bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrochemical and Mechanistic Study of Oxidative Degradation of Favipiravir by Electro-generated Superoxide through Proton-coupled Electron Transfer
Authors: Nakayama Tatsushi , Honda Ryo
Published: February 2022

Electrochemical analyses aided by density functional theory calculations were used to investigate the oxidative degradation of pyrazine antiviral drugs, 3-hydroxypyrazine-2-carboxamide (T-1105) and 6-fluoro-3-hydroxypyrazine-2-carboxamide (favipiravir, T-705), by electro-generated superoxide radical anion. T-1105 and T-705 are antiviral RNA nucleobase analogs that selectively inhibit the RNA-dependent RNA polymerase. They are expected as a drug candidate against various viral infections, including COVID-19. The pyrazine moiety was decomposed by superoxide through proton-coupled electron transfer (PCET). Our results show that its active form, pyrazine-ribofuranosyl-5'-triphosphate, is easily oxidized under inflamed organs by overproduced superoxide through the PCET mechanism in the immune system. This mechanistic study implies that the oxidative degradation of pyrazine derivatives will be prevented by controlling the PCET through simple modification of the pyrazine structure.
Lipid cubic mesophases combined with Superparamagnetic Iron Oxide Nanoparticles: a hybrid multifunctional platform with tunable magnetic properties for nanomedical applications
Authors: Caselli Lucrezia , Mendozza Marco , Muzzi Beatrice , Toti Alessandra , Montis Costanza , Mello Tommaso , Di Cesare Mannelli Lorenzo , Ghelardini Carla , Sangregorio Claudio , Berti Debora
Published: February 2022

Hybrid materials composed of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) and lipid self-assemblies possess a considerable applicative potential in the biomedical field, specifically, for drug/nutrients delivery. In recent works we have shown that SPION-doped lipid cubic liquid crystals undergo a cubic-to-hexagonal phase transition under the action of temperature or of an alternating magnetic fields (AMF). This transition triggers the release of drugs embedded in the lipid scaffold or in the water channels. In this contribution, we address this phenomenon in depth, to fully elucidate the structural details and optimize the design of hybrid multifunctional carriers for drug delivery. Combining Small-Angle X-Ray Scattering (SAXS) with a magnetic characteri-zation, we find that in bulk lipid cubic phases the cubic-to-hexagonal transition determines the magnetic response of SPIONs. We then extend the investigation from bulk liquid-crystalline phases to colloidal dispersions, i.e. to lipid/SPIONs nanoparticles with cubic internal structure (“magnetocubosomes”). Through Synchrotron SAXS, we monitored the structural response of magnetocubosomes while exposed to an AMF: the magnetic energy, converted into heat by SPIONs, activates the cubic-to-hexagonal transition, and can thus be used as a remote stimulus to spike drug release “on-demand”. In addition, we show that the AMF-induced phase transition in magnetocubosomes steers the re-alignment of SPIONs into linear string assemblies and connect this effect with the change in their magnetic properties, observed at the bulk level. Finally, we assess the internalization ability and cytotoxicity of magnetocubosomes in vitro on HT29 ade-nocarcinoma cancer cells, in order to test the applicability of these smart carriers in drug delivery applications
Enzyvitands: versatile evolvable colorimetric chembioreceptors
Authors: Rossel Thibaud , Bing zhang , Gobat Raphael
Published: February 2022

Designing the perfect sensor is the dream of any chemist. Since decades, a wide diversity of synthetic receptors targeting analytes has been explored in chemistry. Their chemical optimization is hard and with no guarantee of success. In this context, we propose a fast and self assembling colorimetric bio-chemical receptor coined Enzyvitand. It consists only of commercial chemicals. It relies on the reunification of combinatorial chemistry , first and second coordination spheres interactions and indicators displacement assays. All harbored within a protein cavity. The sensor is highly modular, cheap and evolvable. Thanks to its solved X-ray structure, we rationally designed it for the selectiv naked-eye recognition of dopamine over other neutrotransmitters through second coordination sphere. Hence, our sensor imitates a biological receptor for the recognition of neurotransmitters. Finally, it works in complex samples such as urine. Its immediate high versatility and evolvability is valuable for the selective detection of a wide assortment of analytes from small molecules up to micro-organisms. For the future, we anticipate new biotechnological or immunotherapeutic applications of our synthetic oligomer.
PhotothermalPhage: A Virus-Based Photothermal Therapeutic Agent
Authors: Shahrivarkevishahi Arezoo , Luzuriaga Michael A. , Herbert Fabian C. , Tumac Alisia C. , Brohlin Olivia R. , Wijesundara Yalini H. , Adlooru Abhinay V. , Benjamin Candace , Lee Hamilton , Parsamian Perouza , Gadhvi Jashkaran , De Nisco Nicole J. , Gassensmith Jeremiah J.
Published: February 2022

