bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of semiconducting electrides via electron-metal hybridization: the case of Sc2C
Authors: McRae Lauren , Radomsky Rebecca , Pawlik Jacob , Druffel Daniel , Sundberg Jack , Lanetti Matthew , Donley Carrie , White Kelly , Warren Scott
Published: February 2022

Electrides are exotic materials that have electrons present in well-defined lattice sites. The existence of Y2C and Gd2C as 2D electrides inspired us to examine other trivalent metal carbides, including Sc2C and Al2C. It has been proposed that design rules for electride materials include the need for an electropositive cation adjacent to the electride site, but the effect of cation electronegativity on electronic structure in electride materials is not yet known. Here, we examine trivalent metal carbides with varying degrees of electronegativity and experimentally synthesize a 2D electride, Sc2C, containing the most electronegative metal yet found neighboring the electride site. Further, we find that higher electronegativity of the cation drives greater hybridization between metal and electride orbitals. Our calculations predict that Sc2C is a small band gap semiconductor with a band gap of 0.305 eV, with an experimental conductivity of 1.62 S/cm at room temperature. This is the first 2D electride material to exhibit semiconducting behavior, and we propose that electronegativity of the cation drives the change in band structure.
First d0 Metal-Catalyzed Alkyl–Alkyl Cross Coupling Enabled by a Redox-Active Ligand
Authors: Belli Roman , Tafuri Victoria , Joannou Matthew , Roberts Courtney
Published: February 2022

Alkyl–alkyl cross coupling through well-defined mechanisms that allow for controlled oxidative addition, prevent beta-hydride elimination, and tolerate hindered electrophiles are still challenging. We describe the first report of a redox-active ligand-enabled alkyl–alkyl cross coupling using a d0 metal. This (tris)amido ScIII complex as well as the oxidized variant are thor-oughly characterized (NMR, X-ray, EPR, CV, UV-Vis, DFT). Insight into the likely radical nature of the mechanism is dis-closed. Additionally, a substrate scope that includes functional groups incompatible with late transition metal catalysis, and both coupling partners bearing beta-hydrogens is reported.
Ambient Conversion of Carbon Dioxide into Liquid Fuel by a Heterogeneous Synergetic Dual Single-Atom Catalyst
Authors: Ren Guoqing , Sun Jikai , Zhai Shengliang , Yang Li , Yu Tie , Sun Lei , Deng Weiqiao
Published: February 2022

Ambient conversion of carbon dioxide into various liquid fuels or chemicals is a potential economical solution for reducing CO2 emissions, which may be responsible for recent climate change. Here, we report a highly active dual single-Pd-atom catalyst for ambient conversion of CO2 to formic acid using a step-by-step catalyst design strategy by the density functional theory (DFT) method. The theoretically predicted catalyst is synthesized experimentally and verified to capture a significant amount of CO2 (5.05 mmol/g, 273 K), and it can efficiently convert CO2 to formic acid under ambient conditions (30 °C, 1 bar) with a turnover frequency (TOF) as high as 13.46 h-1, which is the first such report in the field of heterogeneous catalysts. Two major factors contributing to this extraordinary catalytic activity include a pore enrichment effect of the microporous structures of the covalent triazine framework and a ternary synergetic effect among two neighbouring Pd atoms and rich nitrogen environment. Our work may aid the development of heterogeneous catalysts to produce other commonly used fuels from CO2 under ambient conditions.
Unsupported Pt nanoparticles: Synthesis, Deactivation, and Hydrogen Electrocatalysis in Unpurified Electrolytes
Authors: Patil Rituja , Meng Qiudi , McKone James
Published: February 2022

We synthesized clean unsupported Pt nanoparticles (NPs) which can be used for any electrochemical measurements without the need for additional cleaning steps. In this report, we demonstrated the use of these unsupported Pt NPs for electrochemical reactions involving hydrogen. We further identified conditions under which Pt NPs deactivate in unpurified, reagent grade acid, and alkaline electrolytes, and differentiated between degradation mechanisms involving catalyst poisoning and particle growth. We monitored the degradation of Pt NPs as a function of a decrease in the electrochemically active surface area (ECSA) at different applied potentials. The results obtained from the ECSA measurements were then correlated with the identical location transmission electron microscopy (IL-TEM) observations. At potentials less than 1 V vs RHE, catalyst poisoning was found to be a dominant cause for degradation while particle growth was dominant at 1.5 V vs RHE in both acid and alkaline electrolytes.
Data-driven discovery of small electroactive molecules for energy storage in aqueous redox flow batteries
Authors: Zhang Qi , Khetan Abhishek , Sorkun Elif , Niu Fang , Loss Andrea , Pucher Ilaria , Er Süleyman
Published: February 2022

Owing to advancements in computing power and improvements in automation of modelling, high-throughput virtual screening (HTVS) has increasingly been used for materials data generation. Here, we applied a HTVS-guided experimental study for the large-scale exploration of quinone-like anolytes for aqueous redox flow batteries (ARFBs). This includes the design of a focused virtual chemical library inspired by small colorant molecules, quantum chemical prediction of redox properties, machine learning prediction of aqueous solubility, automated search for commercial availability on vendor databases, and electrochemical characterization of the most promising compounds. Screening efforts in a chemical space of 3,257 redox pairs led to 205 predicted candidates with higher solubility and lower redox potential than that of the state-of-the-art anthraquinone-2,7- disulfonic acid (AQDS) anolyte used in ARFBs. Through the electrochemical studies on the commercially available compounds, we identified the molecules that show good performance in an ARFB setup. Among them, indigo trisulfonate [Indigo-3(SO3H)] showed higher solubility, capacity retention, and coulombic efficiency than AQDS and its predecessors. The data-driven material design methodology presented here is flexible and applicable for the future exploration of small compounds for electrochemical energy storage.
Human Carboxylesterase 2 in Cocaine Metabolism
Authors: Figueiredo Pedro R. , González Ricardo D. , Carvalho Alexandra T.P.
Published: February 2022

