bluuebunny/crossref_metadata_2025 huggingface dataset:
Light-Fuelled Dissipative Replication and Selection in Adaptive Biomimetic Chemical Networks
Authors: Bartus Éva , Mag Beáta , Bajcsi Áron , Tököli Attila , Kecskeméti Gábor , Wéber Edit , Kele Zoltán , Fenteany Gabriel , Martinek Tamás A.
Published: February 2022

Evolvability of chemical replicator systems requires non-equilibrium energy dissipation, effective decomposition pathways and transfer of structural information in the autocatalytic cycles. We engineered a chemical network with peptidic foldamer components, with UV light-fuelled dissipative sequence-dependent replication and replicator decomposition. The light-harvesting formation-recombination cycle of thiyl radicals was coupled with the molecular recognition steps in the replication cycles. Thiyl radical-mediated chain reaction was responsible for the replicator breakdown. The competing and kinetically asymmetric replication and decomposition processes led to light intensity-dependent selection, which differs from the equilibrium composition. The results contribute to the development of chemically evolvable dissipative replicator systems.
Tailoring the Reactivity of the Langlois Reagent and Styrenes with Cyanoarenes Organophotocatalysts under Visible-Light.
Authors: Louvel Dan , Souibgui Amel , TAPONARD ALEXIS , Rouillon Jean , ben mosbah Mongi , moussaoui younes , PILET GUILLAUME , Khrouz Lhoussain , MONNEREAU Cyrille , Tlili Anis
Published: February 2022

The unprecedented selective and straightforward one-step access to fluoroalkylated hexestrol derivatives, nonsteroidal estrogens, is achieved in good to excellent isolated yields under organophotoredox conditions by using the stable and easy to handle Langlois reagent. Furthermore, the challenging selective hydrotrifluoromethylation of styrenes proceeds under mild reaction conditions without the requirement of any additive. We assume that the solvent drives the reaction pathway towards either the reduction or the dimerization of the radical intermediate generated after initial addition of the fluoroalkyl radical to the styrene. The versatility of the developed system is also extended to encompass radical-radical cross-coupling as exemplified here using cyanopyridine. Mechanistic investigations including luminescence and EPR spectroscopy allow to shed the light on the different mechanisms.
Light-Driven Reduction of Aromatic Olefins in Aqueous Media Catalysed by Aminopyridine Cobalt Complexes.
Authors: Lloret-Fillol Julio , Casadevall Carla , Pascual David , Aragón Jordi , Call Arnau , Casitas Alicia , Casademont-Reig Irene
Published: February 2022

A catalytic system based on earth-abundant elements that efficiently hydrogenates aryl olefins using visible light as driving-force and H2O as the sole hydrogen atoms source is reported. The catalytic system involves a robust and well-defined aminopyridine cobalt complex and a heteroleptic Cu photoredox catalyst. The system shows the reduction of styrene in aqueous media with a remarkable selectivity (> 20000) versus water reduction (WR). Reactivity and mechanistic studies support the formation of a [Co-H] intermediate, which reacts as a hydrogen transfer agent (HAT). Synthetically useful deuterium-labelled compounds can be straightforwardly obtained by replacing H2O with D2O and using only catalysts based on earth-abundant elements. Moreover, the dual photocatalytic system and the photocatalytic conditions can be rationally designed to tune the selectivity for aryl olefin vs aryl ketone reduction; not only by changing the structural and electronic properties of the cobalt catalysts, but also by modifying the reduction properties of the light-harvesting system
Anisotropic Foams Via Frontal Polymerization
Authors: Alzate-Sanchez Diego M. , Cencer Morgan M. , Rogalski Michael , Kersh Mariana , Sottos Nancy , Moore Jeffrey S.
Published: February 2022

The properties of foams, an important class of cellular solids, are most sensitive to the volume fraction and openness of its elementary compartments; size, shape, orientation, and the interconnectedness of the cells are other important design attributes. Control of these morphological traits would allow the tailored fabrication of useful materials including highly porous solids, anisotropic heat conductors, tough composites, among others. While approaches like ice templating has produced foams with elongated cells, there is a need for rapid, versatile, and energy efficient methods that also control the local order and macroscopic alignment of cellular elements. Here we describe a fast and convenient method to obtain anisotropic structural foams using frontal polymerization. We fabricated foams by curing mixtures of dicyclopentadiene and a physical blowing agent via frontal ring opening metathesis polymerization (FROMP). The materials were characterized using micro-computed tomography and an image analysis protocol to quantify morphological characteristics including volume fraction and anisotropy. The cellular structure, porosity, and hardness of the foams changed with blowing agent, concentration, and resin viscosity. Moreover, we used a full factorial combination of variables to correlate each parameter with the structure of the obtained foams. We found a strong correlation between the resin viscosity and the foam’s cellular structure. Furthermore, a specific combination of input parameters controlled the transitions from (i) isotropic to anisotropic cellular structures, (ii) porous to non-porous, and (iii) soft to hard foams. Our results demonstrate the controlled production of foams with specific morphologies using the simple and efficient method of frontal polymerization. This work shows promise for creating foams with aligned cellular structures that allow anisotropic mass and energy transport properties in high performance structural solids.
Catalytic Activation via π –Backbonding in Halogen Bonds?
Authors: Wang Andrew , Kennepohl Pierre
Published: February 2022

