tryptophans, histidines and arginines as well as novel tailored probes for methionines, aspartates and glutamates. | Patrick R. A. Zanon; Fengchao Yu; Patricia Musacchio; Lisa Lewald; Michael Zollo; Kristina Krauskopf; Dario Mrdović; Patrick Raunft; Thomas E. Maher; Marko Cigler; Christopher Chang; Kathrin Lang; F. Dean Toste; Alexey I. Nesvizhskii; Stephan M. Hacker | Biological and Medicinal Chemistry; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2021-07-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60e97c1eb95bdd5c9f60c0ee/original/profiling-the-proteome-wide-selectivity-of-diverse-electrophiles.pdf |
60c74f89567dfe6f13ec56e9 | 10.26434/chemrxiv.12918983.v1 | Chemical Vapor Deposition of Fe-N-C Oxygen Reduction Catalysts with Full Utilization of Dense Fe-N4 Sites | Replacing scarce and expensive platinum (Pt)
with metal-nitrogen-carbon (M-N-C) catalysts for the oxygen reduction reaction
(ORR) in proton
exchange membrane fuel cells (PEMFCs) has largely been
impeded by the low activity of M-N-C, in turn limited by low site density and
low site utilization. Herein, we overcome these limits by implementing chemical
vapor deposition (CVD) to synthesize Fe-N-C, an approach fundamentally different
from previous routes. The Fe-N-C catalyst, prepared by flowing iron chloride
vapor above a N-C substrate at 750 ℃, has a record Fe-N<sub>4</sub> site
density of 2×10<sup>20</sup> sites·gram<sup>-1</sup> with 100% site utilization. A combination of
characterizations shows that the Fe-N<sub>4</sub> sites formed via CVD are
located exclusively on the outer-surface, accessible by air, and
electrochemically active. This catalyst delivers an unprecedented current
density of 33
mA·cm<sup>-2</sup> at 0.90 V<i><sub>i</sub></i><sub>R-free</sub> (<i>iR</i>-corrected)
in an H<sub>2</sub>-O<sub>2</sub> PEMFC at 1.0 bar and 80 ℃. | Li Jiao; Jingkun Li; Lynne Larochelle Richard; Qiang Sun; Thomas Stracensky; Ershuai Liu; Moulay-Tahar Sougrati; Zipeng Zhao; Fan Yang; Sichen Zhong; Hui Xu; Sanjeev Mukerjee; Yu Huang; David A Cullen; Deborah J. Myers; Frederic Jaouen; Qingying Jia | Electrocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2020-09-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74f89567dfe6f13ec56e9/original/chemical-vapor-deposition-of-fe-n-c-oxygen-reduction-catalysts-with-full-utilization-of-dense-fe-n4-sites.pdf |
65cf7939e9ebbb4db9820780 | 10.26434/chemrxiv-2024-6ktbm | Rapid Preparation of beta-Ketoenamine-based Covalent Organic Frameworks (COFs) via Amino-yne Click Polymerization | As a new class of crystalline porous organic polymer materials, covalent organic frameworks (COFs) have permanent porosity and broad application prospects. The synthesis of COFs has strict requirements for both the reaction equations and the reaction conditions. Therefore, it is critical for researchers to develop new, scalable synthetic reactions. In this work, for the first time, we report an in-situ synthetic strategy toward COFs via the amino-yne click polymerization by taking advantage of its produced dynamic beta-ketoenamine bond. This strategry also enjoys the advantages of high efficiency and atomic economy. The crystallinity and BET measurements indicated that the resultant COFs have excellent crystallinity and high porosity. Thus, this work not only provides a new strategy for the rapid preparation of COFs with excellent atom economy, but also enriches their family. | Wei Bai; Qi Tian; Xinyao Fu; Anjun Qin; Ben Zhong Tang | Polymer Science; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-02-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65cf7939e9ebbb4db9820780/original/rapid-preparation-of-beta-ketoenamine-based-covalent-organic-frameworks-co-fs-via-amino-yne-click-polymerization.pdf |
6128e53327d90640c076e6b4 | 10.26434/chemrxiv-2021-bqpfn-v2 | Molecular Environment Specific Atomic Charges Improve Binding Affinity Predictions of SAMPL5 Host-Guest Systems | Host-guest systems are widely used in benchmarks as model systems to improve
computational methods for absolute binding free energy predictions. Recent advances
in sampling algorithms for alchemical free energy calculations and the increase in computational power have made their binding affinity prediction primarily dependent on
the quality of the force field. Here, we propose a new methodology to derive the
atomic charges of host-guest systems based on QM/MM calculations and the MBIS
partitioning of the polarized electron density. A newly developed interface between
the OpenMM and ORCA software package provides D-MBIS charges that best represent the guest’s average electrostatic interactions in the hosts or the solvent. The
simulation workflow also calculates the average energy required to polarize the guest
in the bound and unbound state. Alchemical free energy calculations using the GAFF
force field parameters with D-MBIS charges improve the binding affinity prediction of
six guests bound to two octa-acid hosts compared to the AM1-BCC charge set after correction with the average energetic polarization cost. This correction results from
the difference in the energetic polarization cost between the bound and unbound state
and contributes significantly to the binding affinity of anionic guests.
| Duvan Gonzalez; Luis Macaya; Esteban Vöhringer-Martinez | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-08-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6128e53327d90640c076e6b4/original/molecular-environment-specific-atomic-charges-improve-binding-affinity-predictions-of-sampl5-host-guest-systems.pdf |
66cf7e1120ac769e5f241caf | 10.26434/chemrxiv-2024-pk105-v2 | Integrating Machine Learning and Large Language Models to Advance Exploration of Electrochemical Reactions | Electrochemical C-H oxidation reactions offer a sustainable route to functionalize hydrocarbons, yet the identification of competent substrates and their synthesis optimization remains challenging. Here, we report an integrated approach combining machine learning (ML) and large language models (LLMs) to streamline the exploration of electrochemical C-H oxidation reactions. Utilizing a batch rapid screening electrochemical platform, we evaluated a wide range of reactions, initially classifying substrates by their reactivity, while LLMs text-mined literature data to augment the training set. The resulting ML models, one for reactivity prediction and the other one for site selectivity, both achieved high accuracy (>90%) and enabled virtual screening of a large set of commercially available molecules. To optimize reaction conditions of substrates of interest upon the screening, LLMs were prompted to generate code to iteratively improve yield, lowering the barrier for scientists to access ML programs, and this strategy efficiently identified high-yield conditions for eight drug-like substances or intermediates. Notably, we benchmarked the accuracy and reliability of 10 different LLMs, including llama, Claude, and GPT-4, on generating and executing codes related to ML based on natural language prompts given by chemists to showcase their tool-making and tool-using capabilities and potentials for accelerating research across four diverse tasks. In addition, we collected an experimental benchmark dataset comprising 1071 reaction conditions and yields for electrochemical C-H oxidation reactions, and our findings revealed that integrating LLMs and ML outperformed using either method alone. We envision that this combined approach offers a robust and generalizable pathway for advancing synthetic chemistry research | Zhiling Zheng; Federico Florit; Brooke Jin; Haoyang Wu; Shih-Cheng Li ; Kakasaheb Y. Nandiwale ; Chase A. Salazar; Jason G. Mustakis; William H. Green; Klavs F Jensen | Physical Chemistry; Organic Chemistry; Chemical Engineering and Industrial Chemistry; Organic Synthesis and Reactions; Electrochemistry - Mechanisms, Theory & Study | CC BY 4.0 | CHEMRXIV | 2024-08-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66cf7e1120ac769e5f241caf/original/integrating-machine-learning-and-large-language-models-to-advance-exploration-of-electrochemical-reactions.pdf |
64a76b946e1c4c986bf0e058 | 10.26434/chemrxiv-2023-4ln4x | Electrochemical synthesis of gold-N-heterocyclic carbene complexes | An electrochemical synthesis of gold(I)-N-heterocyclic carbene (Au-NHC) complexes has been developed. The electrochemical methodology uses only imidazolium salts, gold metal electrodes, and electricity to produce these complexes and the only by-product is hydrogen gas. This high-yielding and operationally simple procedure has been used to produce seven mononuclear and three dinuclear Au-NHC complexes. The electrochemical procedure facilitates a clean reaction with no by-products. As such, Au-NHC complexes can be directly transferred to catalytic reactions without work-up or purification. The Au-NHC complexes were produced on-demand and tested as catalysts in a vinylcyclopropanation reaction. All mononuclear Au-NHC complexes performed similarly to or better than the isolated complexes, showcasing how the electrochemical procedure can speed up catalyst screening and reaction development. | Thomas P. Nicholls; Zhongfan Jia; Justin M. Chalker | Inorganic Chemistry; Catalysis; Electrochemistry; Organometallic Compounds; Homogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2023-07-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64a76b946e1c4c986bf0e058/original/electrochemical-synthesis-of-gold-n-heterocyclic-carbene-complexes.pdf |
621776e1c3e9da0d30755e2b | 10.26434/chemrxiv-2022-dccgz | Empowering Visible Light Catalysis: Brominative Dearomatizationof Biaryl Ynones | A step-economic photo-oxidative brominative carbannulation of biaryl ynones employing bromide source and riboflavin tetraacetate (RFTA) have
been developed. The switchable reactivity between distal phenyl C-H activatedortho-annulation and dearomative ipso-annulation are well exemplified.The eminent features of the methodology include metal-free, externaladditive free, low-cost photocatalyst, use of simple precursor. Further, we
elaborately discussed about the mechanistic investigation and the applicabilityof additional functional group incorporation. | Barnali Roy; Puspendu Kuila; Dr. Debayan Sarkar | Organic Chemistry; Organic Synthesis and Reactions; Photochemistry (Org.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-03-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/621776e1c3e9da0d30755e2b/original/empowering-visible-light-catalysis-brominative-dearomatizationof-biaryl-ynones.pdf |
60c755440f50db4154397e83 | 10.26434/chemrxiv.14061047.v1 | Chemical Space Mapping for Multicomponent Gas Mixtures | In our manuscript, we present our protocol for data processing to mitigate the effects of interfering analytes on the identification of the chemical species detected by sensors. Considering NO2 and CO2, we designed electrochemical sensors whose response yielded the cyclic voltammetry data that we analyzed to classify single-species components and their mixtures using a data-driven approach to generate a chemical space where their mixtures can be deconvoluted.<br /> | Airat Kotliar-Shapirov; Fedor S. Fedorov; Henni Ouerdane; Stanislav Evlashin; Albert G. Nasibulin; Keith
J. Stevenson | Analytical Chemistry - General; Chemoinformatics; Electrochemical Analysis; Environmental Analysis | CC BY NC ND 4.0 | CHEMRXIV | 2021-02-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c755440f50db4154397e83/original/chemical-space-mapping-for-multicomponent-gas-mixtures.pdf |
60c74898f96a001f292870ad | 10.26434/chemrxiv.11935722.v1 | Molecular Docking Study of Novel COVID-19 Protease with Low Risk Terpenoides Compounds of Plants | <p><b><i>Background</i></b> :Due
to the reported high
ability of virulence of COVID_19
in recent months, several studies have
been conducted to discover and introduce COVID_19 antiviral drugs. The results
of numerous studies have shown that protease inhibitors and compounds, which
make up the major part of plant derivatives, especially terpenoids, can
therefore be very effective in controlling virus-induced infection. The aim of this research is the bioinformatical study of COVID_19 inhibition by terpenoids of plant origin. </p>
<p><b><i>Materials and
Methods</i></b>: This is a
descriptive-analytic study. In the present study , the structure of terpene
comounds and COVID_19 protease was received from the databases such as PubChem
and Protein Data Bank (PDB). After that, molecular docking was performed by MVD(molegro
virtual docker) software.</p>
<p><b><i> Results</i></b>: The
results are identified to have inhibitory activities against novel COVID-19
protease. Of these
compounds, Ginkgolide A has a stronger bond and high affinity with protease</p>
<p><b><i>Conclusion</i></b>: Finally, with due attention to the high effectiveness function of
terpenoids, we can conclude that these compounds may be considered as effectire
COVID_19 antiprotease drugs</p> | Neda Shaghaghi | Bioinformatics and Computational Biology; Drug Discovery and Drug Delivery Systems; Plant Biology | CC BY NC ND 4.0 | CHEMRXIV | 2020-03-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74898f96a001f292870ad/original/molecular-docking-study-of-novel-covid-19-protease-with-low-risk-terpenoides-compounds-of-plants.pdf |
66431a4221291e5d1d33f214 | 10.26434/chemrxiv-2024-03h99 | Copolymer-Coated Gold Nanoparticles: Enhanced Stability and Customizable Functionalization for Biological Assays | Gold nanoparticles (AuNPs) play a vital role in biotechnology, medicine, and diagnostics due to their unique optical properties. Their conjugation with antibodies, antigens, proteins, or nucleic acids enables precise targeting and enhances biosensing capabilities. Functionalized AuNPs, however, may experience reduced stability, leading to aggregation or loss of functionality, especially in complex biological environments. Additionally, they can show non-specific binding to unintended targets impairing assay specificity. Within this work, citrate-stabilized and silica coated AuNPs (GNPs and SiGNPs, respectively) have been coated using N,N-dimethylacrylamide-based copolymers to increase their stability and enable their functionalization with biomolecules. AuNPs stability after modification has been assessed by a combination of techniques including spectrophotometric characterization, nanoparticle tracking analysis, transmission electron microscopy and functional microarray tests. Two different copolymers were identified to provide a stable coating of AuNPs while enabling further modification through click chemistry reactions, due to the presence of azide groups in the polymers. Following this experimental design, AuNPs decorated with ssDNA and streptavidin were synthesized and successfully used in a biological assay. In conclusion, a functionalization scheme for AuNPs has been developed that offers ease of modification, often requiring single steps and short incubation time. The obtained functionalized AuNPs offer huge flexibility, as the functionalization protocol can be personalized to match requirements of multiple assays. | Dario Brambilla; Federica Panico; Lorenzo Zarini; Alessandro Mussida; Anna Maria Ferretti; Mete Aslan; M. Selim Ünlü; Marcella Chiari | Polymer Science; Nanoscience; Organic Polymers | CC BY 4.0 | CHEMRXIV | 2024-05-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66431a4221291e5d1d33f214/original/copolymer-coated-gold-nanoparticles-enhanced-stability-and-customizable-functionalization-for-biological-assays.pdf |