Increased hydrolysis of cocaine to non-toxic compounds is a promising way to prevent cocaine-induced toxicity. However, the short half-life of cocaine in the blood and the rapid conversion in the body to the hydrolysis-resistant metabolite benzoylecgonine, limits the therapeutic potential of serum proteins. Therefore, hydrolysis by tissue-specific hydrolases that do not generate benzoylecgonine deserves further investigation. Here, we report for the first time, the mechanism of cocaine hydrolysis by the human Carboxylesterase 2. We have combined conventional and accelerated Molecular Dynamics, which allowed us to identify the structural motions of the α1 and α10’ helices that act as a putative lid. Quantum Mechanics/Molecular Mechanics calculations on the full cycle showed that the rate-limiting step is the formation of benzoic acid (deacylation step) with an ΔG of 18.3 kcal.mol-1 (a value in close conformity with the experimental value of 19.7 kcal.mol-1).
AtomNet PoseRanker: Enriching Ligand Pose Quality for Dynamic Proteins in Virtual High Throughput Screens
Authors: Stafford Kate , Anderson Brandon M. , Sorenson Jon , van den Bedem Henry
Published: February 2022

Structure-based, virtual High Throughput Screening (vHTS) methods for predicting ligand activity in drug discovery are important when there are no or relatively few known compounds that interact with a therapeutic target of interest. State-of-the-art computational vHTS necessarily relies on effective methods for pose sampling and docking to generate an accurate affinity score from the docked poses. However, proteins are dynamic; in vivo, ligands bind to a conformational ensemble. In silico docking to the single conformation represented by a crystal structure can adversely affect the pose quality. Here we introduce AtomNet PoseRanker, a graph convolutional network trained to identify, and re-rank crystal-like ligand poses from a sampled ensemble of protein conformations and ligand poses. In contrast to conventional vHTS methods that incorporate receptor flexibility, a deep learning approach can internalize valid cognate and non-cognate binding modes corresponding to distinct receptor conformations. AtomNet PoseRanker significantly enriched pose quality in docking to cognate and non-cognate receptors of the PDBbind v2019 dataset. Improved pose rankings that better represent experimentally observed ligand binding modes improve hit rates in vHTS campaigns, and thereby advance computational drug discovery, especially for novel therapeutic targets or novel binding sites.
Photoinduced bond oscillations in ironpentacarbonyl(FeCO)5 give delayed, synchronous bursts of carbonmonoxide(CO) release
Authors: Banerjee Ambar , Coates Michael , Kowalewski Markus , Wikmark Hampus , Jay Raphael M. , Wernet Philippe , Odelius Michael
Published: February 2022

The early excited state dynamics in the photodissociation of transition metal carbonyls determines the chemical nature of short-lived catalytically active reaction intermediates. However, time-resolved experiments have not yet revealed the mechanistic details in the sub-picosecond regime. Hence in this study, the photoexcitation of ironpentacarbonyl Fe(CO)5 has been simulated by semi-classical surface-hopping excited state molecular dynamics based on time-dependent density functional theory. We �find that the bright metal-to-ligand charge-transfer (MLCT) transition induces Fe-C oscillations in the trigonal bipyramidal complex leading to periodically reoccurring release of predominantly axial CO. Metaphorically the photoactivated Fe(CO)5 acts as a CO geyser, which we explain in terms of dynamics in the potential energy landscape of the axial Fe-C distances and non-adiabatic transitions between manifolds of bound MLCT and dissociative metal-centered(MC) excited states. The predominant release of axial CO ligands and a delayed release of equatorial CO ligands are explained in an unified mechanism based on the (sigma*)(Fe-C) anti-bonding character of the receiving orbital in the dissociative MC states both in the Franck-Condon region and at distorted geometries.
Photoinduced bond oscillations in ironpentacarbonylFe(CO)5 give delayed, synchronous bursts of carbonmonoxide(CO) release
Authors: Banerjee Ambar , Coates Michael R. , Kowalewski Markus , Wikmark Hampus , Jay Raphael M. , Wernet Philippe , Odelius Michael
Published: February 2022

The early excited state dynamics in the photodissociation of transition metal carbonyls determines the chemical nature of short-lived catalytically active reaction intermediates. However, time-resolved experiments have not yet revealed the mechanistic details in the sub-picosecond regime. Hence in this study, the photoexcitation of ironpentacarbonyl Fe(CO)5 has been simulated by semi-classical surface-hopping excited state molecular dynamics based on time-dependent density functional theory. We �find that the bright metal-to-ligand charge-transfer (MLCT) transition induces Fe-C oscillations in the trigonal bipyramidal complex leading to periodically reoccurring release of predominantly axial CO. Metaphorically the photoactivated Fe(CO)5 acts as a CO geyser, which we explain in terms of dynamics in the potential energy landscape of the axial Fe-C distances and non-adiabatic transitions between manifolds of bound MLCT and dissociative metal-centered(MC) excited states. The predominant release of axial CO ligands and a delayed release of equatorial CO ligands are explained in an unified mechanism based on the (sigma*)(Fe-C) anti-bonding character of the receiving orbital in the dissociative MC states both in the Franck-Condon region and at distorted geometries.
Lewis Acid-Promoted Oxidative Addition at a [Ni0(diphosphine)2] Complex: The Critical Role of a Secondary Coordination Sphere
Authors: Zurakowski Joseph , Austen Brady , Dufour Maeve , Nelson David , Drover Marcus
Published: February 2022