ABSTRACT: Virus-like particles (VLPs) are multifunctional nanocarriers that mimic the architecture of viruses. They can serve as a safe platform for specific functionalization and immunization, which provides benefits in a wide range of biomedical applications. In this work, a new generation immunophotothermal agent is developed that adjuvants photothermal ablation using a chemically modified VLP called bacteriophage Qβ. The design is based on the conjugation of near-infrared absorbing croconium dyes to lysine residues located on the surface of Qβ, which turns it to a powerful NIR-absorber called Photothermal Phage. This system can generate more heat upon 808 nm NIR laser radiation than free dye and possesses a photothermal efficiency comparable to gold nanostructures, yet it is biodegradable and acts as an immunoadjuvant combined with the heat it produces. The synergistic combination of thermal ablation with the mild immunogenicity of the VLP leads to effective suppression of primary tumors, reduced lung metastasis, and increased survival time.
Influence of non-protein amino-acid mimosine in peptide conformational propensities from novel Amber force field parameters
Authors: Urriolabeitia Asier , De Sancho David , López Xabier
Published: February 2022

Mimosine is a non-protein amino acid derived from plants known for its ability to bind to divalent or trivalent metal cations such as Zn$^{2+}$, Ni$^{2+}$, Fe$^{2+}$ or Al$^{3+}$. This results in interesting antimicrobial and anti-cancer properties, which make mimosine a promising candidate for therapeutic applications. One possibility is to incorporate mimosine into synthetic short peptide drugs. However, our understanding of how this amino acid affects peptide structure is still limited, reducing our ability to design effective therapeutic compounds. In this work, we used computer simulations to understand this question. We first build parameters for the mimosine residue to be used in combination with two classical force fields of the Amber family. Then, we used atomistic molecular dynamics simulations with the resulting parameter sets to evaluate the influence of mimosine in the structural propensities for this amino acid. We compared the results of these simulations with identical peptides where mimosine is replaced by either phenylalanine or tyrosine. We found that the strong dipole in mimosine induces a preference for conformations where the amino acid rings are stacked over more traditional conformations. We validated our results using quantum mechanical calculations, which provide a robust foundation to the outcome of our classical simulations.
Heterocyclic Hypervalent Iodine(III) Compounds with Fused Benziodazole and Tetrazole Rings (I-Substituted Tetrazolo[1,5-b][1,2]Benziodazoles)
Authors: Kumar Rajesh , Sayala Kapil Dev , Camdzic Lejla , Siegler Maxime , Vaish Avichal , Tsarevsky Nicolay
Published: February 2022

A series of heterocyclic hypervalent (HV) iodine(III) compounds containing fused tetrazole and benziodazole rings, i.e., derivatives of benziodazolotetrazole (BIAT) with various ligands attached to the iodine atom were prepared and studied. BIAT-Cl was synthesized via chlorination of 5-(2-iodophenyl)-1H-tetrazole and subsequent spontaneous cyclo-dehydrochlorination of the initially formed dichloroiodo compound. The oxidation of the aforementioned parent monovalent iodine substrate with NaIO4 yielded BIAT-OH, which was in turn reacted with acetic anhydride to afford the I-acetoxy derivative BIAT-OAc. BIAT-OMe was obtained by refluxing the latter compound or by dissolving (2-(1H-tetrazol-5-yl)phenyl)(hydroxy)iodonium tosylate in methanol. All heterocyclic HV iodine(III) compounds were characterized by 1H and 13C NMR spectroscopy, ESI-HRMS, and single crystal X-ray crystallography. The reaction of alkenes with BIAT-Cl in the presence of Cu(OTf)2 at room temperature afforded chloro-tetrazolylated products in 70-88% isolated yields. The oxidation of thioanisole with BIAT-Cl under various reaction conditions is also reported. The thermal stabilities of all BIAT derivatives were examined as well. The enthalpies of exothermic degradation were measured by thermal gravimetric analysis coupled with differential scanning calorimetry and were determined to be in the range between −35.3 and −305.3 kJ mol-1, i.e., significantly larger than the enthalpy of decomposition (−29.4 kJ mol-1) of the parent monovalent iodine-containing tetrazole – 5-(2-iodophenyl)-1H-tetrazole.
Photoredox α-Arylation of Carbonyl Compounds
Authors: Hossain MdMubarak , Shaikh Aslam , Moutet Jules , Gianetti thomas
Published: February 2022