The role of halogen bonding (XB) in chemical catalysis has largely involved using XB donors as Lewis acid activators to modulate the reactivity of partner Lewis bases. We explore a more uncommon scenario, where a Lewis base modulates reactivity via a spectator halogen bond interaction. Our computational studies reveal that spectator halogen bonds may play an important role in modulating the rate of SN2 reactions. Most notably, π acceptors such as PF3 significantly decrease the barrier to substitution by decreasing electron density in the very electron-rich transition state. Such π-backbonding represents an example of a heretofor unexplored situation in halogen bonding: the combination of both s-donation and π-backdonation in this “non-covalent” interaction.
Evaluating the Performance of a Transformer-based Organic Reaction Prediction Model
Authors: Borrelli William , Schrier Joshua
Published: February 2022

Forward and retrosynthetic organic reaction prediction are challenging applications of artificial intelligence (AI) research in chemistry. IBM’s freely available RXN for Chemistry (https://rxn.res.ibm.com) treats reaction prediction as a translation problem, by using transformer-based machine learning models trained on patent data to convert reactant SMILES string sequences into product strings. Here we characterize the performance of transformer models on 100 undergraduate text-book problems to expose reaction classes where the fundamentals of organic chemistry are violated. The forward prediction model is generally successful in predicting outcomes for substitution reactions and unsuccessful for elimination and organocopper reactions. For the retrosynthesis model, we found characteristic examples of a lack of atom conservation and nonsensical chemical transformations. We also compared the dif- ferences in molecular complexity and synthetic accessibility between predicted and literature reactions to probe how AI plans reactions compared to humans. Forward predictions replicated a similar distribution of differences in molecular complexity as the human reactions from the literature, whereas retrosynthetic predictions resulted in both positive and negative deviations from literature complexity. Finally, we analyzed the atom mapping in test reactions to expose errors in how the model identifies reactive atoms and species.
Covalent Functionalization of Nickel Phosphide Nanocrystals with Aryl-Diazonium Salts
Authors: Murphy Ian , Rice Peter , Monahan Madison , Zasada Leo , Miller Elisa , Raugei Simone , Cossairt Brandi
Published: February 2022

Covalent functionalization of Ni2P nanocrystals was demonstrated using aryl-diazonium salts. Spontaneous adsorption of aryl functional groups was observed, with surface coverages ranging from 20-96% depending on the native reactivity of the salt as determined by the aryl substitution pattern. Increased coverage was possible for low reactivity species using a sacrificial reductant. Functionalization was confirmed using thermogravimetric analysis, FTIR and X-ray photoelectron spectroscopy. The structure and energetics of this nanocrystal electrocatalyst system, as a function of ligand coverage, was explored with density functional theory calculations. The Hammett parameter of the surface functional group was found to linearly correlate with the change in Ni and P core-electron binding energies and the nanocrystal’s experimentally and computationally determined work-function. The electrocatalytic activity and stability of the functionalized nanocrystals for hydrogen evolution were also improved when compared to the unfunctionalized material, but a simple trend based on electrostatics was not evident. We used density functional theory to understand this discrepancy and found that H adsorption energies on the covalently functionalized Ni2P also do not follow the electrostatic trend and are predictive descriptors of the experimental results.
Ultra-small PbS nanocrystals as sensitizers for red-to-blue triplet-fusion upconversion
Authors: Imperiale Christian J. , Green Philippe B. , Hasham Minhal , Wilson Mark W.B.
Published: February 2022

Photon upconversion is a strategy to generate high-energy excitations from low-energy photon input, enabling advanced architectures for imaging and photochemistry. Here, we show that ultra-small PbS nanocrystals can sensitize red-to-blue triplet-fusion upconversion with a large anti-Stokes shift (ΔE=1.04 eV), and achieve max-efficiency upconversion at near-solar fluences (Ith=220 mW/cm2) despite endothermic triplet sensitization. This system facilitates the photo-initiated polymerization of methylmethacrylate using only long-wavelength light (λ: 637 nm); a demonstration of nanocrystal-sensitized upconversion photochemistry. Time-resolved spectroscopy and kinetic modelling clarify key loss channels, highlighting the benefit of long-lifetime nanocrystal sensitizers, but revealing that many (48%) excitons that reach triplet-extracting carboxyphenylanthracene ligands decay before they can transfer to free-floating acceptors—emphasizing the need to address the reduced lifetimes that we determine for molecular triplets near the nanocrystal surface. Finally, we find that the inferred thermodynamics of triplet sensitization from these ultra-small PbS quantum dots are surprisingly favourable—completing an advantageous suite of properties for upconversion photochemistry—and do not vary significantly across the ensemble, which indicates minimal effects from nanocrystal heterogeneity. Together, our demonstration and study of red-to-blue upconversion using ultra-small PbS nanocrystals in a quasi-equilibrium sensitization scheme offer design rules to advance implementations of triplet fusion, especially where large anti-Stokes wavelength shifts are sought.
Accelerating AutoDock VINA with GPUs
Authors: Shidi Tang , Ruiqi Chen , Mengru Lin , Qingde Lin , Yanxiang Zhu , Jiansheng Wu , Haifeng Hu , Ming Ling
Published: February 2022

