bluuebunny/crossref_metadata_2025 huggingface dataset:
An Efficient Synthesis of [n]Cycloparaphenylenes (n = 9, 12, 15) via the Self-Assembly into Macrocyclic Gold(I)-Oligophenylene Complexes Based on Dynamic Au–C σ-Bonds
Authors: Tanji Yohei , Yoshigoe Yusuke , Saito Shinichi , Osakada Kohtaro , Tsuchido Yoshitaka , Kawai Hidetoshi
Published: February 2022

The transmetalation of the digold(I) complex [Au2Cl2(Cy2PCH2PCy2)] with oligophenylene diboronic acids gave the triangu-lar macrocyclic complexes [Au2(C6H4)x(Cy2PCH2PCy2)]3 (x = 3, 4, 5) with yields of over 70%. A series of [n]cycloparaphenylenes (n = 9, 12, 15) was isolated in 78–88% yield via the oxidative chlorination of the macrocyclic gold complexes. A kinetics study employing two acyclic dinuclear gold(I) complexes, [Au2R2(Cy2PCH2PCy2)] (R = Ph and/or C6H4-4-F), revealed that an intermolecular Au(I)–C σ-bond-exchange reaction proceeded. These results indicate that the trian-gular complexes were obtained selectively via reversible intermolecular Au(I)–C σ-bond exchanges. By reacting two different oligophenylene diboronic acids with the digold(I) complex, a mixture of macrocyclic complexes incorporating different oli-gophenylene linkers was formed. The oxidative chlorination of this mixture gave [n]cycloparaphenylenes with various num-bers of phenylene units.
Ionization differences between weak and strong electrolytes: the role of protonic quantum effects as perturbed by dielectric relaxation spectroscopy
Authors: Artemov Vasily , Ryzhov Alexander , Ouerdane Henni , Stevenson Keith
Published: February 2022

Revealing the microscopic dynamics, including protonic quantum effects, in aqueous electrolyte solutions has been a challenge for modern experimental methods and molecular dynamics simulations of the past decade. These properties are out of the scope of the standard electrolytic dissociation model and leave a gap between theory and experiment due to the lack of details of the fast molecular dynamics during solvation. We report a dielectric-spectroscopy study (1Hz to 20 GHz), which unambiguously demonstrates a net difference in the dynamic structures of weak and strong electrolytes, shedding new light on the mechanism of solvation via proton exchange reactions. Based on these data, we suggest an extension of Arrhenius’ seminal model, providing a more accurate description of the electrical properties of electrolytes over a wide range of concentrations (10$^{-7}$ to 10 M). We show that dissolved species of weak electrolytes more likely interact with each other than with the solvent, preventing dissociation and explaining a sharp difference between weak and strong electrolytes. These results extend our understanding of the molecular dynamics of aqueous electrolyte solutions in biology, electrochemical systems, and nanofluidics.
Biodegradable polysarcosine with inserted alanine residues: Synthesis and enzymolysis
Authors: Zhou Peng , Ling Jun
Published: February 2022

Polysarcosine (PSar), a water-soluble polypeptoid, is gifted with biodegradability via random ring-opening copolymerization of sarcosine- and alanine-N-thiocarboxyanhydrides catalyzed by acetic acid in controlled manners. Kinetic investigation reveals the copolymerization behavior of the two monomers. The random copolymers, named PAS, with high molecular weights between 22.0 and 43.6 kg/mol and tunable Ala molar fractions varying from 6% to 43% are able to be degraded by porcine pancreatic elastase within 50 days in mild conditions (pH=8.0 at 37 °C). Both the biodegradation rate and water solubility of PAS depend on the content of Ala residues. PAS with Ala fractions below 43% are soluble in water while the one with 43% Ala self-assembles in water into nanoparticles. Moreover, PAS are non-cytotoxic at the concentration of 5 mg/mL. The biodegradability and biocompatibility endow the Ala-containing PSar with potential to replace PEG as protective shield in drug-delivery.
Synthesis of Phenanthridine by Palladium Catalyzed Suzuki Coupling and Condensation Reaction
Authors: Ray Jayanta Kumar , Dhara Suvendu
Published: February 2022

Transition metal catalyzed cross-coupling reactions such as Suzuki-Miyaura, Heck, Stille, Negishi, and Sonogashira reactions are likely to be the most power tool for the formation of C-C bonds for the past four decades. All these reactions have shown their widespread applicability ranging from academic area to research. Some of the reactions have also been applied in pharmaceuticals, agrochemicals, and fine material industries. Herein we report a one-pot strategy to achieve phenanthridine and analogous derivatives via Suzuki coupling of suitably substituted aromatic ortho-bromoaldehyde and ortho-aminobenzenboronic acid in quantitative to good yields
Engineering a Cytidine Aminotransferase for Biocatalytic Production of the Antiviral Molnupiravir
Authors: Burke Ashleigh , Birmingham William , Zhuo Ying , Costa Bruna Zuculoto da , Crawshaw Rebecca , Thorpe Thomas , Rowles Ian , Finnigan James , Charnock Simon J. , Lovelock Sarah , Turner Nicholas , Green Anthony
Published: February 2022

The COVID-19 pandemic highlights the urgent need for cost-effective processes to rapidly manufacture antiviral drugs at scale. Here we report a concise biocatalytic process for Molnupiravir, a nucleoside analogue currently in phase 3 clinical trials as an orally available treatment for SARS-CoV-2. Key to the success of this process was the development of a cytidine aminotransferase for the production of N-hydroxy-cytidine through evolutionary adaption of the hydrolytic enzyme cytidine deaminase. This engineered biocatalyst performs >100,000 turnovers in less than 30 minutes, operates at 180 g/L substrate loading and benefits from in situ crystallization of the N-hydroxy-cytidine product (>90% yield), which can be converted to Molnupiravir by a selective 5’-acylation using Novozym® 435.
SBMOpenMM: A Builder of Structure-Based Models for OpenMM
Authors: Floor Martin
Published: February 2022

