bluuebunny/crossref_metadata_2025 huggingface dataset:
Contact Map Fingerprints of Protein-Ligand Unbinding Trajectories Reveal Mechanisms Determining Residence Times Computed from Scaled Molecular Dynamics
Authors: Bianciotto Marc , Gkeka Paraskevi , Kokh Daria B. , Wade Rebecca , Hervé Minoux
Published: February 2022

The binding kinetic properties of potential drugs may significantly influence their subsequent clinical efficacy. Predictions of these properties based on computer simulations provide a useful alternative to their expensive and time-demanding experimental counterparts, even at an early drug discovery stage.Herein, we perform Scaled Molecular Dynamics (ScaledMD) simulations on a set of 27 ligands of HSP90 belonging to more than 7 chemical series in order to estimate their relative residence time. We introduce two new techniques for the analysis and the classification of the simulated unbinding trajectories. The first technique, which helps in estimating the limits of the free energy well around the bound state and the second one, based on a new contact map fingerprint, allows the description and the comparison of the paths that lead to unbinding.Using these analyses, we find that ScaledMD’s relative residence time generally enables the identification of the slowest unbinders. We propose an explanation for the underestimation of the residence times of a subset of compounds and we investigate how the biasing in ScaledMD can affect the mechanistic insights that can be gained from the simulations.
Ultrafast intersystem crossing in xanthone from wavepacket dynamics
Authors: Alías Rodríguez Marc , De Graaf Coen , Huix-Rotllant Miquel
Published: February 2022

Most aromatic ketones containing first-row elements undergo unexpectedly fast intersystem crossing in few tens of picoseconds and a quantum yield close to unity. Among them, xanthone (9H-xanthen-9-one) possesses one of the fastest singlet-triplet rates of ~1.5 ps. The exact mechanism of this unusually fast transition is still under debate. Here, we perform the wavepacket dynamics of the photochemistry of xanthone in the gas phase and in polar solvents. We show that xanthone follows El-Sayed's rule for intersystem crossing. From the second singlet excited state, the mechanism is sequential: (i) an internal conversion between singlets 1pipi*-1npi* (85 fs), (ii) an intersystem crossing 1npi*-3pipi* (2.0 ps), and (iii) an internal conversion between triplets 3pipi*-3npi* (602 fs). Each transfer finds its origin in a barrierless access to electronic state intersections. These intersections are close to minimum energy structures, allowing for efficient transitions from the initial singlet state to the triplets.
Synthesis and styrene copolymerization of novel trisubstituted ethylenes: 5. Dimethyl and dimethoxy ring-substituted octyl phenylcyanoacrylates
Authors: Wasilewski Martin S. , Boyson Grant W. , Canavesio Georgina N. , Keaton Sarah N. , Lee Matthew R. , Meyer Luke , Ryan Zoe A. , Seeger Eric , Shah Mahmood I. , Toolabian Anahi F. , Tojo Suárez Rebeca M. , Rocus Sara M , Kharas Gregory B. , Tudor Bernadette C. , Kharas Gregory B , Schjerven William S.
Published: February 2022

Novel trisubstituted ethylenes, dimethyl and dimethoxy ring-substituted octyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2(CH2)6CH3 (where R is 2,3-dimethyl, 2,4-dimethyl, 2,5-dimethyl, 2,6-dimethyl, 3,4-dimethyl, 3,5-dimethyl, 2,3-dimethoxy, 2,4-dimethoxy, 2,5-dimethoxy, 2,6-dimethoxy, 3,4-dimethoxy, 3,5-dimethoxy) were prepared and copolymerized with styrene. The ethylenes were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-disubstituted benzaldehydes and octyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C NMR. All the ethylenes were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis.
Synthesis and styrene copolymerization of novel trisubstituted ethylenes: 7. Fluoro, methyl and methoxy ring-disubstituted octyl phenylcyanoacrylates
Authors: Awadallah Mahmoud D. , Awan Izza A. , Carlino Grace M. , Cherian Zachary K. , J. Dimonte Sophia , Purkey Madeline A. , Singapori Yash Y. , Rabelas Juvy L. , Wisniewski Victoria J. , Kharas Gregory B , Rocus Sara , Kharas Gregory B. , Syeda Bajeel , Schjerven William
Published: February 2022

Novel trisubstituted ethylenes, fluoro, methyl and methoxy ring-disubstituted octyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2(CH2)6CH3 (where R is 2-fluoro-3-methoxy, 2-fluoro-4-methoxy, 2-fluoro-5-methoxy, 2-fluoro-6-methoxy, 3-fluoro-4-methoxy, 4-fluoro-3-methoxy, 2-fluoro-5-methyl, 2-fluoro-6-methyl, 3-fluoro-4-methyl, 4-fluoro-2-methyl, 4-fluoro-3-methyl) were prepared and copolymerized with styrene. The ethylenes were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and octyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C NMR. All the ethylenes were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis.
Synthesis and styrene copolymerization of novel trisubstituted ethylenes: 8. Dichloro and difluoro ring-substituted octyl phenylcyanoacrylates
Authors: Ibarra Christian , La Andy N. , Orban Victoria , Raziuddin Taha , Sedighzadeh Amir , Torlo Amina , Wild Crea Peter A. , Tyrawa Ania , Block Stephanie , Schjerven William S. , Dainko David C. , Kharas Gregory B. , Youngs Jessica E. , Rocus Sara M. , Kharas Gregory
Published: February 2022

