bluuebunny/crossref_metadata_2025 huggingface dataset:
The Gas diffusion electrode setup as a testing platform for evaluating fuel cell catalysts: a comparative RDE-GDE study
Authors: Nösberger Sven , Du Jia , Quinson Jonathan , Berner Etienne , Zana Alessandro , Wiberg Gustav K.H. , Arenz Matthias
Published: February 2022

Gas diffusion electrode (GDE) setups have been recently introduced as a new experimental approach to test the performance of fuel cell catalysts. As compared to the state-of-the-art in fundamental research, i.e., rotating disk electrode (RDE) measurements, GDE measurements offer several advantages. Most importantly mass transport limitations, inherent to RDE measurements are avoided. In a GDE setup the reactant, e.g., oxygen gas, is not dissolved into a liquid electrolyte but distributed through a gas diffusion layer (GDL), as it is actually the case in fuel cells. Consequently, much higher current densities can be achieved, and the catalysts can be studied in a wider and more relevant potential range. Furthermore, direct contact to a liquid electrolyte can be avoided and elevated temperatures can be employed in a straight-forward manner. However, the use of GDE setups also comes with some challenges. The determined performance is not strictly related to the catalyst itself (intrinsic activity), but also to the quality of the catalyst film preparation. Therefore, it might be even more important than in RDE testing to develop standardized procedures to prepare catalysts inks and films that can be reproduced effortlessly in research laboratories for fundamental and applied experimentation. To develop such standardized testing protocols, we present a comparative RDE – GDE study, where we investigate several commercial standard Pt/C fuel cell catalysts with respect to the oxygen reduction reaction (ORR). The study highlights the strengths of the GDE approach as an intermediate “testing step” between RDE and membrane electrode assembly (MEA) tests when developing new fuel catalysts.
Water Capture Mechanisms at Zeolitic Imidazolate Framework Interfaces
Authors: Wagner Jackson , Hunter Kelly , Paesani Francesco , Xiong Wei
Published: February 2022

Water capture mechanisms of zeolitic imidazolate framework ZIF-90 are revealed by differentiating the water clustering and the center pore filling step, using vibrational sum-frequency generation spectroscopy (VSFG) at a one-micron spatial resolution and state-of-the-art molecular dynamics (MD) simulations. Through spectral lineshape comparison between VSFG and IR spectra, the relative humidity dependence of VSFG intensity, and MD simulations, based on MB-pol, we found water clustering and center pore filling happen nearly simultaneously within each pore, with water filling the other pores sequentially. The integration of nonlinear optics with MD simulations provides critical mechanistic insights into the pore filling mechanism and suggests that the relative strength of the hydrogen bonds governs the water uptake mechanisms. This molecular-level detailed mechanism can inform the rational optimization of metal-organic frameworks for water harvesting.
Synthesis and Exploitation of the Biological Profile of Novel Guanidino Xylofuranose Derivatives
Authors: Xavier Nuno Manuel , Fortuna Andreia , Gonçalves-Pereira Rita , Costa Paulo J. , Jorda Radek , Vojáčková Veronika , Heise Niels V. , Csuk René , Oliveira M. Conceição
Published: February 2022

The synthesis of novel guanidino sugars as potential mimetics of nucleosides and their biological evaluation is described. 5-Guanidino xylofuranoses containing different O-substituents at C-3, including saturated/unsaturated hydrocarbon chains and aromatic-containing moieties, were accessed from 5-azido xylofuranose precursors through reduction followed by guanidinylation of the obtained amines with N,N′-bis(tert-butoxycarbonyl)-N′′-triflylguanidine. A 5-azido 3-O-methyl-branched N-benzyltriazole isonucleoside was converted into the corresponding 5-guanidino-containing isonucleoside, whose structure includes both the guanidine and triazole moieties as nucleobase-like motifs connected to the xylofuranose template. In alternative, this structurally new type of compound was synthesized via cycloaddition between a 5-guanidino-3-O-propargyl xylofuranose derivative and benzyl azide in the presence of a CuI/Amberlyst A-21 catalytic system, along with the 5-iodotriazole derivative as a secondary product, which, in turn was the sole product when using equimolar CuI and a catalytic amount of 4-dimethylaminopyridine. A guanidinomethyltriazole 3′-O-dodecyl xylofuranos-5′-yl isonucleoside, which comprise a novel isonucleosidic framework having a guanidine system appended on the sugar-linked triazole motif, was obtained from the related aminomethyltriazole 5’-isonucleoside via guanidinylation. Bioactivity screening revealed 2 compounds as selective inhibitors of acetylcholinesterase (AChE), namely the guanidinomethyltriazole derivative, with moderate inhibition (Ki = 22.87 µM) and the 3-O-dodecyl (N-Boc)guanidino xylofuranose, which was the most active compound (Ki = 7.49 µM) acting as a non-competitive inhibitor. The latter also displayed moderate antiproliferative effects in chronic myeloid leukemia (K562, GI50 =31.02 μM) and in breast cancer (MCF-7, GI50 = 26.89 μM) cells. The aminomethyltriazole 5’-isonucleoside was the most potent molecule with single-digit micromolar GI50 values against both cells (GI50 = 6.33 μM and 8.45 μM), similar to that of the standard drug 5-fluorouracil against MCF-7 cells.
Thermal atomic layer deposition of In2O3 thin films using a homoleptic indium triazenide precursor and water
Authors: Mpofu Pamburayi , Rouf Polla , O'Brien Nathan , Forsberg Urban , Pedersen Henrik
Published: February 2022