Oxidative addition represents a critical elementary step in myriad catalytic transformations. Here, the importance of thoughtful ligand design cannot be overstated. In this work, we report the intermolecular activation of iodobenzene (PhI) at a coordinatively saturated 18-electron [Ni0(diphosphine)2] complex bearing a Lewis acidic secondary coordination sphere. Whereas alkyl-substituted diphosphine complexes of Group 10 are known to be unreactive in such reactions, we show that [Ni0(P2BCy4)2] (P2BCy4 = 1,2-bis(di(3-dicyclohexylboraneyl)-propylphosphino)ethane) is competent for room-temperature PhI cleavage to give [NiII(P2BCy4)(Ph)(I)]. This difference in oxidative addition reactivity has been scruti-nized computationally – an outcome that is borne out in ring-opening to provide the reactive precursor – for [Ni0(P2BCy4)2], a “boron-trapped” 16-electron κ1-diphosphine Ni(0) complex. Moreover, formation of [NiII(P2BCy4)(Ph)(I)] is inherent to the P2BCy4 secondary co-ordination sphere: treatment of the Lewis adduct, [Ni0(P2BCy4)2(DMAP)8] with PhI provides [NiII(P2BCy4)2(DMAP)8(I)]I via iodine-atom abstraction and not a [NiII(Ph)(I)(diphosphine)] compound – an interesting secondary sphere effect. Last, the reactivity of [Ni0(P2BCy4)2] with 4-iodopyridine was surveyed, which resulted in a pyridyl-borane linked oligomer. The implica-tions of these outcomes are discussed in the context of designing strongly donating, and yet labile diphosphine ligands for use in a critical bond activation step relevant to catalysis.
Cis-Divacant Octahedral Fe(II) in a Dimensionally Reduced Family of 2-(Pyridin-2-yl)pyrrolide Complexes
Authors: Hyun Sung-Min , Reid Kaleb , Vali Shaik Waseem , Lindahl Paul , Powers David
Published: February 2022

Four-coordinate transition metal complexes can adopt a diverse array of coordination geometries, with square planar and tetra- hedral coordination being the most prevalent. Previously, we reported the synthesis of a trinuclear Fe(II) complex, Fe3TPM2, supported by a three-fold symmetric 2-pyridylpyrrolide ligand (i.e., tris(5-(pyridin-2-yl)-1H-pyrrol-2-yl)methane), that featured a rare cis-divacant octahedral (CDO) geometry at each Fe(II) center. Here, a series of truncated 2-pyridylpyrrolide ligands is described that support mono- and binuclear Fe(II) complexes that also exhibit CDO geometries. Metallation of tetradentate ligand bis(5-(pyridin-2-yl)-1H-pyrrol-2-yl)methane (H2BPM) in THF results in a binuclear complex Fe2(BPM)2(THF)2 in which both Fe(II) ions are octahedrally coordinated. The coordinated THF solvent ligands are labile: THF dissociation leads to Fe2(BPM)2, which features five-coordinate Fe(II) ions. The Fe–Fe distance in these binuclear complexes can be elongated by ligand methylation. Metalation of bis(5-(6-methylpyridin-2-yl)-1H-pyrrol-2-yl)methane (H2BPMMe) in THF leads to the formation of four-coordinate, CDO Fe(II) centers in Fe(BPMMe)2. Further ligand truncation affords bidentate ligands 2- (1H-pyrrol-2-yl)pyridine (PyrPyrrH) and 2-methyl-6-(1H-pyrrol-2-yl)pyridine (PyrMePyrrH). Metalation of these ligands in THF affords six-coordinate complexes Fe(PyrPyrr)2(THF)2 and Fe(PyrMePyrr)2(THF)2. Dissociation of labile solvent ligands provides access to four- coordinate Fe(II) complexes. Ligand disproportionation at Fe(PyrPyrr)2 results in the formation of Fe(PyrPyrr)3 and Fe(0). Ligand methyl- ation suppresses this disproportionation and enables isolation of Fe(PyrMePyrr)2, which is rigorously CDO. Complete ligand truncation, by separating the 2-pyridylpyrrolide ligands into the constituent monodentate pyridyl and pyrrolide donors, affords Fe(Pyr)2(Pyrr)2 in which the Fe(II) is tetrahedrally coordinated. Computational analysis indicates that the potential energy surface that dictates the coordination geometry in this family of four-coordinate complexes is fairly flat in the vicinity of CDO coordination. These synthetic studies provide the structural basis to explore the implications of CDO geometry on Fe-catalyzed reactions.
Structure determination of small molecule compounds by an electron diffractometer Synergy-ED
Authors: Ito Sho , White Fraser , Okunishi Eiji , Aoyama Yoshitaka , Yamano Akihito , Sato Hiroyasu , Ferrara Joseph , Jasnowski Michał , Meyer Mathias
Published: February 2022