633a353c114b7e4ee125d8b5 | 10.26434/chemrxiv-2022-wx3nl | Development of a manufacturing process toward the convergent synthesis of the COVID-19 antiviral Ensitrelvir | We describe the development of the practical manufacturing of Ensitrelvir, which was discovered as a SARS-CoV-2 antiviral candidate. Scalable synthetic methods of indazole, 1,2,4-triazole and 1,3,5-triazinone structures were established, and convergent couplings of these fragments enabled the development of a concise and efficient scale-up process to Ensitrelvir. In this process, introducing a meta-cresolyl moiety successfully enhanced the stability of intermediates. Compared to the initial route in the medicinal synthetic stage, the overall yield of the longest linear sequence (six steps) was improved by approximately 7-fold. Furthermore, nine out of the twelve isolated intermediates were crystallized directly from each reaction mixture without any extractive work-up (direct isolation). This led to an efficient and environmentally friendly manufacturing process that minimizes waste of organic solvents, reagents, and processing time. This practical process for manufacturing Ensitrelvir should contribute to protection against COVID-19. | Takahiro Kawajiri; Akihito Kijima; Atsuhiro Iimuro; Eisaku Ohashi; Katsuya Yamakawa; Kazushi Agura; Kengo Masuda; Kensuke Kouki; Koji Kasamatsu; Shuichi Yanagisawa; Sho Nakashima; Setsuya Shibahara; Takashi Toyota; Takafumi Higuchi; Takahiro Suto; Tadashi Oohara; Toshikatsu Maki; Naoto Sahara; Nobuaki Fukui; Hisayuki Wakamori; Hidaka Ikemoto; Hiroaki Murakami; Hiroyasu Ando; Masahiro Hosoya; Mizuki Sato; Yusuke Suzuki; Yuta Nakagawa; Yuto Unoh; Yoichi Hirano; Yoshitomo Nagasawa; Satoshi Goda; Takafumi Ohara; Takayuki Tsuritani | Organic Chemistry; Organic Synthesis and Reactions; Process Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-10-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/633a353c114b7e4ee125d8b5/original/development-of-a-manufacturing-process-toward-the-convergent-synthesis-of-the-covid-19-antiviral-ensitrelvir.pdf |
63c32741d19cc56398060770 | 10.26434/chemrxiv-2023-dzw3d | Enantioselective cobaltaelectro-catalyzed C–H activations enabled by hydrogen evolution | Despite the significant progress in enantioselective catalysis during the past decades, asymmetric redox transformations typically rely on costly transition metals as catalysts, along with the use of stoichiometric amounts of chemical redox agents. The exploitation of electrocatalysis in molecular synthesis represents a sustainable alternative towards value-added molecules through the hydrogen evolution reaction (HER). We herein, describe strategies for enantioselective cobaltaelectro-catalyzed C–H activations that avoid superstoichiometric chemical oxidants. Thus, highly enantioselective C–H/N–H annulations of carboxylic amides were achieved giving access to point and axially chiral compounds. Furthermore, the cobalta-electrocatalysis enabled the preparation of various P-stereogenic compounds by selective desymmetrization through dehydrogenative C–H activation reactions. These examples show how the valuable HER can be coupled to versatile enantioselective electrocatalytic organic transformations leading to relevant molecular scaffolds. | Lutz Ackermann; Tristan von Münchow; Suman Dana; Yang Xu; Binbin Yuan | Organic Chemistry; Catalysis; Electrocatalysis | CC BY 4.0 | CHEMRXIV | 2023-01-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63c32741d19cc56398060770/original/enantioselective-cobaltaelectro-catalyzed-c-h-activations-enabled-by-hydrogen-evolution.pdf |
662667bb91aefa6ce118caf0 | 10.26434/chemrxiv-2024-0hdbp | Solid-state cathode heterogeneity impact on utilization and fracture dynamics | Structural heterogeneity in solid-state batteries can impact material utilization and fracture mechanisms. Dense crystallographically oriented lithium cobalt oxide cathodes serve as a model electrode system for exploring how density variability contributes to stress relief and build up during cycling. Real- and reciprocal-space operando and ex-situ synchrotron based experiments are utilized to understand structural changes across multiple length scales contribute to stress generation and fracture. Nanotomography uncovers a depth-dependent porosity variation in the pristine electrode and highlights preferential fracture in regions of lower porosity during delithiation. Energy-dispersive X-ray diffraction and 3D X-ray absorption near-edge spectroscopy (XANES) reveal the underutilization of cathode material in these regions. 3D XANES also confirms preferential delithiation near the subgrain boundaries. Chemo-mechanical modeling coupled with site-specific mechanical characterization demonstrate how stress accumulation in dense regions of the electrode leads to fracture and underutilization of active material. Our findings reveal the importance of materials design to alleviate stress in small-volume changing cathodes. | Se Hwan Park; Carlos Juarez Yescas; Kaustubh Naik; Yingjin Wang; Yuting Luo; Dhanya Puthusseri; Patrick Kwon; Bairav S. Vishnugopi; Badri Shyam; Heng Yang; John Cook; John Okasinki; Andrew Chaung; Xianghui Xiao; Julia Greer; Partha P. Mukherjee; Beniamin Zahiri; Paul Braun; Kelsey Hatzell | Materials Science; Nanostructured Materials - Materials | CC BY NC ND 4.0 | CHEMRXIV | 2024-04-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/662667bb91aefa6ce118caf0/original/solid-state-cathode-heterogeneity-impact-on-utilization-and-fracture-dynamics.pdf |
60c759a0702a9bad4d18cf0b | 10.26434/chemrxiv.14248550.v3 | Trans-cis Photoisomerization of a Biomimetic Cyclocurcumin Analogue Rationalized by Molecular Modelling | <div>
<p>Cyclocurcumin is a natural compound
extracted from turmeric and showing, in addition to antiinfective, antibacterial, and
intinflammatory capabilities, solvent-dependent phtoswitching ability. The
solvent-dependent photochemistry of cyclocurcumin has been rationalized on the
basis of a competition between π-π* and n-π* states. Recently we
have reported the synthesis of a biomimetic analogue showing enhanced
photochemical properties and in particular presenting photoswitching capacity
in various media. In the present contribution we rely on the use of molecular
modeling and simulation, incuding density functional and wavefunction based
methods to explore the excited states potential energy surface landscape. We
see that the addition of a carbon-carbon double bond to the core of the natural
compounds favors the population of the π-π* state, whatever the choice of the
solvent, and hence leads to photoisomerisation, with fluorescence reduced to
only a minor channel, rationalizing the experimental observations. In addition,
the two photon absorption cross section is also strongly increased compared to
the parent compound, paving the way to the use in biologically oriented
applications.</p></div> | Raúl Losantos; Jeremy Pecourneau; Maxime Mourer; Stephane Parant; Andreea Pasc; Antonio Monari | Computational Chemistry and Modeling; Photochemistry (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2021-05-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c759a0702a9bad4d18cf0b/original/trans-cis-photoisomerization-of-a-biomimetic-cyclocurcumin-analogue-rationalized-by-molecular-modelling.pdf |
671a3a6e1fb27ce1246b2be9 | 10.26434/chemrxiv-2024-cd158 | High time resolution ambient observations of gas-phase perfluoroalkyl carboxylic acids: Implications for atmospheric sources | Atmospheric formation of persistent perfluoroalkyl carboxylic acids (PFCAs) is a route to global contamination, including drinking water sources. We present high time resolution measurements of C2-C6 PFCAs in ambient air made over 6 weeks each in winter and summer 2022 in Toronto, Canada. Observations were made using chemical ionization mass spectrometry with acetate ionization with care taken to avoid system contamination. Measurements of trifluoroacetic acid (C2 PFCA) are reported at 1-minute time resolution, while those for C3-C6 PFCAs are at 10-minute time resolution. Variations with time and relationships to meteorology and other pollutants show evidence of secondary formation of all observed PFCAs except perfluoropropionic acid (C3 PFCA). High time resolution data allows these unique observations, allowing for improved process and source understanding moving forward. Mixing ratios of TFA were higher than predicted from models that describe TFA formation from known precursors indicating additional atmospheric sources of this molecule have yet to be identified. | Cora Young; Shira Joudan; Ye Tao; Jeremy Wentzell; John Liggio | Analytical Chemistry; Earth, Space, and Environmental Chemistry; Atmospheric Chemistry; Mass Spectrometry | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/671a3a6e1fb27ce1246b2be9/original/high-time-resolution-ambient-observations-of-gas-phase-perfluoroalkyl-carboxylic-acids-implications-for-atmospheric-sources.pdf |
6707d4cdcec5d6c142c816e4 | 10.26434/chemrxiv-2024-7c8kt-v2 | The green synthesis of Zinc Oxide nanoparticles utilizing Camellia Sinensis var. Assamica found in commercial tea dust, and their broad spectrum antibacterial activity | The antibacterial activity of biosynthesized Zinc Oxide (ZnO) nanofluid was investigated against three gram-positive bacteria (Enterococcus faecalis, Methicillin-resistant Staphylococcus aureus, Staphylococcus saprophyticus) and two gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa). Tea dust, obtained from “Lipton® black tea decaffeinated” tea bags, and distilled water was used to prepare an extract; with zinc acetate and sodium hydroxide as precursors to synthesize the ZnO nanoparticles, the extract was used as a reducing agent. ZnO nanoparticles were synthesized using a green method involving tea extract and characterized by EDX, TEM, and UV-VIS spectroscopy, revealing particles between 40–60 nm, with some particles as small as 18 nm, and the nanoparticles exhibited an agglomerated, sponge-like asymmetrical shape and maximum absorption at 380 nm. Despite its performance being slightly lower than standard antibiotics like Ciprofloxacin, Meropenem and Vancomycin, the ZnO nano-fluid still demonstrated significant antibacterial activity. | Ronith Lahoti; Dusty Carroll | Biological and Medicinal Chemistry; Nanoscience; Nanostructured Materials - Nanoscience | CC BY 4.0 | CHEMRXIV | 2024-10-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6707d4cdcec5d6c142c816e4/original/the-green-synthesis-of-zinc-oxide-nanoparticles-utilizing-camellia-sinensis-var-assamica-found-in-commercial-tea-dust-and-their-broad-spectrum-antibacterial-activity.pdf |
660b0557e9ebbb4db92455fa | 10.26434/chemrxiv-2024-x6031 | Molecular dynamics simulation of complex reactivity with the Rapid Approach for Proton Transport and Other Reactions (RAPTOR) soft- ware package | Simulating chemically reactive phenomena such as proton transport on nanosecond to microsecond and beyond time- scales is a challenging task. Ab initio methods are unable to currently access these timescales routinely, and traditional molecular dynamics methods feature fixed bonding arrangements that cannot account for changes in the system’s bonding topology. The Mul- tiscale Reactive Molecular Dynamics (MS-RMD) method, as implemented in the Rapid Approach for Proton Transport and Other Reactions (RAPTOR) software package for the LAMMPS molecular dynamics code, offers a method to routinely sample longer timescale reactive simulation data with statistical precision. RAPTOR may also be interfaced with enhanced sampling methods to drive simulations towards the analysis of reactive rare events, and a number of collective variables (CVs) have been developed to facilitate this. Key advances to this methodology, including GPU acceleration efforts and novel CVs to model water wire formation are reviewed, along with recent applications of the method which demonstrate its versatility and robustness. | Scott Kaiser; Zhi Yue; Yuxing Peng; Trung Nguyen; Sijia Chen; Da Teng; Gregory Voth | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Theory - Computational; Physical and Chemical Processes | CC BY NC ND 4.0 | CHEMRXIV | 2024-04-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/660b0557e9ebbb4db92455fa/original/molecular-dynamics-simulation-of-complex-reactivity-with-the-rapid-approach-for-proton-transport-and-other-reactions-raptor-soft-ware-package.pdf |
619f74ccdff1cc61fc31eacf | 10.26434/chemrxiv-2021-vm2hs | Molecular Communications in Complex Systems of Dynamic Supramolecular Polymers | Supramolecular polymers are composed of monomers that self-assemble non-covalently, generating distributions of monodimensional fibres in continuous communication with each other and with the surrounding solution. Fibres, exchanging molecular species, and external environment constitute a sole complex system, which intrinsic dynamics is hard to elucidate. Here we report coarse-grained molecular simulations that allow studying supramolecular polymers at the thermodynamic equilibrium, explicitly showing the complex nature of these systems, which are composed of exquisitely dynamic molecular entities. Detailed studies of molecular exchange provide insights into key factors controlling how assemblies communicate with each other, defining the equilibrium dynamics of the system. Using minimalistic and finer chemically relevant molecular models, we observe that a rich concerted complexity is intrinsic in such self-assembling systems. This offers a new dynamic and probabilistic (rather than structural) picture of supramolecular polymer systems, where the travelling molecular species continuously shape the assemblies that statistically emerge at the equilibrium. | Martina Crippa; Claudio Perego; Anna de Marco; Giovanni M. Pavan | Theoretical and Computational Chemistry; Physical Chemistry; Materials Science; Computational Chemistry and Modeling; Self-Assembly; Statistical Mechanics | CC BY 4.0 | CHEMRXIV | 2021-11-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/619f74ccdff1cc61fc31eacf/original/molecular-communications-in-complex-systems-of-dynamic-supramolecular-polymers.pdf |