Indium oxide (In2O3) is an important transparent conducting material widely used in optoelectronic applications. Herein, we study the deposition of In2O3 by thermal atomic layer deposition (ALD) using our recently reported indium(III) triazenide precursor and H2O. A temperature interval with self-limiting growth was found between ~270–385°C with a growth per cycle of ~1.0 Å. The deposited films were polycrystalline cubic In2O3 with In/O ratios of ~1.20, and low levels of C and no detectable N impurities. The transmittance of the films was found to be >70% in visible light and the resistivity was found to be 0.2 mΩcm. The high growth rates, low impurities, high optical transmittance, and low resistivity of these films give promise to this process being used for ALD of In2O3 films that are good candidates for potential display and touch-screen applications.
Quantum Dynamics of Water from Møller-Plesset Perturbation Theory via a Neural Network Potential
Authors: Lan Jinggang , Wilkins David , Rybkin Vladimir , Iannuzzi Marcella , Hutter Juerg
Published: February 2022

We report the static and dynamical properties of liquid water at second-order Møller-Plesset perturbation theory level (MP2) with classical and quantum dynamics simulations using a neural network potential. We examined the temperature-dependent radial distribution function, diffusion and vibrational dynamics. MP2 theory predicts an over-structured liquid water at ambient conditions, which may be attributed to the incomplete basis set. The excellent agreement with experimental structural properties as well as the diffusion constant is observed at an elevated temperature of 340K.
Solute effects on dynamics and deformation of emulsion droplets during freezing
Authors: Tyagi Sidhanth , Monteux Cécile , Deville Sylvain
Published: February 2022

Soft or rigid particles, suspended in a liquid melt, interact with an advancing solidification front in various industrial and natural processes, such as fabrication of particle-reinforced-composites, growth of crystals, cryopreservation, frost heave, and growth of sea ice. The particle dynamics relative to the front determine the microstructure as well as the functional properties of the solidified material. The previous studies have extensively investigated the interaction of foreign objects with a moving solid-liquid interface in pure melts while in most real-life systems, solutes or surface active impurities are almost always present. Here we study experimentally the interaction of spherical oil droplets with a moving planar ice-water interface, while systematically increasing the surfactant concentration in the bulk liquid, using in situ cryo-confocal microscopy. We demonstrate that a small amount of surfactant in the bulk liquid can instigate long-range droplet repulsion, extending over a length scale of 40 to 100µm, in contrast to the short-range predicted previously (<1µm). We report on the droplet deformation, while they are in contact with the ice-water interface, as a function of the bulk surfactant concentration, the droplet size, and the crystal growth rate. We also depict the dynamic evolution of solute-enriched premelted films (~5µm). Our results demonstrate how an increasing concentration of surfactant in the bulk and its subsequent segregation during solidification can dramatically alter the solidification microstructures. We anticipate that our experimental study can serve for the development of theoretical models incorporating solute effects.
Chemically Fueled Self-sorted Hydrogels
Authors: Singh Nishant , Lopéz-Acosta Álvaro , Formon Georges , Hermans Thomas
Published: February 2022

Narcissistic self-sorting in supramolecular assemblies can help to construct materials with more complex hierarchies. Whereas controlled changes in pH or temperature have been used to this extent for two-component self-sorted gels, here we show that a chemically fueled approach can provide three-component materials with high precision. The latter materials have interesting mechanical properties, such as enhanced or suppressed stiffness, and intricate multi-step gelation kinetics. In addition, we show that we can achieve supramolecular templating, where pre-existing supramolecular fibers first act as a templates for growth of a second gelator, after which they can selectively be removed.
Process for coating surfaces with a copolymer made from sulfur and dicyclopentadiene
Authors: Mann Maximilian , Zhang Bowen , Tonkin Samuel , Gibson Christopher , Jia Zhongfan , Hasell Tom , Chalker Justin
Published: February 2022

The reaction between sulfur and dicyclopentadiene was optimised to form a shelf stable and soluble low molecular weight oligomer. After a simple curing process at 140 °C the material was rendered insoluble and resistant to acids and solvents. Taking advantage of the soluble oligomer, a metal surface was coated with the dissolved material which was then cured to show that a copolymer layer can act as a corrosion resistant material. Further, silica gel was coated with the soluble oligomer to test mercury removal applications. Even after curing, the polymer coated silica was an effective mercury sorbent. Additionally, the sorbent was also used to remove mercury form a diesel and water mixture indicating that mercury removal from a mixture of organic and aqueous substances is possible with this system.
Covalent Bonding Aptamer with Enhanced SARS-CoV-2 RBD-ACE2 Blocking and Pseudovirus Neutralization Activities
Authors: Qin Zichen , Zhu Yiying , Xiang Yu
Published: February 2022