AutoDock VINA is one of the most-used docking tools in the early stage of modern drug discovery. It uses a Monte-Carlo based iterated search method and multithreading parallelism scheme on multicore machines to improve docking accuracy and speed. However, virtual screening from huge compound databases is common for modern drug discovery, which puts forward a great demand for higher docking speed of AutoDock VINA. Therefore, we propose a fast method VINA-GPU, which expands the Monte-Carlo based docking lanes into thousands of ones coupling with a largely reduced number of search steps in each lane. Furthermore, we develop a heterogeneous OpenCL implementation of VINA-GPU that leverages thousands of computational cores of a GPU, and obtains a maximum of 403-fold acceleration on docking runtime when compared with a quad-threaded AutoDock VINA implementation. In addition, a heuristic function was fitted to determine the proper size of search steps in each lane for a convenient usage. The VINA-GPU code can be freely available at https://github.com/DeltaGroupNJUPT/VINA-GPU for academic usage.
Peculiar anharmonicity of Ruddlesden Popper metal halides: Temperature-dependent phonon dephasing
Authors: Rojas Gatjens Esteban , Silva Acuña Carlos , Srimath Kandada Ajay Ram
Published: February 2022

The anharmonicity of the Ruddlesden Popper metal-halide lattice, and its consequences on their electronic and optical properties, is paramount in their basic semiconductor physics. It is thus critical to identify specific anharmonic optical phonons that govern their photophysics . Here, we address the nature of phonon-phono scattering probabilities of the resonantly excited optical phonons that dress the electronic transitions in these materials by means of variable-temperature resonant impulsive stimulated Raman measurements. Based on the temperature dependence of the coherent phonon lifetimes, we isolate the dominant anharmonic phonon and quantify its phonon-phonon interaction strength. Intriguingly, we also observe that the anharmonicity is distinct for different phonons, with a few select modes exhibiting temperature-independent coherence lifetimes, indicating their predominantly harmonic nature. However, the population and dephasing dynamics of excitons are dominated by the anharmonic phonon.
Diffuson-mediated thermal and ionic transport in superionic conductors
Authors: Bernges Tim , Hanus Riley , Wankmiller Bjoern , Imasato Kazuki , Lin Siqi , Ghidiu Michael , Gerlitz Marius , Peterlechner Martin , Graham Samuel , Hautier Geoffroy , Pei Yanzhong , Hansen Michael Ryan , Wilde Gerhard , Snyder G. Jeffrey , George Janine , Agne Matthias , Zeier Wolfgang
Published: February 2022

Ultra-low lattice thermal conductivity as often found in superionic compounds is greatly beneficial for thermoelectric performance, however, a high ionic conductivity can lead to device degradation. Conversely, high ionic conductivities are searched for materials in solid-state battery applications. It is commonly thought that ionic transport induces low thermal conductivity and that ion and thermal transport are not completely independent properties of a material. However, no direct comparison or underlying physical relationship has been shown between the two. Here we establish that ionic transport can be varied independent of thermal transport in Ag+ superionic conductors, even though both phenomena arise from atomic vibrations. Thermal conductivity measurements, in conjunction with two-channel lattice dynamics modeling, reveals that the vast majority of Ag+ vibrations have non-propagating diffuson-like character, which provides a rational for how these two transport properties can be independent. Our results provide conceptually novel lattice dynamical insights to ionic transport and confirm that ion transport is not a requirement for ultra-low thermal conductivity. Consequently, this work bridges the fields of solid state ionics and thermal transport, thus providing design strategies for functional ionic conducting materials from a vibrational perspective.
Strong bidentate coordination for surface passivation and ligand-shell engineering of lead halide perovskite nanocrystals in the strongly quantum confined regime
Authors: Malinoski Aaron , Hu Guoxiang , Wang Chen
Published: February 2022

The surface of lead halide perovskite nanocrystals (PNCs) is unique compared to conventional metal chalcogenide or pnictogenide semiconductor nanoparticles for its ionic character and the dynamic ligand layer, which makes them unstable in stock solutions and hinders the development of surface engineering strategies. This work employs a chelating strategy to form stable coordination on the PNC surface. Through screening a series of heterocyclic aromatic carboxylates, we found the best ligand, picolinate (PIC), with exceptional passivation effect to the surface traps of CsPbBr3 PNCs in the strongly quantum confined regime, resulting in > 0.8 photoluminescence quantum yields. The exciton lifetime in the passivated PNC approaches the radiative decay limit in various solvents. From an NMR titration experiment, the binding affinity of PIC is estimated to be at least 15 to 30 folds stronger than the original ligand from synthesis. The NMR and FTIR spectroscopic data and first-principles calculations elucidate the bidentate nature of the PIC coordination at the surface Pb site and the coadsorption of the ammonium-PIC ion pair. In apolar solvents, such as cyclohexane, the binding of PIC is stoichiometric to the available surface sites, suggesting the structure as a potent candidate for anchoring functional molecular structures to the PNC surface. In polar solvents, the strong affinity of PIC on the PNC surface provides protection for carrying out the precipitation-redissolution purification procedure that removes synthetic residual from the as-synthetic PNC samples. By modifying the purification procedure, we also develop a cation exchange procedure to replace the original oleylammonium cation with desired structures that consist of an ammonium anchoring group. Our results provide a direction for constructing strong interactions to protect the vulnerable surface of PNCs and pave the road for developing surface engineering strategies to functionalize these nanoparticles.
Screening for inhibitors of main protease in SARS-CoV-2: in silico and in vitro approach avoiding secondary amides
Authors: Yamamoto Kazuki , Yasuo Nobuaki , Sekijima Masakazu
Published: February 2022