Molecular dynamics (MD) simulations have become a standard tool to correlate the structure and function of biomolecules, and significant advances have been made in the study of proteins and their complexes. A major drawback of conventional MD simulations is the difficulty and cost of obtaining converged results, especially when exploring potential energy surfaces containing considerable energy barriers. This limits the wide use of MD calculations to determine the thermodynamic properties of biomolecular processes. Alternatively, a wide range of Structure-Based Models (SBMs) has been used in the literature to unravel the basic mechanisms of biomolecular dynamics. Here we introduce SBMOpenMM, a Python library to build force fields for SBMs, that uses the OpenMM framework to create and run SBM simulations. The code is flexible, user-friendly, and profits from the high customizability and performance provided by the OpenMM platform.
Conduction Band Engineering of Half-Heusler Thermoelectrics Using Orbital Chemistry
Authors: Guo Shuping , Anand Shashwat , Brod Madison K. , Zhang Yongsheng , Snyder G. Jeffrey
Published: February 2022

Semiconducting half-Heusler (HH, XYZ) phases are promising thermoelectric materials owing to their versatile electronic properties. Because the valence band of half-Heusler phases benefit from the valence band extrema at several high-symmetry points in the Brillouin zone (BZ), it is possible to engineer better p-type HH materials through band convergence. However, the thermoelectric studies of n-type HH phases have been lagging behind since the conduction band minimum is always at the same high-symmetry point (X) in the BZ, giving the impression that there is little opportunity for band engineering. Here we study the n-type orbital diagram of 69 HHs, and show that there are two competing conduction bands with very different effective masses actually at the same X point in the BZ, which can be engineered to be converged. The two conduction bands are dominated by the d orbitals of X and Y atoms, respectively. The energy offset between the two bands depends on the difference in electron configuration and electronegativity of the X and Y atoms. Based on the orbital phase diagram, we provide the strategy to engineer the conduction band convergence by mixing the HH compounds with the reverse band offsets. We demonstrate the strategy by alloying VCoSn and TaCoSn. The V0.5Ta0.5CoSn mixture presents the high conduction band convergence and corresponding significantly larger density-of-states effective mass than either VCoSn or TaCoSn. Our work indicates that analyzing the orbital character of band edges provides new insight into engineering thermoelectric performance of HH compounds.
Computational Scaling Relationships Predict Experimental Activity and Rate Limiting Behavior in Homogenous Water Oxidation
Authors: Harper Daniel , Kulik Heather
Published: February 2022

While computational screening with first-principles density functional theory (DFT) is essential for evaluating mechanisms of candidate catalysts, limitations in accuracy typically prevent prediction of experimentally relevant activities. Exemplary of these challenges are homogeneous water oxidation catalysts (WOCs) where differences in experimental conditions along with small changes in ligand structure can alter rate constants by over an order of magnitude. To leverage computational screening for homogeneous WOC design, a distinct approach is needed. Here, we compute mechanistically-relevant electronic and energetic properties for 19 mononuclear Ru transition metal complexes (TMCs) from three experimental water oxidation catalysis studies. We discover that 15 of these TMCs have experimental activities that can be correlated to a single property, the ionization potential of the Ru(II)-O2 catalytic intermediate. This scaling parameter is well correlated with experimentally-reported rate constants, allowing quantitative understanding activity trends and insight into rate-limiting behavior. We use this approach to rationalize differences in activity with differing experimental conditions, and we qualitatively analyze the source of distinct behavior for differing electronic states in the other four catalysts. Comparison to closely related single-atom catalysts and modified WOCs enables rationalization of the source of rate enhancement in these experimental WOC catalysts.
An Easily Prepared Monomeric Cobalt(II) Tetrapyrrole Complex that Efficiently Promotes the 4e–/4H+ Peractivation of O2 to Water
Authors: Cai Qiuqi , Tran Linh , Qiu Tian , Eddy Jennifer , Yap Glenn , Rosenthal Joel
Published: February 2022

The selective 4e–/4H+ reduction of dioxygen to water is an important reaction that takes place at the cathode of fuel cells. Monomeric aromatic tetrapyrroles (such as porphyrins, phthalocyanines, and corroles) coordinated to Co(II) have been considered as oxygen reduction catalysts due to their low cost and relative ease of synthesis. How- ever, these systems have been repeatedly shown to be selective for O2 reduction by the less desired 2e –/2H+ pathway to yield hydrogen peroxide. Herein, we report the initial synthesis and study of a Co(II) tetrapyrrole complex based upon a non-aromatic isocorrole scaffold that is competent for 4e–/4H+ ORR. This Co(II) 10,10-dimethyl isocorrole (Co[10- DMIC]) is obtained in a just four simple steps and excellent yield from a known dipyrromethane synthon. Evaluation of the steady state spectroscopic and redox properties of Co[10-DMIC] against those of Co(II) porphyrin ([Co(TPFPP)]) and corrole ([Co(TPFPC)(PPh3)]) homologs demonstrated that the light harvesting and electrochemical properties of the isocorrole are distinct from those displayed by more traditional aromatic tetrapyrroles. Further, investigation of the ORR activity of Co[10-DMIC] using a combination of electrochemical and chemical reduction studies revealed that this simple, unadorned monomeric Co(II) tetrapyrrole is ~85% selective for the 4e–/4H+ reduction of O2 to H2O over the more kinetically facile 2e–/2H+ process that delivers H2O2. By contrast, the same ORR evaluations conducted for the Co(II) porphyrin and corrole homologs demonstrated that these traditional aromatic systems catalyze the 2e–/2H+ conversion of O2 to H2O2 with near complete selectivity. Despite being a simple, easily prepared, monomeric tetrapyrrole platform, Co[10-DMIC] supports an ORR catalysis that has historically only been achieved using elaborate porphyrinoid-based architectures that incorporate pendant proton-transfer groups, ditopic molecular clefts, or which impose cofacially ori- ented O2 binding sites. Accordingly, Co[10-DMIC] represents the first simple, unadorned, monomeric metalloisocorrole complex that can be easily prepared and which shows a privileged performance for the 4e–/4H+ peractivation of O2 to water as compared to other simple Co(II) tetrapyrroles.
Temperature Regulates Stability, Ligand Binding (Mg2+ and ATP) and Stoichiometry of GroEL/GroES Complexes
Authors: Walker Thomas E , Shirzadeh Mehdi , Sun He Mirabel , McCabe Jacob W , Roth Andrew , Moghadamchargari Zahra , Clemmer David E , Laganowsky Arthur , Rye Hays , Russell David H
Published: February 2022