Novel trisubstituted ethylenes, dichloro and difluoro ring-substituted octyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2(CH2)6CH3 (where R is 2,3-dichloro, 2,4-dichloro, 2,5-dichloro, 2,6-dichloro, 3,4-dichloro, 2,3-difluoro, 2,4-difluoro, 2,5-difluoro, 2,6-difluoro, 3,4-difluoro, 3,5-difluoro) were prepared and copolymerized with styrene. The ethylenes were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and octyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C NMR. All the ethylenes were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis.
Synthesis and styrene copolymerization of novel trisubstituted ethylenes: 11. Acetyl, methoxy, and halogen ring-substituted octyl phenylcyanoacrylates
Authors: Adekale Hannah A. , Alessi Ami L. , Arsalanuddin Mohammed A. , Avak Alexander M. , Buechner Daniel R. , Kharas Gregory B. , Wiser Natalie J. , Rocus Sara , Hebblethwaite Jason A. , Sanchez Giovanny , Schjerven William , Nagy Sabrina J. , Zygula Monica
Published: February 2022

Novel trisubstituted ethylenes, acetyl, methoxy, and halogen ring-substituted octyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2(CH2)6CH3 (where R is 2-acetyl, 2,3,4-trimethoxy, 2,4,5-trimethoxy, 2,4,6-trifluoro, 3,4,5-trifluoro, 2,3,5,6-tetrafluoro, 2,3,4,5,6-pentafluoro, 3-bromo-4,5-dimethoxy, 5-bromo-2,3-dimethoxy, 3-chloro-2,6-difluoro) were prepared and copolymerized with styrene. The ethylenes were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and octyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C NMR. All the ethylenes were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis.
Synthesis and styrene copolymerization of novel trisubstituted ethylenes: 11. Acetyl, methoxy, and halogen ring-substituted octyl phenylcyanoacrylates
Authors: Adekale Hannah A. , Alessi Amy L. , Arsalanuddin Mohammed A. , Avak Alexander M. , Buechner Daniel R. , Kharas Gregory B. , Wiser Natalie J. , Rocus Sara , Hebblethwaite Jason A. , Sanchez Giovanny , Schjerven William , Nagy Sabrina J. , Zygula Monica
Published: February 2022

Novel trisubstituted ethylenes, acetyl, methoxy, and halogen ring-substituted octyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2(CH2)6CH3 (where R is 2-acetyl, 2,3,4-trimethoxy, 2,4,5-trimethoxy, 2,4,6-trifluoro, 3,4,5-trifluoro, 2,3,5,6-tetrafluoro, 2,3,4,5,6-pentafluoro, 3-bromo-4,5-dimethoxy, 5-bromo-2,3-dimethoxy, 3-chloro-2,6-difluoro) were prepared and copolymerized with styrene. The ethylenes were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and octyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C NMR. All the ethylenes were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis.
Supramolecular Catalysis of a Catalysis-Resistant Diels-Alder Reaction: Rapid Dimerization of Cyclopentadiene inside Cucurbit[7]uril
Authors: Tehrani Foad , Assaf Khaleel , Hein Robert , Nugent Thomas , Nau Werner
Published: February 2022

In contrast to Diels-Alder reactions involving heteroatom-containing substrates, the endo dimerization of cyclopentadiene responds only very weakly to changes in microenvironment or the presence of potential catalysts (less than factor of 10 variation), although this pure hydrocarbon reaction has been used as an early model to predict the maximum possible catalytic effect (kcat/kuncat ca. 106 M) due to entropic contributions of a transition-state confinement (Page, M. I.; Jencks, W. P. Proc. Natl. Acad. Sci. USA 1971, 68, 1678). In the presence of cucurbit[n]uril homologues the reaction is selectively and almost maximally (kcat/kuncat ca. 4 × 105 M) accelerated by the intermediary sized cucurbit[7]uril in aqueous solution, while the other macrocyclic homologues display no acceleration or an inhibitory effect. The expected product inhibition due to the strong binding of the dicyclopentadiene reaction product can be overcome by addition of 10% methanol, which affords catalytic turnover numbers above 10. The reaction was monitored using 1H NMR spectroscopy as well as UV spectrophotometry. The analysis of the kinetic data, combined with packing coefficient considerations, modelling of Lennard-Jones potentials, and dispersion-corrected DFT calculations, suggest that the catalysis is due to an entropy-dominated transition-state stabilization in the tightly packed ternary complex.
Rationally Tailoring Catalysts for the CO Oxidation Reaction by Using DFT Calculations
Authors: Yan Dengxin , Kristoffersen Henrik , Pedersen Jack , Rossmeisl Jan
Published: February 2022

Rational design of catalysts by tailoring specific surface sites with different elements could result in catalysts with high activity, selectivity and stability. In this work, we show that *CO on-top and O* on-top adsorption energies are good descriptors for catalysis of the CO oxidation reaction (COOR) on pure metals and binary alloys. The observed Brønsted-Evans-Polanyi (BEP) and scaling relations for COOR on different surfaces are incorporated into a predictive model that uses the binding strength of the four adjacent metal atoms making up the active site for COOR catalysis to estimate reaction and activation energies. The model is used to screen 161 multi-metallic catalyst candidates made by combining Ru, Pt, Pd, Cu and Au at these four sites. The screening and subsequent calculations suggest that Ru-Pt-Cu alloys are good catalysts for COOR. Our study shows that it is possible to use information from pure metals and binary alloys to predict the catalytic behavior of more complex alloys, and hereby reduce the computational cost of identifying new catalyst candidates for COOR.
Insight into subsurface adsorption derived from a lattice-gas model of atomic oxygen on Ag(111)
Authors: Mize Carson , Isbill Sara , Roy Sharani
Published: February 2022