The direct α-arylation of unactivated carbonyl compounds using aryl halides represents a powerful method to synthesize criti-cal building blocks for diverse useful compounds. Numerous synthetic methods exist to forge C(sp2)-C(sp3) bonds, albeit metal free direct α-arylation of unactivated cyclic ketones has long been an elusive transformation. Herein, we report a green-light-mediated α-arylation of unactivated ketones from readily available aryl halides via activation of a C(sp2)-X bond (X=I, Br, Cl) and an α-carbonyl C(sp3)-H bond in a single photocatalytic cycle. This approach is characterized by its mild reaction conditions, operational simplicity, and wide functional group tolerance. Importantly, the impressive outcome from multi-gram photocatalytic reaction underpins the strength of this method as a potentially practical and attractive approach for scale-up industrial purposes. The utility and scope of this reaction were further demonstrated by new syntheses of several feedstock chemicals that are commercially expensive but critical for synthesizing numerous pharmaceutical agents.
Photoredox α-Arylation of cyclic ketones
Authors: Hossain MdMubarak , Shaikh Aslam , Moutet Jules , Gianetti thomas
Published: February 2022

The direct α-arylation of unactivated carbonyl compounds using aryl halides represents a powerful method to synthesize criti-cal building blocks for diverse useful compounds. Numerous synthetic methods exist to forge C(sp2)-C(sp3) bonds, albeit metal free direct α-arylation of unactivated cyclic ketones has long been an elusive transformation. Herein, we report a green-light-mediated α-arylation of unactivated ketones from readily available aryl halides via activation of a C(sp2)-X bond (X=I, Br, Cl) and an α-carbonyl C(sp3)-H bond in a single photocatalytic cycle. This approach is characterized by its mild reaction conditions, operational simplicity, and wide functional group tolerance. Importantly, the impressive outcome from multi-gram photocatalytic reaction underpins the strength of this method as a potentially practical and attractive approach for scale-up industrial purposes. The utility and scope of this reaction were further demonstrated by new syntheses of several feedstock chemicals that are commercially expensive but critical for synthesizing numerous pharmaceutical agents.
Weldable and Closed-loop Recyclable Monolithic Dynamic Covalent Polymer Aerogels
Authors: Zhang Xinhai , Zhao Jun , Liu Kai , Li Guangfeng , Zhao Dong , Zhao Zhaoming , Wan Junjun , Yang Xue , Bai Ruixue , Wang Yongming , Zhang Wei , Yan Xuzhou
Published: February 2022

Owing to their low density, high porosity and unique micro-nanostructures, aerogels are attractive for applications in various aspects, but at the same time, suffer from shrinkage and/or cracking during preparation, mechanical brittleness, low production efficiency, and non-degradation. Herein, we introduce the concept of dynamic covalent polymer chemistry to produce a new class of aerogelsreferred to as DCPAs. The resulting light DCPAs display large-scale preparation prospect and feature high porosity (90.7-91.3%), large degrees of compression (80% strain) and bending (diametral deflection of 30 mm) without any cracks, as well as considerable tensile property (elongation at break of 32.7%). In addition, our DCPAs showcase emergent characteristics of weldability, repairability, and closed-loop recyclability that are highly desirable for affording versatile materials platforms but hardly achieved by traditional aerogels. Benefiting from the robust porous structures, we demonstrate the potential of the DCPAs for applications in thermal insulation and emulsion separation.
New Modular Organic Platform For Understanding The Effect Of Structural Changes On Slow Magnetic Relaxation In Mononuclear Octahedral Copper(II) Complexes
Authors: Marcinkowski Dawid , Adamski Ariel , Kubicki Maciej , Consiglio Giuseppe , Patroniak Violetta , Ślusarski Tomasz , Açıkgöz Muhammed , Szeliga Daria , Vadra Nahir , Karbowiak Mirosław , Stefaniuk Ireneusz , Rudowicz Czesław , Gorczyński Adam , Korabik Maria
Published: February 2022