Chaperonins are nanomachines that harness ATP hydrolysis to power and catalyze protein folding, chemical action that is directly linked to the maintenance of cell function through protein folding/refolding and assembly. GroEL and the GroEL-GroES complex are archetypal examples of such protein folding machines. Here, variable-temperature-electrospray ionization (vT-ESI) native mass spectrometry is used to delineate the effects of solution temperature and ATP concentrations on the stabilities of GroEL and GroEL/GroES complexes. The results show clear evidences for destabilization of both GroEL14 and GroES7 at temperatures of 50 oC and 45 oC, respectively, substantially below the previously reported melting temperature (Tm ~ 70 oC). This destabilization is accompanied by temperature-dependent reaction products that have previously unreport-ed stoichiometries, viz. GroEL14-GroESx-ATPy, where x = 1, 2, 8 and y = 0, 1, 2, that are also dependent on Mg2+ and ATP concentrations. Variable-temperature native mass spectrometry reveals new insights about the stability of GroEL in response to several environmental effects: (i) temperature-dependent ATP binding to GroEL (ii) effects of temperature as well as Mg2+ and ATP concentrations on the stoichiometry of the GroEL-GroES complex, with Mg2+ showing greater effects compared to ATP; and, (iii) a change in the temperature-dependent stoichiometries of the GroEL-GroES complex (GroEL14-GroES7 vs GroEL14-GroES8) between 24 to 56 oC. The similarities between results obtained using native MS and cryo-EM (Clare et al., An expanded protein folding cage in the GroEL-gp31 complex. J Mol Biol 2006, 358, 905-11; Ranson et al., Allosteric signaling of ATP hydrolysis in GroEL–GroES complexes. Nat. Struct. Mol. Biol. 2006, 13, 147-152.) underscores the util-ity of native MS for investigations of molecular machines as well as identification of key intermediates involved in the chaperone-assisted protein folding cycle.
Nuclear Singlet Relaxation by Chemical Exchange
Authors: Bengs Christian , Dagys Laurynas , Moustafa Gamal , Whipham James , Sabba Mohamed , Kiryutin Alexey , Ivanov Konstantin , Levitt Malcolm
Published: February 2022

The population imbalance between nuclear singlet states and triplet states of strongly coupled spin-1/2 pairs, also known as nuclear singlet order, is well protected against several common relaxation mechanisms. We study the nuclear singlet relaxation of 13C pairs in aqueous solutions of 1,2-13C2 squarate, over a range of pH values. The 13C singlet order is accessed by introducing 18O nuclei in order to break the chemical equivalence. The squarate dianion is in chemical equilibrium with hydrogen-squarate (SqH−) and squaric acid (SqH2) characterised by the dissociation constants pKa1 = 1:5 and pKa2 = 3:4. Surprisingly, we observe a striking increase in the singlet decay time constants TS when the pH of the solution exceeds ~ 10, which is far above the acid-base equilibrium points. We derive general rate expressions for chemical-exchange-induced nuclear singlet relaxation and provide a qualitative explanation of the TS behaviour of the squarate dianion. We identify a kinetic contribution to the singlet relaxation rate constant which depends explicitly on kinetic rate constants. Qualitative agreement is achieved between the theory and the experimental data. This study shows that infrequent chemical events may have a strong effect on the relaxation of nuclear singlet order.
Thermoresponsive hydrogels for atmospheric water vapor harvesting
Authors: Cherukupally Pavani , Hao Boyuan , Zhang Zhongshen , Williams Daryl R
Published: February 2022

Currently, freshwater scarcity is a global challenge that is threatening four billion people across the world. To satisfy people’s increasing freshwater demand, harvesting atmospheric water from the air could be an alternative way. This work developed copolymer P(NIPAM-co-15%BzDMA) hydrogels to harvest atmospheric water vapor. Two methods were investigated to improve its adsorption performance: decreasing synthesis temperature below the LCST and copolymerizing with the optimum amount of quaternary ammonium salt (QAS). We found these two methods can effectively improve the water vapor uptake. After copolymerizing NIPAM with 15% QAS at 20°C, the water vapor uptake could be increased by almost 20% to 232 mg/g at 20°C and P/P0 of 0.75 compared with pure PNIPAM prepared at 60°C (194 mg/g). The significant increase can be attributed to the more uniform porous structure and the hygroscopicity of QAS. After coating PNIPAM onto the PESPU sponge skeleton, the PESPU-PNIPAM_60 could adsorb 180 mg/g gas water at 20°C and P/P0 of 0.75, and the modified sponges inherit the switchable wettability from PNIPAM. This research provides polymer processing parameters and their character for harvesting water vapor from the air with hydrogels.
A Facile Transformation of Amino acids into 1,4-dihydropyridines and their Crystallographic Analysis
Authors: Adak Anindita , Koppal Puneeth
Published: February 2022