MicroED has extended the limits of crystallography by enabling the determination of 3D-molecular structures from sub-μm microcrystals. However, measurements using microED require experts in both electron microscopy and crystallography, and its use is not easy for researchers who need structures. Here, we present a diffractometer specifically designed for microED and show how it works for determining crystal structures. The newly developed electron diffractometer will provide many researchers with an easy path to microcrystal structure determination.
Prediction of Protein pKa with Representation Learning
Authors: Gokcan Hatice , Isayev Olexandr
Published: February 2022

The behavior of proteins is closely related to the protonation states of the residues. Therefore, prediction and measurement of pKa are essential to understand the basic functions of proteins. In this work, we develop a new empirical scheme for protein pKa prediction that is based on deep representation learning. It combines machine learning with atomic environment vector (AEV) and learned quantum mechanical representation from ANI-2x neural network potential (J. Chem. Theory Comput. 2020, 16, 4192). The scheme requires only the coordinate information of a protein as the input and separately estimates the pKa for all five titratable amino acid types. The accuracy of the approach was analyzed with both cross-validation and an external test set of proteins. Obtained results were compared with the widely used empirical approach PROPKA. The new empirical model provides accuracy with MAEs below 0.5 for all amino acid types. It surpasses the accuracy of PROPKA and performs significantly better than the null model. Our model is also sensitive to the local conformational changes and molecular interactions.
Exploring the Chemical Space of Antiparasitic Peptides and Discovery of New Promising Leads through a Novel Approach based on Network Science and Similarity Searching
Authors: Ayala-Ruano Sebastián , Marrero-Ponce Yovani , Aguilera‑Mendoza Longendri , Pérez Noel , Agüero-Chapin Guillermin , Antunes Agostinho , Aguilar Ana Cristina
Published: February 2022

Antimicrobial peptides (AMPs) are small bioactive chemicals that have appeared as promising compounds to treat a wide range of diseases. The effectiveness of AMPs resides in the wide range of mechanisms they can use for both killing microbes and modulating immune responses. However, the AMPs’ chemical space (AMPCS) is huge, it is estimated that there exist more than 1065 unique sequences of peptides with 50 residues or fewer, which represent a big challenge for the discovery of new promising sequences and the identification of common features, motifs, or relevant biological functions shared by these peptides. Therefore, we present a new approach based on network science and similarity searching to discover new potential AMPs, specifically antiparasitic peptides (APPs). We have taken advantage of network-based representation of APPs’ chemical space (APPCS) to retrieve valuable information, using three types of networks: chemical space (CSN), half-space proximal (HSPN), and metadata (METN). Some centrality measures were applied to identify the most important and non-redundant nodes, and these peptides were taken as queries (Qs) against the graph database starPepDB to discover new potential APPs with similarity searching by group fusion (MAX-SIM rule) models. We evaluated the multi-query similarity searching models (mQSSMs) performance with five benchmarking data sets of APP/non-APPs. It can be stated that the predictions performed by the best mQSSMs present a strong-to-very strong predictive agreement since their external Matthews correlation coefficient (MCC) values ranged from 0.834 to 0.965. Outstanding outcomes were attained by the mQSSM with 219 Qs from both networks CSN and HSPN (219Q_0.5_HB-HC-Singletons_CSN-HSPN) and by using 0.5 as similarity threshold, with MCC values greater than 0.85 in external datasets. Then, we compared the performance metrics of our mQSSMs with APPs prediction servers AMPDiscover and AMPFun. The model proposed in this report outperformed the machine learning approaches with statistically significant differences, showing the enormous potential of this method. After applying our method and additional filters, we proposed 95 repurposed leads as potential APPs, which have not been associated with this activity until now. In addition, we explored sequence similarities and motifs shared by these peptides, which can serve as templates for searching and designing new promising APPs. The analyses show that the similarity models proposed in this study could contribute to identifying APPs with high effectivity and reliability. Our models and pipeline are freely available through the starPep toolbox software at http://mobiosd-hub.com/starpep.
Influence of the Preparation Conditions on the Reaction Performance on Steam Reforming of Methanol in a Cu/Zn/Al model catalyst
Authors: Li Meng-qian , Yao Sen , Li Xing-yu , Du Fen-fen , Shi Hao-ran , Guan Xu-bin , Zhang Zhao-shun
Published: February 2022

The model Cu/Zn/Al catalysts with different calcination temperature were prepared by hydrothermal method. The catalysts were characterized by XRD, BET, SEM, CO2-TPD, H2-TPR, TG, CH3OH-TPD and CO2+H2-TPSR. The effect of different calcination temperature on structure, stability and catalytic performance for methanol steam reforming at the conditions of 200-320℃ was also represented. The results of present study show that the different calcination temperature of Cu/Zn/Al catalysts had an obvious influence on the physical characteristics and catalytic performance of the methanol steam reforming.
MALDI TIMS IMS of Disialoganglioside Isomers – GD1a and GD1b in Murine Brain Tissue
Authors: Djambazova Katerina , Dufresne Martin , Migas Lukasz , Kruse Angela , Van de Plas Raf , Caprioli Richard , Spraggins Jeffrey
Published: February 2022