Current advances in molecular magnetism are aimed at the construction of molecular nanomagnets and spin qubits for their utilization as high-density data storage materials and quantum computers. Mononuclear coordination compounds with low spin values of S=½ are excellent candidates for this endeavour, but their construction via rational design is limited. This particularly applies to the single copper(II) spin center, having been only recently demonstrated to exhibit slow relaxation of magnetisation in the appropriate octahedral environment. We have thus prepared a novel, modular organic scaffold that would allow one to gain in-depth insight into how purposeful structural differences affect the slow magnetic relaxation in monometallic, transition metal complexes. As a proof-of-principle, we demonstrate how one can construct two, structurally very similar complexes with isolated Cu(II) ions in an octahedral ligand environment, the magnetic properties of which differ significantly. The differences in structural symmetry effects and in magnetic relaxation are corroborated with a series of experimental and theoretical techniques, showing how symmetry distortions and crystal packing affect the relaxation behaviour in these isolated Cu(II) systems. Our highly modular organic platform can be efficiently utilized for the construction of various transition-metal ion systems in the future, effectively providing a model system for investigation of magnetic relaxation via targeted structural distortions.
Actinic Wavelength Action Spectroscopy of the IO− Reaction Intermediate
Authors: McKinnon Benjamin , Marlton Samuel , Ucur Boris , Bieske Evan , Poad Berwyck , Blanksby Stephen , Trevitt Adam
Published: February 2022

Iodinate anions are important in the chemistry of the atmosphere where they are implicated in ozone depletion and particle formation. The atmospheric chemistry of iodine is a complex overlay of neutral-neutral, ion-neutral and photochemical processes, where many of the reactions and intermediates remain poorly characterised. This study targets the visible spectroscopy and photostability of the gas-phase hypoiodite anion (IO−), the initial product of the I− + O3 reaction, by mass spectrometry equipped with resonance-enhanced photodissociation and total ion-loss action spectroscopies. It is shown that IO− undergoes photodissociation to I− + O (3P) over 637 – 459 nm (15700 – 21800 cm−1) due to excitation to the bound first singlet excited state. Electron photodetachment competes with photodissociation above the electron detachment threshold of IO− at 521 nm (19200 cm−1) with peaks corresponding to resonant autodetachment involving the singlet excited state and the ground state of neutral IO possibly mediated by a dipole-bound state.
Connecting lab experiments with computer experiments: Making "routine" simulations routine
Authors: Jablonka Kevin Maik , Zasso Michaël , Patiny Luc , Marzari Nicola , Pizzi Giovanni , Smit Berend , Yakutovich Aliaksandr V.
Published: February 2022

Nowadays, computer simulations and experiments are closely interlocked. However, the data and analysis workflows are often barred into "silos" of knowledge — even for routine simulations. Here, we show how a typical electronic laboratory notebook (ELN) environment can be seamlessly integrated with a computational modelling infrastructure. We developed a protocol to initiate advanced molecular or atomic simulations directly from an ELN. Such integration ensures that all the relevant sample and experimental data are transferred from the ELN to the modelling infrastructure, and — once the calculations have completed — back to the ELN. The presented protocol works similar to sending out a sample for external characterisation and enables experimentalists to routinely perform "routine" simulations to compare with their experiments while keeping track of the full experiment and simulation provenance. We illustrate our protocol with some examples of geometry optimisation followed by the calculation of adsorption isotherms, but the implementation can be readily generalised to other techniques such as optical absorption or X-ray photoelectron spectroscopy.
Stretchable and durable inverse vulcanized polymers with chemical and thermal recycling
Authors: Hasell Tom , Yan Peiyao , Zhao Wei , Tonkin Samuel , Chalker Justin , Schiller Tara
Published: February 2022

