bluuebunny/crossref_metadata_2025 huggingface dataset:
One-Pot Synthesis of High-Capacity Silicon-Lithium Anodes via On-Copper Growth of a Semi-Conducting, Porous Polymer
Authors: Bojdys Michael J.
Published: February 2022

Silicon-based anodes with lithium ions as charge carriers have the highest predicted charge density of 3579 mA h g-1 (for Li15Si4). Contemporary electrodes do not achieve this theoretical value largely because conventional production paradigms rely on the mixing of weakly coordinated components. In this paper, a semi-conductive triazine-based graphdiyne polymer network is grown around silicon nanoparticles directly on the current collector, a copper sheet. The porous, semi-conducting organic framework (i) adheres to the current collector on which it grows via cooperative van der Waals interactions, (ii) acts effectively as conductor for electrical charges and binder of silicon nanoparticles via conjugated, covalent bonds, and (iii) enables selective transport of electrolyte and Li-ions through pores of defined size. The resulting anode shows extraordinarily high capacity at the theoretical limit of fully lithiated silicon. Finally, we combine our anodes in proof-of-concept battery assemblies using a conventional cathode, NCM811.
Using pH dependence to understand mechanisms in electrochemical CO reduction
Authors: Kastlunger Georg , Wang Lei , Govindarajan Nitish , Heenen Hendrik H. , Ringe Stefan , Jaramillo Thomas , Hahn Christopher , Chan Karen
Published: February 2022

Electrochemical conversion of CO(2) into hydrocarbons and oxygenates is envisioned as a promising path towards closing the carbon cycle in modern technology. To this day, however, the reaction mechanisms towards the plethora of products are disputed, complicating the search for novel catalyst materials. In order to conclusively identify the rate-limiting steps in CO reduction on Cu, we analyzed the mechanisms on the basis of constant potential DFT calculations and experiments at a wide range of pH values (3 - 13). We find that *CO dimerization is energetically favoured as the rate limiting step towards multi-carbon products. This finding is consistent with experiments, where the reaction rate is nearly unchanged on an SHE potential scale, even under acidic conditions. For methane, both theory and experiments indicate a change in the rate-limiting step with electrolyte pH from the first protonation step in acidic/neutral conditions to a later one in alkaline conditions. We also show, through a detailed analysis of the microkinetics, that a surface combination of *CO and *H is inconsistent with the measured current densities and Tafel slopes. Finally, we discuss the implications of our understanding for future mechanistic studies and catalyst design.
Sustainable Fiber-Based Materials as Super-bridging Agents, Adsorbents, and Ballast Media
Authors: Lapointe Mathieu , Jahandideh Heidi , Farner Jeffrey , Tufenkji Nathalie
Published: February 2022

Aggregation combined with gravitational separation is the most commonly used method to treat water globally, but it carries a significant economic and environmental burden as the chemicals used in the process (e.g., coagulants) generate ~8 million tons of metal-based sludge waste annually. To simultaneously deal with the issues of process sustainability, cost, and efficiency, we developed materials reengineered from pristine or waste fibers (e.g., cellulose, polyester, cotton, and keratin) to serve as super-bridging agents, adsorbents and ballast media. This study shows that these sustainable materials (fibers, microspheres, and flakes functionalized with Si, Al and/or Fe) considerably increased the floc size (~6630 µm) compared to conventional physicochemical treatment (~520 µm; using alum and polyacrylamide). The fiber-based materials also reduced chemical usage (20–60 %) and improved contaminant removal during settling by increasing floc size and density. Moreover, the unprecedented size of flocs produced using fiber-based materials (13 times larger compared to conventional treatment) enabled easy floc removal by screening, thereby eliminating the need for a settling tank, a large and costly process unit used to treat more than 70% of water globally. Our results show that fiber-based materials can be effective solutions at removing classical (e.g., natural organic matter (NOM) and phosphorus, via electrostatic affinities) and emerging contaminants (e.g., microplastics and nanoplastics). Due to their large size (> 3000 µm), some Si-grafted and Fe-grafted fiber-based materials were easily recovered from settled/screened sludge and reused multiple times for coagulation/flocculation. These reusable materials combined with separation via screening could allow global water treatment facilities to reduce their capital and operating costs as well as their environmental footprint. Finally, our results also show that these materials could be used in synergy with coagulants and flocculants to improve existing water treatment plants for the removal of NOM, phosphorus, turbidity, total suspended solids and microplastics.
Universal Nanopore Platform Integrating Multiple Resistive Pulse Sensors into a Single Microfluidic Device
Authors: pollard marcus , Maugi Rhushabh , Holzinger Angelika , Scanlon Micheal , Platt Mark
Published: February 2022