In addition to vaccines, antiviral drugs are essential for suppressing COVID-19. Although several inhibitor candidates were reported for SARS-CoV-2 main protease, most are highly polar peptidomimetics with poor oral bioavailability and cell membrane permeability. Here, we conducted structure-based virtual screening and in vitro assays to obtain hit compounds belonging to a new chemical space excluding secondary amides. In total, 180 compounds were subjected to the primary assay at 20 μM, and nine compounds with inhibition rates higher than 5% were obtained. The IC50 of six compounds was determined in dose-response experiments, with the values on the order of 10-4 μM. Although nitro groups were enriched in the substructure of the hit compounds, they did not significantly contribute to the binding interaction in the predicted docking poses. Physicochemical properties prediction showed good oral absorption. These new scaffolds are promising candidates for future optimization.
Characterization of Cisplatin/Membrane Interactions by QM/MM Energy Decomposition Analysis
Authors: Cárdenas Gustavo , Pérez-Barcia Álvaro , Mandado Marcos , Nogueira Juan J.
Published: February 2022

The intermolecular interactions established between anticancer drugs and lipid membranes play a key role in the permeation mechanism of the drugs inside the cells. Herein we extend a quantum mechanical energy decomposition analysis scheme based on deformation electron densities to a hybrid multiscale electrostatic embedding quantum mechanics/molecular mechanics (QM/MM) framework, and apply it to characterize the interactions between the cisplatin drug and a dioleyl-phosphatidylcholine lipid membrane. The interaction energy decomposition into electrostatic, induction, dispersion and Pauli repulsion contributions is performed for ensembles of geometries taken from molecular dynamics simulations to account for conformational sampling and, thus, obtain a distribution of each of the energy components. Contrary to a previous energy decomposition using force fields, it is evidenced that the electrostatic component is predominant in both polar and non-polar regions of the bilayer, and the repulsive component is strong when considered quantum mechanically, while being largely underestimated by the force field.
Strategies for the De Novo Synthesis of Highly Substituted Pyridine Scaffolds: Unified Total Synthesis of the Limonoid Alkaloids
Authors: Newhouse Timothy , Schuppe Alexander , Liu Yannan , Zhao Yizhou , Ibarran Sebastian , Huang David , Wang Emma , Lee Jaehoo , Loria Patrick
Published: February 2022

Highly substituted pyridine scaffolds are found in many biologically active natural products and therapeutics. Accordingly, numerous complementary de novo approaches to obtain differentially substituted pyridines have been disclosed. This article delineates the evolution of the synthetic strategies designed to assemble the demanding tetrasubstituted pyridine core present in the limonoid alkaloids isolated from Xylocarpus granatum, including xylogranatopyridine B, granatumine A and related congeners. The most efficient and convergent construction of the core framework present in xylogranatopyridine B involved a Liebeskind pyridine synthesis and late-stage benzylic oxidation. By contrast, the synthesis of the bislactone limonoid alkaloids, such as granatumine A which exhibited moderate PTP1B-inhibitory activities, necessitated the development of a novel pyran-to-pyridine conversion. In addition, NMR calculations suggested structural misassignment of several limonoid alkaloids, and predicted their C3-epimers as the correct structures, which was further validated unequivocally through chemical synthesis. While preliminary results of the pNPP assays showed that these bislactone limonoid alkaloids were only weakly inhibitory against PTP1B, C3-deoxy-xylogranatin F, an unnatural synthetic analog, was demonstrated to be more potent than the other congeners.
Principles of Melting in Hybrid Organic-Inorganic Perovskite and Polymorphic ABX3 Structures
Authors: Kumar Shaw Bikash , Castillo-Blas Celia , Thorne Michael , Gómez Maria Laura Rios , Forrest Tom , Lopez Maria Diaz , Chater Philip , McHugh Lauren , Keen David , bennett thomas
Published: February 2022

Four novel dicyanamide-containing hybrid organic-inorganic ABX3 structures are reported, and the thermal behaviour of a series of nine perovskite and non-perovskite ABX3 structures in total are analysed. Structure-property relationships are investigated by varying both A-site organic and B-site transition metal cations. The introduction of larger tetraalkylammonium cations into the A-site reduces the melting temperature, and raises the Tolerance Factor. Total scattering methods are used to provide a greater understanding of the melting mechanism.
Protective Effect of Starch-stabilized Selenium Nanoparticles against Melamine-induced Hepato-renal Toxicity in Male Albino Rats
Authors: Ahmed Zainab Sabry Othman , Galal Mona K. , Drweesh Elsayed A. , Abou-El-Sherbini Khaled S. , Elzahany Eman A.M. , Elnagar Mohamed , Yasin Noha A. E.
Published: February 2022