Inverse vulcanized polymer materials have received considerable attention as a way to use sulfur, an industrial by-product, as starting material for synthesis. The resulting high-sulfur content polymers have also been investigated because their properties give rise to promising applications like infrared imaging, energy storage, and heavy metal capture due to their unique structure. However, synthesis of a flexible sulfur polymer network which shows good mechanical properties combining high strength, high elongation, and high toughness is still a significant challenge. Moreover, further exploration of the properties of sulfur polymers to better understand the relationship between the polymers’ structure with their performance is still needed. Here, a range of crosslinked sulfur polymers with high tensile elongation and toughness, and without losing high strength were successfully synthesized. The obtained crosslinked sulfur polymers show high solvent tolerance in most organic solvents but are demonstrated to be chemically de-crosslinked in polar solvents dimethylformamide, dimethylacetamide and N-methyl-2-pyrrolidone and can be re-crosslinked after removing the solvent due to the high sulfur ranks present in the polymer network. Despite the significantly improved mechanical properties, highly efficient thermal recycling performance typical of inverse vulcanized polymers was retained. Flexibility and durability, combined with chemical and thermal recycling, could open a new door for wider applications of inverse vulcanized polymers.
Precise control of the degree and regioselectivity of functionalization in nitro- and amino-functionalized di(trispyrazolylborato)iron(II) spin crossover complexes
Authors: Ma Chenyang , Besson Claire
Published: February 2022

Di(trispyrazolylborato)iron(II) ([Tp2Fe]) complexes represent one of the most robust class of spin crossover complexes. Their stability renders them particularly suitable for integration in nanoscale devices, e.g. as sensors or information storage units. Prior studies of the functionalization of those derivatives have been limited to the steric effect alkyl groups in position 3. The pyrazole exchange reaction between nitropyrazole and either trispyrazolylborate or its iron complex allows the regioselective installation of nitro substituents in positions 3, 4 and 5 of [Tp2Fe] complexes. The degree of substitution can be varied from 1 to 4 functionalized pyrazoles per complex. The amine functionalized analogues are accessed by reduction of the nitro analogues under hydrogen transfer conditions. With the exception of di- and tetra-3-NO2 substituted complexes, all derivatives display spin crossover properties in the solid state, with transition temperatures ranging from 180 to 380 K and showing different degree of abruptness, but no hysteresis. The Slichter-Drickamer model was used to extract empirical thermodynamic transition parameters, allowing a systematic investigation of the influence of stoichiometry, position, and electronic nature of the substitution on the magnetic properties of the complexes. Steric effects dominate for substitution in position 3, but electronic effects are significant for the other positions.
Comprehensive Basis-Set Testing of Extended Symmetry-Adapted Perturbation Theory and Assessment of Mixed-Basis Combinations to Reduce Cost
Authors: Gray Montgomery , Herbert John
Published: February 2022

Hybrid or "extended" symmetry-adapted perturbation theory (XSAPT) replaces traditional SAPT's treatment of dispersion with better-performing alternatives, while at the same time extending two-body (dimer) SAPT to a many-body treatment of polarization using a self-consistent charge-embedding procedure. The present work presents a systematic study of how XSAPT interaction energies and energy components converge with respect to the choice of Gaussian basis set. Although errors can be reduced in a systematic way using correlation-consistent basis sets, similar performance at lower cost is obtained using Karlsruhe basis sets, and we introduce new versions with limited augmentation (diffuse functions) that are even more efficient. Pople-style basis sets, which are even more efficient, often afford good results if a large number of polarization functions are included. The dispersion models used in XSAPT afford much faster basis-set convergence as compared to the perturbative description of dispersion in conventional SAPT, meaning that "compromise" basis sets (such as jun-cc-pVDZ) are no longer required and benchmark-quality results can be obtained using basis sets of triple-zeta quality. The use of diffuse functions proves to be essential, especially for the description of hydrogen bonds. The "delta(Hartree-Fock)" correction that accounts for high-order induction can be performed in double-zeta basis sets without significant loss of accuracy, leading to a mixed-basis approach that offers 4x speedup over the existing (cubic-scaling) XSAPT approach.
Computational Design of Thermoelectric Alloys Through Optimization of Transport and Dopability
Authors: Qu Jiaxing , Balvanz Adam , Baranets Sviatoslav , Bobev Svilen , Gorai Prashun
Published: February 2022