SARS-CoV-2 uses its spike protein receptor-binding domain (RBD) to interact with the angiotensin-converting enzyme 2 (ACE2) receptor on host cells. Inhibitors of the RBD-ACE2 interaction are therefore promising drug candidates in treating COVID-19. Here, we report a covalent bonding aptamer that can block the RBD-ACE2 interaction and neutralize SARS-CoV-2 pseudovirus infection by forming covalent bonds on RBD, resulting in more than 25-fold enhancement of pseudovirus neutralization efficacy over the original binding aptamer. The chemically modified aptamer is equipped with sulfur(VI) fluoride exchange (SuFEx) modifications and covalently targets important RBD residues within the RBD-ACE2 binding interface, including Y453 and R408. The covalent bonding is highly specific to RBD over other proteins such as human serum albumin (HSA), ACE2 and immunoglobulin G1 (IgG1) Fc. Our study demonstrates the promise of introducing covalent inhibition mechanisms for developing robust RBD-ACE2 inhibitors against SARS-CoV-2 infection.
Mebendazole’s Conformational Space and its Predicted Binding to Human Heat-Shock Protein 90
Authors: Fiedler Walter , Freisleben Fabian , Wellbrock Jasmin , Kirschner Karl
Published: February 2022

Recent experimental evidence suggest that mebendazole, a popular antiparasitic drug, binds to heat shock protein 90 (Hsp90) and inhibit acute myeloid leukemia cell growth. In this study we use quantum mechanics (QM), molecular similarity and molecular dynamics (MD) calculations to predict possible binding poses of mebendazole to the adenosine triphosphate (ATP) binding site of Hsp90. Extensive conformational searches and minimization of the five tautomers of mebendazole using MP2/aug-cc-pVTZ theory level resulting in 152 minima being identified. Mebendazole-Hsp90 complex models were created using the QM optimized conformations and protein coordinates obtained from experimental crystal structures that were chosen through similarity calculations. Nine different poses were identified from a total of 600 ns of explicit solvent, all-atom MD simulations using two different force fields. All simulations support the hypothesis that mebendazole is able to bind to the ATP binding site of Hsp90.
Using voltammetry augmented with physics-based modeling and Bayesian hypothesis testing to identify analytes in electrolyte solutions
Authors: Fenton, Jr. Alexis , Brushett Fikile
Published: February 2022

Voltammetry is a foundational electrochemical technique that can qualitatively and quantitatively probe electroactive species in solutions and as such has been used in numerous fields of study. Recently, automation has been introduced to extend the capabilities of voltammetric analysis through approaches such as Bayesian parameter estimation and compound identification. However, opportunities exist to enable more versatile methods across a wider range of solution compositions and experimental conditions. Here, we present a protocol that uses experimental voltammetry, physics-driven models, binary hypothesis testing, and Bayesian inference to enable robust labeling of analytes in multicomponent solutions across multiple techniques. We first describe the development of this protocol, and we subsequently validate the methodology in a case study involving five N-functionalized phenothiazine derivatives. In this analysis, the protocol correctly labeled solutions each containing 10H-phenothiazine and 10-methylphenothiazine from both cyclic voltammograms and cyclic square wave voltammograms, demonstrating the ability to identify redox-active constituents of a multicomponent solution. Finally, we identify areas of further improvement—such as achieving greater detection accuracy—and future applications to potentially enhance in situ or operando diagnostic workflows.
Spatiotemporal urban water profiling for the assessment of environmental and public exposure to antimicrobials (antibiotics, antifungals, and antivirals) in the Eerste River Catchment, South Africa
Authors: Holton ELizabeth , Archer Edward , Fidal James , Kjeldson Thomas , Wolfaardt Gideon , Kasprzyk-Hordern Barbara
Published: February 2022

Antibiotic usage, excretion, and persistence are all important factors in association with the occurrence and dissemination of antimicrobial resistance. Urban water profiling was utilised in the Eerste River catchment (South Africa) to establish antibiotic usage in a catchment where comprehensive prescription records were not readily available and where portions of the community did not have sufficient access to sanitation. This technique enabled the environmental exposure to be quantified throughout the catchment area and the identification of contamination hotspots. Monitoring occurred over a 10-month period. 812 samples were processed using UPLC-MS/MS for the quantitation of 56 antimicrobials and 26 of their metabolites. Spatiotemporal trends were established, with consideration to community behaviour, seasonal changes, and physiochemical properties of the analytes. The Eerste River samples collected upstream from the town of Stellenbosch had the lowest antibiotic loads (< 4 g/day), unafflicted by industrial presence and with only small impact from farming activity. This was followed by sites downstream from a treated wastewater treatment plant (serving 178K people) discharge point (influent: 500-800 g/day and effluent 50-100 g/day), which indicates a high efficiency of wastewater treatment allowing for an effective reduction of ABs and a lower environmental burden compared to the river sites receiving untreated waste from communities in informal settlements (6-12K people) that are not connected to the sewer infrastructure (with AB levels accounting for 100-600 g/day). Temporal trends exhibited reduced daily loads during the summer to early autumn. This is likely due to seasonal patterns in community health. However, weather patterns are also important to consider – particularly for the river sites. South Africa has notable rainfall and temperature seasonality. ARVs, emtricitabine and lamivudine, were the most prevalent drugs throughout the monitoring campaign, followed by tuberculosis drugs and sulfonamides. ARVs were, however, effectively reduced via wastewater treatment processes (>97%). This was also the case for beta-lactams, nitrofurantoin, and trimethoprim. The treatment efficacy for other drugs was more variable, that did not appear to have temporal significance.
The Total Synthesis of Proposed Immunoactive Glycolipids from S. Pneumoniae and a Re-evaluation of Their Immunological Activity
Authors: Sadraei Seyed Iraj , Yousif Greg , Taimoory S. Maryamdokht , Kosar Maryam , Mehri Samaneh , Al Olabi Raghd , Igbokwe Emmanuel , Toma Jason , Rahim Mir Munir A. , Trant John F.
Published: February 2022