Resistive pulse sensors have been used to characterise everything from whole cells to small molecules. Their integration into microfluidic devices have simplified sample handling whilst increasing throughput. Typically, these devices measure a limited size range or a specific analyte, making them prone to blockages in complex sample matrixes. To prolong their life and facilitate their use, samples are often filtered or prepared to match the sample with the sensor diameter. Here, we advance our tuneable flow resistive pulse sensor which utilises additively manufactured parts. The sensor allows parts to be easily changed, washed and cleaned, its simplicity and versatility allows components from existing nanopore fabrication techniques such as silicon nitride, polyurethane and glass pipettes to be integrated into a single device. This creates a multi-nanopore sensor that can simultaneously measure particles from 0.1 to 30 m in diameter. The orientation and controlled fluid flow in the device allows the sensors to be placed in series, whereby smaller particles can be measured in the presence of larger ones without the risk of being blocked. We demonstrate the device with a range of nanopore materials commonly found within the literature, the easiest to set up was the pulled glass pipette and glass nanopore membrane. However, the glass nanopore membrane was by far the most robust and reusable component tested. We illustrate the concept of a multi-pore flow resistive pulse sensor, by combining an additively manufactured tuneable sensor, termed sensor 1, with a fixed nanopore sensor, termed sensor 2. Sensor 1 measures particles 2 to 30 m in diameter, whilst sensor 2 can be used to characterise particles as small as 100 nm, depending upon its dimensions.
Unravelling the impact of Ta doping on the electronic and structural properties of titania: A combined theoretical and experimental approach
Authors: Kumaravel Vignesh , Maccioni Maria Barbara , Mathew Snehamol , Hinder Steven , Bartlett John , Nolan Michael , Pillai Suresh
Published: February 2022

The introduction of new energy levels in the forbidden band through the doping of metal ions is an effective strategy to improve the thermal stability of TiO2. In the present study, the impact of Ta doping on the anatase to rutile transition (ART), structural characteristics, anion and cation vacancy formation were investigated in detail using Density Functional Theory (DFT) and experimental characterisation including, X-ray diffraction (XRD), Raman, and X-ray photoelectron spectroscopy (XPS). The average crystallite size of TiO2 decreases with an increase in the Ta concentration. At high temperatures, more oxygen atoms entered the crystal lattice and occupy the vacancies, leading to lattice expansion. Importantly, we find that Ta doping preserved the anatase content of TiO2 up to annealing temperatures of 850 °C which allows anatase stability to be maintained at typical ceramic processing temperatures. The substitution of Ti4+ by the Ta5+ ions increased the electron concentration in the crystal lattice through formation of Ti3+ defect states. Raman studies revealed the formation of new Ta bonds via disturbing the Ti-O-Ti bonds in the crystal lattice. It is concluded that under the oxidising conditions, Ta5+ ions could be enhanced on Ta-TiO2 surface due to the slow diffusion kinetics.
Amorphous mesoporous calcium carbonate and magnesium carbonate as effective sorbents for the removal of phosphate in aqueous solutions
Authors: Croket Eveline , Åhlén Michelle , Strømme Maria , Cheung Ocean
Published: February 2022

In this work, highly porous amorphous calcium carbonate (HPACC) and mesoporous magnesium carbonate (MMC) were tested as potential phosphate (PO43-) sorbents in water. The performance of these sorbents at a PO43- initial concentration between 0 – 1000 mg/L was evaluated. These highly porous materials were found to have enhanced PO43- uptake at low concentrations (<100 mg/L) when compared with commercial CaCO3 and MgCO3. The enhanced uptake on HPACC and MMC at low concentration was due to the high surface area and the porosity of these sorbents. The presence of NaCl salt of up to 1000 mg/L had very little effect on the performance of HPACC (<10% decreased uptake capacity), but the PO43- uptake on MMC reduced to close to zero. HPACC with its high PO43- uptake at low concentration could be relevant for real life application of PO43- ions removal from water.
Double Excitations in Molecules from Ensemble Density Functionals: Theory and Approximations
Authors: Gould Tim , Kronik Leeor , Pittalis Stefano
Published: February 2022

Double excitations, which are dominated by a Slater-determinant with both electrons in the highest occupied molecular orbital promoted to the lowest unoccupied orbital(s), pose significant challenges for low-cost electronic structure calculations based on density functional theory (DFT). Here, we demonstrate that recent advances in ensemble DFT [{\it Phys. Rev. Lett.} {\bf 125}, 233001 (2020)], which extend concepts of ground-state DFT to excited states via a rigorous physical framework based on the ensemble fluctuation-dissipation theorem, can be used to shed light on the double excitation problem. We find that the exchange physics of double excitations is reproducible by standard DFT approximations using a linear combination formula, but correlations are more complex. In passing, to analyze correlation, we extend the random-phase approximation to ensembles. We then show, using selected test systems, that standard DFT approximations may be adapted to tackle double excitations based on theoretically motivated simple formulae that employ ensemble extensions of expressions that use the on-top pair density.
Mechanochemical Nucleophilic Substitution of Alcohols via Isouronium Intermediates
Authors: Dalidovich Tatsiana , Varma Nallaparaju Jagadeesh , Shalima Tatsiana , Aav Riina , Kananovich Dzmitry G.
Published: February 2022