Gangliosides are classified as acidic glycosphingolipids, containing ceramide moieties and oligosaccharide chains with one or multiple sialic acid residue(s). The presence of multiple sialylation sites gives rise to highly diverse isomeric structures with distinct biological roles. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) enables the untargeted spatial analysis of gangliosides, among other biomolecules, directly from tissue sections. Integrating trapped ion mobility mass spectrometry (TIMS), a gas-phase separation technology, with MALDI IMS allows for the investi-gation of isomeric lipid structures in situ. Here we demonstrate the gas-phase separation of disialoganglioside isomers GD1a and GD1b that differ in the position of a sialic acid residue, in a standard mixture of both isomers, a total ganglioside extract, and directly from thin tissue sections. The unique spatial distributions of GD1a/b (d36:1) and GD1a/b (d38:1) were deter-mined from rat hippocampus, as well as in a spinal cord tissue section.
Homogenization of Continuum-Scale Transport Properties from Molecular Dynamics Simulations: An Application to Aqueous-Phase Methane Diffusion in Silicate Channels
Authors: Pace Tom , Rahmaninejad Hadi , Sun Bin , Kekenes-Huskey Peter
Published: February 2022

Silica-based materials including zeolites are commonly used for wide ranging applications including separations and catalysis. Substrate transport rates in these materials can significantly influence the efficiency of such applications. Two factors that contribute to transport rates include 1) the porosity of the silicate matrix and 2) non-bonding interactions between the diffusing species and the silicate surface. These contributions generally emerge from disparate length scales, namely 'microscopic' (roughly nanometer-scale) and 'macroscopic' (roughly micron-scale), respectively. Here, we develop a simulation framework to estimate the simultaneous impact of these factors on methane mass transport in silicate channels. Specifically, we develop a model of methane transport using homogenization theory to obtain transport parameters valid at length scales of hundreds to thousands of nanometers. These parameters implicitly reflect interactions taking place at fractions of a nanometer. The inputs to the homogenization analysis are data from extensive molecular dynamics simulations that incorporate atomistic-scale interactions, processed to yield local diffusion coefficients and mean force potentials. With this model, we demonstrate how nuances in silicate hydration and silica/methane interactions impact methane diffusion rates in silicate materials, including the effects of silicate surface chemistry such as the presence of silanol groups. The molecular dynamics simulations indicate that methane diffusivity at the silica surface is lower than the bulk-like rates observed at the center of channels of sufficient width. However, potentials of mean force generally evidence attractive methane/silica interactions that enhance diffusion overall. By simultaneously accounting for both of these effects, we show that the effective diffusion coefficient for the nanoporous silicate can be approximately double the value of estimates assuming fully bulk-like behavior in the channel. This study therefore demonstrates the importance of determining diffusion coefficients and potentials of mean force at an atomistic level when estimating transport properties in bulk materials. Importantly, we provide a simple homogenization framework to incorporate these molecular-scale attributes into bulk material transport estimates. This hybrid homogenization/molecular dynamics approach will be of general use for describing small molecule transport in materials with detailed molecular interactions.
Binding and Reactivity of a Nitrile Oral Inhibitor of SARS-CoV-2 Main Protease Revealed by Computational Simulations
Authors: Ramos-Guzmán Carlos A. , Ruiz-Pernía Jose Javier , Tuñón Iñaki
Published: February 2022

We present a detailed analysis of the binding mode and reactivity of the novel oral inhibitor PF-07321332 developed against SARS-CoV-2 3CL protease. Classical and QM/MM Molecular Dynamics simulations are used to quantify the contributions to the binding free energy and the reaction mechanism for covalent inhibition. The small size of the nitrile warhead conferes additional advantadges to this inhibitor.
TD-DMRG coupled with n-mode representation potentials for the excited state radiationless decay rate: formalism and application to azulene
Authors: Ren Jiajun , Wang Yuanheng , Li Weitang , Jiang Tong , Shuai Zhigang
Published: February 2022

We propose a method for calculating the nonradiative decay rates for polyatomic molecules including anharmonic effects of the potential energy surface (PES) in the Franck-Condon region. The method combines the n-mode representation method to construct the ab initio PES and the nearly exact time-dependent density matrix renormalization group method (TD-DMRG) to simulate quantum dynamics. In addition, in the framework of TD-DMRG, we further develop an algorithm to calculate the final-state-resolved rate coefficient which is very useful to analyze the contribution from each vibrational mode to the transition process. We use this method to study the internal conversion (IC) process of azulene after taking into account the anharmonicity of the ground state PES. The results show that even for this semi-rigid molecule the intramode anharmonicity enhances the IC rate significantly, and after considering the two-mode coupling effect, the rate increases even further. The reason is that the anharmonicity enables the C-H vibrations to receive electronic energy while C-H vibrations do not contribute on the harmonic PES as the Huang-Rhys factor is close to 0.
Optimization of a Range-Separated UW12 Hybrid Functional
Authors: Williams Zack , Manby Frederick
Published: February 2022

In a previous paper we presented a new hybrid functional B-LYP-osUW12-D3(BJ) containing the Unsöld-w12 (UW12) hybrid correlation model. In this paper we present a new 15-parameter range-separated hybrid density functional using a power series expansion together with UW12 correlation. This functional is optimised using the survival of the fittest strategy developed for the ωB97X-V functional, fitted to data from the Main Group Chemistry Database (MGCDB84). In addition we optimize a standard hybrid and double hybrid using the same method. We show that our fully self-consistent UW12 hybrid functional WM21-D3(BJ) outperforms both of these functionals and other range-separated hybrid functionals.
Phase and facet-engineering of transition alumina leads to (hydro)thermally stable alumina-supported metal catalysts
Authors: Khivantsev Konstantin , Kwak Ja-Hun , Jaegers Nicholas , Wang Yong , Szanyi Janos , Kovarik Libor
Published: February 2022