Melamine and its analogues are illegally added to raise the apparent protein content in foods. The elevated concentrations of these compounds cause adverse effects in humans and animals. In this contribution, the protective effects of the synthesized starch-stabilized selenium nanoparticles (Se-NPs@starch) on melamine-induced hepato-renal toxicity have been systematically investigated. The Se-NPs@starch were characterized by X-ray photoelectron spectroscopy (XPS) analysis, energy dispersive spectroscopy (EDS) mapping analysis, TEM, and FT-IR. Starch plays a crucial role in the stabilization and dispersion of Se NPs, as noticed from the TEM and EDS investigations. Furthermore, the atomic ratio of Se distribution over the starch surface is approximately 1.67%. The current study was conducted on four groups of adult male rats, and the oral daily treatments for 28 days were as follows: group I served as control, group II received Se-NPs@starch, group III was exposed to melamine, while group IV was treated with melamine and Se-NPs@starch. The results reveal a significant alteration in the histoarchitecture of both hepatic and renal tissues induced by melamine. Furthermore, elevated liver and kidney function markers, high malondialdehyde, and increased expression levels of apoptosis-related genes besides a reduction in GSH and expression levels of antioxidant genes were observed in the melamine-exposed group. Interestingly, the administration of the Se-NPs@starch resulted in remarkable protection of rats against melamine-induced toxicity through increasing the antioxidant capacity and inhibiting oxidative damage. Collectively, this study provides affordable starch-stabilized Se-NPs with potent biological activity, making them auspicious candidates for prospective biomedical applications.
Using wide biological pores to cap and contain the COVID-19 spike protein
Authors: Sampath G
Published: February 2022

Geometric analysis shows that the spike (S) protein in the COVID-19 virus (SARS-Cov-2) can fully or partially enter into the channel of a wide biological pore like perforin (PFN) or streptolysin (SLO) when the latter is anchored in a bilayer lipid membrane. The PFN channel is a β barrel formed from multiple monomers, for example a ~14 nm diameter channel is formed from 22 monomers. Coincidentally the wide canopy of S (which has three identical chains) has an enclosing diameter of ~14 nm. While inside the channel peripheral residues in the canopy may bind with residues on the pore side of the barrel. If there are no adverse cross-reactions this would effectively prevent S from interacting with a target cell. Calculations with data obtained from PDB and other sources show that there are ~12 peripheral residue triples in S within a circle of diameter ~14 nm that can potentially bind with 22 exposed residues in each barrel monomer. The revised Miyazawa-Jernighan matrix is used to calculate the binding energy of canopy-PFN barrel residue pairs. The results show a large number of binding pairs over distances of up to 38 Å into the pore. This geometric view of capture and containment points to the possibility of using biological pores to neutralize SARS-Cov-2 in its many variant forms. Some necessary conditions that must be satisfied for such neutralization to occur are noted. A wide pore (such as PFN or SLO) can also be used in an electrolytic cell to detect the presence of SARS-Cov-2, which, by blocking the pore would cause a near total blockade of the base current (the ionic current in a fully open pore).
Anion binding to a cationic europium(III) probe enables the first real-time assay of heparan sulfotransferase activity
Authors: Wheeler Simon , Butler Stephen , Fernig David , Li Yong , Hewitt Sarah , Breen Colum , Robertson Erin
Published: February 2022

Sulfotransferases constitute a ubiquitous class of enzyme which are poorly understood due to the lack of a convenient tool for screening their activity. These enzymes use the anion PAPS (adenosine-3’-phosphate-5’-phosphosulfate) as a donor for a broad range of acceptor substrates, including carbohydrates, producing sulfated compounds and PAP (adenosine-3’,5’-diphosphate) as a side product. We present a europium(III)-based probe that binds reversibly to both PAPS and PAP, producing a larger luminescence enhancement with the latter anion. We exploit this greater emission enhancement with PAP to demonstrate the first direct real-time assay of a heparan sulfate sulfotransferase using multi-well plate format. The selective response of our probe towards structurally similar nucleoside phosphate anions, and over other anions, is investigated and discussed. This work opens the possibility of investigating more fully the roles played by this enzyme class in health and disease, including operationally simple inhibitor screening.
Protein unfolding in freeze frames: intermediate states are revealed by variable temperature ion mobility-mass spectrometry.
Authors: Ujma Jakub , Jhingree Jacquelyn , Norgate Emma , Upton Rosie , Wang Xudong , Benoit Florian , Bellina Bruno , Barran Perdita
Published: February 2022

The gas phase is an idealized laboratory for the study of protein structure, from which it is possible to examine stable and transient forms of mass selected ions in the absence of bulk solvent. With ion mobility-mass spectrometry (IM-MS) apparatus built to operate at both cryogenic and elevated temperatures, we have examined the conformational transitions of the monomeric proteins: ubiquitin, lysozyme and alpha-synuclein as a function of temperature and in source activation. We rationalize the experimental observations with a temperature dependent framework model and comparison to known conformers. Data from ubiquitin shows unfolding transitions that proceed through diverse and highly elongated intermediate states, which converge to more compact structures. These findings contrast with data obtained from lysozyme – a protein where (un)-folding plasticity is restricted by four disulfide linkages, although this is alleviated in its reduced form. For structured proteins, collision activation of the protein ions in- source, enables subsequent “freezing” or thermal annealing of unfolding intermediates whereas disordered proteins restructure substantially at 250 K even without activation, indicating that cold denaturation can occur without solvent. These data are presented in the context of a toy model framework which describes the relative occupancy of the available conformational space.
Broadening the scope of uranyl photoreactivity: The oxidation of a uranyl complex anion in solid-state materials
Authors: Herder Jordan A. , Nicholas Aaron D. , Cahill Christopher L.
Published: February 2022