60c757fc469df4f1b2f4556f | 10.26434/chemrxiv.14481468.v1 | Reply to the Comment on “On the SN2 Reactions Modified in Vibrational Strong Coupling Experiments: Reaction Mechanisms and Vibrational Mode Assignments” | <div>
<div>
<div>
<p>
</p><div>
<div>
<div>
<p>In September 2020, we became aware that a comment (A. Thomas, L. Lethuillier-Karl, J. Moran and T. Ebbesen, 2020,
DOI:10.26434/chemrxiv.12982358.v1.) on our recent paper (C. Climent and J. Feist, Phys. Chem. Chem. Phys., 2020, 22, 23545) had been posted to
ChemRxiv. Since our attempts in October 2020 to reach out to the authors to discuss the points
they raised did not receive a response as of April 2021, and the comment was not submitted as a
formal comment to the original journal either, we here provide a brief reply based on the results
that were already reported in our original manuscript. Most importantly, we show that we did not
“presumably overlook” any data in the supplementary material of their original article, but that our
results are actually fully consistent with those data. </p>
</div>
</div>
</div>
</div>
</div>
</div> | Clàudia Climent; Johannes Feist | Physical Organic Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-04-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c757fc469df4f1b2f4556f/original/reply-to-the-comment-on-on-the-sn2-reactions-modified-in-vibrational-strong-coupling-experiments-reaction-mechanisms-and-vibrational-mode-assignments.pdf |
60c74afb337d6c4014e279cb | 10.26434/chemrxiv.12278354.v1 | 14N1H HMQC Solid-State NMR as a Powerful Tool to Study Amorphous Formulations – an Exemplary Study of Paclitaxel Loaded Polymer Micelles | We present <sup>14</sup>N-<sup>1</sup>H HMQC MAS NMR experiments in the solid state as a promising tool to study
amorphous formulations. Poly(2-oxazoline)
based polymer micelles loaded with different amounts of the cancer drug
paclitaxel serve to highlight the possibilities offered by these experiments:
While the very similar <sup>15</sup>N chemical shifts hamper
a solid-state NMR characterization based on this nucleus, <sup>14</sup>N is a
very versatile alternative. <sup>14</sup>N-<sup>1</sup>H HMQC experiments
yield well-separated signals, which are spread over a large ppm range, provide
information on the symmetry of the nitrogen environment and probe <sup>14</sup>N-<sup>1</sup>H
through-space proximities. | Marvin Grüne; Robert Luxenhofer; Dinu Iuga; Steven P. Brown; Ann-Christin Pöppler | Spectroscopy (Anal. Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-05-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74afb337d6c4014e279cb/original/14n1h-hmqc-solid-state-nmr-as-a-powerful-tool-to-study-amorphous-formulations-an-exemplary-study-of-paclitaxel-loaded-polymer-micelles.pdf |
6341a7edea6a22ceba0edb13 | 10.26434/chemrxiv-2022-bhcf0 | Assessing ternary materials for fluoride-ion batteries | Although lithium‐ion batteries have transformed energy storage, there is a need to develop battery technologies with improved performance. Fluoride‐ion batteries (FIBs) may be promising alternatives in part due to their high theoretical energy density and natural elemental abundance. However, electrode materials for FIBs, particularly cathodes, have not been systematically evaluated, limiting rapid progress. Here, we evaluate ternary fluorides from the Materials Project crystal structure database to identify promising cathode materials for FIBs. Structures are further assessed based on stability and whether fluorination/defluorination occurs without unwanted disproportionation reactions. Properties are presented for pairs of fluorinated/defluorinated materials including theoretical energy densities, cost approximations, and bandgaps. We aim to supply a dataset for extracting property and structural trends of ternary fluoride materials that may aid in the discovery of next‐generation battery materials. | Don McTaggart; Jack Sundberg; Lauren McRae; Scott Warren | Theoretical and Computational Chemistry; Materials Science; Energy; Energy Storage | CC BY NC 4.0 | CHEMRXIV | 2022-10-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6341a7edea6a22ceba0edb13/original/assessing-ternary-materials-for-fluoride-ion-batteries.pdf |
623517415cf71981d0589ab3 | 10.26434/chemrxiv-2022-dq8ql | Cyanine Phototruncation Enables Cell Labeling with Spatiotemporal Control | Photoconvertible tracking strategies examine the dynamic migration of various cell populations. Here we develop phototruncation-assisted cell tracking (PACT) and apply it to evaluate the migration of immune cells into tumor-draining lymphatics. This approach is enabled by a recently discovered cyanine photoconversion reaction that leads to the two-carbon truncation and consequent blue-shift of these commonly used probes. By examining substituent effects on the heptamethine cyanine chromophore, we find that introduction of a single methoxy group increases the yield of the phototruncation reaction in neutral buffer by almost 8-fold. The resulting cell-tracking probes are applied in a series of in vitro and in vivo experiments, including quantitative, time-dependent measurements of the migra-tion of immune cells from tumors to tumor-draining lymph nodes. Unlike previously reported cellular photoconversion approaches, this method does not require genetic engineer-ing. Overall, PACT provides a straightforward approach to labeling cell populations with precise spatiotemporal con-trol. | Hiroshi Fukushima; Siddharth Matikonda; Syed Usama; Aki Furusawa; Takuya Kato; Lenka Štacková; Petr Klan; Hisataka Kobayashi; Martin Schnermann | Biological and Medicinal Chemistry; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2022-03-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/623517415cf71981d0589ab3/original/cyanine-phototruncation-enables-cell-labeling-with-spatiotemporal-control.pdf |
66d9817c12ff75c3a1765eb2 | 10.26434/chemrxiv-2024-f8czr-v3 | Pulsed EPR Methods in the Angstrom to Nanometre Scale Shed Light on the Conformational Flexibility of a Fluoride Riboswitch | Riboswitches control gene regulation upon external stimuli such as environmental factors or ligand binding. The fluoride sensing riboswitch from Thermotoga petrophila is a complex regulatory RNA proposed to be involved in resistance to F- cytotoxicity. The details of structure and dynamics underpinning the regulatory mechanism are currently debated. Here we demonstrate that a combination of pulsed electron paramagnetic resonance (ESR/EPR) spectroscopies, detecting distances in the angstrom to nanometre range, can probe distinct regions of conformational flexibility in this riboswitch. PELDOR (pulsed electron-electron double resonance) revealed a similar preorganisation of the sensing domain in three forms, i.e. the free aptamer, the MgII-bound apo, and the F--bound holo form. 19F ENDOR (electron-nuclear double resonance) was used to investigate the active site structure of the F--bound holo form. Distance distributions without a priori structural information were compared with in silico modelling of spin label conformations based on the crystal structure. While PELDOR, probing longer distances, revealed varying conformational flexibility of the RNA backbone, ENDOR indicated low structural heterogeneity at the ligand binding site. Overall, the combination of PELDOR and ENDOR with sub-angstrom precision gave insight into structural organisation and flexibility of a riboswitch, not easily attainable by other biophysical techniques. | Laura Remmel; Andreas Meyer; Katrin Ackermann; Gregor Hagelüken; Marina Bennati; Bela Bode | Physical Chemistry; Biological and Medicinal Chemistry; Biophysical Chemistry; Spectroscopy (Physical Chem.); Structure | CC BY 4.0 | CHEMRXIV | 2024-09-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66d9817c12ff75c3a1765eb2/original/pulsed-epr-methods-in-the-angstrom-to-nanometre-scale-shed-light-on-the-conformational-flexibility-of-a-fluoride-riboswitch.pdf |
62868c156b12b67f7677e57d | 10.26434/chemrxiv-2022-w2l8r | Generation and Aerobic Oxidative Catalysis of a Cu(II) Superoxo Complex Supported by a Redox-Active Ligand | Cu systems feature prominently in aerobic oxidative catalysis in both biology and synthetic chemistry. Metal ligand cooperativity is a common theme in both areas as exemplified by galactose oxidase and by aminoxyl radicals in alcohol oxidations. This has motivated investigations into the aerobic chemistry of Cu and specifically the isolation and study of Cu superoxo species that are invoked as key catalytic intermediates. While several examples of complexes that model biologically relevant Cu(II) superoxo intermediates have been reported, they are not typically compe-tent aerobic catalysts. Here, we report a new Cu complex of the redox-active ligand tBu,TolDHP (2,5-bis((2-t-butylhydrazono)(p-tolyl)methyl)-pyrrole) that activates O2 to generate a catalytically active Cu(II)-superoxo complex via ligand-based electron transfer. Characterization using UV-visible spectroscopy, Raman isotope labeling studies, and Cu extended X-ray absorption fine structure (EXAFS) analysis confirms the as-signment of an end-on η1 superoxo complex. This Cu-O2 complex engages in a range of aerobic catalytic oxidations with substrates including alcohols and aldehydes. These results demonstrate that bio-inspired Cu systems can not only model important bioinorganic intermediates but can also mediate and provide mechanistic insight on aerobic oxidative transformations. | Maia Czaikowski; Andrew McNeece; Jan-Niklas Boyn; Kate Jesse; Sophie Anferov; Alexander Filatov; David Mazziotti; John Anderson | Inorganic Chemistry; Catalysis; Bioinorganic Chemistry; Small Molecule Activation (Inorg.); Transition Metal Complexes (Inorg.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-05-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62868c156b12b67f7677e57d/original/generation-and-aerobic-oxidative-catalysis-of-a-cu-ii-superoxo-complex-supported-by-a-redox-active-ligand.pdf |
60c73eda567dfe7626ec38c8 | 10.26434/chemrxiv.7152317.v1 | Isotope Depletion Mass Spectrometry (ID-MS) for Enhanced Top-Down Protein Fragmentation | <div>Top-down mass spectrometry has become an important technique for the identification of proteins and characterisation of chemical and posttranslational modifications. However, as the molecular mass of proteins increases intact mass determination and top-down fragmentation efficiency become more challenging due to the partitioning of the mass spectral signal into many isotopic peaks. In large proteins, this results in reduced sensitivity and increased spectral complexity and signal overlap. This phenomenon is a consequence of the natural isotopic heterogeneity of the elements which comprise proteins (notably 13C). Here we present a bacterial recombinant expression system for the production of proteins depleted in 13C and 15N and use this strategy to prepare a range of isotopically depleted proteins. High resolution MS of isotope depleted proteins reveal dramatically reduced isotope distributions, which results in increases in sensitivity and deceased spectral complexity. We demonstrate that the monoisotopic signal is observed in mass spectra of proteins up to ~50 kDa. This allows confident assignment of accurate molecular mass, and facile detection of low mass modifications (such as deamidation). We outline the benefits of this isotope depletion strategy for top-down fragmentation. The reduced spectral complexity alleviates problems of signal overlap; the presence of monoisotopic signals allow more accurate assignment of fragment ions; and the dramatic increase in single-to-noise ratio (up to 7-fold increases) permits vastly reduced data acquisition times. Together, these compounding benefits allow the assignment of ca. 3-fold more fragment ions than analysis of proteins with natural isotopic abundances. Thus, more comprehensive sequence coverage can be achieved; we demonstrate near single amino-acid resolution of the 29 kDa protein carbonic anhydrase from a single top-down MS experiment. Finally, we demonstrate that the ID-MS strategy allows far greater sequence coverage to be obtained in time limited top-down data acquisitions – highlighting potential advantages for top-down LC-MS/MS workflows and top-down proteomics. </div><div><br /></div> | Kelly J. Gallagher; Michael Palasser; Sam Hughes; C. Logan Mackay; David P. A. Kilgour; David Clarke | Mass Spectrometry; Biophysics | CC BY NC ND 4.0 | CHEMRXIV | 2018-10-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73eda567dfe7626ec38c8/original/isotope-depletion-mass-spectrometry-id-ms-for-enhanced-top-down-protein-fragmentation.pdf |
677d97466dde43c908a79466 | 10.26434/chemrxiv-2025-d51r9 | Rapid Acquisition of 103Rh Solid-State NMR Spectra by 31P Detection and Sideband Selective Methods | 103Rh solid-state nuclear magnetic resonance (NMR) spectroscopy is potentially a powerful method for investigating the molecular and electronic structure of rhodium compounds. However, 103Rh is a difficult nucleus to study by NMR spectroscopy because of its small gyromagnetic ratio, broad chemical shift range, and long spin-lattice relaxation times (T1). While there are many prior reports demonstrating acquisition of 103Rh solution NMR spectra, there are few reports establishing a facile method with high sensitivity for acquiring 103Rh solid-state NMR spectra. Here, we utilize the large 31P-103Rh J-couplings (80-200 Hz) to efficiently acquire 31P-detected high-resolution 103Rh SSNMR spectra. We use sideband selective SSNMR techniques originally developed for wideline 195Pt SSNMR experiments. Notably, using these methods, we were able to acquire MAS 103Rh SSNMR spectra in experiment times on the order of 30 minutes to a few hours and from only a few mg of materials. The sideband selective experiments offer significant time savings as compared to existing direct detection methods, which require days of acquisition to obtain a directly detected MAS spectrum, or only yield low-resolution static powder patterns. Numerical fits of the spectra provide chemical shift tensor parameters, with the experimental spectra agreeing well with the DFT-calculated spectra. | Benjamin Atterberry; Piotr Paluch; Andrew Lamkins; Wenyu Huang; Aaron Rossini | Physical Chemistry; Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2025-01-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/677d97466dde43c908a79466/original/rapid-acquisition-of-103rh-solid-state-nmr-spectra-by-31p-detection-and-sideband-selective-methods.pdf |