Inherent thermal instability of gamma-alumina above 800-900 ⁰C leads to deactivation of noble metal-supported alumina catalysts used in automotive applications. This is typically solved by adding toxic (barium) and/or rare-earth (lanthanum, cerium) elements. We show that facet-dependent engineering of transition-alumina leads to (hydro)thermally stable supported metal catalysts in the absence of toxic and rare-earth additives. Since pure high-surface area theta-alumina can be prepared at 1,050-1,100 ⁰C directly from gamma-alumina (or boehmite), and because of its stable major (100) facet with very low surface energy of 597 mJ/m2, we succeeded in preparing ~0.07 wt% Rh and ~3 wt% Pd catalysts active in NO reduction and hydrocarbon oxidation that survive hydrothermal aging up to 1,100 ⁰C with little-to-no deactivation.
Bimodal Evans−Polanyi Relationships in Hydrogen Atom Transfer from C(sp3)--H Bonds to the Cumyloxyl Radical. A Combined Time-Resolved Kinetic and Computational Study
Authors: Salamone Michela , Galeotti Marco , Romero-Montalvo Eduardo , van Santen Jeffrey , Groff Benjamin , Mayer James , DiLabio Gino , Bietti Massimo
Published: February 2022

The applicability of the Evans-Polanyi (EP) relationship to HAT reactions from C(sp3)-H bonds to the cumyloxyl radical (CumO) has been investigated. A consistent set of rate constants kH, for HAT from the C-H bonds of 56 substrates to CumO, spanning a range of more than four orders of magnitude, has been measured under identical experimental conditions. A corresponding set of consistent gas-phase C-H BDEs spanning 26 kcal/mol has been calculated using the (RO)CBS-QB3 method. The log kH vs C-H BDE plot shows two distinct EP relationships, one for substrates bearing benzylic and allylic C-H bonds (unsaturated group) and the other one, with a steeper slope, for saturated hydrocarbons, alcohols, ethers, diols, amines and carbamates (saturated group), in line with the bimodal behavior observed previously in theoretical studies of reactions promoted by other HAT reagents. The parallel use of BDFEs instead of BDEs allows the transformation of this correlation into a linear free energy relationship, analyzed within the framework of the Marcus theory. The ΔG‡ HAT vs ΔG°HAT plot shows again distinct behaviors for the two groups. A good fit to the Marcus equation is observed only for the saturated group, with lambda = 58 kcal mol-1, indicating that with the unsaturated group lambda must increase with increasing driving force. Taken together these results provide a qualitative connection between Bernasconi’s Principle of Nonperfect Synchronization and Marcus theory and suggest that the observed bimodal behavior is a general feature in the reactions of oxygen-based HAT reagents with C(sp3)-H donors.
Self-organization at air-water interfaces emerging from Marangoni and elastocapillary effects directed by amphiphile filament connections.
Authors: Winkens Mitch , Korevaar Peter A.
Published: February 2022

Marangoni and elastocapillary effects are well-known as driving forces in the self-organization of floating objects at air-water interfaces. The release of surface active compounds generates Marangoni flows that cause repulsion, whereas capillary forces drive attraction. Typically, these interactions are non-directional and mechanisms to establish directional connections between the self-organizing elements are lacking. In this work, we unravel the mechanisms involved in the self-organization of a linear amphiphile into millimeter-long filaments that form connections between floating droplets. First, we show how the release of the amphiphile tetra(ethylene glycol) monododecyl ether from a floating source droplet onto the air-water interface generates a Marangoni flow. This flow extrudes self-assembled amphiphile filaments which grow from the source droplet, and concomitantly repels floating droplets in the surroundings. A hydrophobic drain droplet that depletes the amphiphiles from the air-water interface directs the Marangoni flow and thereby the growing filaments. We show how these filaments, upon tethering to the drain, potentially facilitate internal Marangoni convection and elastocapillary effects, which attract the drain back towards the source droplet. Furthermore, this concept establishes connections that are selective to the composition of the drain droplets – which influences the rate at which they deplete the amphiphile – such that repulsive and attractive forces can be balanced. Thereby, we provide a novel method through which directional attraction can be established in synthetic self-organizing systems, and advance our understanding of how complexity arises from simple building blocks.
COVID-19: ABC System and LBP-like Function of ORF7a Activate Monocytes to Induce Diabetes
Authors: wenzhong liu , hualan li
Published: February 2022

Lipopolysaccharide activates the natural immune system response in obese and diabetic patients’ adipose tissue and increases the risk of susceptibility and severity of COVID-19. In this study, bioinformatics techniques such as domain search and molecular docking were used to study the relationship between the ORF7a protein of the SARS-COV-2 virus and lipopolysaccharide. The results show that the transmembrane protein ORF7a has ABC transporter domains: ATP binding and ABC transmembrane domains. ORF7a also has lipopolysaccharide synthesized domains. It bound the lipopolysaccharide synthesized by ORF7a to CD14 molecule through lipopolysaccharide-binding protein (LBP) to activate CD14+ monocytes. The extracellular ORF7a with the N-terminus and C-terminus cut off has a similar function of LBP, binding and activating CD14+ monocytes with the help of two ATP-binding structures. We speculated that more lipopolysaccharides also activated CD14+ monocytes to release various inflammatory factors, damaging adipose and vascular endothelial tissue to induce diabetes and hypertension.
Choosing the right molecular machine learning potential
Authors: Pinheiro Jr Max , Ge Fuchun , Ferré Nicolas , O. Dral Pavlo , Barbatti Mario
Published: February 2022