A facile transformation of amino acids into substituted 1,4-dihydropyridines (1,4-DHP) is reported. The natural amino acids were converted into gamma-amino beta-keto esters and used for the synthesis of substituted 1,4-dihydropyridines from the Hantzsch reaction. Using amino acids as starting materials, a variety of dihydropyridine derivatives have been synthesized and isolated in good yields. This method is found to be efficient and compatible with various amino acid side-chains and amine protecting groups. Results reported here suggested that amino acids can be used to synthesize highly versatile heterocyclic 1,4-dihydropyridine derivatives, without using any catalyst.
Intramolecular, Visible Light-Mediated Aza Paternò-Büchi Reactions of Unactivated Alkenes
Authors: Schindler Corinna , Blackmun Dominique , Chamness Stephen
Published: February 2022

Azetidines are of particular interest in medicinal chemistry for their favorable properties, including increased resistance to oxidative metabolism and lower lipophilicity. The recent development of [2+2] reactions has significantly benefitted the previously limited methods for azetidine synthesis, but access to more complex architectures still requires further development. Herein we report a visible-light enabled intramolecular [2+2] cycloaddition to access tricyclic azetidines with 3D complex structures and high levels of saturation.
Virtual teaching laboratories – hands-on at a distance
Authors: Kobayashi Rika , Gouman Theodorus P. M. , Carstensen N. Ole , Soini Thomas M. , Marzari Nicola , Timrov Iurii , Poncé Samuel , Linscott Edward B. , Sewell Christopher J. , Pizzi Giovanni , Ramirez Francisco , Bercx Marnik , Huber Sebastiaan P. , Adorf Carl S. , Talirz Leopold
Published: February 2022

The COVID-19 pandemic disrupted chemistry teaching practices globally as many courses were forced online necessitating adaptation to the digital platform. The biggest impact was to the practical component of the chemistry curriculum – the so-called wet lab. Naively, it would be thought that computer-based teaching labs would have little problem in making the move. However, this is not the case as there are many unrecognised differences between delivering computer-based teaching in-person and virtually: software issues, technology and classroom management. Consequently, relatively few “hands-on” computational chemistry teaching laboratories are delivered online. In this paper we describe these issues in more detail and how they can be addressed, drawing on our experience in delivering a third-year computational chemistry course as well as remote hands-on workshops for the Virtual Winter School on Computational Chemistry and the European BIG-MAP project.
Virtual computational chemistry teaching laboratories – hands-on at a distance
Authors: Kobayashi Rika , Goumans Theodorus P. M. , Carstensen N. Ole , Soini Thomas M. , Marzari Nicola , Timrov Iurii , Poncé Samuel , Linscott Edward B. , Sewell Christopher J. , Pizzi Giovanni , Ramirez Francisco , Bercx Marnik , Huber Sebastiaan P. , Adorf Carl S. , Talirz Leopold
Published: February 2022

The COVID-19 pandemic disrupted chemistry teaching practices globally as many courses were forced online necessitating adaptation to the digital platform. The biggest impact was to the practical component of the chemistry curriculum – the so-called wet lab. Naively, it would be thought that computer-based teaching labs would have little problem in making the move. However, this is not the case as there are many unrecognised differences between delivering computer-based teaching in-person and virtually: software issues, technology and classroom management. Consequently, relatively few “hands-on” computational chemistry teaching laboratories are delivered online. In this paper we describe these issues in more detail and how they can be addressed, drawing on our experience in delivering a third-year computational chemistry course as well as remote hands-on workshops for the Virtual Winter School on Computational Chemistry and the European BIG-MAP project.
Tuning the Interfacial Stoichiometry of InP Core and InP/ZnSe Core/Shell Quantum Dots
Authors: Park Nayon , Eagle Forrest , DeLarme Asher , Monahan Madison , LoCurto Talia , Beck Ryan , Li Xiaosong , Cossairt Brandi
Published: February 2022

We demonstrate fine-tuning of the atomic composition of InP/ZnSe QDs at the core/shell interface. Specifically, we control the stoichiometry of both anions (P, As, S, and Se) and cations (In, Zn) at the InP/ZnSe core/shell interface and correlate these changes with the resultant steady-state and time-resolved optical properties of the nanocrystals. The use of reactive trimethylsilyl reagents results in surface-limited reactions that shift the nanocrystal stoichiometry to anion-rich and improve epitaxial growth of the shell layer. In general, anion deposition on the InP QD surface results in a redshift in the absorption, quenching of the excitonic photoluminescence, and a relative increase in the intensity of the broad trap-based photoluminescence, consistent with delocalization of the exciton wavefunction and relaxation of exciton confinement. Time-resolved photoluminescence data for the resulting InP/ZnSe QDs show an overall small change in the decay dynamics on the ns timescale, suggesting the relatively low photoluminescence quantum yields may be attributed to the creation of new thermally activated charge trap states and likely a dark population that is inseparable from the emissive QDs. Cluster-model density functional theory calculations show that the presence of core/shell interface anions give rise to electronic defects contributing to the redshift in the absorption. These results highlight a general strategy to atomistically tune the interfacial stoichiometry of InP QDs using surface-limited reaction chemistry allowing for precise correlations with electronic structure and photophysical processes.
CO Reductive Oligomerization by a Divalent Thulium Complex and CO2-Induced Functionalization
Authors: Simler Thomas , McCabe Karl N. , Maron Laurent , Nocton Gregory
Published: February 2022