Reported are the syntheses, structural characterizations and luminescence properties of three novel [UO2Cl4]2 bearing compounds containing substituted 1,1’-dialkyl-4,4’-bipyridinum dications (i.e. viologens). These compounds undergo photoinduced luminescence quenching upon exposure to UV radiation. Kinetic analyses indicate the degree of quenching follows a second-order rate law with a rate constant dependent on viologen substituent. This phenomenon is proposed to involve the formal transfer of one electron from the [UO2Cl4]2- to the viologen species. This proposed mechanism is supported through a series of calculations and computational work including Rehm-Weller analysis, time-dependent density functional theory (TD-DFT), and density of states (DOS). This work constitutes the first study of an oxidized uranyl complex anion which expands the conventional understanding of uranyl photoreactivity.
Molecular prosthetics for long-term functional imaging with fluorescent reporters
Authors: Grenier Vincent , Martinez Kayli , Benlian Brittany , Garcia-Almedina Derek , Raliski Benjamin , Boggess Steven , Maza Johnathan , Yang Samantha , Miller Evan
Published: February 2022

Voltage-sensitive fluorescent reporters can reveal fast changes in membrane potential in neurons and cardiomyocytes. However, in many cases, illumination in the presence of the fluorescent reporters results in disruptions to action potential shape that limits the length of recording sessions. We show here that a molecular prosthetic approach, previously limited to fluorophores, rather than indicators, can be used to substantially prolong imaging in neurons and cardiomyocytes.
Explaining and avoiding failures modes in goal-directed generation
Authors: Langevin Maxime , Vuilleumier Rodolphe , Bianciotto Marc
Published: February 2022

Despite growing interest and success in automated in-silico molecular design, doubts remain regarding the ability of goal-directed generation algorithms to perform unbiased exploration of novel chemical spaces. A specific phenomenon has recently been highlighted: goal-directed generation guided with machine learning models produce molecules with high scores according to the optimization model, but low scores according to control models, even when trained on the same data distribution and the same target. In this work, we show that this worrisome behavior is actually due to issues with the predictive models and not the goal-directed generation algorithms. We show that with appropriate predictive models, this issue can be resolved, and molecules generated have high scores according to both the optimization and the control models.
Model agnostic generation of counterfactual explanations for molecules
Authors: Wellawatte Geemi P , Seshadri Aditi , White Andrew D
Published: February 2022

An outstanding challenge in deep learning in chemistry is its lack of interpretability. The inability of explaining why a neural network makes a prediction is a major barrier to deployment of AI models. This not only dissuades chemists from using deep learning predictions, but also has led to neural networks learning spurious correlations that are difficult to notice. Counterfactuals are a category of explanations that provide a rationale behind a model prediction with satisfying properties like providing chemical structure insights. Yet, counterfactuals are have been previously limited to specific model architectures or required reinforcement learning as a separate process. In this work, we show a universal model-agnostic approach that can explain any black-box model prediction. We demonstrate this method on random forest models, sequence models, and graph neural networks in both classification and regression.
Synthesis of 4-Chloro-1,3-Diazobenzene Bent-Cores Liquid Crystal and Characterizations of Its Mesogenic Behaviors and Photosensitivity
Authors: Zhang Zelong , Lu Jinying , Yan Daoren , Zhang Zhiyong , Guan Jintao , Qiao Junfei
Published: February 2022

In this study, a series of novel compounds were synthesized by adding azo functional groups and chlorine substituent to the central bent-cores to form a 4-chloro-1,3-dizaophenylene bent-core. The structure, mesogenic properties, and photosensitivity of these synthesized compounds were evaluated experimentally. The results show that these compounds exhibit a broad temperature window up to 63.8 °C for nematic phase and fast trans – cis photoisomerization in seconds with 80% conversion. Quantum mechanics modeling confirms that using azos as the central linkages can effectively reduce the molecular dipole moment, which appears to promote favorable mesogenic behaviors and photonic characteristics. Moreover, varying the carbon number in the terminal alkyl chains can alter molecular dipole, especially the polarizability anisotropy, of which the variation is strongly correlated with the phase transition temperature and temperature range of nematic phase. These findings suggest that reducing molecular dipole can promote favorable mesogenic and photonic properties.
Synthesis, Characterization, and Effects of Molecular Structure on Phase Behavior of 4-Chloro-1,3-Diazobenzene Bent-Core Liquid Crystals with High Photosensitivity
Authors: Lu Jinying , Yan Daoren , Zhang Zhiyong , Zhang Zelong
Published: February 2022