Quantum-chemistry simulations based on potential energy surfaces of molecules provide invaluable insight into the physicochemical processes at the atomistic level and yield such important observables as reaction rates and spectra. Machine learning potentials promise to significantly reduce the computational cost and hence enable otherwise unfeasible simulations. However, the surging number of such potentials begs the question of which one to choose or whether we still need to develop yet another one. Here, we address this question by evaluating the performance of popular machine learning potentials in terms of accuracy and computational cost. In addition, we deliver structured information for non-specialists in machine learning to guide them through the maze of acronyms, recognize each potential's main features, and judge what they could expect from each one.
Drug Repurposing for Coronavirus (COVID-19): In Silico Screening of Known Drugs Against the SARS-CoV-2 Spike Protein Bound to Angiotensin Converting Enzyme 2 (ACE2) (6M0J)
Authors: Kalamatianos Konstantinos
Published: February 2022

In this study FDA approved HCV antiviral drugs and their structural analogues – several of them in clinical trials - were tested for their inhibitory properties towards the SARS-CoV-2 Spike protein bound to angiotensin converting enzyme 2 (ACE2) (6M0J) using a virtual screening approach and computational chemistry methods. The most stable structures and the corresponding binding affinities of thirteen such antiviral compounds were obtained. Frontier molecular orbital theory, global reactivity descriptors, molecular docking calculations and electrostatic potential (ESP) analysis were used to hypothesize the bioactivity of these drugs against 6M0J. It is found that increased affinity for the protein is shown by inhibitors with large compound volume, relatively higher electrophilicity index, aromatic rings and heteroatoms that participate in hydrogen bonding. Among the drugs tested, four compounds 10-13 showed excellent results – binding affinities -11.2 to -11.5 kcal.mol-1. These four top scoring compounds may act as lead compounds for further experimental validation, clinical trials and even for the development of more potent antiviral agents against the SARS-CoV-2.
Biocatalytic oxidative cross-coupling reactions for biaryl bond formation
Authors: Zetzsche Lara , Yazarians Jessica , Chakrabarty Suman , Hinze Meagan , Lukowski April , Joyce Leo , Narayan Alison , Murray Lauren
Published: February 2022

Despite their varied purposes, many indispensable molecules in medicine, materials, and asymmetric catalysis share a biaryl core. The necessity of joining arene building blocks to access these valuable compounds has inspired multiple approaches for biaryl bond formation and challenged chemists to develop increasingly concise and robust methods for this task. Oxidative coupling of two C–H bonds offers an efficient strategy for the formation of a biaryl C–C bond, however, fundamental challenges remain in controlling the reactivity and selectivity for uniting a given pair of substrates. Biocatalytic oxidative cross-coupling reactions have the potential to overcome limitations inherent to small molecule- mediated methods by providing a paradigm with catalyst-controlled selectivity. In this article, we disclose a strategy for biocatalytic cross-coupling through oxidative C–C bond formation using cytochrome P450 enzymes. We demonstrate the ability to catalyze cross-coupling reactions on a panel of phenolic substrates using natural P450 catalysts. Moreover, we engineer a P450 to possess the desired reactivity, site- selectivity, and atroposelectivity by transforming a low-yielding, unselective reaction into a highly efficient and selective process. This streamlined method for constructing sterically hindered biaryl bonds provides a programmable platform for assembling molecules with catalyst-controlled reactivity and selectivity.
The repetitive local sampling and the local distribution theory
Authors: TIAN PU
Published: February 2022

Molecular simulation is a mature and versatile tool set widely utilized in many subjects with more than 30,000 publications each year. However, its methodology development has been struggling with a tradeoff between accuracy/resolution and speed, significant improvement of both beyond present state of the art is necessary to reliably substitute many expensive and laborious experiments in molecular biology, materials science and nanotechnology. Previously, the ubiquitous issue regarding severe wasting of computational resources in all forms of molecular simulations due to repetitive local sampling was raised, and the local free energy landscape approach was proposed to address it. This approach is derived from a simple idea of first learning local distributions, and followed by dynamic assembly of which to infer global joint distribution of a target molecular system. When compared with conventional explicit solvent molecular dynamics simulations, a simple and approximate implementation of this theory in protein structural refinement harvested acceleration of about six orders of magnitude without loss of accuracy. While this initial test revealed tremendous benefits for addressing repetitive local sampling, there are some implicit assumptions need to be articulated. Here, I present a more thorough discussion of repetitive local sampling; potential options for learning local distributions; a more general formulation with potential extension to simulation of near equilibrium molecular systems; the prospect of developing computation driven molecular science; the connection to mainstream residue pair distance distribution based protein structure prediction/refinement; and the fundamental difference of utilizing averaging from conventional molecular simulation framework based on potential of mean force. This more general development is termed the local distribution theory to release the limitation of strict thermodynamic equilibrium in its potential wide application in general soft condensed molecular systems.
Structural and Electronic Analysis of the Octarepeat Region of Prion Protein with Four Cu(II) by Polarizable MD and QM/MM Simulations
Authors: Nochebuena Jorge , Quintanar Liliana , Vela Alberto , Cisneros G. Andrés
Published: February 2022