An expansion of the solvent-free synthetic toolbox is essential for advances in the sustainable chemical industry. Mechanochemical reactions offer a superior safety profile and reduced amount of waste compared to conventional solvent-based synthesis. Herein we report a new mechanochemical method for nucleophilic substitution of alcohols using fluoro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (TFFH) and K2HPO4 as an alcohol-activating reagent and a base, respectively. Alcohol activation and reaction with a nucleophile were performed in one milling jar via reactive isouronium intermediates. Nucleophilic substitution with amines afforded alkylated amines in 40–91% yields. The complete stereoinversion occurred for the SN2 reaction of (R)- and (S)-ethyl lactates. Substitution with halide anions (F−, Br−, I−) and oxygen-centered (CH3OH, PhO−) nucleophiles was also tested. Application of the method to the synthesis of active pharmaceutical ingredients (APIs) has been demonstrated.
Synthesis and Use of Versatile [1.1.1]Bicyclopentylaldehyde Building Blocks
Authors: Lasányi Dániel , Máth Dániel , Tolnai Gergely L.
Published: February 2022

The [1.1.1] bicyclopentane (BCP) motif is an emerging scaffold in medicinal chemistry due to its bioisosterism to 1,4-phenylene and 1,2-alkynyl functions. Current drawback of their use is the lack of stable versatile synthetic building blocks. Aldehydes are amongst the most useful functionalities in organic chemistry. In this paper a simple one-pot procedure from aryl-halides and [1.1.1]propellane is described. Preparation of various BCP molecules is conducted to showcase the versatility of these stable in-termediates.
High Resolution Photoelectron Spectroscopy of Vibrationally Excited OHˉ
Authors: DeWitt Marty , Babin Mark , Neumark Daniel
Published: February 2022

The effect of vibrational pre-excitation of anions on their photoelectron spectra is explored, combining slow photoelectron velocity-map imaging of cryogenically cooled anions (cryo-SEVI) with tunable IR radiation to pre-excite the anions. This new IR cryo-SEVI method is applied to OHˉ as a test system, where the R(0) transition of the hydroxyl anion (3591.53 cm-1) is pumped. Vibrational excitation induces a 30% depletion in photodetachment signal from the v = 0, J = 0 ground state of the anion and the appearance of all five allowed photodetachment transitions from the v = 1, J = 1 rovibrational level, each with peak widths between 1-2 cm-1. By scanning the IR laser, IR cryo-SEVI can also serve as a novel action technique to obtain the vibrational spectrum of OHˉ, giving an experimental value for the R(0) transition of 3591(1.2) cm-1.
Synthesis and styrene copolymerization of some ethyl phenylcyanoacrylates
Authors: Cupid Raven-Kiera M. , Leitao Reese C. , Stewart Josiah D. , Turski Michael J. , Rocus Sara , Schjerven William S. , Kharas Gregory
Published: February 2022

Novel styrene copolymers with ring-substituted ethyl phenylcyanoacrylates, RPhCH=C(CN)CO2C2H5 (where R is 2-ethyl, 2-ethoxy, 4-benzyloxy, 2,3-dimethyl) were prepared in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis, being between 18.3 and 42.3 mol% of the acrylate monomer units.
Enabling modular autonomous feedback-loops in materials science through hierarchical experimental laboratory automation and orchestration
Authors: Rahmanian Fuzhan , Flowers Jackson , Guevarra Dan , Richter Matthias , Fichtner Maximilian , Gregoire John , Stein Helge Sören
Published: February 2022

Materials acceleration platforms (MAPs) operate on the paradigm of integrating combinatorial synthesis, high-throughput characterization, automatic analysis, and machine learning. Within these MAPs, one or multiple autonomous feedback loops may aim to optimize materials for certain functional properties or generate new insights. The scope of a given experiment campaign is defined by the range of experiment and analysis actions that are integrated into the experiment framework. Herein we present a method for integrating many actions within a hierarchical experimental laboratory automation and orchestration (HELAO) framework. We demonstrate the capability of orchestrating distributed research instruments that can incorporate data from experiments, simulations, and databases. HELAO interfaces laboratory hardware and software that are distributed across several computers and operating systems for executing experiments, data analysis, provenance tracking, and autonomous planning. Parallelization is an effective approach for accelerating knowledge generation provided that multiple instruments can be effectively coordinated, which we demonstrate with parallel electrochemistry experiments orchestrated by HELAO. Efficient implementation of autonomous research strategies requires device sharing, asynchronous multithreading, and full integration of data management in experiment orchestration, which to the best of our knowledge, is demonstrated for the first time herein.
Enhancing the Throughput of FT Mass Spectrometry Imaging Using Compressed Sensing and Subspace Modeling
Authors: Xie Yuxuan Richard , Castro Daniel C. , Rubakhin Stanislav S. , Sweedler Jonathan V. , Lam Fan
Published: February 2022

Mass spectrometry imaging (MSI) allows for untargeted mapping of the chemical compositions of tissues with attomole detection limits. MSI using Fourier transform-based mass spectrometers, such as FT-ion cyclotron resonance (FT-ICR), grants the ability to examine the chemical space with unmatched mass resolution and mass accuracy. However, direct imaging of large tissue samples on FT-ICR is restrictively slow. In this work, we present an approach that combines the subspace modeling of ICR temporal signals with compressed sensing to accelerate high-resolution FT-ICR MSI. A joint subspace and sparsity constrained reconstruction enables the creation of high-resolution imaging data from the sparsely sampled and short-time acquired transients. Simulation studies and experimental implementation of the proposed acquisition in investigation of brain tissues demonstrate a factor of 10 enhancement in throughput of FT-ICR MSI, without the need for instrumental or hardware modifications.
The transfer and persistence of metals in latent fingermarks
Authors: Boseley Rhiannon , Howard Daryl , Hackett Mark , Lewis Simon
Published: February 2022