In this study, a series of novel compounds were synthesized by adding azo functional groups and chlorine substituent to the central bent-cores to form a 4-chloro-1,3-dizaophenylene bent-core. The structure, mesogenic properties, and photosensitivity of these synthesized compounds were evaluated experimentally. The results show that these compounds exhibit a broad temperature window up to 63.8 °C for nematic phase and fast trans – cis photoisomerization in seconds with 80% conversion. Quantum mechanics modeling confirms that using azos as the central linkages can effectively reduce the molecular dipole moment, which appears to promote favorable mesogenic behaviors and photonic characteristics. Moreover, varying the carbon number in the terminal alkyl chains can alter molecular dipole, especially the polarizability anisotropy, of which the variation is strongly correlated with the phase transition temperature and temperature range of nematic phase. These findings suggest that reducing molecular dipole can promote favorable mesogenic and photonic properties.
Structural insight into an atomic layer deposition (ALD) grown Al2O3 layer on Ni/SiO2: impact on catalytic activity and stability in dry reforming of methane
Authors: Sungmin Kim , Andac Armutlulu , Liao Wei-Chih , Hosseini Davood , Stoian Dragos , Chen Zixuan , Abdala Paula , Copéret Christophe , Müller Christoph Rüdiger
Published: February 2022

The development of stable Ni-based dry reforming of methane (DRM) catalysts is a key challenge owing to the high operating temperatures of the process and the propensity of Ni for promoting carbon deposition. In this work, Al2O3-coated Ni/SiO2 catalysts have been developed by employing atomic layer deposition (ALD). The structure of the catalyst at each individual preparation step was characterized in detail through a combination of in situ XAS-XRD, ex situ 27Al NMR and Raman spectroscopy. Specifically, in the calcination step, the ALD-grown Al2O3 layer reacts with the SiO2 support and Ni, forming aluminosilicate and NiAl2O4. The Al2O3-coated Ni/SiO2 catalyst exhibits an improved stability for DRM when compared to the benchmark Ni/SiO2 and Ni/Al2O3 catalysts. In situ XAS-XRD during DRM together with ex situ Raman spectroscopy and TEM of the spent catalysts confirm that the ALD-grown Al2O3 layer suppresses the sintering of Ni, in turn reducing also coke formation significantly. In addition, the formation of an amorphous aluminosilicate phase by the reaction of the ALD-grown Al2O3 layer with the SiO2 support inhibited catalysts deactivation via NiAl2O4 formation, in contrast to the reference Ni/Al2O3 system. The in-depth structural characterization of the catalysts provided an insight into the structural dynamics of the ALD-grown Al2O3 layer, which reacts both with the support and the active metal, allowing to rationalize the high stability of the catalyst under the harsh DRM conditions.
Breaking the aristotype: featurisation of polyhedral distortions in perovskite crystals
Authors: Morita Kazuki , Davies Daniel , Butler Keith , Walsh Aron
Published: February 2022

While traditional crystallographic representations of structure play an important role in materials science, they are unsuitable for efficient machine learning. A range of effective numerical descriptors have been developed for molecular and crystal structures. We are interested in a special case, where distortions emerge relative to an ideal high-symmetry parent structure. We demonstrate that irreducible representations form an efficient basis for the featurisation of polyhedral deformations with respect to such an aristotype. Applied to dataset of 552 octahedra in ABO3 perovskite-type materials, we use unsupervised machine learning with irreducible representation descriptors to identify four distinct classes of behaviour, associated with predominately corner, edge, face, and mixed connectivity between neighbouring octahedral units. Through this analysis, we identify SrCrO3 as a material with tuneable multiferroic behaviour.
A Theory-guided X-ray Absorption Spectroscopy Approach for Identifying Active Sites in Atomically Dispersed Transition Metal Catalysts
Authors: Chen Yizhen , Rana Rachita , Sours Tyler , VILA FERNANDO D. , Cao Shaohong , Blum Thomas , Hong Jiyun , Hoffman Adam , Fang Chia-Yu , Huang Zhennan , Shang Chunyan , Wang Chuanhao , Zeng Jie , Chi Miaofang , Kronawitter Coleman , Bare Simon , Gates Bruce , Kulkarni Ambarish
Published: February 2022

Atomically dispersed supported metal catalysts offer new properties and the benefits of maximized metal accessibility and utilization. The characterization of these materials, however, remains challenging. Using atomically-dispersed Pt supported on crystalline MgO (chosen for its well-defined bonding sites for Pt) as a prototypical example, in this work, we demonstrate how systematic density functional theory calculations (for assessing all the potentially stable Pt sites) combined with automated EXAFS analysis can lead to unbiased identification of isolated, surface-enveloped platinum cations as the catalytic species for CO oxidation. The catalyst has been characterized by atomic-resolution imaging, EXAFS, and HERFD-XANES spectroscopies; the proposed Pt site are in full agreement with experiment. This theory-guided workflow leads to rigorously determined structural models and provides a more detailed picture of the structure of the catalytically active sites than what is currently possible with conventional EXAFS analysis. As this approach is efficient and agnostic to the metal, support, and catalytic reaction, we posit that it will be of broad interest to the materials characterization and catalysis communities.
Relative Binding Free Energy Predictions for Inhibitors of Tetrameric Influenza Virus Neuraminidase
Authors: Williams-Noonan Billy J , Yuriev Elizabeth , Chalmers David K
Published: February 2022