The prion protein, located mainly in neurons, is believed to play the role of metal ion transporter. A 32-residue region of the N-terminal domain, known as octarepeat, can bind up to four Cu ions. Different coordination modes have been observed and are strongly dependent on Cu concentration. Many theoretical studies carried out so far have focused on studying the coordination modes of a single copper ion. In this work we investigate the octarepeat region coordinated with four copper ions. Molecular dynamics (MD) and hybrid quantum mechanics/molecular mechanics (QM/MM) simulations using the polarizable AMOEBA force field have been carried out. Results indicate that the 4Cu-octarepeat complex forms a globular structure, in agreement with experimental results. Subsequent QM/MM simulations on several snapshots suggests the system is in a high-spin quintet state, with all Cu ions bearing one single electron, and all unpaired electrons are ferromagnetically coupled.
Intramolecular Through-Space Charge-Transfer Emitters Featuring Thermally Activated Delayed Fluorescence for High-Efficiency Electroluminescent Devices
Authors: song Yongjun , he lei , Tian Mingxing , Yu Renyou
Published: February 2022

Through-space charge-transfer (TSCT) emitters have been extensively explored for thermally activated delayed fluorescence (TADF), but arranging various donors and acceptors into rigid cofacial conformations for various efficient TSCT TADF emitters has still remained a challenge. Here we report for the first time a “fixing acceptor” design to reach various efficient TSCT TADF emitters. By chemically fixing the acceptor (benzophenone) with a rigid spiro structure and cofacially aligning various donors with the fixed acceptor, a series of efficient TSCT TADF emitters have been developed. Single-crystal structures and theoretical calculations have verified closely-packed cofacial donor/acceptor conformations and favorable TSCT in the emitters. The emitters afford sky-blue to yellow TADF emission in doped films, with high photoluminescent efficiencies of up to 0.92 and reverse intersystem crossing rates of up to 1.0×106 s−1. Organic light-emitting diodes using the emitters afford sky-blue to yellow electroluminescence with high external quantum efficiencies of up to 20.9%. The work opens a new avenue toward a wide variety of efficient TSCT TADF emitters.
Atomistic and electronic structure of metal clusters supported on transition metal carbides: implications for catalysis
Authors: Prats Hector , Stamatakis Michail
Published: February 2022

Novel research avenues have been explored over the last decade on the use of transition metal carbides (TMCs) as catalytically active supports for metal nanoclusters, which display high catalytic activity despite the poor reactivity (or even inertness) of the bulk metal. It has been postulated that TMCs polarise the electron density of adsorbed metal particles in such a way that their catalytic activity ends up being superior to those dispersed on more traditional metal oxide supports. Herein, we investigate the structural and electronic properties of small clusters of precious metals (Rh, Pd, Pt and Au) and more affordable metals (Co, Ni and Cu) supported on TMCs with 1:1 stoichiometry (TiC, ZrC, HfC, VC, NbC, TaC, MoC and WC) by means of periodic Density Functional Theory calculations. Our high-throughput screening studies indicate that it is possible not only to have strongly bonded and stably dispersed metal nanoparticles on TMC surfaces, but also to manipulate their charge by carefully selecting elements with desired electronegativity for the host TMC and the metal cluster. By doing so, it is possible to tune the amount of charge density on the cluster hollow sites, which can facilitate the bonding of certain molecules. Moreover, we identify Pt, Pd and Rh clusters supported on hexagonal TMC (001) facets as the candidates with the highest potential catalytic activity -as estimated by the significant polarisation of the cluster electron density- and stability -as quantified by the strongly negative values of adsorption energy per atom and formation energy-.
Anharmonic lattice dynamics of superionic lithium nitride
Authors: Krenzer Gabriel , Kim Chang-Eun , Tolborg Kasper , Morgan Benjamin , Walsh Aron
Published: February 2022

Superionic crystals reach an ionic conductivity comparable to liquid electrolytes following a superionic transition at high temperature. The physical mechanisms that lead to this behaviour remain poorly understood. It has been proposed that superionic transitions are accompanied by the breakdown of specific phonon modes linked to characteristic diffusion processes. Any changes in vibrational properties across the superionic transition may therefore provide insights into the underlying physics of this phenomenon. Here, we apply a combination of lattice dynamics and ab initio molecular dynamics to probe the vibrational properties of the archetypal superionic conductor Li3N. We assess harmonic, quasi-harmonic, and anharmonic descriptions of the phonons. The harmonic and quasi-harmonic models show no change in features across the superionic transition. The fully anharmonic model, however, exhibits a phonon breakdown for all modes above the superionic transition temperature. The implications for developing lattice-dynamics based descriptors for superionic conductors are discussed.
SynthI: a new open-source tool for synthon-based library design
Authors: Zabolotna Yuliana , Volochnyuk Dmitriy , Ryabukhin Sergey , Gavrylenko Kostiantyn , Horvath Dragos , Klimchuk Olga , Oksiuta Olexandr , Marcou Gilles , Varnek Alexandre
Published: February 2022

Here we present a new open-source toolkit for library design, called Synthons Interpreter or SynthI that allows merging those chemical space of the retrosynthetically generated fragments and the pool of available reagents into a single synthons space. Here synthons are defined as the actual fragments with valid valences and special labels, defining the position and nature of reactive centers. They can be issued from either the “break-up” of reference compounds according to retrosynthetic rules, or real reagents/BBs, after leaving groups transformation. Such an approach not only enables the design of synthetically accessible libraries and analogs generation but also facilitates BB analysis in the medicinal chemistry context. SynthI code is available in https://github.com/Laboratoire-de-Chemoinformatique/SynthI