Invariant natural killer T cells (iNKT) are responsible for the production of pro-inflammatory cytokines which induce a systemic immune response. They are distinctive in possessing an invariant T-cell receptor that recognizes glycolipid antigens presented by the class I major histocompatibility complex-related protein CD1d, conserved across multiple mammalian species in a class of proteins well-renowned for their high degree of polymorphism. This receptor’s first identified antigen is the potent α-galactose ceramide, KRN7000, a glycosphingolipid isolated from bacteria that were found on a Japanese marine sponge. The corresponding terrestrial antigen remained unidentified until quite recently, when diacylglycerol-containing glycolipids, reported to activate iNKT cells, were isolated from Streptococcus pneumoniae. We report the total synthesis and immunological re-evaluation of these two glycolipids. The compounds are unable to meaningfully activate iNKT cells. Computational modelling shows that these ligands, while being capable of interacting with the CD1d receptor, create a different surface for the binary complex that makes formation of the ternary complex with the iNKT T-cell receptor difficult. Together these results suggest that the reported activity might have been due to an impurity in the original isolated sample and highlights the importance of taking care when reporting biological activity from isolated natural products.
MegaSyn: Integrating Generative Molecule Design, Automated Analog Designer and Synthetic Viability Prediction
Authors: Urbina Fabio , Lowden Christopher , Culberson Christopher , Ekins Sean
Published: February 2022

Drug discovery is a multi-stage process, often beginning with the identification of active molecules from a high-throughput screen or machine learning model. Once structure activity relationship trends become well established, identifying new analogs with better properties is important. Synthesizing these new compounds is a logical next step, and is key to research groups that have a synthetic chemistry team or external collaborators. Generative machine learning models have become widely adopted to generate new molecules and explore molecular space, with the goal of discovering novel compounds with desires properties. These generative models have been composed from recurrent neural networks (RNNs), Variational Autoencoders (VAEs), and Generative Adversarial Networks (GANs) and are often combined with transfer learning or scoring of physicochemical properties to steer generative design. While these generative models have proven useful in generating new molecular libraries, often they are not capable of addressing a wide variety of potential problems, and often converge into similar molecular space when combined with a scoring function for desired properties. In addition, generated compounds are often not synthetically feasible, reducing their capabilities outside of virtual composition and limiting their usefulness in real-world scenarios. Here we introduce a suite of automated tools called MegaSyn representing 3 components: a new hill-climb algorithm which makes use of SMILES-based RNN generative models, analog generation software, and retrosynthetic analysis coupled with fragment analysis to score molecules for their synthetic feasibility. We now describe the development and testing of this suite of tools and propose how they might be used to optimize molecules or prioritize promising lead compounds using test case examples.
Nickel-catalyzed enantioselective annulation/alkynylation and Sonogashira reaction to form C(sp3)-C(sp) and C(sp2)-C(sp) bonds, respectively
Authors: hui chen , xuebin Liao , Boxue Tian , Licheng Yao , Buming Gu , Yixuan Zhang , Yahu A Liu
Published: February 2022

While traditional Sonogashira reaction requires a palladium catalyst and a copper co-catalyst, some recent variants were reported being promoted by single transition metals. Here we report a single nickel-catalyzed tandem Heck-Sonogashira annulation/alkynylation for enantioselectively constructing C(sp3)-C(sp) bond. In addition, using the same catalytic system, Sonogashira C(sp2)-C(sp) cross-coupling has also been achieved. The alkynylations described in this report are important for the three reasons: 1. C(sp3)/(sp2)-C(sp) bonds exist in many bioactive natural products and drug molecules as well as their key synthetic intermediates; 2. There was no precedent for single nickel-catalyzed Sonogashira reaction owing to the difficulties caused by strong coordination of nickel to the triple bond to inactivate the catalyst; 3. Isolation and characterization of single-crystal structure of a resting state intermediate, di-phosphine chelated σ-alkyl-NiII-I complex, which provided crucial evidence to support the mechanistic postulation and guided DFT calculations.
Hybrid QM/MM free energy evaluation of drug-resistant mutational effect on binding of an inhibitor Indinavir to HIV protease
Authors: Taguchi Masahiko , Oyama Ryo , Kaneso Masahiro , Hayashi Shigehiko
Published: February 2022

Human immunodeficiency virus 1 (HIV-1) protease is a homo-dimeric aspartic protease essential for replication of HIV. The HIV-1 protease is a target protein in drug discovery for antiretroviral therapy, and various inhibitor molecules of transition state analog were developed. However, serious drug-resistant mutants have emerged. For understanding molecular mechanism of the drug-resistance, accurate examination of the impacts of the mutations on ligand binding as well as enzymatic activity is necessary. Here, we present a molecular simulation study on the ligand binding of Indinavir, a potent transition state analog inhibitor, to the native protein and a V82T/I84V drug-resistant mutant of HIV-1 protease. We employed a hybrid ab initio quantum mechanical/molecular mechanical (QM/MM) free energy optimization technique which combines highly accurate QM description of the ligand molecule and its interaction with statistically ample conformational sampling of MM protein environment by long-time molecular dynamics simulations. Through free energy calculations of protonation states of catalytic groups at the binding pocket and of ligand binding affinity changes upon the mutations, we successfully reproduced the experimentally observed significant reduction of the binding affinity upon the drug-resistant mutations and elucidated the underlying molecular mechanism. The present study opens the way for understanding the molecular mechanism of drug-resistance through direct quantitative comparison of ligand binding and enzymatic reaction with the same accuracy.
PAH growth in flames and space: Formation of phenalenyl radical
Authors: Levey Zachariah , Laws Benjamin , Sundar Srivathsan , Nauta Klaas , Kable Scott , da Silva Gabriel , Stanton John , Schmidt Timothy
Published: February 2022