In forensic science, knowledge and understanding of material transfer and persistence is inherent to the interpretation of trace evidence and can provide vital information on the activity level surrounding a crime. Detecting metal ions in fingermark residue has long been of interest in the field of forensic science, due to the possibility of linking trace metal ion profiles to prior activity with specific metal objects (e.g. gun or explosive handling). Unfortunately, the imaging capability to visualise trace metal ions at sufficient spatial resolution to determine their distribution within a fingermark (micron level) was not previously available. Here, we demonstrate for the first time transfer and persistence of metals in fingermarks, at micron spatial resolution, using synchrotron sourced x-ray fluorescence microscopy. Fingermarks were taken before and after brief handling of a gun barrel, ammunition cartridge case and party sparkler to demonstrate the transfer of metals. The results reveal increased metal content after contact with these objects, and critically, a differential pattern of metal ion increase was observed after handling different objects. Persistence studies indicate that these metals are removed as easily as they are transferred, with a brief period of hand washing appearing to successfully remove metallic residue from subsequent fingermarks. Preliminary work using x-ray absorption near edge structure spectroscopic mapping highlighted the potential use of this technique to differentiate between different chemical forms of metals and metal ions in latent fingermarks. It is anticipated that these findings can now be used to assist future work for the advancement of trace metal detection tests and fingermark development procedures
PySMILESUtils – Enabling deep learning with the SMILES chemical language
Authors: Bjerrum Esben , Rastemo Tobias , Irwin Ross , Kannas Christos , Genheden Samuel
Published: February 2022

Recent years have seen a large interest in using the Simplified Molecular Input Line Entry System (SMILES) chemical language as input for deep learning architectures solving chemical tasks. Many successful applications have been demonstrated within de novo molecular design, quantitative structure-activity relationship modelling, forward reaction prediction and single-step retrosynthetic planning as examples. PySMILESUtils aims to enable these tasks by providing readyto- use and adaptable Python classes for tokenization, augmentation, dataset, and dataloader creation. Classes for handling datasets larger than memory and speeding up training by minimizing padding are also provided. The framework subclasses PyTorch dataset and dataloaders but should be adaptable for other deep learning frameworks. The project is open-sourced with a permissive license and made available at GitHub: https://github.com/MolecularAI/pysmilesutils
Chemistry-Mediated Ostwald Ripening in Carbon-Rich C/O Systems at Extreme Conditions
Authors: Lindsey Rebecca , Goldman Nir , Fried Laurence , Bastea Sorin
Published: February 2022

There is significant interest in establishing a capability for tailored synthesis of next-generation carbon-based nanomaterials due to their broad range of applications and high degree of tunability. High pressure (e.g. shockwave-driven) synthesis holds promise as an effective discovery method, but experimental challenges preclude elucidating the processes governing nanocarbon production from carbon-rich precursors that could otherwise guide efforts through the prohibitively expansive design space. Here we report findings from large scale atomistically-resolved simulations of carbon condensation from C/O mixtures subjected to extreme pressures and temperatures, made possible by machine-learned reactive interatomic potentials. We find that liquid nanocarbon formation follows classical growth kinetics driven by Ostwald ripening (i.e. growth of large clusters at the expense of shrinking small ones) and obeys dynamical scaling in a process mediated by carbon chemistry in the surrounding reactive fluid. The results provide direct insight into carbon condensation in a representative system and pave the way for its exploration in higher complexity organic materials. They also suggest that simulations using machine-learned interatomic potentials could eventually be employed as in-silico design tools for new nanomaterials.
Aptamers for Detection and Diagnostics (ADD): Can mobile systems process optical data from aptamer sensors to identify molecules indicating presence of SARS-CoV-2 virus? Should healthcare explore aptamers as drugs for prevention as well as its use as adjuvants with antibodies and 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.
Signal responsive transient coacervation in complex coacervate core micelles
Authors: Lewis Reece W. , Klemm Benjamin , Macchione Mariano , Eelkema Rienk
Published: February 2022

Triggered coacervate phase (de)stabilisation in complex coacervate core micelles (C3Ms) has traditionally been limited to changes in pH and salt concentration, limiting options in responsive C3M material design. To expand this toolbox, we have developed C3Ms, that, at constant physiological pH, assemble and disassemble by coupling to a chemical reaction network (CRN) driven by the conversion of electron deficient allyl acetates and thiol or amine nucleophiles. This CRN produces transient quaternization of tertiary amine-functionalised block copolymers, which can then form the complex coacervate phase. We demonstrate triggered C3M assembly using two different allyl acetates, resulting in dramatically different assembly rates from hours to days. These are applied in various combinations with selected nucleophiles, demonstrating sequential signal induced C3M formation and deformation, as well as transient non-equilibrium (de)formation. We expect that timed and signal-responsive control over coacervate phase formation at physiological pH will find application in nucleic acid delivery, nano reactors and protocell research.
Generative AI Design and Exploration of Nucleoside Analogs
Authors: Dablain Damien , Siwo Geoffrey , Chawla Nitesh
Published: February 2022