Alloying is a common technique to optimize the functional properties of materials for thermoelectrics, photovoltaics, energy storage etc. Designing thermoelectric (TE) alloys is especially challenging because it is a multi-property optimization problem, where the properties that contribute to high TE performance are interdependent. In this work, we develop a computational framework that combines first-principles calculations with alloy and point defect modeling to identify alloy compositions that optimize the electronic, thermal, and defect properties. We apply this framework to design n-type Ba2(1-x)Sr2xCdP2 Zintl thermoelectric alloys. Our predictions of the crystallographic properties such as lattice parameters and site disorder are validated with experiments. To optimize the conduction band electronic structure, we perform band unfolding to sketch the effective band structures of alloys and find a range of compositions that facilitate band convergence and minimize alloy scattering of electrons. We assess the n-type dopability of the alloys by extending the standard approach for computing point defect energetics in ordered structures. Through the application of this framework, we identify an optimal alloy composition range with the desired electronic and thermal transport properties, and n-type dopability. Such a computational framework can also be used to design alloys for other functional applications beyond TE.
Nickel-Catalyzed Defluorinative Coupling of Aliphatic Aldehydes with Trifluoromethyl Alkenes
Authors: Xiao Jichao , Montgomery John
Published: February 2022

A simple procedure is reported for the nickel-catalyzed defluorinative alkylation of unactivated aliphatic aldehydes. The process involves the catalytic reductive union of trifluoromethyl alkenes with aldehydes using a nickel complex of a 6,6’-disubstituted bipyridine ligand with zinc metal as the terminal reductant. The protocol is distinguished by its broad substrate scope, mild conditions, and simple catalytic setup. Reaction outcomes are consistent with the intermediacy of an alpha-silyloxy(alkyl)nickel intermediate generated by a low-valent nickel catalyst, silyl electrophile, and the aldehyde substrate.
Elevating Density Functional Theory to Chemical Accuracy for Water Simulations through a Density-Corrected Many-Body Formalism
Authors: Dasgupta Saswata , Lambros Eleftherios , Perdew John , Paesani Francesco
Published: February 2022

Density functional theory (DFT) has been extensively used to model the properties of water. Albeit maintaining a good balance between accuracy and efficiency, no density functional has so far achieved the degree of accuracy necessary to correctly predict the properties of water across the entire phase diagram. Here, we present density-corrected SCAN (DC-SCAN) calculations for water which, minimizing density-driven errors, elevate the accuracy of the SCAN functional to that of “gold standard” coupled-cluster theory. Building upon the accuracy of DC-SCAN within a many-body formalism, we introduce a data-driven many-body potential energy function, MB-SCAN(DC), that quantitatively reproduces coupled cluster reference values for interaction, binding, and individual many-body energies of water clusters. Importantly, molecular dynamics simulations carried out with MB-SCAN(DC) also reproduce the properties of liquid water, which thus demonstrates that MB-SCAN(DC) is effectively the first DFT-based model that correctly describes water from the gas to the liquid phase.
Untargeted identification of alkyne containing natural products using ruthenium catalyzed azide alkyne cycloaddition reactions coupled to LC-MS/MS.
Authors: Back Daniel , Shaffer Brenda , Loper Joyce , Philmus Benjamin
Published: February 2022

Alkyne containing natural products have identified from plants, insects, algae, fungi, and bacteria. This class of natural products have been characterized as having a variety of biological activities. Polyynes are a sub-class of acetylenic natural products that contain conjugated alkynes and are underrepresented in natural product databases due to the fact that they decompose during purification. Here we report a workflow that utilizes alkyne azide cycloaddition (AAC) reactions, using ruthenium or copper catalysts, followed by LC-MS/MS analysis to identify acetylenic natural products. In this report we demonstrate that AAC reactions with p-bromobenzyl azide resulted in p-bromobenzyl substituted triazole products that fragment to a common brominated tropylium ion. We were able to identify a synthetic alkyne spiked into the extract of Anabaena sp. PCC 7120 at a concentration of 10 μg/ml after optimization of MS/MS conditions. We then successfully identified the known natural product fischerellin A in the extract of Fischerella muscicola PCC 9339. Lastly, we identified the recently identified natural products protegenin A and C from P. protegens through a combination of genome mining and RuAAC reactions. We also compare CuAAC and RuAAC reactions and find that CuAAC reactions produce less by-products compared to RuAAC, but is limited to terminal alkyne containing compounds. We believe that both CuAAC and RuAAC reactions coupled to LC-MS/MS represent a method for the untargeted identification of acetylenic natural products.
Untargeted identification of alkyne containing natural products using ruthenium catalyzed azide alkyne cycloaddition reactions coupled to LC-MS/MS.
Authors: Back Daniel , Shaffer Brenda , Loper Joyce , Philmus Benjamin
Published: February 2022