To date, only a very limited number of complexes based on low-valent main group or f-block elements have allowed the reductive coupling of CO molecules to afford multicarbon oxygenates. Herein, we described the reactivity of the divalent thulium complex [Tm(Cpttt)2] (Cpttt = 1,2,4-tris(tert-butyl)cyclopentadienyl) towards CO, leading to selective CO reductive dimerization and trimerization into ethynediolate (C2) and ketenecarboxylate (C3) complexes, respectively. Quantum chemical (DFT) calculations were performed to shed light on the elementary steps of CO homologation and support a stepwise chain growth from the C2 to the C3 product upon addition of extra CO. The attempted decoordination of the ethynediolate frag-ment by treatment with Me3SiI led to dimerization and rearrangement into a 3,4-dihydroxyfuran-2-one complex. Investiga-tion of the reactivity of the C2 and C3 complexes towards other electrophiles led to unusual functionalization reactions: while the reaction of the ketenecarboxylate C3 complex with electrophiles yielded new multicarbon oxygenated complexes, the addition of CO2 to the ethynediolate C2 complex resulted in the formation of a very reactive intermediate, allowing C–H activation of the toluene solvent. This original intermolecular reactivity corresponds to an unprecedented functionalization of CO-derived ligands, which is induced by CO2.
The Ferric-superoxo Intermediate of the TxtE Nitration Pathway Resists Reduction, Facilitating Its Reaction with Nitric Oxide
Authors: Martin Christopher , Chen Manyun , Martinez Maria , Loria Rosemary , Ding Yousong , Caranto Jonathan
Published: February 2022

TxtE is a cytochrome P450 (CYP) homolog that mediates the nitric oxide (NO)-dependent direct nitration of L-tryptophan (Trp) to form 4-nitro-L-tryptophan (4-NO2-Trp). A recent report showed evidence that TxtE activity requires NO to react with a ferric-superoxo intermediate. Given this minimal mechanism, it is not clear how TxtE avoids Trp hydroxylation, a mechanism that also traverses the ferric-superoxo intermediate. Our combined results suggest 1) autoxidation is the sole TxtE uncoupling pathway and 2) the TxtE ferric-superoxo intermediate cannot be reduced by these electron transfer partners. We conclude that resistance of the ferric-superoxo intermediate to reduction is a key feature of TxtE that increases the lifetime of the intermediate and enables its reaction with NO and efficient nitration activity.
Palladium-Catalyzed Nondirected Late-Stage C-H Deuteration of Arenes
Authors: Farizyan Mirxan , Mondal Arup , Mal Sourjya , Deufel Fritz , van Gemmeren Manuel
Published: February 2022

We describe a palladium catalyzed non-directed late-stage deuteration of arenes. Key aspects include the use of D2O as a convenient and easily available deuterium source and the discovery of highly active N,N-bidentate ligands containing an N-acyl sulfonamide group. The reported protocol enables high degrees of deuterium incorporation via a reversible C-H activation step and features an extraordinary functional group tolerance, allowing for the deuteration of complex substrates. This is exemplified by the late-stage isotopic labelling of various pharmaceutically relevant motifs and related scaffolds. We expect that this method, amongst other applications, will prove useful as a tool in drug development processes and for mechanistic studies.
Visualizing reaction fronts and transport limitations in solid-state Li-S batteries via operando neutron imaging
Authors: Bradbury Robert , Dewald Georg F. , Kraft Marvin A. , Arlt Tobias , Kardjilov Nikolay , Janek Jürgen , Manke Ingo , Zeier Wolfgang G. , Ohno Saneyuki
Published: February 2022

The exploitation of high-capacity conversion-type materials such as sulfur in solid-state secondary batteries is a dream combination for achieving improved battery safety and high energy density in the push towards a sustainable future. Yet, the exact rate-limiting step, bottlenecking further development of solid-state lithium-sulfur batteries, has not been determined. Here, we directly visualize the spatial distribution of lithium via neutron imaging during operation and show that sluggish macroscopic ion transport within the composite cathode is rate-limiting. Observing a reaction front propagating from the separator side towards the current collector confirms detrimental influences of a low effective ionic conductivity. Furthermore, irreversibly concentrated lithium in the vicinity of the current collector, revealed via state-of-charge-dependent tomography, highlights a hitherto-overlooked loss mechanism triggered by sluggish effective ionic transport within a composite cathode. This discovery will be a cornerstone for future research on solid-state batteries, irrespective of the type of active material.
Americium preferred: Lanmodulin, a natural lanthanide-binding protein favors an actinide over lanthanides
Authors: Singer Helena , Drobot Björn , Zeymer Cathleen , Steudner Robin , Daumann Lena
Published: February 2022