66158c0091aefa6ce1341dd9 | 10.26434/chemrxiv-2024-h5c6b | Amination of Phenols and Halophenols via Pyridinium–Iridium Dual Photocatalysis | In this study, we present a photochemical method for the amination of phenols (C–H) and halophenols (SNAr), facilitated by dual catalytic pathways involving both Ir(III) photocatalysis and phenol–pyridinium EDA complexation. By incorporating a pyridinium additive, we achieved efficient C–N coupling between phenols and diverse aromatic nitrogen nucleophiles, delivering high yields (up to 99%) across a wide range of substrates, including pharmaceuticals and natural products. We investigate reaction selectivity and substrate compatibility/limitations through a combination of experimental and computational techniques. Moreover, we highlight the synthetic versatility of the amination products through various late-stage functionalizations including the grafting of two different heteroarenes onto one phenol scaffold. | Matthew C. Carson; Cindy R. Liu; Yaning Liu; Marisa C. Kozlowski | Biological and Medicinal Chemistry; Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Photochemistry (Org.); Photocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-04-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66158c0091aefa6ce1341dd9/original/amination-of-phenols-and-halophenols-via-pyridinium-iridium-dual-photocatalysis.pdf |
60c745c5567dfe3080ec4508 | 10.26434/chemrxiv.10263077.v1 | A Free Energy Perturbation Approach to Estimate the Intrinsic Solubilities of Drug-like Small Molecules | <p>Optimizing the solubility of small molecules is important in a wide variety of contexts, including in drug discovery where the optimization of aqueous solubility is often crucial to achieve oral bioavailability. In such a context, solubility optimization cannot be successfully pursued by indiscriminate increases in polarity, which would likely reduce permeability and potency. Moreover, increasing polarity may not even improve solubility itself in many cases, if it stabilizes the solid-state form. Here we present a novel physics-based approach to predict the solubility of small molecules, that takes into account three-dimensional solid-state characteristics in addition to polarity. The calculated solubilities are in good agreement with experimental solubilities taken both from the literature as well as from several active pharmaceutical discovery projects. This computational approach enables strategies to optimize solubility by disrupting the three-dimensional solid-state packing of novel chemical matter, illustrated here for an active medicinal chemistry campaign.</p> | Sayan Mondal; Gary Tresadern; Jeremy Greenwood; Byungchan Kim; Joe Kaus; Matt Wirtala; Thomas Steinbrecher; Lingle Wang; Craig Masse; Ramy Farid; Robert Abel | Biological Materials; Biochemistry; Bioinformatics and Computational Biology; Biophysics; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2019-11-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c745c5567dfe3080ec4508/original/a-free-energy-perturbation-approach-to-estimate-the-intrinsic-solubilities-of-drug-like-small-molecules.pdf |
65840bdf9138d231612da287 | 10.26434/chemrxiv-2023-lplgt | Stable ditriflates of D-glucose in the synthesis of iminosugars and polyhydroxyolated pipecolic acids | A synthesis of the five membered iminosugar DAB and a divergent synthesis of the six membered iminosugar 1-dehydromannojirimycin (DMJ) and the corresponding sugar iminoacid are reported. They involve double nucleophilic displacements of a D-xylose ditriflate by benzyl carbazate and a D-glucose ditriflate by allyl amine, respectively. They are followed by a similar protocol consisting of hydrolysis and oxidation or reduction of the resulting bicyclic glycosides. This allowed DMJ to be obtained from the cheap sugar D-glucose. | Balo Rosalino; Fernandez Andres; Reza David; Lopez Pablo; Fleet George; Estévez Ramon J.; Estevez Juan C. | Biological and Medicinal Chemistry; Organic Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-12-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65840bdf9138d231612da287/original/stable-ditriflates-of-d-glucose-in-the-synthesis-of-iminosugars-and-polyhydroxyolated-pipecolic-acids.pdf |
667d74bc01103d79c546ba89 | 10.26434/chemrxiv-2024-6lvk7 | Modelling ligand exchange in metal complexes with machine learning potentials | Metal ions are irreplaceable in many areas of chemistry, including (bio)catalysis, self-assembly and charge transfer processes. Yet, modelling their structural and dynamic properties in diverse chemical environments remains challenging for both force fields and ab initio methods. Here, we introduce a strategy to train machine learning potentials (MLPs) using MACE, an equivariant message-passing neural network, for metal-ligand complexes in explicit solvents. We explore the structure and ligand exchange dynamics of Mg2+ in water and Pd2+ in acetonitrile as two illustrative model systems. The trained potentials accurately reproduce equilibrium structures of the complexes in solution, including different coordination numbers and geometries. Furthermore, the MLPs can model structural changes between metal ions and ligands in the first coordination shell, and reproduce the free energy barriers for the corresponding ligand exchange. The strategy presented here provides a computationally efficient approach to model metal ions in solution, paving the way for modelling larger and more diverse metal complexes relevant to biomolecules and supramolecular assemblies. | Veronika Juraskova; Gers Tusha; Hanwen Zhang; Lars Schäfer; Fernanda Duarte | Theoretical and Computational Chemistry | CC BY 4.0 | CHEMRXIV | 2024-06-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/667d74bc01103d79c546ba89/original/modelling-ligand-exchange-in-metal-complexes-with-machine-learning-potentials.pdf |
66fb20aecec5d6c142b83c99 | 10.26434/chemrxiv-2024-8hc3r | Optimal Dielectric Boundary for Binding Free Energy Estimates in the Implicit Solvent | Accuracy of binding free energy calculations utilizing implicit solvent models is critically affected by parameters of the underlying dielectric boundary, specifically the atomic and water probe radii. Here, a multidimensional optimization pipeline is used to find optimal atomic radii specifically for binding calculations in the implicit solvent. To reduce over-fitting, the optimization target includes separate, weighted contributions from both binding and hydration free energies. The resulting 5-parameter radii set, OPTBIND5D, is evaluated against experiment for binding free energies of 20 host- guest (H-G) systems, unrelated to the types of structures used in the training. The resulting accuracy for this H-G test set (Root Mean Square Error (RMSE) of 2.03 kcal/mol, Mean Signed Error (MSE) of -0.13 kcal/mol, Mean Absolute Error (MAE) of 1.68 kcal/mol, and a correlation of r=0.79 with the experimental values) is on par with what can be expected from the fixed charge explicit solvent models. Best agreement with experiment is achieved when the implicit salt concentration is set equal or close to the experimental conditions. | Negin Forouzesh; Fatemeh Ghafouri; Igor Tolokh; Alexey Onufriev | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Chemoinformatics - Computational Chemistry | CC BY NC 4.0 | CHEMRXIV | 2024-10-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66fb20aecec5d6c142b83c99/original/optimal-dielectric-boundary-for-binding-free-energy-estimates-in-the-implicit-solvent.pdf |
6414a550dab08ad68f4818a5 | 10.26434/chemrxiv-2023-b36z3-v2 | Larvicidal activity of thiazolidinedione derivatives against Aedes aegypti larvae and toxicological studies with zebrafish embryos | BACKGROUND: Diseases caused by arboviruses are currently a worldwide public health problem. These diseases have the Aedes aegypti mosquito as the main transmission vector, and the main strategy to combat their spread is the interruption of the mosquito life cycle in its early stages. In this study, we synthesized thirteen thiazolidinedione derivatives (3a-3m) that were applied in a larvicide-based strategy against the Ae. aegypti vector and submitted to evaluation of toxicological effects.
RESULTS: Microwave process intensification was utilized for the synthesis of thiazolidinedione derivatives (3a-3m). One thiazolidinedione derivative stands out (3a) with lethal concentrations (LC50-24 h) of 7.71 μg mL-1 (32.16 μmol L-1). It showed embryotoxicity to zebrafish at concentrations up to 1.0 μg mL-1 and mortality from 3.1 up to 100 μg mL-1. No biochemical disturbances occurred based on GST and LDH measurements. A para-substituted chlorine atom instead of hydrogen improves toxicity profile.
CONCLUSION: The substitution pattern with a chlorine atom suggests a larvicidal activity. From the compounds tested, (Z)-5-(4-chlorobenzylidene)thiazolidine-2,4-dione (3a) was the most effective against Ae. Aegypti, showing embryotoxicity to zebrafish. | Yuri R Braga; Mônica S S Mori; Tathyana B Piau; Diego S Moura; Lorena C Albernaz; Laila S Espindola; Cesar K Grisolia; Carlos E M Salvador; Carlos Kleber Zago de Andrade | Biological and Medicinal Chemistry; Organic Chemistry; Organic Synthesis and Reactions; Biochemistry; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2023-03-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6414a550dab08ad68f4818a5/original/larvicidal-activity-of-thiazolidinedione-derivatives-against-aedes-aegypti-larvae-and-toxicological-studies-with-zebrafish-embryos.pdf |
64027b5737e01856dc1c18d4 | 10.26434/chemrxiv-2023-wlqgg | Conjugation And Evaluation of Novel Polymeric Naproxen-PEG Esters
| Nonsteroidal anti-inflammatory drugs (NSAID) are commonly used and prescribed across the globe. A defining characteristic of NSAIDs is their poor water solubility; therefore, in a practical setting this translates directly to poor systemic absorption in the body1. The ability of a drug to effectively enter and carry out microscopic processes within cells depends on its ability to transverse the lipid membrane surrounding cells. The metric used to evaluate this capacity is called the partition coefficient, or the logP. The logP is the logarithm of concentration of a molecule between octanol and water partitions, where membrane permeability can be evaluated from this value as octanol is comparable to the cell membrane2. A logP above >0 indicates a preferential solubility in lipids, a high logP is correlated with poor solubility and absorption3.It is recommended that a drug must be overall lipophilic but still maintain aqueous solubility4. Naproxen is an NSAID that is used to treat inflammation found in many common illnesses. Naproxen has a logP value of 3.3; however a logP value <2.7 is best for traversing barriers in the body such as the blood brain barrier4. By adapting a novel synthesis method to perform the esterification of naproxen to polyethylene glycol, the aqueous solubility can be improved. Thin-layer chromatography studies confirmed an decrease in the logP value. Spectrophotography drug release and solubility tests of the conjugate form reveal a prolonged release time. This indicates the successful development and distribution of the novel molecule. The lower logP value also corresponds to better oral absorption and uptake, therefore, naproxen-PEG ester demonstrates capacity as a drug delivery system with increased therapeutic efficacy. | Syon Schlecht; Haley Fleming; Christina Curtis | Biological and Medicinal Chemistry; Chemical Biology; Drug Discovery and Drug Delivery Systems | CC BY 4.0 | CHEMRXIV | 2023-03-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64027b5737e01856dc1c18d4/original/conjugation-and-evaluation-of-novel-polymeric-naproxen-peg-esters.pdf |
640f1fa9b5d5dbe9e8319c92 | 10.26434/chemrxiv-2023-4zp5t-v3 | Recent advances in studying Toll-like receptors with the use of computational methods | Toll-like receptors (TLRs) are transmembrane proteins which recognise various molecular patterns and activate signalling that triggers the immune response. In this review, our goal was to summarise how, in recent years, various computational solutions contributed to a better understanding of TLRs, regarding both their function and mechanism of action. We updated the recent information about small-molecule modulators and expanded the topic towards next- generation vaccine design, as well as studies of the dynamic nature of TLRs. Also, we underlined problems which remain unsolved. | Maria Bzówka; Weronika Bagrowska; Artur Góra | Biological and Medicinal Chemistry; Bioinformatics and Computational Biology | CC BY 4.0 | CHEMRXIV | 2023-03-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/640f1fa9b5d5dbe9e8319c92/original/recent-advances-in-studying-toll-like-receptors-with-the-use-of-computational-methods.pdf |
66fa5756cec5d6c142a7aa01 | 10.26434/chemrxiv-2024-pq40j | SpaceHASTEN: A structure-based virtual
screening tool for non-enumerated virtual
chemical libraries | Given the size of the drug discovery relevant chemical space, working with fully enumerated
compound libraries (especially in 3D) is unfeasible. Non-enumerated virtual chemical spaces
are a practical solution to this issue; where compounds are described as building blocks
which are then connected by rules. One concrete example of such is the BioSolveIT chemical
spaces file format (.space). Tools to search these space-files exist that are using ligand-based
methods including, 2D fingerprint similarity, substructure matching, and fuzzier similarity
metrics such as FTrees. However, there is no software available that enables the screening of
these spaces using molecular docking. Here, a tool, called SpaceHASTEN, was developed on
top of SpaceLight, FTrees, LigPrep, and Glide to allow efficient virtual screening of nonenumerated
chemical spaces. SpaceHASTEN was validated using three public targets picked
from the DUD-E dataset. It was able to retrieve a large number of diverse and novel high
scoring compounds (virtual hits) from non-enumerated chemical spaces of billions of
molecules, after docking a few million compounds. The software can be freely used and is
available from http://github.com/TuomoKalliokoski/SpaceHASTEN.