Nucleosides are fundamental building blocks of DNA and RNA in all life forms and viruses. In addition, natural nucleosides and their analogs are critical in prebiotic chemistry, innate immunity, signaling, antiviral drug discovery and artificial synthesis of DNA / RNA sequences. Combined with the fact that quantitative structure activity relationships (QSAR) have been widely performed to understand their antiviral activity, nucleoside analogs could be used to benchmark generative molecular design. Here, we undertake the first generative design of nucleoside analogs using an approach that we refer to as the Conditional Randomized Transformer (CRT). We also benchmark our model against five previously published molecular generative models. We demonstrate that AI-generated molecules include nucleoside analogs that are of significance in a wide range of areas including prebiotic chemistry, antiviral drug discovery and synthesis of oligonucleotides. Our results show that CRT explores distinct molecular spaces and chemical transformations, some of which are similar to those undertaken by nature and medicinal chemists. Finally, we demonstrate the potential application of the CRT model in the generative design of molecules conditioned on Remdesivir and Molnupiravir as well as other nucleoside analogs with in vitro activity against SARS-CoV-2. One-Sentence Summary: Generative design of nucleoside analogs relevant to antiviral drug discovery, prebiotic chemistry and synthetic biology.
C2 product formation in the CO2 electroreduction on boron-doped graphene anchored copper clusters
Authors: Höltzl Tibor , Janssens Ewald , Barhács Balázs
Published: February 2022

A possible remedy for the increasing CO2 concentration in the atmosphere is capturing, and reducing it into valuable chemicals like methane, methanol, ethylene, ethanol, etc. However, the suitable catalyst for this process is still under extensive research. Small sized copper clusters have gained attention in the recent years due to their catalytic activity in CO2 reduction reaction. Although C2+ products higher economic value, only the formation of C1 products was investigated thoroughly. For the electrochemical reduction of CO2, a supporting material is needed for small copper clusters. Graphene is a promising candidate, as is exhibits good mechanical and electrical properties however, the weak interaction of copper and graphene needs to be addressed. Our DFT computations also revealed, that small Cu clusters on boron-doped graphene support are promising catalysts for the electrochemical reduction of CO2 towards both C1 and C2 products. We demonstrate the most promising reaction pathways towards various C1 products, and ethanol or ethylene as C2 products on both Cu4 and Cu7 clusters on a boron-doped graphene (BDG) support. We also demonstrate the size-tuneable reactivity of these materials: Cu4 is considered a more reactive agent in general, but Cu7 shows a higher selectivity towards C2 products
Stochastic Generalized Active Space Self-Consistent Field: Theory and Application
Authors: Weser Oskar , Guther Kai , Ghanem Khaldoon , Li Manni Giovanni
Published: February 2022

An algorithm to perform stochastic generalized active space calculations, Stochastic-GAS, is presented, that uses the Slater determinant based FCIQMC algorithm as configuration interaction eigensolver. Stochastic-GAS allows the construction and stochastic optimization of preselected truncated configuration interaction wave functions, either to reduce the computational costs of large active space wave function optimizations, or to probe the role of specific electron correlation pathways. As for the conventional GAS procedure, the preselection of the truncated wave function is based on the selection of multiple active subspaces while imposing restrictions on the interspace excitations. Both local and cumulative minimum and maximum occupation number constraints are supported by Stochastic-GAS. The occupation number constraints are efficiently encoded in precomputed probability distributions, using the precomputed heat bath algorithm, which removes nearly all runtime overheads of GAS. This strategy effectively allows the FCIQMC dynamics to a priori exclude electronic configurations that are not allowed by GAS restrictions. Stochastic-GAS reduced density matrices are stochastically sampled, allowing orbital relaxations via Stochastic-GASSCF, and direct evaluation of properties that can be extracted from density matrices, such as the spin expectation value. Three test case applications have been chosen to demonstrate the flexibility of Stochastic-GAS: (a) the Stochastic-GASSCF optimization of a stack of five benzene molecules, that shows the applicability of Stochastic-GAS towards fragment-based chemical systems; (b) an uncontracted stochastic MRCISD calculation that correlates 96 electrons and 159 molecular orbitals, and uses a large (32, 34) active space reference wave function for an Fe(II)-porphyrin model system, showing how GAS can be applied to systematically recover dynamic electron correlation, and how in the specific case of the Fe(II)-porphyrin dynamic correlation further differentially stabilizes the triplet over the quintet spin state; (c) the study of an Fe4S4 cluster's spin-ladder energetics via highly truncated stochastic-GAS wave functions, where we show how GAS can be applied to understand the competing spin-exchange and charge-transfer correlating mechanisms in stabilizing different spin-states.
Exploring and Expanding the Fe-Terephthalate Metal-Organic Framework Phase Space by Coordination and Oxidation Modulation
Authors: Bara Dominic , Meekel Emily , Pakamorė Ignas , Wilson Claire , Ling Sanliang , Forgan Ross
Published: February 2022