The separation and recycling of lanthanides is an active area of research with a growing demand that calls for more environmentally friendly lanthanide sources. Likewise, the efficient and industrial separation of lanthanides from the minor actinides (Np, Am - Fm) is one of the key questions for closing the nuclear fuel cycle; reducing costs and increasing safety. With the advent of the field of lanthanide dependent bacterial metabolism, bio-inspired applications are in reach. Here, we utilize the natural lanthanide chelator Lanmodulin and the luminescent probes Eu3+ and Cm3+ to investigate the inter-metal competition behavior of all lanthanides (except Pm) and four actinides (Np, Pu, Am, Cm) to Lanmodulin. Using time resolved laser induced fluorescence spectroscopy we show that Lanmodulin has the highest relative binding affinity to Nd3+ and Eu3+ among the lanthanide series. When equimolar mixtures of Cm3+ and Am3+ are added to Lanmodulin, Lanmodulin preferentially binds to Am3+ over Cm3+ whilst Nd3+ and Cm3+ bind with similar relative affinity. The results presented show that a natural lanthanide binding protein can bind various actinides with high relative affinity, paving the way to bio inspired separation applications. In addition, an easy and versatile method was developed, using the fluorescence properties of only two elements, Eu and Cm, for inter-metal competition studies regarding lanthanides and selected actinides and their binding to biological molecules.
Solvation of anthraquinone and Tempo redox-active species in acetonitrile using a polarizable force field
Authors: Berthin Roxanne , Serva Alessandra , Reeves Kyle , Heid Esther , Schroeder Christian , Salanne Mathieu
Published: February 2022

Redox active molecules are of interest in many fields such as medicine, catalysis or energy storage. In particular, in supercapacitor applications, they can be grafted to ionic liquids to form so-called biredox ionic liquids. To completely understand the structural and transport properties of such systems, an insight at the molecular scale is often required but few force fields are developed ad hoc for these molecules. Moreover, they do not include polarization effects, which can lead to inaccurate solvation and dynamical properties. In this work, we developed polarizable force fields for redox-active species anthraquinone (AQ) and 2,2,6,6-tetra-methylpiperidinyl-1-oxyl (TEMPO) in their oxidized and reduced states, as well as for acetonitrile. We validate structural properties of AQ, AQ$^{\bullet-}$, AQ$^{2-}$, TEMPO$^{\bullet}$ and TEMPO$^{+}$ in acetonitrile against density functional theory-based molecular dynamics simulations and we study the solvation of these redox molecules in acetonitrile. This work is a first step toward the characterization of the role played by AQ and TEMPO in electrochemical and catalytic devices.
Ideal Gas Reference for Association and Dissociation Reactions: I. Basic Concepts
Authors: Binninger Tobias , Heinritz Adrian , Mohamed Rhiyaad
Published: February 2022

Starting with a distance-based definition of molecules consisting of non-interacting atoms, which is in line with IUPAC terminology, we construct an ideal gas reference for chemical association and dissociation reactions. The corresponding ideal equations for equilibria and kinetics reveal the mathematical structure, known for real systems, in comprehensible clarity. The ideal gas reference corresponds to the limit of an entirely flat potential energy surface of the system where chemical equilibria and kinetics are determined by "unspecific" particle number combinatorics according to the reaction stoichiometry. The ideal equilibrium and rate constants provide a reference for the definition of excess equilibrium and rate constants of real reactions that quantify all "system-specific" contributions resulting from the particular shape of the potential energy surface. The ideal gas reference therefore enables a distinction between unspecific and system-specific aspects in the equilibria and kinetics of chemical association/dissociation reactions. Whereas conventional equilibrium and rate constants suffer from incompatibility between reactions of different stoichiometry, excess equilibrium and rate constants can be consistently compared across different reaction orders. Furthermore, whereas the conventional treatment requires an arbitrary specification of reference concentrations, e.g. at standard conditions, the ideal gas framework introduces an intrinsic concentration scale that is equal to the inverse of a molecular volume.
Rhodium Catalyzed Stereoselective Mono-alkenylation of Aryl sp2 C-H Bond via C-N Bond Cleavage: N-allylbenzimidazole as Strategic Alkenylating Agent
Authors: Biswal Pragati , Nanda Tanmayee , Banjare Shyam Kumar , Mohanty Smruti Ranjan , Ravikumar Ponneri C.
Published: February 2022

A Rh-catalyzed C(sp2)-H alkenylation has been achieved by taking N-allylbenzimidazole as an allylamine congener. This distinctive transformation has been observed for the first time which is attributed to the rigid benzimidazole unit. Lewis acid assisted cleavage of C(sp3)-N bond by coordinating to the N3 of N-allylbenzimidazole has been established. Thus, herein we have demonstrated an unprecedented protocol of domino C-N bond cleavage followed by aryl C(sp2)-H alkenylation. Further, detailed mechanistic studies, control experiments have been conducted to understand the mechanism. The rhodacycle-intermediates involved in the reaction have been isolated and characterized through NMR, HRMS, and single crystal X-ray.
Radical alpha-Trifluoromethoxylation of Ketones by Means of Organic Photoredox Catalysis
Authors: Dell'Amico Luca , Duhail Thibaut , Bortolato Tommaso , Mateos Javier , Anselmi Elsa , Jelier Benson , Togni Antonio , Magnier Emmanuel , Dagousset Guillaume
Published: February 2022

The first light-driven method for the alpha-trifluoromethoxylation of ketones is reported. Enol carbonates, in particular Boc derivatives, react with N-trifluoromethoxy-4-cyano-pyridinium triflimide (2a) using the photoredox-catalyst 4-CzIPN (5 mol-%) under irradiation at 456 nm affording the corresponding α-trifluoromethoxy ketones in up to 50% isolated yield and virtually complete chemoselectivity. As shown by 35 examples, representing a great variety of substrates, the reaction is general and proceeds rapidly under batch (1h) and flow conditions (2 min). Mechanistic investigations reveal that a radical-chain propagation is operative, as efficiently orchestrated by the activity of the organic photoredox catalyst. Diverse products manipulations, including ketone reduction and reductive amination, demonstrate the synthetic potential of the disclosed method to accessing elusive trifluoromethoxylated potentially bioactive ingredients.
Regulating the dynamic folding of a DNA hairpin at the expense of a small, molecular fuel
Authors: Stasi Michele , Monferrer i Sureda Alba , Babl Leon , Wunnava Sreekar , Dirscherl Christina , Braun Dieter , Schwille Petra , Dietz Hendrik , Boekhoven Job
Published: February 2022