Theoretical gas-surface models that describe adsorption over a wide range of coverages can provide qualitative insight into chemical phenomena that occur at intermediate to high coverages, such as subsurface adsorption, surface reconstruction, and industrial heterogeneous catalysis. However, most atomistic, quantum-mechanical models of gas-surface adsorption are limited to low adsorbate coverage due to the large computational cost of models built using many surface atoms and adsorbates. To investigate adsorption in the subsurface of a crystalline solid with increasing coverage, we present a lattice-gas adsorption model that includes surface and subsurface sites of the solid, and is fully parametrized using density functional theory. We apply the model to study the competition between surface and subsurface adsorption of atomic oxygen on the Ag(111) surface. Oxygen population distributions calculated using the model show the onset of subsurface adsorption at a total coverage of approximately 1/4 monolayer and a greater accumulation of oxygen in the second rather than the first subsurface at total coverages greater than 1/2 monolayer. Computation of core-electron binding energies and projected density of states of an oxygen distribution predicted by the model reveal qualitative differences in oxygen-silver bonding at the surface and subsurface, suggesting that oxygen adsorbed in the two regions could play distinct roles in surface chemistry.
Accurate and Transferable Reactive Molecular Dynamics Models from Constrained Density Functional Theory
Authors: Li Chenghan , Voth Gregory A.
Published: February 2022

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.
MOF Synthesis Prediction Enabled by Automatic Data Mining and Machine Learning
Authors: Luo Yi , Bag Saientan , Zaremba Orysia , Andreo Jacopo , Wuttke Stefan , Tsotsalas Manuel , Friederich Pascal
Published: February 2022

Despite rapid progress in the field of metal-organic frameworks (MOFs), the potential of using machine learning (ML) methods to predict MOF synthesis parameters is still untapped. Here, we show how ML can be used for rationalization and acceleration of the MOF discovery process by directly predicting the synthesis conditions of a MOF based on its crystal structure. Our approach is based on: (i) establishing the first MOF synthesis database via automatic extraction of synthesis parameters from the literature, (ii) training and optimizing ML models by employing the MOF database, and (iii) predicting the synthesis conditions for new MOF structures. The ML models even at an initial stage exhibit a good prediction performance, outperforming human expert predictions, obtained through a synthesis survey.
Suppressing the excitonic effect and reducing the overpotential in narrow band gap covalent organic frameworks of Lieb lattice to enable metal-free photocatalytic overall water splitting
Authors: Yu Hongde , Wang Dong
Published: February 2022

Two-dimensional (2D) layered covalent organic frameworks (COFs) with in-plane conjugation and out-of-plane π-stacked structures have emerged as promising organic photocatalysts for their highly designable skeleton, tunable electronic properties, and inherent pores. Currently, wide band gap COFs are often applied for photocatalytic water splitting to surpass the large kinetic barrier of chemical reactions, which is adverse to solar light harvest and seriously impedes the promotion of energy conversion efficiency. In this work, we propose to exploit narrow band gap COFs as photocatalysts and devote to reduce the overpotential of redox reactions by engineering active catalytic sites on them. By first-principles calculations, we design nine fully conjugated COFs of Lieb lattice with band gaps tunable from 1.72 eV to 1.00 eV, which show broad visible and near-infrared (NIR) light absorption. Further, we unravel that the enhanced optical absorption is accompanied by the suppressed excitonic effect because the narrowed band gap has produced increased dielectric screening within the electron-hole pair. Interestingly, a pre-designed hydrogen bond can significantly reduce the overpotential of hydrogen evolution reaction, solving the dilemma of insufficient driving force posed by the narrow band gap. Finally, we demonstrate that a tandem system based on two of our designed COFs are capable of metal-free overall water splitting under visible and NIR light. Our findings highlight a new route to realize metal-free photocatalysis with COFs and pave the way for the rational design of organic photocatalysts with high energy conversion efficiency.
Combatting AMR: a molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection
Authors: Nasiri Sovari Sara , Radakovic Natasa , Roch Paul , Crochet Aurélien , Pavic Aleksandar , Zobi Fabio
Published: February 2022

In this study, we present the antimicrobial and antifungal efficacy of a family of rhenium tricarbonyl diimine complexes with varying ligands, charge and lipophilicity. Our study allowed the identification of potent and non-toxic complexes active in vivo against antimicrobial infections at MIC doses as low as 330 ng/mL and C. albicans-MRSA mixed co-infection. The compounds are capable of suppressing the C. albicans morphogenetic yeast-to-hyphal transition, eradicating fungal-S. aureus co-infection, while showing no sign of cardio-, hepato-, hematotoxiciy or teratogenicity.
Visualization of spatial electrochemical activity via a combined thermal-electric potentiostat
Authors: Iglesias van Montfort Hugo-Pieter , Burdyny Thomas
Published: February 2022