The synthesis of phase pure metal-organic frameworks (MOFs) – network solids of metal clusters connected by organic linkers – is often complicated by the possibility of forming multiple diverse phases from one metal-ligand combination. For example, there are at least six Fe-terephthalate MOFs reported to date, with many examples of erroneous assignment of phase based on diffraction data alone. Herein, we show that modulated self-assembly can be used to influence the kinetics of self-assembly of Fe-terephthalate MOFs. We comprehensively assess the effect of addition of both coordinating modulators and pH modulators to the outcome of syntheses, as well as probing the influence of the oxidation state of the Fe precursor (oxidation modulation) and the role of the counteranion on the phase(s) formed. In doing so, we shed light on the thermodynamic landscape of this phase system, uncover mechanistics of modulation, provide robust routes to phase pure materials, often as single crystals, and introduce two new Fe-terephthalate MOFs to an already complex system. The results highlight the potential of modulated self-assembly to bring precision control and new structural diversity to systems that have already received significant study.
Vinyl Copolymers with Faster Hydrolytic Degradation than Aliphatic Polyesters and Tunable Upper Critical Solution Temperatures
Authors: Bossion Amaury , Zhu Chen , Nicolas Julien
Published: February 2022

Radical ring-opening polymerization (rROP) of cyclic ketene acetals (CKAs) is considered the most promising approach to impart degradability to vinyl polymers. However, rROP-synthesized materials still exhibit poor hydrolytic degradation and thus cannot yet compete with traditional polyesters. Here we show that a simple copolymerization system based on acrylamide and CKA can lead to well-defined copolymers with faster hydrolytic degradation than that of polylactide and poly(lactide-co-glycolide). Moreover, by changing the nature of the CKA, the copolymers were either water-soluble or exhibited tunable upper critical solution temperatures (UCST) relevant for mild hyperthermia-triggered drug release. To illustrate the interest of these new copolymers, we showed that they were cytocompatible on different cell lines and we synthesized amphiphilic diblock copolymers that were formulated into UCST nanoparticles by an all-water nanoprecipitation process. We anticipate this copolymerization system to offer new avenues in different applications such as biodegradation of commodity polymers, drug delivery or tissue engineering.
Assessing Catalytic Rates of Bimetallic Nanoparticles with Active Site Specificity - A Case Study using NO Decomposition
Authors: Halldin Stenlid Joakim , Streibel Verena , Choksi Tej S. , Abild-Pedersen Frank
Published: February 2022

Bimetallic alloys have emerged as an important class of catalytic materials, spanning a wide range of shapes, sizes, and compositions. The combinatorics across this wide materials space makes predicting catalytic turnovers of individual active sites challenging. Herein, we introduce the stability of active sites as a descriptor for site-resolved reaction rates. The site stability unifies structural and compositional variations in a single descriptor. We compute this descriptor using coordination-based models trained with DFT calculations. Our approach enables instantaneous predictions of catalytic turnovers for nanostructures up to 12 nm in size. Using NO dissociation as probe reaction, we identify that octahedral Au-Pt core-shell nanoparticles and 3 nm 0.5:0.5 AuPt random alloys yield greater than 10 times higher compared to monometallic Pt nanoparticles. By prescribing specific sizes, morphologies, and compositions of optimal catalytic nanoparticles, our method provides tailored guidance to experiments for rationally designing bimetallic catalysts.
Probing the Impact of Solvent on Lewis Acid Catalysis via Fluorescent Lewis Adducts
Authors: Laturski Amy , Bentley Jordan , Gaffen Joshua , Caputo Christopher , Baumgartner Thomas
Published: February 2022

Over the years, various multiparameter methods have been developed to measure the strength of a Lewis acid. However, a major challenge for these measurements lies in the complexity that arises from variables such as solvent and other fundamental interactions, as well as perturbations of Lewis acids as their reaction environment changes. Herein, we evaluate the impact of solvent effects on the Fluorescent Lewis Adduct (FLA) method using a series of representative Lewis acids. The solution-state nature of the FLA method in particular, offers the ability to correlate Lewis Acid Units (LAUs) obtained from the FLA measurement with chemical reactivity. The binding of a Lewis acid in various solvents reveals a measurable dichotomy between both polarity and donor ability of the solvent. While not strictly separable, we observe that, as solvent polarity increases observed LAUs increase; however, as solvent donor ability increases, the observed LAUs decrease. This dichotomy was confirmed by titration data and catalytic Diels-Alder cycloaddition and hydrosilylation reactions, illustrating that solvation effects can be appropriately gauged by LAU values determined from the FLA method.
The Brazilian Compound Library (BraCoLi) Database: A Brazilian Repository of Chemical and Biological Information for Drug Design
Authors: Veríssimo Gabriel Corrêa , dos Santos Junior Valtair Severino , Almeida Ingrid Ariela do Rosário de , Ruas Marina Sant'Anna Mitraud , Coutinho Lukas Galuppo , Oliveira Renata Barbosa de , Maltarollo Vinicius Gonçalves , Alves Ricardo José
Published: February 2022