Polycyclic aromatic hydrocarbons (PAHs) are intermediates in the formation of soot particles and interstellar grains. However, their formation mechanisms in combustion and interstellar environments are not fully understood. The production of tricyclic PAHs and, in particular, the conversion of a PAH containing a five-membered ring to one with a six-membered ring is of interest to explain PAH abundances in combustion processes. In the present work, resonant ionization mass spectrometry in conjunction with isotopic labelling is used to investigate the formation of the phenalenyl radical from acenaphthylene and methane in an electrical discharge. We show that in this environment, the CH cycloaddition mechanism converts a five-membered ring to a six-membered ring. This mechanism can occur in tandem with other PAH formation mechanisms such as hydrogen abstraction/ acetylene addition (HACA) to produce larger PAHs in flames and the interstellar medium.
Infinitene: A Helically Twisted Figure-Eight [12]Circulene Topoisomer
Authors: Itami Kenichiro , Krzeszewski Maciej , Ito Hideto
Published: February 2022

New forms of molecular nanocarbons particularly looped polyarenes adopting various topologies contribute to the fundamental science and practical applications. Here we report on the synthesis of an infinity-shaped polycyclic aromatic hydrocarbon, infinitene 1 (cyclo[c.c.c.c.c.c.e.e.e.e.e.e]dodecakisbenzene) comprising consecutively fused 12-benzene rings forming an enclosed loop with a strain energy of 60.2 kcal·mol-1. Infinitene 1 represents a topoisomer of still-hypothetical [12]circulene, and its scaffold can be formally visualized as the outcome of the “stitching” of two homochiral [6]helicene subunits by their both ends. The synthetic strategy encompasses transformation of a rationally designed dithiacyclophane to cyclophadiene through the Stevens rearrangement and pyrolysis of the corresponding S,S′-bis(oxide) followed by the UV-light mediated twofold photocyclization. The structure of infinitene 1 is a unique hybrid of helicene and circulene with a molecular formula C48H24, which can be regarded as an isomer for kekulene, [6,6]carbon nanobelt ([6,6]CNB), [12]cyclacene, and tetrabenzo[8]circulene as well. Infinitene 1 is a bench-stable yellow solid with green fluorescence, and soluble to common organic solvents. The figure-eight molecular structure of 1 was unambiguously confirmed by X-ray crystallography. The scaffold of 1, reminiscent of a squeezed spring, stem from its enclosed, fully-fused architecture, is significantly compressed as manifested by a remarkably shortened distance (3.152–3.192 Å) between the centroids of two π-π stacked central benzene rings and the closest C···C distance of 2.920 Å. Combined lamellar and herringbone-like crystal packing suggested three-dimensional electronic inter-actions. Fundamental photophysical properties of infinitene 1 were thoroughly elucidated by means of UV-vis absorption and fluorescence spectroscopic studies as well as density functional theory (DFT) calculations. Its configurational stability enabled separation of the corresponding enantiomers (P,P) and (M,M) by a chiral HPLC. Circular dichroism (CD) and circularly polarized luminescence (CPL) measurements revealed that 1 has moderate |gCD| and |gCPL| values.
Lifting the discrepancy between experimental results and the theoretical predictions for the catalytic activity of RuO2 (110) towards Oxygen Evolution Reaction
Authors: Divanis Spyridon , Frandsen Adrian , Kutlusoy Tugce , Rossmeisl Jan
Published: February 2022

Developing new efficient catalyst materials for the oxygen evolution reaction (OER) is essential for widespread proton exchange membrane water electrolyzer use. Both RuO2 (110) and IrO2 (110) have been shown to be highly active OER catalysts, however DFT predictions have been unable to explain the high activity of RuO2. We propose that this discrepancy is due to RuO2 utilizing a different reaction pathway, as compared to the conventional IrO2 pathway. This hypothesis is supported by comparisons between experimental data, DFT data and the proposed reaction model. Furthermore, our findings indicate that the reaction pathway utilized by RuO2 (110) might be pH dependent, following the conventional pathway at high pH.
LT-LiMn0.5Ni0.5O2: A Unique Co-Free Cathode for High Energy Li-Ion Cells
Authors: Shi Boyu , Gim Jihyeon , Li Linze , Wang Chongmin , Vu Anh , Croy Jason , Thackeray Michael , Lee Eungje
Published: February 2022