Molecular machines, such as ATPases or motor proteins, couple the catalysis of a chemical reaction, most commonly hydrolysis of nucleotide triphosphates, to their conformational change. In essence, they continuously convert a chemical fuel to drive their motion. An outstanding goal of nanotechnology remains to synthesize a nanomachine with similar functions, precision, and speed. The field of DNA nan- otechnology has given rise to the engineering precision required for such a device. Simultaneously, the field of systems chemistry developed fast chemical reaction cycles that convert fuel to change the function of molecules. In this work, we thus combined a fast, chemical reaction cycle with the precision of DNA nanotechnology to yield kinetic control over the conformational state of a DNA hairpin. Future work on such systems will result in fast and precise DNA nanodevices.
Efficient discovery of visible light-activated azoarene photoswitches with long half-lives using active search
Authors: Mukadum Fatemah , Nguyen Quan , Adrion Daniel , Appleby Gabriel , Chen Rui , Dang Haley , Chang Remco , Garnett Roman , Lopez Steven
Published: February 2022

Photoswitches are molecules that undergo a reversible, structural isomerization after exposure to different wavelengths of light. The dynamic control offered by molecular photoswitches is favorable for applications in materials chemistry, photopharmacology, and catalysis. Ideal photoswitches absorb visible light and have long-lived metastable isomers. We used high throughput virtual screening to predict the absorption maxima (λmax) of the E-isomer and half-lives (t1/2) of the Z-isomer. However, computing the photophysical and kinetic properties of each entry of a virtual molecular library containing 103–106 entries with density functional theory is prohibitively time-consuming. We applied active search, a machine learning technique to intelligently search a chemical search space of 255991 photoswitches based on 29 known azoarenes and their derivatives. We iteratively trained the active search algorithm based on whether a candidate absorbed visible light (λmax > 450 nm). Active search was found to triple the discovery rate compared to random search. Further, we projected 1962 photoswitches to 2D using the Uniform Manifold Approximation and Projection (umap) algorithm and found that λmax depends on the core, which is tunable with substituents. We then incorporated a second stage of screening with to predict the stabilities of the Z-isomers for the top 1% of candidates. We identified four ideal photoswitches that concurrently satisfy λmax > 450 nm and t1/2 > 2 hours; the range of λmax and t1/2 range from 465 to 531 nm and hours to years, respectively.
Thiol Catalyzed Aerobic Debenzylation of Alcohols and Amines
Authors: Lardy Samuel , Schmidt Valerie
Published: February 2022

We report a radical method for the removal of benzyl and p-methoxybenzyl groups from amines and alcohols using a selec-tive hydrogen-atom abstraction under aerobic conditions. The key usage of the strongly electrophilic thiyl radical derived from commercially available pentafluorothiophenol allowed for a chemoselective abstraction process leading to C-N or C-O bond cleavage. This approach is applicable to an array of alcohols and amines without addition of a stoichiometric external oxidant or hazardous reagents.
Study of Pseudomonas aeruginosa PPF-1 biofilm formation using microfluidics: effect of magnesium on biofilm detachment in engineered conduits
Authors: Harvey William Y. , Gagné-Thivierge Cynthia , Fakari Sepideh , Barbeau Jean , Charette Steve , Greener Jesse
Published: February 2022

The bacterium Pseudomonas aeruginosa is an opportunistic pathogen in certain organisms, including humans, but can also survive and proliferate in natural and engineered water systems. Microfluidic technology can address hydrodynamic questions related to bacterial contamination of water flow systems and infrastructure. In this work, a microfluidic approach was devised to study the effect of shear stresses on biofilms from a dental unit waterline (DUWL)-isolated P. aeruginosa strain, PPF-1. During application of relevant shear stress levels to DUWLs, the response of the PPF-1 biofilm was observed and compared to a clinical P. aeruginosa reference strain, PAO1. The response measurements were repeated for biofilms exposed to additional Mg2+ ions. Using a microfluidic approach to transforming optical density maps into three-dimensional images, we applied computational fluid dynamics simulations and determined the critical shear stresses for biofilm sloughing. In the absence of Mg2+, PPF-1 biofilms showed weaker attachment than PAO1 biofilms, resulting in continuous slough/regrowth cycles triggered by applied shear stresses of 1.42 +/- 0.32 Pa. Introducing Mg2+ into the PPF-1 biofilm culture medium seemed to place the biofilm into a viscoplastic mechanical state, thereby increasing mechanical stability, which resulted in elevated tolerances to shear stresses up to a critical value of 5.43 +/- 1.52 Pa. This resulted in a propensity for less frequent but more catastrophic sloughing events like that observed for the PAO1 reference strain. This suggests that in a low ionic environment, biofilms from the PPF-1 strain can result in higher and more continuous ejection of biofilm materials, possibly leading to increased downstream colonization of engineered flow systems.
Examining the Modular Synthesis of [Cp*Rh] Monohydrides Supported by Chelating Diphosphine Ligands
Authors: Comadoll Chelsea , Henke Wade , Hopkins Leseberg Julie , Douglas Justin , Oliver Allen , Day Victor , Blakemore James
Published: February 2022