The electrolysis of water, CO2 and N2 provide options for producing fossil-free fuels and feedstocks at global scales. Technological advancements are challenged by the complexity of phenomena spanning broad physical scales (angstroms to meters) and scientific domains. Further, activity is presently quantified indirectly, hindering disambiguation of catalytic and system effects. Here, we present a spatial thermal-electric potentiostat (STEP) which links local electrochemical activity to an associated operando heat signature. The STEP then directly maps catalytic activity with fine resolutions in temperature (10 mK), time (0.2 s) and space (0.1 mm), capturing operational phenomena as they occur. We demonstrate STEP’s potential for catalyst screening, degradation measurements and spatial mapping through water and CO2 electrolysis experiments up to 0.2 A cm-2. We identify rapid catalytic temperature spikes with activity (>10 K at 0.2 A cm-2) and localized activity fluctuations in operation, both which challenge many perceptions of the electrocatalyst and reaction environment during operation.
Polyhydroxylated cyclopentane β-amino acids derived from D-mannose and D-galactose: synthesis and protocol for incorporation into peptides
Authors: Fernández Fernando , Fernández Alberto G. , Balo Rosalino , Sánchez-Pedregal Víctor M. , Royo Miriam , Soengas Raquel G. , Estévez Ramón J. , Estévez Juan C.
Published: February 2022

A stereoselective synthesis of polyhydroxylated cyclopentane β-amino acids from hexoses is reported. The reaction sequence comprises as key steps a Ring Closing Metathesis of a polysubstituted diene intermediate, followed by the stereoselective aza-Michael functionalization of the resulting cyclopent-1- ene-1-carboxylic acid ester. Examples of synthesis of polysubstituted 2-aminocyclopentanecarboxylic acid derivatives starting from protected D-mannose and D-glucose are presented. A general protocol for the incorporation of these highly functionalized alicyclic β-amino acids into peptides is also reported.
Hydrodeoxygenation of Guaiacol Over Orthorhombic Molybdenum Carbide: A DFT and Microkinetic Study
Authors: Agrawal Kushagra , Roldan Alberto , Kishore Nanda , Logsdail Andrew J
Published: February 2022

The hydrodeoxygenation of guaiacol is modelled over a (100) β-Mo2C surface using density functional theory and microkinetic simulations. The thermochemistry of the process shows that the demethoxylation of the guaiacol, to form phenol, will be the initial steps, with a reaction energy of 29 kJ/mol (i.e. endothermic) and a highest activation barrier of 112 kJ/mol. Subsequently, the dehydroxylation of the phenol, which has a rate-determining activation barrier of 145 kJ/mol, will lead to the formation of benzene, with an overall reaction energy for conversion from guaiacol of -91 kJ/mol (i.e. exothermic).
Low-Valent Tungsten Catalysis Enables Site-Selective Isomerization–Hydroboration of Unactivated Alkenes
Authors: Jankins Tanner , Martin-Montero Raul , Cooper Phillippa , Martin Ruben , Engle Keary
Published: February 2022

A tungsten-catalyzed hydroboration of unactivated alkenes at distal C(sp3)–H bonds aided by native directing groups is described herein. The method is characterized by its simplicity, exquisite regio- and chemoselectivity and wide substrate scope, offering a complementary site-selectivity pattern to other metal-catalyzed borylation reactions and chain-walking protocols.
Revisiting Thin-Layer Electrochemistry in a Chip-Type Cell for the Study of Electroorganic Reactions
Authors: Shin Samuel Jaeho , Kim Ji Yong , An Sohee , Kim Moonjoo , Seo Minjee , Go Su Yong , Chung Hyunho , Lee MinKeun , Kim Min-Gyeong , Lee Hong Geun , Chung Taek Dong
Published: February 2022

It is important but challenging to elucidate the electrochemical reaction mechanisms of organic compounds using electroanalytical methods. Particularly, a rapid and straightforward method may be helpful if it can provide information on reaction intermediates or other key electrochemical parameters. In this work, we exploited the advantages of classic thin-layer electrochemistry to develop a thin-layer electroanalysis microchip (TEAM). TEAM provided better resolved voltammetric peaks than under semi-infinite diffusion condition owing to the small height. Importantly, rapid and accurate determination of the number of electrons transferred, n, was enabled by mechanically confining the microliter-scale volume analyte at the electrode, while securing ionic conduction using polyelectrolyte gels. The performance of the TEAM was validated using voltammetry and coulometry of standard redox couples. Utilizing TEAM, a (spectro)electrochemical analysis of FM 1-43, an organic dye widely used in neuroscience, was successfully performed. It was also applied to study the electrochemical oxidation mechanism of pivanilides and alkyltrifluoroborate salts with different substituents and solvents. This work suggests the TEAM as a promising tool to provide invaluable mechanistic information and promote the rational design of electrosynthetic strategies.
Pd(II)-Catalyzed Synthesis of Benzocyclobutenes by β-Methylene-Selective C(sp3)‒H Arylation with a Transient Directing Group
Authors: Provencher Philip , Hoskin John , Wong Jonathan , Chen Xiangyang , Yu Jin-Quan , Houk KN , Sorensen Erik
Published: February 2022

Methylene-selective C‒H functionalization is a significant hurdle that remains to be addressed in the field of Pd(II) cataly-sis. In this paper we report a Pd(II) catalyzed synthesis of benzocyclobutenes by methylene-selective C(sp3)‒H arylation of ketones using a transient directing group. The reaction utilizes glycine as a transient directing group and an electron poor pyridone ligand which is expected to promote concerted metallation deprotonation, but also controls methylene selectivity by intimate interactions with the substrate. These reaction conditions are shown to be highly selective for in-tramolecular methylene C(sp3)‒H arylation, and thus enable sequential C(sp3)‒H functionalization.
Bagasse derived C@Fe3C/Fe3O4 composite: An Approach towards low cost electrocatalyst for oxygen reduction reaction
Authors: Manippady Rashmi , Khan Ziyauddin , Samal Akshaya , Saxena Manav
Published: February 2022