Keywords: | Tuomo Kalliokoski; Ainoleena Turku; Heikki Käsnänen | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Computational Chemistry and Modeling; Chemoinformatics - Computational Chemistry | CC BY 4.0 | CHEMRXIV | 2024-10-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66fa5756cec5d6c142a7aa01/original/space-hasten-a-structure-based-virtual-screening-tool-for-non-enumerated-virtual-chemical-libraries.pdf |
62d6d04c13e365fc5ddcb8d5 | 10.26434/chemrxiv-2022-nbwr4 | Evolution of Ge wetting layers growing on smooth and rough Si (001) surfaces: isolated {105} facets as a kinetic factor of stress relaxation | The results of STM and RHEED studies of a thin Ge film grown on the Si/Si(001) epitaxial layers with different surface relief are presented. Process of the partial stress relaxation was accompanied by changes in the surface structure of the Ge wetting layer. Besides the well-known sequence of surface reconstructions (2 × 1 → 2 × N → M × N patches) and hut-clusters faceted with {105} planes, the formation of isolated {105} planes, which faceted the edges of M × N patches, has been observed owing to the deposition of Ge on a rough Si/Si (001) surface. A model of the isolated {105} facet formation has been proposed based on the assumption that the mutual arrangement of the monoatomic steps on the initial Si surface promotes the wetting layer formation with the inhomogeneously distributed thickness that results in the appearance of M × N patches partially surrounded by deeper trenches than those observed in the usual Ge wetting layer grown on the smooth Si(001) surface. Isolated {105} facets are an inherent part of the Ge wetting layer structure and their formation decreases the surface energy of the Ge wetting layer. | Larisa V. Arapkina; Kirill V. Chizh; Vladimir P. Dubkov; Mikhail S. Storozhevykh; Vladimir A. Yuryev | Materials Science; Nanoscience; Thin Films; Nanostructured Materials - Nanoscience | CC BY NC ND 4.0 | CHEMRXIV | 2022-07-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62d6d04c13e365fc5ddcb8d5/original/evolution-of-ge-wetting-layers-growing-on-smooth-and-rough-si-001-surfaces-isolated-105-facets-as-a-kinetic-factor-of-stress-relaxation.pdf |
6274e1823f1e7cc897b35b7b | 10.26434/chemrxiv-2022-dr12s | Crystallize it before it diffuses: Kinetic stabilization of thin-film phosphorus-rich semiconductor CuP2 | Numerous phosphorus-rich metal phosphides containing both P-P bonds and metal-P bonds are known from the solid-state chemistry literature. A method to grow these materials in thin-film form would be desirable, since thin films are required in many applications and they are an ideal platform for high-throughput studies. In addition, the high density and smooth surfaces achievable in thin films are a significant advantage for characterization of transport and optical properties. Despite these benefits, there is hardly any published work on even the simplest binary phosphorus-rich phosphides. Here, we demonstrate growth of single-phase CuP2 films by a two-step process involving reactive sputtering of amorphous CuP{2+x} and rapid annealing in an inert atmosphere. At the temperature required for crystallization, CuP2 tends to decompose into Cu3P and gaseous phosphorus. However, CuP2 can still be synthesized if the amorphous precursors are mixed on the atomic scale and are sufficiently close to the desired composition (neither too P poor nor too P rich). Fast formation of polycrystalline CuP2, combined with a short annealing time, makes it possible to bypass the diffusion processes responsible for decomposition. We find that thin-film CuP2 is a 1.5 eV band gap semiconductor with interesting properties, such as a high optical absorption coefficient (above 1e5 cm-1), low thermal conductivity (1.1 W/Km), and composition-insensitive electrical conductivity (around 1 S/cm).
We anticipate that our processing route can be extended to other phosphorus-rich phosphides that are still awaiting thin-film synthesis, and will lead to more complete understanding of these materials and of their potential applications. | Andrea Crovetto; Danny Kojda; Feng Yi; Karen N. Heinselman; David A. LaVan; Klaus Habicht; Thomas Unold; Andriy Zakutayev | Materials Science; Materials Processing; Thermal Conductors and Insulators; Thin Films; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2022-05-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6274e1823f1e7cc897b35b7b/original/crystallize-it-before-it-diffuses-kinetic-stabilization-of-thin-film-phosphorus-rich-semiconductor-cu-p2.pdf |
677f46cb81d2151a0263a9b8 | 10.26434/chemrxiv-2025-v4h7d | Discovering Ni/Cu Single Atom Alloy as a Highly Active and Selective Catalyst for Direct Methane Conversion to Ethylene: A First-Principles Kinetic Study | Direct methane conversion to liquid fuels or value-added chemicals is a promising technology to utilize natural resources without resorting to further petroleum extraction. However, discovering efficient catalysts for this reaction is challenging due to either coke formation or unfavorable C-H bond activation. Here, we design single atom alloy (SAA) catalysts to simultaneously eliminate the above two bottlenecks based on mechanism-guided strategies: (1) active single atom enables favorable C-H bond breaking, and (2) less reactive host metal facilitates C-C coupling and thus avoids strong binding of carbonaceous species. Employing electronic structure theory calculations, we screened stability of multiple SAAs with 3d-5d transition metals atomically dispersed on a copper surface in terms of avoiding dopant aggregation and segregation. We then evaluated reactivities of the stable SAAs as catalysts for direct methane conversion to C2 products, including methane dehydrogenation and C-C coupling mechanisms. Combining selectivity analysis with kinetic modeling, we predicted that nickel dispersed on copper, i.e., Ni/Cu SAA, is a highly active and selective catalyst that can efficiently transform methane to ethylene. This work designs efficient SAA catalysts for direct methane activation and provides chemical insights into engineering compositions of SAAs to tune their catalytic performances. | Manish Kothakonda; Sarah LaCroix; Chengyu Zhou; Ji Yang; Ji Su; Qing Zhao | Theoretical and Computational Chemistry; Catalysis; Theory - Computational; Heterogeneous Catalysis | CC BY 4.0 | CHEMRXIV | 2025-01-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/677f46cb81d2151a0263a9b8/original/discovering-ni-cu-single-atom-alloy-as-a-highly-active-and-selective-catalyst-for-direct-methane-conversion-to-ethylene-a-first-principles-kinetic-study.pdf |
6651f857418a5379b042b271 | 10.26434/chemrxiv-2023-nz8hc-v2 | Advancing Force Fields Parameterization: A Directed Graph Attention Networks Approach | Force Fields (FFs) are an established tool for simulating large and complex molecular systems. However, parametrizing FFs is a challenging and time-consuming task that relies on empirical heuristics, experimental data, and computational data. Recent efforts aim to automate the assignment of FF parameters using pre-existing databases and on-the-fly ab-initio data. In this study, we propose a Graph-Based Force Fields (GB-FFs) model to directly derive parameters for the Generalized Amber Force Field (GAFF) from chemical environments and research into the influence of functional forms. Our end-to-end parameterization approach eliminates the need for expert-defined procedures and enhances the accuracy and transferability of GAFF across a broader range of molecular complexes. The GB-FFs model, which is only grounded on ab initio data, is implemented in the highly parallel Tinker-HP GPU package. Simulation results are compared to the original GAFF parameterization and validated on various experimentally and computationally derived properties, including free energies. | Gong Chen; Théo Jaffrelot Inizan; Thomas Plé; Louis Lagardère; Jean-Philip Piquemal; Yvon Maday | Theoretical and Computational Chemistry; Theory - Computational; Machine Learning | CC BY 4.0 | CHEMRXIV | 2024-05-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6651f857418a5379b042b271/original/advancing-force-fields-parameterization-a-directed-graph-attention-networks-approach.pdf |
61a4e19c568d33820a4aaca7 | 10.26434/chemrxiv-2021-rh3nt | Effect of Photolysis on Zirconium Amino Phenoxides for the Hydrophosphination of Alkenes: Improving Catalysis | A comparative study of amino phenoxide zirconium catalysts in the hydrophosphination of alkenes with diphenylphosphine reveals enhanced activity upon irradiation. The origin of improved reactivity is hypothesized to result from substrate insertion upon an n to d charge transfer of a Zr–P bond in the excited state of putative phosphido (Zr–PR2) intermediates. TD-DFT analysis reveals the lowest lying excited state in the proposed active catalysts are dominated by a P 3p to Zr 4d MLCT, presumably leading to enhanced catalysis. This hypothesis follows from triamidoamine-supported zirconium catalysts but demonstrates the generality of photocatalytic hydrophosphination with d0 metals. | Bryan Novas; Jacob Morris; Matthew Liptak; Rory Waterman | Catalysis; Organometallic Chemistry; Homogeneous Catalysis; Photocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2021-12-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61a4e19c568d33820a4aaca7/original/effect-of-photolysis-on-zirconium-amino-phenoxides-for-the-hydrophosphination-of-alkenes-improving-catalysis.pdf |
6695124001103d79c511667f | 10.26434/chemrxiv-2024-t9m7z | Geometry Optimization using the Frozen Domain and Partial Dimer Approach with the Fragment Molecular Orbital Method: Implementation, Benchmark, and Application for Ligand-Binding Site of Proteins | The frozen domain (FD) approximation with fragment molecular orbital (FMO) method is efficient for partial geometry optimization of large systems. We implemented the FD formulation (FD and frozen domain dimer [FDD] methods) already proposed by Fedorov, D. G. et al. (J. Phys. Chem. Lett. 2011, 2 (4), 282–288.); proposed a variation of it, namely frozen domain and partial dimer (FDPD) method; and applied it to several protein-ligand complexes. The computational time for geometry optimization at the FDPD/HF/6-31G* level for the active site (six fragments) of the largest β2-adrenergic G protein-coupled receptor (440 residues) was almost half that of the conventional partial geometry optimization method. In the human estrogen receptor, the crystal structure was refined by FDPD geometry optimization of estradiol, surrounding hydrogen-bonded residues and a water molecule. The rather polarized ligand binding site of influenza virus neuraminidase was also optimized by FDPD optimization, which relaxed steric repulsion around the ligand in the crystal structure and optimized hydrogen bonding. For Serine-Threonine Kinase Pim1 and six inhibitors, the structures of the ligand binding site, Lys67, Glu121, Arg122, and benzofuranone ring and indole/azaindole ring of the ligand, were optimized at FDPD/HF/6-31G* and the ligand binding energy was estimated at the FMO-MP2/6-31G* level. As a result, the correlation coefficient between pIC50 and ligand binding energy was considerably improved as compared to results from both molecular mechanics- and quantum mechanics/molecular mechanics-optimized geometries. Thus, this approach is promising as a high-precision structure refinement method for structure-based drug discovery. | Koji Okuwaki; Naoki Watanabe; Koichiro Kato; Chiduru Watanabe; Naofumi Nakayama; Akifumi Kato; Yuji Mochizuki; Tatsuya Nakano; Teruki Honma; Kaori Fukuzawa | Theoretical and Computational Chemistry; Physical Chemistry; Biological and Medicinal Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6695124001103d79c511667f/original/geometry-optimization-using-the-frozen-domain-and-partial-dimer-approach-with-the-fragment-molecular-orbital-method-implementation-benchmark-and-application-for-ligand-binding-site-of-proteins.pdf |
66f5a388cec5d6c142505cd2 | 10.26434/chemrxiv-2024-36w9w | Resolving the Coverage Dependence of Surface Reaction Kinetics with Machine Learning and Automated Quantum Chemistry Workflows | Microkinetic models for catalytic systems require estimation of many thermodynamic and kinetic parameters that can be calculated for isolated species and transition states using ab initio methods. However, the presence of nearby co-adsorbates on the surface can dramatically alter these thermodynamic and kinetic parameters causing them to be dependent on species coverage fractions. As there are combinatorially many co-adsorbed configurations on the surface, computing the coverage dependence of these parameters is far less straightforward. We present a framework for generating and applying machine learning models to predict coverage dependent parameters for microkinetic models. Our toolkit enables automatic calculation and evaluation of co-adsorbed configurations allowing us to sample 2000 co-adsorbed adsorbates and transition states (TSs) for a diverse set of 9 reactions on Cu111, a challenging surface, with four possible co-adsorbates. This dataset was then used to train subgraph isomorphic decision trees (SIDTs) to predict the stability and association energy of configurations. With which we were able to achieve mean absolute errors (MAEs) of 0.106 eV on adsorbates, 0.172 eV on TSs, and due to natural error cancellation in SIDTs for relative properties 0.130 eV on reaction energies and 0.180 eV on activation barriers. We then explain how to use these models to predict coverage dependent corrections for arbitrary adsorbates and TSs and demonstrate on H∗, HO∗ and O∗ comparing the generated SIDT model with an iteratively refined version. | Matthew S. Johnson; David H. Bross; Judit Zador | Theoretical and Computational Chemistry; Physical Chemistry; Catalysis; Computational Chemistry and Modeling; Machine Learning; Heterogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-09-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66f5a388cec5d6c142505cd2/original/resolving-the-coverage-dependence-of-surface-reaction-kinetics-with-machine-learning-and-automated-quantum-chemistry-workflows.pdf |