Accurate methods to predict the free energies of protein-ligand interactions have great potential to assist rational drug design. In this work, we used molecular dynamics simulations with alchemical perturbation to predict the binding of carbohydrate-based ligands to influenza virus neuraminidase (N2). This specific drug target is a challenging test system for alchemical free energy methods because it has flexible binding site motifs. We use a molecular dynamics protocol that works for longer time scales than are often reported in previous molecular dynamics studies of N2. We demonstrated that N2-ligand complex stability and that accurate N2 150-loop dynamics, on a 350 ns time scale, are both force field-dependent (AMBER99SB-ILDN, GAFF and TIP4P water are required). Further, we showed that crystallographic waters must be retained to maintain stability of N2-ligand complexes over 350 ns. Using our modelling protocol, we were able to determine relative binding free energy values between neuraminidase ligands which correlated strongly with experimental differences in pIC50 values (R = -0.96, ρ = 0.86, N = 13, sig < 0.0001). It is anticipated that the molecular dynamics protocol and the relative binding free energy methods reported here, will both be useful in expediting the discovery of novel therapeutics for N2 and other homologous glycohydrolases.
From Photoredox Catalysis to the Direct Excitation of EthynylBenziodoXolones: Accessing Alkynylated Quaternary Carbons from Alcohols via Oxalates
Authors: Amos Stephanie G. E. , Cavalli Diana , Le Vaillant Franck , Waser Jerome
Published: February 2022

EthynylBenziodoXolones (EBXs) are commonly used as radical traps in photocatalytic alkynylations. Herein, we report their application in two complementary deoxygenation strategies allowing the synthesis of valuable alkynylated all-carbon quaternary centers from tertiary alcohols via stable oxalate salts. Our first approach involves a photocatalytic process using 4CzIPN as an organic dye to promote oxidative degradation of the oxalate and EBXs to trap the formed radical. In our second approach, we demonstrate the direct photoexcitation of an EBX, which then acts as both oxidant and radical trap, alleviating the need for a photocatalyst in several EBX-mediated alkynylation processes.
Open Science Discovery of Oral Non-Covalent SARS-CoV-2 Main Protease Inhibitors
Authors: Consortium The COVID Moonshot , Chodera John , Lee Alpha , London Nir , Delft Frank von
Published: February 2022

The COVID-19 pandemic is a stark reminder that a barren global antiviral pipeline has grave humanitarian consequences. Future pandemics could be prevented by accessible, easily deployable broad-spectrum oral antivirals and open knowledge bases that derisk and accelerate novel antiviral discovery and development. Here, we report the results of the COVID Moonshot, a fully open-science structure-enabled drug discovery campaign targeting the SARS-CoV-2 main protease. We discovered a novel chemical scaffold that is differentiated to current clinical candidates in terms of toxicity and pharmacokinetics liabilities, and developed it into orally-bioavailable inhibitors with clinical potential. Our approach leverages crowdsourcing, high throughput structural biology, machine learning, and exascale molecular simulations. In the process, we generated a detailed map of the structural plasticity of the main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. In a first for a structure-based drug discovery campaign, all compound designs (>18,000 designs), crystallographic data (>500 ligand-bound X-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2,400 compounds) for this campaign were shared rapidly and openly, creating a rich open and IP-free knowledgebase for future anti-coronavirus drug discovery.
Gender Distribution and Geography of Highly Cited Papers in ACS Catalysis
Authors: Szilvasi Tibor
Published: February 2022

Following the editorial series presented in ACS Catalysis in 2020, I investigated the gender distribution in highly cited ACS Catalysis papers. As a main result, I found that from the 155 highly cited papers that showed up in my analysis, only 15 papers have female corresponding author(s) (9.7%), and only 5 of these 15 papers have solely female corresponding author(s) (3.2%). I also analyzed geographical distribution and found that two new categories "Small Countries", including for example Cyprus, Greece, Iceland, and Ireland, and "Developing Countries", including Mexico, South Africa, Thailand, and Vietnam, provide significant contributions to ACS Catalysis, larger than Canada or UK, based on the defined metrics.
Biexciton Hamiltonian for the correlated triplet pair states in singlet fission: Revealing the contest between triplet-triplet exchange and triplet-triplet energy transfer coupling
Authors: Abraham Vibin , Mayhall Nicholas
Published: February 2022

The correlated triplet pair state 1(TT) is a key intermediate in the singlet fission process, and understanding the mechanism by which it separates into two independent triplet states is critical for leveraging singlet fission for improving solar cell efficiency. This separation mechanism is dominated by two key interactions: (i) the exchange interaction (K) between the triplets which leads to the spin splitting of the biexciton state into 1(TT),3(TT) and 5(TT) states, and (ii) the triplet-triplet energy transfer integral (t) which enables the formation of the spatially separated (but still spin entangled) state 1(T...T). In this work, we use simple ab inito calculations to compute the triplet-triplet exchange (K) and triplet-triplet energy transfer coupling (t). For a model 1D system, we show how these parameters affect the biexciton energy manifold using a steady state approximation. Our key findings reveal a new condition for successful correlated triplet pair state dissociation. If the K to t ratio is comparable to or less than one, biexction dissociation is favored for large chromophore assemblies. Additionally, for smaller chromophore assemblies, the biexciton exchange interaction needs to be negligible compared to the triplet energy transfer for favourable dissociation. We also explore the effect of chromophore packing to reveal geometries where the triplet energy transfer integral is significantly larger compared to the triplet-triplet exchange.