[Cp*Rh] hydride complexes are invoked as intermediates in certain catalytic cycles, but few of these species have been successfully prepared and isolated, contributing to a relative shortage of information on the properties of such species. Here, the synthesis, isolation, and characterization of two new [Cp*Rh] hydrides are reported; the hydrides are supported by the chelating diphosphine ligands bis(diphenylphosphino)methane (dppm) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos). In both systems, reduction of precursor Rh(III) chloride complexes with Na(Hg) results in clean formation of isolable, formally 18e– Rh(I) species, and subsequent protonation by addition of near-stoichiometric quantities of anilinium triflate to the Rh(I) species returns high yields of the desired monohydride complexes. Single-crystal X-ray diffraction data for these compounds provide evidence of direct Rh–H interactions, confirmed by complementary infrared spectra showing Rh–H stretching frequencies at 1982 cm–1 (for the dppm-supported hydride) and 1936 cm–1 (for the Xantphos-supported hydride). Findings from comprehensive multinuclear NMR experiments reveal the properties of the unique and especially rich spin systems for the dppm-supported hydride; multifrequency NMR studies in concert with spectral simulations enabled full characterization of splitting patterns attributable to couplings involving diastereotopic methylene protons for this complex. Taken together with prior reports of related monohydrides, the results show that the reduction/protonation reaction sequence is modular for preparation of [Cp*Rh] monohydrides supported by diverse diphosphine ligands spanning from four- to eight-membered rhodacycles.
Effect of Vanadium Substitution on the Ni-Site in P2-Type Na0.67Ni0.33Mn0.67O2 in Optimized Carbonate Ester Electrolytes as Cathode for Sodium-Ion Batteries
Authors: Pahari Debanjana , Puravankara Sreeraj
Published: February 2022

Solid-state synthesis of novel electrode materials of P2-type layered oxides Na0.67Ni0.33-xVxMn0.67O2 (where, x = 0, 0.05, and 0.11) for the application as cathode materials in rechargeable non-aqueous sodium-ion batteries is reported. Na0.67Ni0.22V0.11Mn0.67O2 electrode delivers significantly improved capacity retention than the pristine P2-Na0.67Ni0.33Mn0.67O2 when cycled between 1.5 and 4.3 V. The effect of organic ester electrolytes with 1.0 M NaClO4 shows diverse effects in the cathode material. The best capacity retention for V-substituted electrodes is observed in Ethylene carbonate (EC): Propylene carbonate (PC): Dimethyl carbonate (DMC) (0.45: 0.45: 0.1) with 1.0 M NaClO4 salt at a C-rate of 0.2C among four different ester electrolytes investigated [PC, EC: PC (1: 1), EC: DEC (1: 1) and EC: PC: DMC (0.45: 0.45: 0.1)].
Coumarin-bisureas as potent fluorescent transmembrane anion transporters
Authors: Fares Mohamed , Wu Xin , McNaughton Daniel A. , Gilchrist Alexander M. , Lewis William , Keller Paul A. , Arias-Betancur Alain , Pérez-Tomás Ricardo , Gale Philip Alan
Published: February 2022

A series of fluorescent coumarin bis-ureas have been synthesised and their anion transport properties studied. The compounds function as highly potent HCl co-transport agents in lipid bilayer membranes.
In-liquid plasma for surface engineering of Cu electrodes with incorporated SiO2 nanoparticles: From micro to nano
Authors: V. Menezes Pramod , M. Elnagar Mohamed , Al-Shakran Mohammad , Eckl Maximilian , W. Menezes Prashanth , A. Kibler Ludwig , Jacob Timo
Published: February 2022

A robust and efficient route to modify the chemical and physical properties of polycrystalline Cu wires via versatile plasma electrolysis is presented. Silica nanoparticles (11 nm) have been introduced during the electrolysis to tailor the surface structure of the Cu electrode. The influence of these silica nanoparticles on the structure of the Cu electrodes during plasma electrolysis over a wide array of applied voltages and processing time is investigated systematically. Homogeneously distributed 3D coral-like microstructures are observed by scanning electron microscopy on the Cu surface after the in-liquid plasma treatment. These 3D microstructures grow with increasing plasma processing time. Interestingly, the microstructured copper electrode is composed of Cu(II) oxide as a thin outer shell and a significant amount of inner Cu(I) oxide. Furthermore, the oxide film thickness (between 1 and 70 μm), the surface morphology, and the chemical composition can be tuned by controlling the plasma parameters. Remarkably, the fabricated microstructures can be transformed to nanospheres assembled in coral-like microstructures by a simple electrochemical treatment.
In silico identification and validation of organic triazole based ligands as potential inhibitory drug compounds of SARS-CoV-2 main protease
Authors: Sur Vishmapratap , Sen Madhab Kumar , Komrsková Kateřina
Published: February 2022

The SARS-CoV-2 virus is highly contagious to humans and has caused a pandemic of global proportions. Despite worldwide research efforts, efficient targeted therapies against the virus are still lacking. With the ready availability of the macromolecular structures of coronavirus and its known variants, the search for anti-SARS-CoV-2 therapeutics through in silico analysis, has become a highly promising field of research. In this study, we investigate the inhibiting potentialities of triazole-based compounds against the SARS-CoV-2 main protease (Mpro). The SARS-CoV-2 main protease (Mpro) is known to play a prominent role in the processing of polyproteins that are translated from the viral RNA. Compounds were pre-screened from 171 candidates (collected from the DrugBank database). The results showed that four candidates (Bemcentinib, Bisoctrizole, PYIITM and NIPFC) had high binding affinity values and had the potential to interrupt the main protease (Mpro) activities of the SARS-CoV-2 virus. The pharmacokinetic parameters of these candidates were assessed and they were then put through molecular dynamic (MD) simulation for stability, interaction and conformation analysis. In summary, we successfully identified the most suitable compounds for targeting SARS-CoV-2 main protease (Mpro). Based on our computational studies, we can suggest that the identified compounds can be used for further experimental approach as potential drug molecules against SARS-CoV-2.