As the world is heading towards sustainable future, it is highly important to develop low-cost electrocatalysts for energy generation devices. Herein, we report synthesis of iron-carbon hybrid (C@Fe3C/Fe3O4) nanocomposite for oxygen reduction reaction (ORR), synthesized using bagasse as a carbon source material and Fe(III) precursor at 900 ˚C. The synthesized C@Fe3C/Fe3O4 composite exhibits a high surface area of ~930 m2/g. The electrode material has a 0.86 V overpotential vs RHE. Moreover, the electrocatalyst shows catalytic stability upto 44,000 s at the static potential of 0.25 V vs RHE at the rotation speed of 1600 rpm. Herein, the electron transfer number is calculated to be 3.76-3.94 which suggest that the electrocatalyst could catalyze ORR nearly through a 4 electron transfer process in alkaline solution.
Microporous covalent organic frameworks for sulfur hexafluoride capture and separation
Authors: Liao Qiaobo , Xu Haocheng , Ke Can , Zhang Yiying , Han Qingwen , Zhang Yifan , Xu Yang , Xi Kai
Published: February 2022

Sulfur hexafluoride (SF6) is the most potent greenhouse gas whose emission is in great need of reducing during the indus-trial processes. Here, a variety of covalent organic frameworks with varying topologies, surface areas, pore size distribu-tions is designed and synthesized for systematically studying structure-property relationships of COF-based SF6 adsor-bents. Surface area was found to be a prerequisite for achieving high SF6 uptakes, and small pore size at ca. 0.9 nm could effectively enhance the adsorbate-adsorbent interaction and hence the SF6/N2 selectivity. With a large specific surface area and a suitable pore size, RCOF-1 showed superior SF6 adsorption capacities up to 4.13 mmol g-1 and large SF6/N2 se-lectivity up to 125 (273 K, 100 kPa), which can be considered one of the most high-performance porous materials for SF6 capture and separation. This work not only provides a series of high-performance SF6 adsorbents, but also broadens the horizon of applications of the emerging COFs, pointing out their development direction in the field of SF6 capture and separation.
Novel functional copolymers of vinyl acetate: 1. Alkyl ring-substituted ethyl 2-cyano-3-phenyl-2-propenoates
Authors: Killam Benjamin Y. , Barkauskas Rima T. , Dembiec Daniel P. , Farrell Rebecca S. , Gallego Maritza A. , Kaiser Kelly A. , Keeling Michelle L. , Kang Kari Y. , Verdoorn Gretchen R. , Kharas Gregory
Published: February 2022

Alkyl ring-substituted ethyl 2-cyano-3-phenyl-2-propenoates, RPhCH=C(CN)CO2C2H5 (where R is 2-methyl, 3-methyl, 4-methyl, 4-ethyl, 4-isopropyl, 4-t-butyl, 4-trifluoromethyl, 2-trifluoromethyl) were prepared and copolymerized with vinyl acetate in solution with radical initiation. The compositions of the copolymers were calculated from nitrogen analysis and the structures were analyzed by IR, 1H and 13C-NMR. Thermal behavior of the copolymers was studied by DSC and TGA. Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200-500ºC range with residue (13-16 wt%), which then decomposed in the 500-800ºC range.
Photocatalyst-free, visible-light-mediated nickel catalyzed carbon–heteroatom cross-couplings
Authors: Cavedon Cristian , Gisbertz Sebastian , Vogl Sarah , Richter Noah , Schrottke Stefanie , Teutloff Christian , Seeberger Peter H. , Thomas Arne , Pieber Bartholomäus
Published: February 2022

Metallaphotocatalysis typically requires a photocatalyst to harness the energy of visible-light and transfer it to a transition metal catalyst to trigger chemical reactions. The most prominent example is the merger of photo- and nickel catalysis that unlocked various cross-couplings. However, the high reactivity of excited photocatalyst can lead to unwanted side reactions thus limiting this approach. Here we show that a bipyridine ligand that is subtly decorated with two carbazole groups forms a nickel complex that absorbs visible-light and promotes several carbon–heteroatom cross-couplings in the absence of an exogenous photocatalysts. The ligand can be polymerized in a simple one-step procedure to afford a porous organic polymer that can be used for heterogeneous nickel catalysis in the same reactions. The material can be easily recovered and reused multiple times maintaining high catalytic activity and selectivity.
Enantioselective Synthesis of Alkylidenecyclobutanones via Formal Vinylidene Insertion into Cyclopropanone Equivalents
Authors: Poteat Christopher , Lindsay Vincent
Published: February 2022

1-Sulfonylcyclopropanols are employed here as efficient cyclopropanone equivalents in a formal vinylidene insertion process, providing the first general synthetic route to enantioenriched alkylidenecyclobutanones. The addition of an alkenyl-Grignard reagent to the cyclo-propanone leads to an alkenylcyclopropanol capable of electrophilic activation by NBS, triggering a regio- and stereospecific 1,2-migration and the formation of a brominated cyclobutanone intermediate prone to elimination. The parent β-amino ketone can also be accessed by one-pot aza-Michael addition to the resulting product, and activation of the alkenylcyclopropanol intermediate with other electrophiles such as HCl or mCPBA led to the controlled formation of a variety of chiral cyclobutanones and γ-lactones via alternative pathways.
A Small Organic molecule Based on Benzothiadiazole for Electrocatalytic Hydrogen Production
Authors: Axelsson Martin , Marchiori Cleber F. N. , Huang Ping , Araujo C. Moyses , Tian Haining
Published: February 2022