A new Li-ion battery cathode, ‘LT-LiMn0.5Ni0.5O2’, where LT refers to its relatively low synthesis temperature (400 oC), has been identified. Electrochemical data indicate that Li/LT-LiMn0.5Ni0.5O2 cells operate between 5.0 and 2.5 V with good cycling stability, yielding a cathode capacity of 225 mAh/g. The electrochemical reactions occur in two distinct steps centered at ~3.75 V and ~4.7 V during charge, and at ~4.6 V and ~3.5 V during discharge. High-angle, annular-dark-field (HAADF) scanning-transmission electron microscopy (STEM) provide evidence that LT-LiMn0.5Ni0.5O2 consists of a unique, partially-disordered LiMn0.5Ni0.5O2 structure with predominant lithiated-spinel- and layered-like character. Structural analysis of LT-LiMn0.5Ni0.5O2 with synchrotron X-ray diffraction data shows, surprisingly, that lithiated-spinel and layered models with approximately 16% (~1/6) disorder between the lithium and manganese/nickel ions, yield an identical fit to the data, complicating the determination of the exact nature and level of disorder in each structural model. We believe that this is the first report of a Mn-stabilized, lithium-nickel-oxide spinel-related structure in which the redox reactions occur almost entirely on the nickel ions, with the likelihood that oxygen redox also contributes to some capacity above 4.7 V.
Discovery of a Potent and Highly Isoform-Selective Inhibitor of the Neglected Ribosomal Protein S6 Kinase Beta 2 (S6K2)
Authors: Gerstenecker Stefan , Haarer Lisa , Schröder Martin , Kudolo Mark , Schwalm Martin P. , Wydra Valentin , Serafim Ricardo , Chaikuad Apirat , Knapp Stefan , Laufer Stefan , Gehringer Matthias
Published: February 2022

The ribosomal protein S6 kinase beta 2 (S6K2) is thought to play an important role in malignant cell proliferation but is understudied compared to its closely related isoform S6 kinase beta 1 (S6K1). To better understand the biological function of S6K2, chemical probes are needed but the high structural homology between S6K2 and S6K1 makes it challenging to selectively address S6K2 with small molecules. We were able to design the first potent and highly isoform-specific S6K2 inhibitor by merging a known S6K1-selective inhibitor with a covalent inhibitor known to engage a cysteine located in the hinge region in the fibroblast growth factor receptor kinase (FGFR) 4 via a nucleophilic aromatic substitution (SNAr) reaction. The title compound shows high selectivity over kinases with an equivalently positioned cysteine as well as in a larger kinase panel. Good stability towards glutathione indicated a non-promiscuous reactivity pattern. Thus, the title compound represents an important step towards a high-quality chemical probe to study S6K2-specific signalling.
Elucidating the formation and structural evolution of platinum single-site catalysts for hydrogen evolution reaction
Authors: Tang Peng , Lee Hyeon Jeong , Hurlbutt Kevin , Huang Po-Yuan , Narayanan Sudarshan , Wang Chenbo , Gianolio Diego , Arrigo Rosa , Chen Jun , Warner Jamie , Pasta Mauro
Published: February 2022

Platinum single-site catalysts (SSCs) are a promising technology for the production of hydrogen from clean energy sources. They have high activity and maximal platinum-atom utilisation. However, the bonding environment of platinum during operation is poorly understood. In this work, we use operando, synchrotron-X-ray absorption spectroscopy to study the platinum bonding in SSCs. First, we synthesise an atomically dispersed platinum complex with aniline and chloride ligands onto graphene and characterise it with ex-situ electron microscopy, X-ray diffractometry, X-ray photoelectron spectroscopy, X-ray absorption near edge structure spectroscopy (XANES), and extended X-ray absorption fine structure spectroscopy (EXAFS). Then, by operando EXAFS and XANES, we show that as a negatively biased potential is applied, the Pt-N bonds break first followed by the Pt-Cl bonds. The platinum is reduced from platinum(II) to metallic platinum(0) by the onset of the hydrogen-evolution reaction at 0 V. Furthermore, we observe an increase in Pt-Pt bonding, indicating the formation of platinum agglomerates. Together, these results indicate that while aniline is used to prepare platinum SSCs, the single-site complexes are decomposed and platinum agglomerates at operating potentials. This work is an important contribution to the understanding of the bonding environment and the evolution of the molecular structure of platinum complexes in SSCs.
Albumin nanoparticles loaded with hemin as peroxidase mimics for immunoassay
Authors: Khramtsov Pavel , Bochkova Maria , Timganova Valeria , Kiselkov Dmitriy , Zamorina Svetlana , Rayev Mikhail
Published: February 2022

Contemporary immunoassays commonly used in clinical diagnostics mostly utilize enzymes, such as horseradish peroxidase, for signal generation. Numerous research is dedicated to the development of artificial peroxidase-mimicking catalysts with lower cost, high activity, better operational stability, and tunable properties. Herein we synthesized hemin-loaded bovine serum albumin (BSA) nanoparticles and applied them as catalytic labels (nanozymes) in colorimetric immunoassay of anti-tetanus antibodies. Hemin is a key part of the peroxidase catalytic center, possessing peroxidase like-activity. Albumin nanoparticles were loaded with multiple hemin molecules and decorated with Streptococcal protein G. Resulting nanozymes possessed good colloidal stability and allowed for antibody detection in blood serum. The sensitivity of antibody detection was sufficient for the assessment of post-vaccination immunity.
A Practical Guide to Analyzing and Reporting the Movement of Nanoscale Swimmers
Authors: Wang Wei , Mallouk Thomas
Published: February 2022