672116047be152b1d02bf443 | 10.26434/chemrxiv-2023-jp112-v4 | The power of Hellmann-Feynman theorem: Kohn-Sham DFT energy derivatives with respect to the parameters of exchange-correlation functional at linear cost | Efficient methods for computing derivatives with respect to the parameters of scientific models are crucial for applications in machine learning. These methods are important when training is done using gradient-based optimization algorithms or when the model is integrated with deep learning, as they help speed up calculations during the backpropagation pass. In the present work, we applied the Hellmann-Feynman theorem to calculate the derivatives of the Kohn-Sham DFT energies with respect to the parameters of the exchange-correlation functional. This approach was implemented in a prototype program on the basis of Python package PySCF. Using the LDA and GGA functionals as examples, we have shown that this approach scales approximately linear with the system size for a series of n-alkanes (CnH2n+2, n=4...64) with a double-zeta basis set. We demonstrated a significant speedup in the derivative calculations in comparison with the widely used automatic differentiation approach such as pytorch based DQC, which has a computational complexity of O(n^2.0) - O(n^2.5). | Evgeny M. Kadilenko; Roland Grinis | Theoretical and Computational Chemistry; Theory - Computational; Machine Learning | CC BY NC ND 4.0 | CHEMRXIV | 2024-11-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/672116047be152b1d02bf443/original/the-power-of-hellmann-feynman-theorem-kohn-sham-dft-energy-derivatives-with-respect-to-the-parameters-of-exchange-correlation-functional-at-linear-cost.pdf |
615c6738be1074af4092b4d0 | 10.26434/chemrxiv-2021-svw4f | The Volumetric Properties of the Transition State Ensemble for Protein Folding | Hydrostatic pressure together with the temperature is an important environmental variable that plays an essential role in biological adaptation of extremophilic organisms. In particular, the effects of hy-drostatic pressure on the rates of the protein folding/unfolding reaction are determined by the magni-tude and sign of the activation volume changes. Here we provide computational description of the ac-tivation volume changes for folding/unfolding reaction, and compare them with the experimental data for six different globular proteins. We find that the volume of the transition state ensemble is always in-between the folded and unfolded states. Based on this, we conclude that hydrostatic pressure will invariably slow down protein folding and accelerate protein unfolding. | Samvel Avagyan; George Makhatadze | Physical Chemistry; Biological and Medicinal Chemistry; Bioinformatics and Computational Biology; Biophysics; Biophysical Chemistry | CC BY NC 4.0 | CHEMRXIV | 2021-10-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/615c6738be1074af4092b4d0/original/the-volumetric-properties-of-the-transition-state-ensemble-for-protein-folding.pdf |
60c74475469df444d2f43337 | 10.26434/chemrxiv.9796874.v1 | GEN: Highly Efficient SMILES Explorer Using Autodidactic Generative Examination Networks | Recurrent neural networks have been widely used to generate millions of de novo molecules in a known chemical space. These deep generative models are typically setup with LSTM or GRU units and trained with canonical SMILES. In this study, we introduce a new robust architecture, Generative Examination Network GEN, based on bidirectional RNNs with concatenated sub-models to learn and generate molecular SMILES within a trained target space. GENs autonomously learn the target space in a few epochs while being subjected to an independent online examination to measure the quality of the generated set. Here we have used online statistical quality control (SQC) on the percentage of valid molecular SMILES as examination measure to select the earliest available stable model weights. Very high levels of valid SMILES (95-98%) can be generated using multiple parallel encoding layers in combination with SMILES augmentation using unrestricted SMILES randomization. Our architecture combines an excellent novelty rate (85-90%) while generating SMILES with strong conservation of the property space (95-99%). Our flexible examination mechanism is open to other quality criteria. | Ruud van Deursen; Peter Ertl; Igor Tetko; Guillaume Godin | Machine Learning; Artificial Intelligence; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 1970-01-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74475469df444d2f43337/original/gen-highly-efficient-smiles-explorer-using-autodidactic-generative-examination-networks.pdf |
60c7449e702a9b7cdb18a882 | 10.26434/chemrxiv.9874454.v1 | Arene Dearomatization via Radical Hydroarylation | A photocatalytic system for the dearomative hydroarylation of benzene derivatives has been developed. Using a combination of an organic photoredox catalyst and an amine reductant, this process operates through a reductive radical-polar crossover mechanism where aryl halide reduction triggers a regioselective cyclization event, giving rise to a range of complex spirocyclic cyclohexadienes. This light-driven protocol functions at room temperature in a green solvent system (aq. MeCN), without the need for precious metal-based catalysts or reagents, or the generation of stoichiometric metal byproducts. | Autumn Flynn; Kelly McDaniel; Meredith Hughes; David Vogt; Nathan Jui | Photochemistry (Org.) | CC BY NC ND 4.0 | CHEMRXIV | 2019-09-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7449e702a9b7cdb18a882/original/arene-dearomatization-via-radical-hydroarylation.pdf |
64488aeadf78ec501564238e | 10.26434/chemrxiv-2023-mkw7h-v2 | Nanodroplet-based reagent delivery into water-in-fluorinated-oil droplets | In vitro compartmentalization is a technique for generating water-in-oil microdroplets to establish the genotype (DNA information)-phenotype (biomolecule function) linkage required by many biological applications. Recently, fluorinated oils have become more widely used for making microdroplets due to their better biocompatibility. However, it is difficult to perform multi-step reactions requiring the addition of reagents in water-in-fluorinated-oil microdroplets. On-chip droplet manipulation is usually used for such purposes, but it may encounter some technical issues of low throughput or time delay of reagent delivery into different microdroplets. Hence, to address the above issues, we evaluated the feasibility of employing a nanodroplets-based approach for the delivery of copper ions and peptide molecules of middle-size (2 kDa). | Bo Zhu; Zhe Du; Yancen Dai; Tetsuya Kitguchi; Sebastian Behrens; Burckhard Seelig | Biological and Medicinal Chemistry; Nanoscience; Nanofluidics; Bioengineering and Biotechnology; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2023-04-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64488aeadf78ec501564238e/original/nanodroplet-based-reagent-delivery-into-water-in-fluorinated-oil-droplets.pdf |
63a418b804902a3f760bf57e | 10.26434/chemrxiv-2022-b33mt | One-Pot Synthesis of 3-Functionalized (Z)-Silyl Enol Ethers from 1-Arylallylic Alcohols by C,O-Difunctionalization of Dipotassio α,β-Dianion Intermediates | Previously reported syntheses of 3-functionalized silyl enol ethers using allyloxysilanes are hindered by undesirable reactions owing to retro Brook rearrangements. In this study, various 3-functionalized (Z)-silyl enol ethers were synthesized from readily available 1-arylallylic alcohols using (trimethylsilyl)methylpotassium as a base. C,O-Difunctionalization of the in-situ-generated dipotassio α,β-dianion with electrophiles and silyl chlorides is the key to the success of this transformation. Control experiments confirmed that the dianion has higher nucleophilicity and thermal stability than related siloxyallylpotassiums. | Rikuo Hayashi; Masahiro Sai | Organic Chemistry; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2022-12-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63a418b804902a3f760bf57e/original/one-pot-synthesis-of-3-functionalized-z-silyl-enol-ethers-from-1-arylallylic-alcohols-by-c-o-difunctionalization-of-dipotassio-dianion-intermediates.pdf |
67125ce0cec5d6c142838525 | 10.26434/chemrxiv-2024-9w6v0 | Palladium Catalyzed Distal gamma- and epsilon-Alkylation of Enones | We report herein a palladium-catalyzed distal alkylation of silyldienol and silyltrienol ethers of enones through coupling with activated halides to achieve new endo- and exo-alkylated motifs. Additionally, by employing propargyl bromides, synthetically useful linear allenes along with functionalized enones have been synthesized. Low-catalyst loading, and late-stage transformations of pharmaceutically relevant molecules further showcase the importance of the present protocol. | Pooja Sah; Manmohan Kapur | Organic Chemistry; Catalysis; Organometallic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67125ce0cec5d6c142838525/original/palladium-catalyzed-distal-gamma-and-epsilon-alkylation-of-enones.pdf |
67c766a8fa469535b9f4daac | 10.26434/chemrxiv-2025-jzgrj | Engineering antisense oligonucleotides for targeted mRNA degradation through lysosomal trafficking | Antisense oligonucleotides (ASOs) can modulate gene expression at the mRNA level, providing the ability to tackle conventionally undruggable targets and usher in an era of personalized medicine. A key mode of action for ASOs relies upon RNase H-engagement in the nucleus, however, the site for mature mRNA is the cytoplasm. This disconnect limits the efficacy and biomedical applications of ASOs. In this paper, we have established a new mechanism of action for achieving potent and targeted mRNA knockdown by leveraging a lysosomal degradation pathway. To achieve this, we employ autophagosome-tethering compound (ATTEC) technology that utilises bifunctional small molecules for lysosomal trafficking. In this manner, to achieve degradation of target mRNA located in the cytoplasm, we conjugated an ATTEC warhead, ispinesib, to RNase H-inactive ASOs. These fully 2′-O-Methylated RNase H-inactive ASOs have higher chemical stability and tighter mRNA binding than conventional ‘gapmer’ sequences, but cannot be recognised by RNase H. Our RNase H-inactive ASO-ispinesib conjugates produced a higher degree of knockdown than even state-of-the-art RNase H-active ‘gapmer’ ASOs. Using lysosomal trafficking antisense oligonucleotide (LyTON) technology, we knock down Menin (MEN1), a promising clinical target in leukemias. Engineered to degrade mRNA independent of RNase H recognition, LyTONs will enable gene silencing using oligonucleotide chemistries with higher chemical stability, tighter mRNA binding affinity, and improved cell delivery profiles. This will enable us to target a wider range of disease-relevant mRNA, potentially leading to the development of new therapies. | Disha Kashyap; Thomas Milne; Michael Booth | Biological and Medicinal Chemistry; Organic Chemistry; Bioengineering and Biotechnology; Chemical Biology; Drug Discovery and Drug Delivery Systems | CC BY 4.0 | CHEMRXIV | 2025-03-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67c766a8fa469535b9f4daac/original/engineering-antisense-oligonucleotides-for-targeted-m-rna-degradation-through-lysosomal-trafficking.pdf |
622f78e2702f04d771bc001c | 10.26434/chemrxiv-2022-k831h | Mechanistic basis for the Iridium-Catalyzed Enantioselective Al-lylation of Alkenyl Boronates | Iridium(phosphoramidite) complexes catalyze an enantio- and diastereoselective three-component coupling reaction of alkenyl boronic esters, organolithium reagents and secondary allylic aryl carbonates. The reaction proceeds through an allylation-induced 1,2-metalate shift of the alkenyl boronate forming non-adjacent stereocenters. Mechanistic investiga-tions outline the overall catalytic cycle and reveal trends in reactivity and selectivity. Analysis of relative stereochemistry in a variety of 1,1-disubtituted alkenyl boronates provides insight into the transition state of the addition and indicates a concerted pathway. Kinetic analysis of the reaction revealed the kinetic order dependance in boronate, catalyst, and both the slow- and fast-reacting enantiomer of allylic carbonate as well as the turnover-limiting step of the reaction. Hammett studies explored substituent effects in both aryl-derived alkenyl boronates and aryl carbonates. Initial investigations into the migratory selectivity of the 1,2-metalate shift were also examined using (bis)alkenyl boronates. | Colton Davis; Joseph Ready | Organic Chemistry; Organic Synthesis and Reactions; Physical Organic Chemistry; Stereochemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-03-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/622f78e2702f04d771bc001c/original/mechanistic-basis-for-the-iridium-catalyzed-enantioselective-al-lylation-of-alkenyl-boronates.pdf |
626505b9bdc9c2461ee0d8de | 10.26434/chemrxiv-2022-gwdxf | CelloZIFPaper: Cellulose-ZIF Hybrid Paper for Heavy Metal Removal and Electrochemical Sensing | The processing of hierarchical porous zeolitic imidazolate frameworks (ZIF-8) into a cellulose paper using sheet former Rapid-Köthen (R.K.) is reported. The procedure is a promising route to overcome a significant bottleneck towards applying metal-organic frameworks (MOFs) in commercial products. ZIF-8 crystals were integrated into cellulose pulp (CP) or TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)-oxidized cellulose nanofibrils (TOCNF) following an in-situ or ex-situ process; the materials were denoted as CelloZIFPaper_In Situ and CelloZIFPaper_Ex Situ. The materials were applied as adsorbents to remove heavy metals from water, with adsorption capacities of 66.2 - 354.0 mg/g. CelloZIFPaper can also be used as a stand-alone working electrode for the selective sensing of toxic heavy metals, for instance, lead ions (Pb2+), using electrochemical-based methods with a detection limit of 8 µM. The electrochemical measurements may advance 'Lab-on-CelloZIFPaper' technologies for label-free detection of Pb2+ ions. | Hani Nasser Abdelhamid; Dimitrios Georgouvelas; Ulrica Edlund; Aji Mathew | Materials Science; Inorganic Chemistry; Chemical Engineering and Industrial Chemistry | CC BY 4.0 | CHEMRXIV | 2022-04-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/626505b9bdc9c2461ee0d8de/original/cello-zif-paper-cellulose-zif-hybrid-paper-for-heavy-metal-removal-and-electrochemical-sensing.pdf |
6123cd2b1d1cc28e3bcab5a1 | 10.26434/chemrxiv-2021-kcpmn-v2 | Accurate and Transferable Reactive Molecular
Dynamics Models from Constrained Density
Functional Theory | Chemical reactions constitute the central feature of many liquid, material, and biomolecular processes. Conventional molecular dynamics (MD) is inadequate for simulating
chemical reactions given the fixed bonding topology of most force fields, while modeling chemical reactions using ab initio molecular dynamics is limited to shorter time and length scales given its high computational cost. As such, the multiscale reactive molecular dynamics method provides one promising alternative for simulating complex chemical systems at atomistic detail on a reactive
potential energy surface. However, the parameterization of such models is a key barrier to their applicability and success. In this work, we present reactive MD models derived from constrained density functional theory that are both accurate and transferable. We illustrate the features of these models for proton dissociation reactions of amino acids in both aqueous and protein environments.