A small organic molecule 2,1,3-benzothiadiazole-4, 7-dicarbonitrile (BTDN) is assessed for electrocatalytic hydrogen, showing a hydrogen production faradaic efficiency of 82% in presence of salicylic acid. The key catalytic intermediates of reduced species BTDN−• and protonated intermediates are identified and characterized by using various spectroscopic methods and density functional theory (DFT) based calculations. With the experimental and theoretical results, a catalytic mechanism of BTDN for electrocatalytic H2 evolution is proposed.
Cation and light-responsive frameworks from non-canonical amphiphilic DNA nanostructures
Authors: Fabrini Giacomo , Minard Aisling , Brady Ryan A. , Di Antonio Marco , Di Michele Lorenzo
Published: February 2022

Thanks to its biocompatibility, versatility and programmable interactions, DNA has been proposed as a building block for functional, stimuli-responsive frameworks with applications in biosensing, tissue engineering and drug delivery. Of particular importance for in vivo applications is the possibility of making such nano-materials responsive to physiological stimuli. Here we demonstrate how combining noncanonical DNA G-quadruplex (G4) structures with amphiphilic DNA constructs yields nanostructures, which we termed "Quad-Stars", capable of assembling into responsive hydrogel particles via a straightforward, enzyme-free, one-pot reaction. The embedded G4 structures allow one to trigger and control the assembly/disassembly in a reversible fashion by adding or removing K+ ions. Furthermore, the frameworks can be rendered responsive to near-UV light through the addition of a porphyrin photosensitiser. The combined reversibility of assembly, responsiveness and cargo-loading capabilities of the hydrophobic moieties make Quad-Stars a promising candidate for biosensors and responsive drug delivery carriers.
Cation-responsive and photocleavable hydrogels from non-canonical amphiphilic DNA nanostructures
Authors: Fabrini Giacomo , Minard Aisling , Brady Ryan A. , Di Antonio Marco , Di Michele Lorenzo
Published: February 2022

Thanks to its biocompatibility, versatility and programmable interactions, DNA has been proposed as a building block for functional, stimuli-responsive frameworks with applications in biosensing, tissue engineering and drug delivery. Of particular importance for in vivo applications is the possibility of making such nano-materials responsive to physiological stimuli. Here we demonstrate how combining noncanonical DNA G-quadruplex (G4) structures with amphiphilic DNA constructs yields nanostructures, which we termed "Quad-Stars", capable of assembling into responsive hydrogel particles via a straightforward, enzyme-free, one-pot reaction. The embedded G4 structures allow one to trigger and control the assembly/disassembly in a reversible fashion by adding or removing K+ ions. Furthermore, the hydrogel aggregates can be photodisassembled upon near-UV irradiation in the presence of a porphyrin photosensitiser. The combined reversibility of assembly, responsiveness and cargo-loading capabilities of the hydrophobic moieties make Quad-Stars a promising candidate for biosensors and responsive drug delivery carriers.
Development and Benchmarking of Open Force Field v1.0.0, the Parsley Small Molecule Force Field
Authors: Qiu Yudong , Smith Daniel , Boothroyd Simon , Jang Hyesu , Wagner Jeffrey , Bannan Caitlin C. , Gokey Trevor , Lim Victoria T. , Stern Chaya , Rizzi Andrea , Lucas Xavier , Tjanaka Bryon , Shirts Michael R. , Gilson Michael , Chodera John , Bayly Christopher I. , Mobley David , Wang Lee-Ping
Published: February 2022

We present a methodology for defining and optimizing a general force field for classical molecular simulations, and we describe its use to derive the Open Force Field 1.0.0 small molecule force field, code-named Parsley. Rather than traditional atom-typing, our approach builds on the SMIRKS-native Open Force Field (SMIRNOFF) parameter assignment formalism, which handles increases in the diversity and specificity of the force field definition without needlessly increasing the complexity of the specification. Parameters are optimized with the ForceBalance tool, based on reference quantum chemical data that include torsion potential energy profiles, optimized gas-phase structures, and vibrational frequencies. These quantum reference data are computed and are maintained with QCArchive, an open-source and freely available distributed computing and database software ecosystem. In this initial application of the method, we present essentially a full optimization of all valence parameters and report tests of the resulting force field against compounds and data types outside the training set. These tests show improvements in optimized geometries and conformational energetics and demonstrate that Parsley's accuracy for liquid properties is similar to that of other general force fields, as is accuracy on binding free energies. We find that this initial Parsley force field affords accuracy similar to that of other general force fields when used to calculate relative binding free energies spanning 199 protein-ligand systems. Additionally, the resulting infrastructure allows us to rapidly optimize an entire new force field with minimal human intervention.
Deprotonation and Cation Adsorption on the NiOOH/Water Interface: A Grand-Canonical First-Principles Investigation
Authors: Eslamibidgoli Mohammad , Huang Jun , Kowalski Piotr , Eikerling Michael , Gross Axel
Published: February 2022