The Brazilian Compound Library (BraCoLi) is a novel open access and manually curated electronic library of compounds developed by Brazilian research groups to support further computer-aided drug design works. Herein, the first version of the database is described comprising 1,176 compounds. Also, the chemical diversity and drug-like profiles of BraCoLi were defined to analyze its chemical space. A significant amount of the compounds fitted Lipinski and Veber’s rules, alongside other drug-likeness properties. A comparison using principal component analysis showed that BraCoLi is similar to other databases (FDA-approved drugs and NuBBEDB) regarding structural and physicochemical patterns. Furthermore, a scaffold analysis showed that BraCoLi presents several privileged chemical skeletons with great diversity. Despite the similar distribution in the structural and physicochemical spaces, similarity analysis indicated that compounds present in the BraCoLi are generally different from the two other databases showing an interesting innovative aspect, which is a desirable feature for novel drug design purposes.
Cross-conjugation controls the stabilities and photophysical properties of heteroazoarene photoswitches
Authors: Adrion Daniel , Lopez Steven
Published: February 2022

Azoarene photoswitches are versatile molecules that interconvert from their E-isomer to their Z-isomer with light. Azobenzene is a prototypical photoswitch but its derivatives can be poorly suited for in vivo applications such as photopharmacology due to undesired photochemical reactions promoted by ultraviolet light and its relatively short half-life (t1/2) of the Z-isomer (2 days). Experimental and computational studies suggest that these properties (λmax of the E isomer and t1/2 of the Z-isomer) are inversely related. We identified isomeric azobisthiophenes and azobisfurans from a high-throughput screening study of 1700 azoarenes as photoswitch candidates with improved λmax and t1/2 values relative to azobenzene. We used density functional theory to predict the activation free energies, reaction free energies, and vertical excitation energies of the E- and Z-isomers of 2,2- and 3,3-substituted azobisthiophenes and azobisfurans. The half-lives depend on whether the heterocycles are 𝜋-conjugated or cross-conjugated with the diazo 𝜋-bond. The 2,2-substituted azoarenes both have t1/2 values on the scale of 1 hour, while the 3,3-analogues have computed half-lives of 40 (thiophene) and 230 (furan) years. The 2,2-substituted heteroazoarenes have significantly higher λmax absorptions than their 3,3-substituted analogs: 76 nm for azofuran and 77 nm for azothiophene.
Identification of Enzymatic Active Sites with Unsupervised Language Modeling
Authors: Kwate Dassi Loïc , Manica Matteo , Probst Daniel , Schwaller Philippe , Nana Teukam Yves Gaetan , Laino Teodoro
Published: February 2022

The first decade of genome sequencing saw a surge in the characterization of proteins with unknown functionality. Even still, more than 20% of proteins in well-studied model animals have yet to be identified, making the discovery of their active site one of biology's greatest puzzle. Herein, we apply a Transformer architecture to a language representation of bio-catalyzed chemical reactions to learn the signal at the base of the substrate-active site atomic interactions. The language representation comprises a reaction simplified molecular-input line-entry system (SMILES) for substrate and products, complemented with amino acid (AA) sequence information for the enzyme. We demonstrate that by creating a custom tokenizer and a score based on attention values, we can capture the substrate-active site interaction signal and utilize it to determine the active site position in unknown protein sequences, unraveling complicated 3D interactions using just 1D representations. This approach exhibits remarkable results and can recover, with no supervision, 31.51% of the active site when considering co-crystallized substrate-enzyme structures as a ground-truth, vastly outperforming approaches based on sequence similarities only. Our findings are further corroborated by docking simulations on the 3D structure of few enzymes. This work confirms the unprecedented impact of natural language processing and more specifically of the Transformer architecture on domain-specific languages, paving the way to effective solutions for protein functional characterization and bio-catalysis engineering.
Protein Modification at Tyrosine with Iminoxyl Radicals
Authors: Maruyama Katsuya , Ishiyama Takashi , Seki Yohei , Sakai Kentaro , Togo Takaya , Oisaki Kounosuke , Kanai Motomu
Published: February 2022

Post-translational modifications (PTMs) of proteins are a biological mechanism for reversibly controlling protein function. Synthetic protein modifications (SPMs) at specific canonical amino acids can mimic PTMs. However, reversible SPMs at hydrophobic amino acid residues in proteins are especially limited. Here we report a tyrosine (Tyr)-selective SPM utilizing persistent iminoxyl radicals, which are readily generated from sterically hindered oximes via single electron oxidation. The reactivity of iminoxyl radicals with Tyr was dependent on the steric and electronic demands of oximes; isopropyl methyl piperidinium oxime 1f formed stable adducts, whereas the reaction of tert-butyl methyl piperidinium oxime 1o was reversible. The difference in reversibility between 1f and 1o, differentiated only by one methyl group, is due to the stability of iminoxyl radicals, which is partly dictated by the bond dissociation energy of oxime O‒H groups. The Tyr-selective modifications with 1f and 1o proceeded under physiologically-relevant, mild conditions. Specifically, the stable Tyr-modification with 1f introduced functional small molecules, including an azobenzene photoswitch, to proteins, whereas the reversible modification of Tyr with 1o switched protein function on and off in an enzyme and in a monoclonal antibody by modification and deconjugation processes.
Anti-Fouling Performance of Mixed Matrix PVDF Membranes with Mono-Hydroxyl Poly(dimethylsiloxane) (PDMS-OH) Grafted Silica Nanoparticles
Authors: AL-SHAELI MUAYAD , Smith Stefan J. D. , Jiang Shanxue , Wang Huanting , Zhang Kaisong , Ladewig Bradley P.
Published: February 2022