The recent invention of nanoswimmers– synthetic, powered objects with characteristic lengths in the range of 10-500 nm - has sparked widespread interest among scientists and the general public. As more researchers from different backgrounds enter the field, the study of nanoswimmers gains new opportunities but also significant experimental and theoretical challenges. In particulr, the accurate characterization of nanoswimmers is often hindered by strong Brownian motion and the lack of a clear way to visualize them. When coupled with improper experimental design and imprecise practices in data analysis, these issues can translate to results and conclusions that are inconsistent and poorly reproducible. In light of the increasing popularity of nanoswimmer research and its challenges, we here offer suggestions of best practices for reporting and analyzing their movement. A particular emphasis is on the calculation and analysis of mean squared displacement, the key method for quantifying the mobility of a nanoswimmer. When applied carefully and systematically, the suggested practices can significantly improve the reliability of analyses and prevent embarrassing mistakes
Quantitative Characterization of Partitioning in Selection of DNA Aptamers for Protein Targets by Capillary Electrophoresis
Authors: Le An T. H. , Wang Tong Y. , Krylova Svetlana M. , Beloborodov Stanislav S. , Krylov Sergey
Published: February 2022

Partitioning of protein–DNA complexes from protein-unbound DNA is a key step in selection of DNA aptamers. Conceptually, the partitioning step is characterized by two parameters: transmittance for protein-bound DNA (binders) and transmittance for unbound DNA (nonbinders). Here we present the first study to reveal how these transmittances depend on experimental conditions; such studies are pivotal to the effective planning and control of selection. Our focus was capillary electrophoresis (CE) which is a partitioning approach of high efficiency. By combining a theoretical model and experimental data, we evaluated the dependence of transmittances of binders and nonbinders on the molecular weight of protein target in two modes of CE-based partitioning: nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) and ideal-filter capillary electrophoresis (IFCE). Our data suggest that as the molecular weight of the protein target decreases: (i) the transmittance for binders remains close to unity in NECEEM but decreases drastically in IFCE and (ii) the transmittance for nonbinders increases orders of magnitude in NECEEM but remains relatively stable at a very low level in IFCE. To determine the optimal CE conditions for a given size of protein target, a balance between transmittances of binders and nonbinder must be reached; such a balance would ensure the collection of binders of sufficient purity and quantity. We conclude that, as a rule of thumb, IFCE is preferable for large-size protein targets while NECEEM should be the method of choice for small-size protein targets
Structure of the active pharmaceutical ingredient bismuth subsalicylate
Authors: Svensson Grape Erik , Rooth Victoria , Nero Mathias , Willhammar Tom , Inge A. Ken
Published: February 2022

Structure determination of pharmaceutical compounds is invaluable for drug development but is challenging for those that form as small crystals with defects. Bismuth subsalicylate (BSS), among the most commercially significant bismuth compounds, is an active ingredient in over-the-counter medications such as Pepto-Bismol, used to treat dyspepsia and H. pylori infections. Despite its century-long history, the structure has remained unknown. Three-dimensional electron diffraction and hierarchical clustering analysis were applied on select data from ordered crystals, revealing a layered structure. In other less ordered crystals, high-resolution scanning transmission electron microscopy revealed variations in the stacking of layers. Together, these modern electron crystallography techniques provide a new toolbox for structure determination of active pharmaceutical ingredients and drug discovery, demonstrated by this study of BSS.
Tuning the porosity, water interaction and redispersion of nanocellulose hydrogels by osmotic dehydration
Authors: Guccini Valentina , Phiri Josphat , Trifol Jon , Rissanen Ville , Mousavi Maryam , Vapaavuori Jaana , Tammelin Tekla , Maloney Thaddeus , Kontturi Eero
Published: February 2022

Cellulose nanofibre hydrogels are produced by osmotic dehydration. We analyse the evolution of their hierarchical porosity in wet state depending on solid content (0.7‐12 wt%). We measure water physical characteristics, mechanical properties, ion‐conductivity and redispersion. This method is straight forward, reproducible, does not require heat or vacuum, and minimizes nanofibrillar aggregation.
REverSe TRanscrIptase Chain Termination (RESTRICT) for Selective Measurement of Nucleotide Analogs Used in HIV Care and Prevention
Authors: Olanrewaju Ayokunle Oluwafemi , Sullivan Benjamin , Gim Alicia , Sevenler Derin , Bender Andrew , Drain Paul , Posner Jonathan
Published: February 2022

Sufficient drug concentrations are required for efficacy of antiretroviral drugs used in human immunodeficiency virus (HIV) care and prevention. Measurement of nucleotide analogs, included in most HIV medication regimens, enables monitoring of short- and long-term adherence and the risk of treatment failure. The REverSe TRanscrIptase Chain Termination (RESTRICT) assay rapidly infers the concentration of intracellular nucleotide analogs based on the inhibition of DNA synthesis by HIV reverse transcriptase (RT) enzyme. Here, we introduce a probabilistic predictive model for RESTRICT and demonstrate selective measurement of multiple nucleotide analogs using DNA templates designed according to the chemical structure of each drug. We measure clinically relevant concentrations of tenofovir diphosphate (TFV-DP), emtricitabine triphosphate (FTC-TP), and azidothymidine triphosphate (AZT-TP) with agreement between experiment and theory. RESTRICT represents a new class of activity-based assays for therapeutic drug monitoring and precision dosing in HIV care and could be extended to other diseases treated with nucleotide analogs.
Asymmetric Total Synthesis of Clionastatins A and B
Authors: Ju Wei , Wang Xudong , Tian Hailong , Gui Jinghan
Published: February 2022