Nickel-based oxides are highly active, cost effective materials for the oxygen evolution reaction in alkaline conditions. Recent experimental studies have revealed the importance of surface deprotonation and alkali metal cation adsorption on the activity of Ni oxide surfaces, in contact with aqueous alkaline electrolyte. As a first step to elucidate the role of the alkali adsorption for the activity, we performed first-principles electronic structure calculations to address the stable surface structures of beta-NiOOH(0001) as a function of the operating conditions in an electrochemical environment. We present a grand-canonical approach to compute the surface Pourbaix diagram of the beta-NiOOH/water interface for the processes of deprotonation and alkali metal cation adsorption. The results of this study emphasize the importance of double layer effects, including the adsorbate-induced change of surface dipole moments and the rearrangement of water molecules due to their strong interaction with the adsorbed species, for the most stable interface structure.
Identifying signatures of proteolytic stability and monomeric propensity in O-glycosylated insulin using molecular simulation
Authors: Hsu Wei-Tse , Ramirez Dominique , Sammakia Tarek , Tan Zhongping , Shirts Michael
Published: February 2022

Insulin has been commonly adopted as a peptide drug to treat diabetes given its ability to facilitate the uptake of glucose from the blood. The development of oral insulin remains elusive over decades owing to its susceptibility to the enzymes in the gastrointestinal tract and poor permeability through the intestinal epithelium upon dimerization. Recent experimental studies have revealed that certain O-linked glycosylation patterns could enhance insulin’s proteolytic stability and reduce its dimerization propensity, but the understanding of such phenomena at the molecular level is still evasive. To address this challenge, we propose and test several structural determinants that could potentially in uence insulin’s proteolytic stability and dimerization propensity. We used these as the metrics to assess the properties of interest from 10  s aggregate molecular dynamics of each of 12 targeted insulin glyco-variants from multiple wild-type crystal structures. We found that glycan-involved hydrogen bonds and glycan-dimer occlusion were useful metrics predicting the proteolytic stability and dimerization propensity of insulin, as was in part the solvent accessible surface area of proteolytic sites, while other plausible metrics were not generally predictive. This work helps better explain how O-linked glycosylation in uences the proteolytic stability and monomeric propensity of insulin, illuminating a path towards rational molecular design of insulin glycoforms.
Aptamers for Detection and Diagnostics (ADD): Can mobile systems linked to biosensors support molecular diagnostics of SARS-CoV-2? Should molecular medicine explore multiple alternatives as adjuvants to or replacement for traditional and non-traditional vaccines?
Authors: Datta Shoumen
Published: February 2022

Proposed SARS-CoV-2 surveillance tool using a mobile app for non-invasive monitoring of humans and animals. Engineering a biomedical device as a low-cost, non-invasive, detection, and diagnostic platform for surveillance of infections in humans, and animals. The system embraces the IoT “digital by design” metaphor by incorporating elements of connectivity, data sharing and (secure) information arbitrage. Using an array of aptamers to bind viral targets may help in detection, diagnostics, and potentially prevention in case of SARS-CoV-2. The ADD tool may become part of a broader platform approach.
Essential Terminology Connects NMR and qNMR Spectroscopy to Its Theoretical Foundation
Authors: Pauli Guido , Ray G. Joseph , Bzhelyansky Anton , Jaki Birgit , Corbett Charlotte , Szabo Christina , Setinbeck Christoph , Sørensen Dan , Jeannerat Damien , Ferreira Daneel , Lankin David , McAlpine James , Dumez Jean-Nicholas , Bisson Jonathan , Krishnamurty Krish , Niemitz Matthias , Nelson Michael , Giraudeau Patrick , Korhonen Samuli-Petrus , Kuhn Stefan , Miura Toru , Botros Lucy
Published: February 2022

Classical 1D 1H NMR spectra are prototypic for NMR spectroscopy in that they represent a wealth of chemical information encoded into convoluted graphs or patterns that contain complex features (aka multiplets), even for seemingly simple molecules. Accordingly, the utility of NMR depends on the theoretical and visual skills required to extract all the physical parameters that represent usable structural and quantitative information. Moreover, it depends on the ability of the analyst to communicate them effectively and reproducibly. After decades of continuous development, NMR spectroscopy has reached a stage where its analytical capabilities have outgrown the typical level of detail of interpretation, especially of 1D NMR spectra. The quantum-mechanical (QM) foundation, history, evolution, and (in-)consistency of widely applied terminology calls for re-examination and recalibration. In order to develop new perspectives on solution-state NMR analysis, including the rapidly evolving quantitative NMR (qNMR), the present study draws on the well-established NMR model systems and molecules (AB2C2, strychnine, testosterone, α-santonin). Through well-documented key topics related to spectral acquisition and analysis, the study builds the foundation for a modular, coherent, and standardized nomenclature of NMR terminology. This is a necessary condition for a healthy research data lifecycle including their management and reuse. This work presents experimental evidence and connects with essential concepts of QM theory that clarify the distinct meaning of the primary terms: resonance, signal, pattern, peak, line, transition; as well as other widely used terms: splitting, multiplicity/multiplet, resolution, and dispersion. The proposed NMR terminology was built through a consensus-finding process that evolved from extended pharmacopoeial and research coordination efforts. It is supported by detailed figures and NMR data interpretation that employs QM-based full spin analysis.
Beyond conformational control: effects of noncovalent interactions on electronic properties of conjugated polymers
Authors: Liu Bin , Rocca Dario , Yan He , Pan Ding
Published: February 2022