In this study, we investigate the use of surface-modified silica nanoparticles to improve the anti-fouling performance of PVDF ultrafiltration membranes. Here, fouling resistant nanoparticles were prepared by grafting monohydroxy-polydimethylsiloxane onto the surface of silica nanoparticles using Steglich esterification. The mixed matrix PVDF membranes were prepared at a range of nanoparticle concentrations (0, 1.6, 3.2, 6.3, and 11.8%) to understand how PDMS modified silica content affected membrane performance. The resulting hybrid membranes were characterised using a range of techniques including scanning electron microscopy (SEM), water contact angle (CA), porosity, and pore size measurements, in order to determine how morphological features of the nanocomposite membranes affected fouling and pure water flux. Embedding silica nanoparticles resulted in a significant reduction in membrane fouling, including lower protein adsorption and a flux recovery ratio of 97 %. Although water flux was reduced by the addition of nanoparticles, the change in the porosity, mean pore size and the hydrophilicity of the membrane caused the rejection rate to be increased significantly. Together, these results are of particular benefit to the ultrafiltration industry, where improved antifouling and flux recovery can help reduce operating and maintenance costs in these membrane processes.
Reinforcement Learning Configuration Interaction
Authors: Goings Joshua , Hu Hang , Yang Chao , Li Xiaosong
Published: February 2022

A reinforcement learning algorithm is developed for the selected configuration interaction problem. We explore how reinforcement learning can obtain compact wave functions at near full configuration interaction accuracy.
Small Peptides for Inhibiting Serum Amyloid A Aggregation
Authors: Jana Asis , Greenwood Augustus , Hansmann Ulrich H.E.
Published: February 2022

Deposition of human Serum Amyloid A (SAA) amyloids in blood vessels, causing inflammation, thrombosis and eventually organ damage, are a commonly seen as a consequence of certain cancers and inflammatory diseases. Several attempts have been made to develop peptide-based drugs that inhibit or at least slow down SAA amyloidosis. We use extensive all-atom molecular dynamic simulations to compare three of these drug candidates for their ability to destabilize SAA fibrils, and to propose for the best candidate, the N-terminal sequence SAA1-5, a mechanism for inhibition. As the life-time of peptide drugs can be increased by replacing L-amino acids with their mirror D- amino acids, we have also studied corresponding D-peptides. We find that DRI-SAA1-5, formed of D-amino acids with the sequence of the peptide reversed, has similar inhibitory properties than the original L-peptide, and therefore may be a promising candidate for drugs targeting SAA amyloidosis.
Fluorescent Staining of Silicone Micro-and Nano-patterns for Their Optical Imaging
Authors: Varol H. Samet , Seeger Stefan
Published: February 2022

Performance of engineered surfaces can be enhanced by making them hydrophobic or superhydrophobic via coating them with low-surface-energy micro-and nano-patterns. However, the wetting phenomena of particularly irregular shape and spacing (super)hydrophobic patterns such as polysiloxane coatings are not yet fully understood from a microscopic perspective. Here, we show a new method to collect 3D confocal images from irregular polysiloxane micro-and nanorods from a single rod resolution to discuss their wetting response over long liquid/solid interaction times and quantify the length and diameter of these rods. To collect such 3D confocal images, fluorescent dye containing water droplets were left on our superhydrophobic and hydrophobic polysiloxane coated surfaces. Then their liquid/solid interfaces were imaged at different staining scenarios: (i) using different fluorescent dyes, (ii) when the droplets were in contact with surfaces, or (iii) after the droplets were taken away from the surface at the end of staining. Using such staining strategies, we could resolve the micro-and nanorods from root to top and determine their length and diameter, which were then found to be in good agreement with those obtained from their electron microscopy images. 3D confocal images in this paper, for the first time, present the long-time existence of more than one wetting state under the same droplet in contact with surfaces, as well as external and internal three-phase contact lines shifting and pinning. In the end, these findings were used to explain the time-dependent wetting kinetics of our surfaces. We believe that the proposed imaging strategy here will, in the future, be used to study many other irregular patterned (super)antiwetting surfaces to describe their wetting theory, which is today impossible due to the complicated surface geometry of these irregular patterns.
Evaluating cepharanthine analogues as natural drugs against SARS-CoV-2
Authors: Hijikata Atsushi , Shionyu-Mitsuyama Clara , Nakae Setsu , Shionyu Masafumi , Ota Motonori , Kanaya Shigehiko , Hirokawa Takatsugu , Nakajima Shugo , Watashi Koichi , Shirai Tsuyoshi
Published: February 2022

Cepharanthine is a natural of plant origin, and recently demonstrated to have anti-SARS-CoV-2 activity. In order to evaluate the other natural analogues as a potential COVID-19 drug, a total of 24 compounds resembling cepharanthine were extracted from the KNApSAcK database, and their binding affinities to supposed target proteins, namely, spike protein and main protease of SARS-CoV-2, NPC1, and TPC2, were predicted via molecular docking simulations. Selected analogues were further evaluated by a cell-based SARS-CoV-2 infection assay, and the efficacies of cepharanthine (IC50 1.90 uM) and tetrandrine (IC50 10.37 uM) were demonstrated. From a comparison of the docking conformations of these compounds, the diphenyl ester moiety of the molecules was suggested for a putative pharmacophore of the cepharanthine-analogues.