Specifically, we present models for ionizable glutamate and lysine that predict accurate absolute pKa values in water, as well as their significantly shifted pKa in staphylococcal nuclease (SNase) without any modification of the models. As one outcome of the new methodology, the simulations
show that the deprotonation of ionizable residues in SNase can be closely coupled with sidechain rotations, which is a concept likely generalizable to many other proteins. Furthermore, the present approach is not limited to only pKa prediction, but can enable the fully atomistic simulation of
many other reactive systems along with a determination of the key aspects of the reaction
mechanisms. | Chenghan Li; Gregory A. Voth | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2021-08-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6123cd2b1d1cc28e3bcab5a1/original/accurate-and-transferable-reactive-molecular-dynamics-models-from-constrained-density-functional-theory.pdf |
6421719891074bccd05c2d59 | 10.26434/chemrxiv-2023-zb8fd | Metal-free and Atom-efficient Protocol for Diarylation of Selenocyanate by Diaryliodonium Salts | The rational search for the efficient protocols for atom-efficient arylation utilizing iodonium salts is the genuine need for the sustainability and green chemistry. We developed a novel approach toward metal-free diarylation of selenocyanate using trimethoxyphenyl-substituted iodonium salts with the formation of appropriate diarylselenides. The suggested procedure allows the preparation of a series of diarylselenides without isolation and purification of intermediate products in two-step one-pot sequence. | Amirbek Radzhabov; Natalia Soldatova; Daniil Ivanov; Mekhman Yusubov; Vadim Kukushkin; Pavel Postnikov | Organic Chemistry; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2023-03-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6421719891074bccd05c2d59/original/metal-free-and-atom-efficient-protocol-for-diarylation-of-selenocyanate-by-diaryliodonium-salts.pdf |
60c9e3f31fd5333f1256ac8b | 10.26434/chemrxiv.14315963.v2 | Holistic Evaluation of Biodegradation Pathway Prediction: Assessing Multi-Step Reactions and Intermediate Products | The prediction of metabolism and biotransformation pathways
of xenobiotics is a highly desired tool in environmental and life
sciences. There are several systems that currently predict single
transformation steps or complete pathways as series of parallel
and subsequent steps. Their accuracy is often evaluated on the
level of a single transformation step. Such an approach cannot
account for some specific challenges that are related to the nature of the biotransformation experiments. This is particularly
true for missing transformation products in the reference data
that occur only in low concentrations, e.g. transient intermediates or higher-generation metabolites. Furthermore, some rulebased prediction systems evaluate accuracy only based on the
defined set of transformation rules. Therefore, the performance
of different models cannot be directly compared. | Jason Tam; Tim Lorsbach; Sebastian Schmidt; Jörg Wicker | Computational Chemistry and Modeling; Machine Learning; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-06-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c9e3f31fd5333f1256ac8b/original/holistic-evaluation-of-biodegradation-pathway-prediction-assessing-multi-step-reactions-and-intermediate-products.pdf |
6661ba59418a5379b037082f | 10.26434/chemrxiv-2024-07rl1 | Boosting Chemiexcitation of Phenoxy-1,2-Dioxetanes through 7-Norbornyl and Homocubanyl Spirofusion | The chemiluminescent light-emission pathway of phenoxy-1,2-dioxetane luminophores is increasingly attracting the scientific community's attention. Dioxetane probes that undergo rapid, flash-type chemiexcitation demonstrate higher detection sensitivity than those with a slower, glow-type chemiexcitation rate. This is primarily because the rapid flash-type produces a greater number of photons within a given time. Herein, we discovered that dioxetanes fused to 7-norbornyl and homocubanyl units, present accelerated chemiexcitation rates supported by DFT computational simulations. Specifically, the 7-norbornyl and homocubanyl spirofused dioxetanes exhibited a chemiexcitation rate of 14.2-fold and 230-fold faster than the spiro-adamantyl-dioxetane, respectively. A turn-ON dioxetane probe for the detection of the enzyme β-galactosidase, containing the 7-norbornyl spirofused unit, exhibited an S/N value of 415 with low enzyme concentration. This probe demonstrated an increase in detection sensitivity towards β-galactosidase with a limit-of-detection value that is 9-fold more sensitive than that obtained by the adamantyl counterpart. Interestingly, the computed activation free energies of the homocubanyl and 7-norbornyl units were correlated with their CCsC spiro-angle, to corroborate the measured chemiexcitation rates. | Sara Gutkin; Omri Shelef; Zuzana Babjaková; Laura Anna Tomanová; Matej Babjak; Urs Spitz; Qingyang Zhou; Pengchen Ma; Kendall N. Houk; Doron Shabat | Organic Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-06-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6661ba59418a5379b037082f/original/boosting-chemiexcitation-of-phenoxy-1-2-dioxetanes-through-7-norbornyl-and-homocubanyl-spirofusion.pdf |
66de9b5e12ff75c3a1d6b507 | 10.26434/chemrxiv-2024-qhg51 | Exploring the Potential of Natural Orbital Functionals: A Perspective | Natural Orbital Functional (NOF) theory has become a cornerstone of quantum chemistry in recent years, successfully addressing one of the field's most challenging problems: providing an accurate and balanced description of systems with strong electronic correlation. The quest for NOFs that strike the delicate balance between computational tractability and predictive accuracy represents a holy grail for researchers. Today, NOFs provide an alternative formalism to both density functional and wavefunction-based methods, with their appeal rooted in a wonderfully simple conceptual framework. This perspective outlines the basic concepts, strengths and weaknesses, and current status of NOFs, while offering suggestions for their future development. | Mario Piris | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2024-09-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66de9b5e12ff75c3a1d6b507/original/exploring-the-potential-of-natural-orbital-functionals-a-perspective.pdf |
635f4b191db0bd27a4403427 | 10.26434/chemrxiv-2022-2pclz | Strategies for developing flavonoids with multiple reactivities against pathological features in Alzheimer’s disease | The etiology of Alzheimer’s disease (AD) is still unknown because of its complicated nature associated with various pathological components, including free radicals, acetylcholinesterase, and metal-free and metal-bound amyloid-beta. Thus, chemical reagents with modulating reactivities against multiple pathogenic factors are necessary for advancing our understanding of the complex pathogenesis. Here we report rational strategies for developing flavonoids that can control multiple pathological elements found in the brains of AD patients. Our investigations employing a series of flavonoids illuminated structural features critical for regulatory reactivities against desired targets. Moreover, the most promising flavonoid with multiple functions was developed based on our complete structure–activity relationship. Mechanistic studies confirmed that such versatile reactivities of the flavonoid are achieved by its redox potential and direct interactions with pathogenic factors. Overall, our studies demonstrate the feasibility of devising small molecules as multifunctional chemical reagents against pathological features found in AD. | Seongmin Park; Mingeun Kim; Yuxi Lin; Mannkyu Hong; Geewoo Nam; Adam Mieczkowski; Young-Ho Lee; Mi Hee Lim | Biological and Medicinal Chemistry; Organic Chemistry; Inorganic Chemistry; Bioorganic Chemistry; Bioinorganic Chemistry; Chemical Biology | CC BY 4.0 | CHEMRXIV | 2022-11-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/635f4b191db0bd27a4403427/original/strategies-for-developing-flavonoids-with-multiple-reactivities-against-pathological-features-in-alzheimer-s-disease.pdf |
60c751e70f50db3316397879 | 10.26434/chemrxiv.13200491.v1 | Clusteroluminescence from Cluster Excitons in Small Heterocyclics Free of Aromatic Rings | The study on <a></a><a>non-conventional
luminescence</a> is important for revealing the luminescence of natural
systems and has gradually drawn the attention of researchers in recent years.
However, the underlying mechanism is still inexplicable. Herein, the
luminescence behaviors of two series of simple,
heteroatom-containing small molecules without aromatic rings, <i>i.e</i>.
maleimide and succinimide derivatives, are studied to gain further mechanistic
insight into the non-conventional
luminescence process.
It has been unveiled that <a>all the molecules exhibit
bright and visible luminescence in concentrated solution and solid state </a>and
the formation of clusters is the root cause for such behaviors, which can
effectively increase the possibility of both the non-radiative n-π* and
favorable π-π* transitions and stabilize the excitons formed in the excited
state. The distinctive luminescent phenomena and intriguing mechanism presented
in this work will be significant for understanding
the mechanism of clusteroluminescence and provide new strategies for the
rational design of novel luminescent materials. | Benzhao He; Jing Zhang; Jianyu Zhang; Haoke Zhang; Xiuying Wu; Xu Chen; Konnie H. S. Kei; Anjun Qin; Herman H.-Y. Sung; Jacky W. Y. Lam; Ben Zhong Tang | Aggregates and Assemblies; Clusters | CC BY NC ND 4.0 | CHEMRXIV | 2020-11-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c751e70f50db3316397879/original/clusteroluminescence-from-cluster-excitons-in-small-heterocyclics-free-of-aromatic-rings.pdf |
6502b58fb6ab98a41c6bccf1 | 10.26434/chemrxiv-2023-59cp5 | Prediction of Protein B-factor Profiles based on Bidirectional Long Short-Term Memory Network | B-factor is a measure of ray attenuation or scattering caused by atomic thermal motion during X-ray diffraction of protein crystal structure. B-factor reflects the vibration of atoms; hence, it is the most common experimental descriptor of protein flexibility and has been extensively applied in the studies of protein dynamics, screening of bioactive small molecules, and protein engineering. The prediction of B-factor profiles has considerable significance for analyzing the dynamic properties of unknown proteins. Deep learning technology has developed rapidly in recent years and has been widely implemented in many research fields, especially structural biology. In this paper, a deep neural network model based on bidirectional long short-term memory (biLSTM) network is proposed to predict the B-factor profile of a protein by combining its sequence-based features and structure-based features. Based on a large dataset of high-resolution proteins, our method predicts the B-factor profiles with an average Pearson correlation coefficient (PCC) of 0.71, and 85% of the B-factor profiles have a PCC greater than 0.6, which indicates a strong correlation between predicted and experimental values. In addition, our method remarkably outperforms the existing methods on four test datasets with different protein sizes. | Qianqian Wang; Xiongjie Xiao; Zhiwei Miao; Xu Zhang; Bin Jiang; Maili Liu | Analytical Chemistry; Chemoinformatics | CC BY NC ND 4.0 | CHEMRXIV | 2023-09-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6502b58fb6ab98a41c6bccf1/original/prediction-of-protein-b-factor-profiles-based-on-bidirectional-long-short-term-memory-network.pdf |
60c751359abda2516bf8db99 | 10.26434/chemrxiv.10060331.v3 | porE: A Code for Deterministic and Systematic Analyses of Porosities | Accurate numerical calculations of porosities and related properties are of importance when analyzing metal-organic frameworks (MOFs). <br />We present porE, an open-source, general-purpose implementation to compute such properties and discuss <br />all results regarding their sensitivity to numerical parameters.<br />Our code combines the numerical efficiency of Fortran with the user-friendliness of Python.<br />Three different approaches to calculate porosities are implemented in porE, and<br />their advantages and drawbacks are discussed. In contrast to commonly used implementations, <br />our approaches are entirely deterministic and do not require any stochastic averaging.<br />In addition to the calculation of porosities, porE can calculate pore size distributions and offers the possibility to analyze pore windows. <br />The underlying approaches are outlined, and pore windows are discussed concerning their impact on the analyzed porosities. <br />Comparisons with reference values aim for a clear differentiation <br />between void and accessible porosities, which we provide for a small benchmark set consisting of 8 MOFs.<br />In addition, our approaches are used for a bigger benchmark set containing 370 MOFs, <br />where we determine linear relationships within our approaches as well as to reference values. <br />We show how these relationships can be used to derive corrections to a give porosity approach, <br />minimizing its mean error. As a highlight we show how complex workflows can be <br />designed with a few lines of Python code using porE.<br /> | Kai Trepte; Sebastian Schwalbe | Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2020-10-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c751359abda2516bf8db99/original/por-e-a-code-for-deterministic-and-systematic-analyses-of-porosities.pdf |
60c74aa7337d6c5b6ee27951 | 10.26434/chemrxiv.12235949.v1 | Screening and Druggability Analysis of Some Plant Metabolites Against SARS-CoV-2 | <p>The sudden outbreak of novel corona virus at
the end of 2019 has caused a global threat to mankind due to its extreme
infection rate and mortality. Despite extensive research, still there is no an
approved drug or vaccine to combat SARS-CoV-2 infections. Hence, the study was
designed to evaluate some plant-based active compounds for drug candidacy against
SARS-CoV-2 by using virtual screening methods and various computational
analysis. A total of 27 plant metabolites were screened against SARS-Cov-2 main
protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding
domain, spike ecto-domain and <a href="https://www.rcsb.org/structure/6LVN">HR2 domain</a> using molecular docking approach. Four
metabolites i.e. asiatic acid, avicularin, guajaverin and withaferin showed
maximum binding affinity with all key proteins in terms of lowest global
binding energy. The top candidates were further employed for ADME (<a href="https://en.wikipedia.org/wiki/Absorption_(pharmacokinetics)">absorption</a>, <a href="https://en.wikipedia.org/wiki/Distribution_(pharmacology)">distribution</a>, <a href="https://en.wikipedia.org/wiki/Metabolism">metabolism</a>, and <a href="https://en.wikipedia.org/wiki/Excretion">excretion</a>) analysis to investigate their drug
profiles. Results suggest that none of the compounds render any undesirable
consequences that could reduce their drug likeness properties. The analysis of
toxicity pattern revealed no significant tumorigenic, mutagenic, irritating or
reproductive effects by the compounds. However, witheferin was comparatively
toxic among the top four candidates with considerable cytotoxicity and
immunotoxicity. Most of the target class by top drug candidates belonged to
enzyme groups (e.g. oxidoreductases hydrolases, phosphatases). Moreover, results of drug similarity prediction