Tuning the electronic properties of polymers is of great importance in designing highly efficient organic solar cells. Noncovalent intramolecular interactions have been often used as conformational control to enhance the planarity of polymers or molecules, which may reduce band gaps and promote charge transfer. However, it is little known if noncovalent interactions may alter the electronic properties of conjugated polymers through some mechanism other than the conformational control. Here, we studied the effects of various noncovalent interactions, including sulfur-nitrogen, sulfur-oxygen, sulfur-fluorine, oxygen-nitrogen, oxygen-fluorine, and nitrogen-fluorine, on the elec- tronic properties of polymers with planar geometry using unconstrained and constrained density functional theory. We found that the sulfur-nitrogen intramolecular interaction may reduce the band gaps of polymers and enhance the charge transfer more obviously than other noncovalent interactions. Our findings are also consistent with the experi- mental data. For the first time, our study shows that the sulfur-nitrogen noncovalent interaction may further affect the electronic structure of coplanar conjugated polymers, which cannot be only explained by the enhancement of molecular planarity. Our work suggests a new mechanism to manipulate the electronic properties of polymers to design high-performance small-molecule-polymer and all-polymer solar cells.
Red-to-NIR Emissive Radical Cations Derived from Simple Pyrroles for Bio-Imaging
Authors: Gao Meng , Tang Ben Zhong , Liu Kai , Zheng Lihua , Zhu Wenchao , Zhou Zikai
Published: February 2022

Red-to-near-infrared (NIR) fluorophores are highly desirable for bio-imaging with advantages of excellent tissue penetration ability and less interference from auto-fluorescence, but their synthesis usually require tedious procedures and it’s thus highly desirable for red-to-NIR fluorophores directly generated from easily available substrates. Compared with the conventional closed-shell fluorophores, radical cations are featured with a large red-shift absorption, but most of them are not fluorescent due to the fast internal conversion between excited and ground state with a small energy gap. Moreover, radical cations suffer from instability because they can easily undergo radical coupling or nucleophilic addition reactions. Herein, we found that 2,5-dimethylpyrroles can rapidly generate red-to-NIR emissive radical cations, which can be stabilized by adsorption on thin layer chromatography (TLC) plate or being encapsulated in cucurbit[7]uril (CB[7]). The NIR-emissive radical cations derived from pyrroles were verified by electron paramagnetic resonance (EPR) spectroscopy and theoretical calculations. Importantly, the pyrrole-derived radical cations encapsulated in CB[7] can be used for mitochondrial imaging in living cells and tumor imaging in vivo with a high signal-to-noise ratio. The easily available and red-to-NIR emissive radical cations derived from simple pyrroles are promising for applications in biomedical study.
Calculation of Metallocene Ionization Potentials via Auxiliary Field Quantum Monte Carlo: Towards Benchmark Quantum Chemistry for Transition Metals
Authors: Rudshteyn Benjamin , Weber John L. , Coskun Dilek , Devlaminck Pierre A. , Zhang Shiwei , Reichman David R. , Shee James , Friesner Richard A.
Published: February 2022

The accurate ab initio prediction of ionization energies is essential to understanding the electrochemistry of transition metal complexes in both materials science and biological applications. However, such predictions have been complicated by the scarcity of gas-phase experimental data, the relatively large size of the relevant molecules, and the presence of strong electron correlation effects. In this work, we apply all-electron phase-less auxiliary-field quantum Monte Carlo (ph-AFQMC) utilizing multi-determinant trial wavefunctions to six metallocene complexes to compare the computed adiabaticand vertical ionization energies to experimental results. We find the ph-AFQMC mean averaged errors (MAE) of 1.69±1.02 kcal/mol for the adiabatic energies and 2.85±1.13 kcal/mol for the vertical energies. This significantly outperforms density functional theory (DFT), which has MAE’s of 3.62 to 6.98 and 3.31 to 9.88 kcal/mol, as well as a localized coupled cluster approach (DLPNO-CCSD(T0) with moderate PNO cut-offs), which has MAEs of 4.96 and 6.08 kcal/mol, respectively. We also test the reliability of DLPNO-CCSD(T0) and DFT on acetylacetonate (acac) complexes for adiabatic energies measured in the same manner experimentally, and find higher MAE’s, ranging from 4.56 kcal/mol to 10.99 kcal/mol (with a different ordering) for DFT and 6.97 kcal/mol for DLPNO-CCSD(T0), indicating that none of these approaches can be considered benchmark methods, at least for these complexes. We thus demonstrate that ph-AFQMC should be able to handle metallocene redox chemistry with the advantage of systematically improvable results. By utilizing experimental solvation energies, we show that accurate reduction potentials in solution can be obtained.
Chemoselective, Scalable Nickel-Electrocatalytic O-Arylation of Alcohols
Authors: baran phil , Zhang Hai-Jun , Chen Longrui , Oderinde Martins , Edwards Jacob , Kawamata yu
Published: February 2022

The formation of aryl-alkyl ether bonds through cross coupling of alcohols with aryl halides represents a useful strategic departure from classical SN2 methods. Numerous tactics relying on Pd-, Cu-, and Ni-based catalytic systems have emerged over the past several years. Herein we disclose a Ni-catalyzed electrochemically driven protocol to achieve this useful transformation with a broad substrate scope in an operationally simple way. This electrochemical method does not require strong base, exogenous expensive transition metal catalysts (e.g. Ir, Ru), and can easily be scaled up in either a batch or flow setting. Interestingly, e-etherification exhibits an enhanced substrate scope over the mechanistically related photochemical variant as it tolerates tertiary amine functional groups in the alcohol nucleophile.