Herein we report the first total synthesis of polychlorinated steroids clionastatins A and B, which was accomplished asymmetrically by means of a convergent, radical fragment coupling approach. Key features of the synthesis include an Ireland–Claisen rearrangement to introduce the C5 stereocenter (which was ultimately transferred to the C10 quaternary stereocenter of the clionastatins via a traceless stereochemical relay), a regioselective acyl radical conjugate addition to join the two fragments, an intramolecular Heck reaction to install the C10 quaternary stereocenter, and a diastereoselective olefin dichlorination to establish the synthetically challenging pseudoequatorial dichlorides. This work also enabled us to determine that the true structures of clionastatins A and B are in fact C14 epimers of the originally proposed structures.
Engineering a Non-Natural Photoenzyme for Improved Photon Efficiency
Authors: Nicholls Bryce , Oblinsky Daneil , Kurtoic Sarah , Grosheva Daria , Ye Yuxuan , Scholes Gregory , Hyster Todd
Published: February 2022

Photoenzymes are biological catalysts that use light to convert starting materials to products. These catalysts require photon absorption for each catalyst turnover, making quantum efficiency an important optimization parameter. Flavin-dependent 'ene’-reductases (EREDs) display latent photoenzymatic activity for synthetically valuable hydroalkylations; however, protein engineering has not been used to optimize this non-natural function. Here, we describe a protein engineering platform for the high throughput optimization of photoenzymes. A single round of engineering results in improved catalytic function toward the synthesis of 𝛾, 𝛿, 𝜀-lactams, and acyclic amides. Mechanistic studies indicate that key mutations can alter the enzyme's excited state dynamics, enhance its photon efficiency, and ultimately increase catalyst performance. Transient absorption spectroscopy reveals that engineered variants display dramatically decreased radical lifetimes – indicating a shift toward a concerted mechanism. Overall, this platform enables the development and optimization of photoenzymes for tailored applica-tions in chemical synthesis.
Increased Excited State Metallicity in Neutral Cr2On Clusters (n < 5) Upon Sequential Oxidation
Authors: Garcia Jacob , Sayres Scott
Published: February 2022

Excited state lifetimes of neutral Cr2On (n < 5) clusters were measured using femtosecond pump-probe spectroscopy. Density functional theory calculations reveal that the excited state dynamics are correlated with changes in the cluster’s electronic structure with increasing oxidation. Upon absorption of a UV (400 nm) photon, the clusters exhibit features attributed to three separate relaxation processes. All clusters exhibit similar sub-picosecond lifetimes, attributed to vibrational relaxation. However, the ~30 fs transient signal fraction grows linearly with oxidation, matching the amount of O to Cr charge transfer character of the photoexcitation and highlighting a gradual transition between semiconducting and metallic behavior at the molecular level. A long-lived (>2.5 ps) response is recorded only in clusters with significant d-electron character, suggesting that adiabatic relaxation back to the ground state is efficient in heavily oxidized clusters, due to the presence of terminal O atoms. The simple picture of sequential oxidation of Cr2On reveals a linear variation in the contributions of each relaxation component to the total transient signals, therefore opening possibilities for the design of new molecular spintronic materials.
On the Role of Heterojunctions of Core-Shell Heterostructures in Gas Sensing
Authors: Raze Muhammad Hamid , Di Chio Roberto , Movlaee Kaveh , Amsalem Patrick , Koch Norbert , Barsan Nicolae , Neri Giovanni , Pinna Nicola
Published: February 2022

Heterostructures made from semiconducting metal oxides (SMOX) are fundamental for the development of high-performance gas sensors. Yet, despite the recognition of their importance in real applications, the understanding of the transduction mechanism either related to the heterojunction, or simply to the core and shell materials is still lacking. A better understanding of the sensing response of heterostructured nanomaterials requires the engineering of heterojunctions with well-defined core and shell layers. Here, we introduce a series of prototypes nSMOX-CNT, pSMOX-CNT, and pSMOX-nSMOX-CNT and nSMOX-pSMOX-CNT hierarchical core-shell heterostructures (CSHS) permitting us to directly relate the sensing response to the SMOX shell, or to the p-n heterojunction. The carbon nanotubes are here used as highly conductive substrates permitting to operate the devices at relatively low temperature and are not involved in the sensing response. NiO and SnO2 are selected as representative p- and n-type SMOX, respectively, and the response of a set of samples is studied toward hydrogen considered as model analyte. The n,pSMOX-CNT CSHS exhibit response related to the n,pSMOX-shell layer. On the other hand, the pSMOX-nSMOX-CNT and nSMOX-pSMOX-CNT CSHS show sensing responses, which in certain cases are governed by the heterojunctions between nSMOX and pSMOX and strongly depends on the thickness of the SMOX layers. Due to the fundamental nature of this study, these findings are important for the development of next generation gas sensing devices.
First Principles Approach to Extracting Chemical Information from X-Ray Absorption Near-Edge Spectra of Ga-Containing Materials
Authors: Groden Kyle , VILA FERNANDO D. , Li Li , Bare Simon , Scott Susannah , McEwen Jean-Sabin
Published: February 2022

The X-ray absorption near edge structure (XANES) can provide uniquely detailed information on the coordination environments of important Ga-containing materials with unknown structures, including catalytically-active materials. In this study, the Ga K-edge XANES was simulated using first principles-based methods for seven molecular Ga complexes, as well b-Ga2O3, in order to explore the chemical origins of the experimentally observed features. The theoretical spectra were computed using FEFF, CASTEP and StoBE, in order to assess the sensitivity of the results to the computational approach. While the XANES features depend on the Ga coordination environment, they are also sensitive to the electronegativity of the ligands and the symmetry at Ga. The white line position responds to changes in both the core state (due to differential screening) and the valence “p” states (arising from differences in ligand coordination).