identified two approved structural analogs of Asiatic acid from DrugBank,
Hydrocortisone (DB00741) (previously used for SARS-CoV-1 and MERS) and
Dinoprost-tromethamine (DB01160). In addition, two other biologically active
compounds, Mupirocin (DB00410) and Simvastatin (DB00641) could be an
alternative choice to witheferin for the treatment of viral infections. The
study may pave the way to develop effective medications and preventive measure
against SARS-CoV-2 in the future. However, the results were based solely on
computational tools and algorithms. Due to the encouraging results, we highly
recommend further in vivo trials for the experimental validation of our
findings. </p> | Kazi Faizul Azim; Sheikh Rashel Ahmed; Anik Banik; Md. Mostafigur Rahman Khan; Anamika Deb | Bioinformatics and Computational Biology | CC BY NC ND 4.0 | CHEMRXIV | 2020-05-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74aa7337d6c5b6ee27951/original/screening-and-druggability-analysis-of-some-plant-metabolites-against-sars-co-v-2.pdf |
60c748b6702a9bb72018b040 | 10.26434/chemrxiv.11960748.v1 | Exploring Na_5M(PO_4)_2 F_2 (M=Cr,V) Frameworks as Superionic Cathode Materials for Sodium Ion Batteries Through A First Principles Approach | The rising needs to develop high-performance energy storage systems fuelled us to rationally design a system of frameworks Na5M(PO4)2F2 (M=Cr, v), which can find use as Superionic cathode materials for Sodium Ion Batteries.<div>The findings of the work provide a theoretical basis with respect to their thermodynamics as well as Na ion migration kinetics. In addition to DFT studies, we have also performed Ab-Initio Molecular Dynamics simulations to obtain a more realistic understanding of the systems at finite temperatures. </div><div>We believe that this work is novel and has contemporary relevance.</div> | Madhulika Mazumder; Swapan K. Pati | Energy Storage | CC BY NC ND 4.0 | CHEMRXIV | 2020-03-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c748b6702a9bb72018b040/original/exploring-na-5m-po-4-2-f-2-m-cr-v-frameworks-as-superionic-cathode-materials-for-sodium-ion-batteries-through-a-first-principles-approach.pdf |
6449ae54df78ec501570cef6 | 10.26434/chemrxiv-2023-0cwdz-v2 | Parametrically Managed Activation Function for a Fitting a Neural Network Potential with Physical Behavior Enforced by a Low-Dimensional Potential | Machine-learned representations of potential energy surfaces generated in the output layer of a feedforward neural network are becoming increasingly popular. One difficulty with neural-network output is that it is often unreliable in regions where training data is missing or sparse. Human-designed potentials often build in proper extrapolation behavior by choice of functional form. Because machine learning is very efficient, it is desirable to learn how to add human intelligence to machine-learned potentials in a convenient way. One example is the well understood feature of interaction potentials that they vanish when subsystems are too far separated to interact. In this article, we present a way to add a new kind of activation function to a neural network to enforce low-dimensional constraints. In particular the activation function depends parametrically on all the input variables. We illustrate the use of this step by showing how it can force an interaction potential to go to zero at large subsystem separations with either inputting a specific functional form for the potential or adding data to the training set in the asymptotic region of geometries where the subsystems are separated. In the process of illustrating this, we present an improved set of potential energy surfaces for the 14 lowest 3A´ states of O3. The method is more general than this example, and it may be used to add other low-dimensional knowledge or lower-level knowledge to machine-learned potentials. In addition to the O3 example, we present a greater-generality method called parametrically managed diabatization by deep neural network (PM-DDNN) that is an improvement on our previously presented permutationally restrained diabatization by deep neural network (PR-DDNN). | Farideh Badichi Akher; Yinan Shu; Zoltan Varga; Suman Bhaumik; Donald Truhlar | Theoretical and Computational Chemistry; Physical Chemistry; Theory - Computational; Machine Learning; Physical and Chemical Processes | CC BY 4.0 | CHEMRXIV | 2023-04-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6449ae54df78ec501570cef6/original/parametrically-managed-activation-function-for-a-fitting-a-neural-network-potential-with-physical-behavior-enforced-by-a-low-dimensional-potential.pdf |
677d1b03fa469535b912a1d0 | 10.26434/chemrxiv-2025-bdgh6 | Primitive chemically fueled reaction cascade for dissipative droplets | A primitive, chemically fueled phosphonodithiolates reaction cascade was constructed using phosphate-based T3P as the chemical fuel and 4-methoxybenzenethiol as the precursor molecule. This reaction cascade functions as a primitive metabolism network, utilizing higher-energy phosphate-based fuel and phosphonodithiolates formation to drive molecular assembly. The resulting assembly is energy-dissipative and transient. This primitive reaction cascade also implies a possible pathway for phosphor entry into the primitive metabolic networks. | Ali Wang; Morten Jannik Bjerrum; Preben Graae Sørensen; Junjun Tan | Organic Chemistry | CC BY 4.0 | CHEMRXIV | 2025-01-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/677d1b03fa469535b912a1d0/original/primitive-chemically-fueled-reaction-cascade-for-dissipative-droplets.pdf |
60c73d0ebdbb8911baa37bfd | 10.26434/chemrxiv.5393947.v1 | On the reliability of volume-based thermodynamics for inorganic-organic salts and coordination compounds with uncharged ligands | In
the present work, the reliability of the volume-based thermodynamics (VBT)
methods in the calculation of lattice energies is investigated by applying the
“traditional” Kapustinskii equation [8],
as well as Glasser-Jenkins [3] and Kaya [5] equations to calculate the lattice
energies for Na, K and Rb pyruvates [9-11] as well as for the coordination
compound [Bi(C<sub>7</sub>H<sub>5</sub>O<sub>3</sub>)<sub>3</sub>C<sub>12</sub>H<sub>8</sub>N<sub>2</sub>]
[17] (in which C<sub>12</sub>H<sub>8</sub>N<sub>2</sub> = 1,10 phenathroline
and C<sub>7</sub>H<sub>5</sub>O<sub>3</sub><sup>-</sup>= <i>o</i>-hyddroxybenzoic acid anion).
As comparison, the lattice energies are also calculated using formation
enthalpy values for sodium pyrivate and [Bi(C<sub>7</sub>H<sub>5</sub>O<sub>3</sub>)<sub>3</sub>C<sub>12</sub>H<sub>8</sub>N<sub>2</sub>]. For the pyruvates, is verified that none of the considered approach,
Kapustinskii, Glasser, Kaya or density, provides values that agrees in an
acceptable % difference, with the lattice energy values calculated from the
formation enthalpy values. However, it
must be pointed out that Kaya approach, with deals with a chemical hardness
approach is the better one for such kind of inorganic-organic salts. Based on data obtained for [Bi(C<sub>7</sub>H<sub>5</sub>O<sub>3</sub>)<sub>3</sub>C<sub>12</sub>H<sub>8</sub>N<sub>2</sub>]
is concluded that the only one VBT
method that provides reliable lattice energies for compounds with bulky
uncharged ligands is that one based on density values (derived by
Glasser-Jenkins). | Robson de Farias | Solid State Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2017-09-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d0ebdbb8911baa37bfd/original/on-the-reliability-of-volume-based-thermodynamics-for-inorganic-organic-salts-and-coordination-compounds-with-uncharged-ligands.pdf |
60c742f0567dfed275ec3fe0 | 10.26434/chemrxiv.8858078.v1 | Divergent Access to Histone Deacetylase Inhibitory Cyclopeptides via Late- Stage Cyclopropane Ring Cleavage Strategy. Short Synthesis of Chlamydocin | We present a unified step-economical strategy to access histone deacetylase inhibitory peptides, based on late-stage installation of zinc-binding functionalities via the cleavage of the strained cyclopropane ring in the common pluripotent cyclopropanol precursor. The efficacy of the proposed diversity-oriented approch has been validated by short stereoselective synthesis of a natural product chlamydocin and a number of its analogs.<br /> | Gabor Zoltan Elek; Kaur Koppel; Dzmitry Zubrytski; Nele Konrad; Ivar Järving; Margus Lopp; Dzmitry Kananovich | Natural Products; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2019-07-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c742f0567dfed275ec3fe0/original/divergent-access-to-histone-deacetylase-inhibitory-cyclopeptides-via-late-stage-cyclopropane-ring-cleavage-strategy-short-synthesis-of-chlamydocin.pdf |
630a5ea8d858fb3d3d5e8d60 | 10.26434/chemrxiv-2022-p7xs2-v2 | Spacer Switched Two Dimensional Tin Bromide Perovskites Leading to Ambient Stable Near Unity Photoluminescence Quantum Yield | Semiconductor nanostructures with near-unity photoluminescence quantum yields (PLQYs) are imperative for light-emitting diodes and display devices.A PLQY of 99.7±0.3% has been obtained by stabilizing 91% of the Sn2+ state in the Dion-Jacobson (8N8)SnBr4 (8N8-DJ) perovskite with 1,8 diaminooctane (8N8) interlayer spacer. The PLQY is favoredby a longerchain length of the hydrophobic spacer molecule, the extent of octahedral tilting and the preference of Sn2+at theB-site over Pb2+.The near-unity PLQY of 8N8-DJ has outstanding ambient stability under relative humidity (RH) of 55%for30 days throughout the entire excitation wavelength range, RH 75% for 3 days and 100°C for 3 h. By changing the spacer to n-octylamine (8N), Ruddlesden-Popper (8N)2SnBr4 (8N-RP) also has an appreciable PLQY of 91.7±0.6%, but having poor ambientstability due to increased lattice strain and structural degradation. The PL experiments from 5K to 300K decipher the room temperature PLQY to be due to the self-trapped excitons (STE) where the self-trapping depth is 25.6±0.4 meV below the conduction band as a result of strong carrier-phonon coupling. With 34.7-37.3meV exciton binding energy, the ~5.5 s long-lived STE emission dominates over the band edge (BE) peaks at lower excitation wavelengths and higher temperatures. The higher PLQY and stability of 8N8-DJ are due to the stronger interaction between SnBr64- octahedra and 1,8 diammonium octane cation leading to a more rigid structure. The near-unity PLQY of 8N8-DJ also remains unchanged from its powder form to the polymer-embedded perovskite films. | ARNAB MANDAL; SAMRAT ROY; ANAMIKA MONDAL; BIPUL PAL; SAYAN BHATTACHARYYA; Shresth Gupta | Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-08-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/630a5ea8d858fb3d3d5e8d60/original/spacer-switched-two-dimensional-tin-bromide-perovskites-leading-to-ambient-stable-near-unity-photoluminescence-quantum-yield.pdf |
60c74a244c8919977ead31ae | 10.26434/chemrxiv.12123978.v1 | A Droplet Microfluidic Platform for High-Throughput Photochemical Reactions | <div>We report the development of a droplet microfluidic/mass spectrometry platform for performing high-throughput photochemical reaction discovery on picomole scale. We also describe the successful translation of picomole scale flow screening conditions to millimole scale flow operations, highlighting the utility of this platform for discovery chemistry applications. </div> | Alexandra Sun; Daniel Steyer; Anthony Allen; Emory Payne; Robert Kennedy; Corey Stephenson | Photochemistry (Org.); Pharmaceutical Industry; Photocatalysis; Redox Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2020-04-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74a244c8919977ead31ae/original/a-droplet-microfluidic-platform-for-high-throughput-photochemical-reactions.pdf |
664b94a191aefa6ce18881ab | 10.26434/chemrxiv-2024-ddm5r | Water-Vapor Responsive and Erasable Metallo-Peptide Nanofibers | Short peptides are versatile molecules for the construction of supramolecular materials. Most reported peptide materials are hydrophobic, stiff, and show limited response to environmental conditions in the solid-state. Herein, we describe a design strategy for minimalistic supramolecular metallo-peptide nanofibers that, depending on their sequence, change stiffness, or reversibly assemble in the solid-state, in response to changes in relative humidity (RH). We tested a series of histidine (H) containing dipeptides with varying hydrophobicity, XH, where X is G, A, L, Y (glycine, alanine, leucine, and tyrosine). The one-dimensional fiber formation is supported by metal coordination and dynamic H-bonds. Solvent conditions were identified where GH/Zn and AH/Zn formed gels that upon air-drying gave rise to nanofibers. Upon exposure of the nanofiber networks to increasing RH, a reduction in stiffness was observed with GH/Zn fibers reversibly (dis-)assembled at 60-70 % RH driven by a rebalancing of H-bonding interactions between peptides and water. When these metallo-peptide nanofibers were deposited on the surface of polyimide films and exposed to varying RH, peptide/water-vapor interactions in the solid-state mechanically transferred to the polymer film, leading to the rapid and reversible folding-unfolding of the films, thus demonstrating RH-responsive actuation. | Avishek Dey; Rein V Ulijn; Xi Chen; Elma Naranjo; Ranajit Saha; Sheng Zhang; Maya Narayanan Nair; Tai-De Li | Organic Chemistry; Nanoscience; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-05-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/664b94a191aefa6ce18881ab/original/water-vapor-responsive-and-erasable-metallo-peptide-nanofibers.pdf |
62f6966269f3a5df46b5584b | 10.26434/chemrxiv-2022-cljcp | A Multi-Objective Active Learning Platform and Web App for Reaction Optimization | We report the development of an open-source Experimental Design via Bayesian Optimization platform for multi-objective reaction optimization. Using high-throughput experimentation (HTE) and virtual screening datasets containing high-dimensional continuous and discrete variables, we optimized the performance of the platform by fine-tuning the algorithm components such as reaction encodings, surrogate model parameters and initialization techniques. Having established the framework, we applied the optimizer to real-word test scenarios for the simultaneous optimization of reaction yield and enantioselectivity in a Ni/photoredox-catalyzed enantioselective cross-electrophile coupling of styrene oxide with two different aryl iodide substrates. Starting with no previous experimental data, the Bayesian optimizer identified reaction conditions that surpassed the previously human-driven optimization campaigns within 15 and 24 experiments, for each substrate, among 1,728 possible configurations available in each optimization. To make the platform more accessible to non-experts, we developed a Graphical User Interface (GUI) that can be accessed online through a web-based application and incorporated features such as conditions modification on-the-fly and data visualization. This web-application does not require software installation, removing any programming barrier to use the platform, which enables chemists to integrate Bayesian optimization routines into their everyday laboratory practices. | Jose Garrido Torres; Sii Hong Lau; Pranay Anchuri; Jason Stevens; Jose Tabora; Jun Li; Alina Borovika; Ryan Adams; Abigail Doyle | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Process Chemistry; Photocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2022-08-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62f6966269f3a5df46b5584b/original/a-multi-objective-active-learning-platform-and-web-app-for-reaction-optimization.pdf |
Subsets and Splits