Alkyne containing natural products have been identified from plants, insects, algae, fungi, and bacteria. This class of natural products have been characterized as having a variety of biological activities. Polyynes are a sub-class of acetylenic natural products that contain conjugated alkynes and are underrepresented in natural product databases due to the fact that they decompose during purification. Here we report a workflow that utilizes alkyne azide cycloaddition (AAC) reactions followed by LC-MS/MS analysis to identify acetylenic natural products. In this report, we demonstrate that AAC reactions with p-bromobenzyl azide result in p-bromobenzyl substituted triazole products that fragment to a common brominated tropylium ion. We were able to identify a synthetic alkyne spiked into the extract of Anabaena sp. PCC 7120 at a concentration of 10 μg/ml after optimization of MS/MS conditions. We then successfully identified the known natural product fischerellin A in the extract of Fischerella muscicola PCC 9339. Lastly, we identified the recently identified natural products protegenin A and C from Pseudomonas protegens Pf-5 through a combination of genome mining and RuAAC reactions. This is the first report of RuAAC reactions to detect acetylenic natural products. We also compare CuAAC and RuAAC reactions and find that CuAAC reactions produce less by-products compared to RuAAC, but is limited to terminal alkyne containing compounds. In contrast, RuAAC is capable of identification of both terminal and internal acetylenic natural products, but by-products need to be eliminated from analysis by creation of an exclusion list. We believe that both CuAAC and RuAAC reactions coupled to LC-MS/MS represent a method for the untargeted identification of acetylenic natural products, but each method has strengths and weaknesses.
Determining the Acetic Acid Concentration in White Vinegar: An At-Home Undergraduate Chemistry Experiment During the COVID-19 Pandemic
Authors: Parel Philip , Burnett Lydia , Geoffroy Morgan , Parel John , Hao Ling
Published: February 2022

Due to the COVID-19 pandemic, many university-level chemistry laboratory experiments transitioned online. This created an educational challenge because students are unable to access reagents and instruments typical in a university lab setting. It is also difficult for students to connect theory to practice since real-lab experimentation is not possible in a virtual online for-mat. In our online Introductory Quantitative Analysis Laboratory course (GW Chem 2123W) in spring 2021, students were required to design and perform an experiment that could be safely conducted at home which can also demonstrate key princi-ples of quantitative analysis. Herein, we conducted a reliable at-home experiment that utilizes university-level acid/base titra-tion techniques to determine the acetic acid concentration in white vinegar. The experiment used sodium bicarbonate in the form of baking soda to titrate the Whole Foods white vinegar which is advertised to contain 6% of acetic acid. We reliably obtained an equivalence point for the titration from which the actual concentration of acetic acid in the vinegar was calculated with error analysis to be 19% higher than the advertised value. The analytical techniques demonstrated in this experiment supplement practical knowledge of acid/base techniques learned in the online classroom and prompt adoption of this meth-odology in online laboratory curriculum. This experiment can also be readily applied to measure other acidic solutions such as vinegar and juice for at-home experiment
Aliovalent doping response and impact on ionic conductivity in the antiperovskite solid electrolyte Li3OCl
Authors: Squires Alex , Dean Jacob M. , Morgan Benjamin J.
Published: February 2022

Aliovalent doping of solid electrolytes with the intention of increase the concentration of charge carrying mobile defects is a common strategy for enhancing their ionic conductivities. For the antiperovskite lithium-ion solid electrolyte Li3OCl, both supervalent (donor) and subvalent (acceptor) doping schemes have previously been proposed. The effectiveness of these doping schemes depends on two conditions: first, that aliovalent doping promotes the formation of mobile lithium vacancies or interstitials rather than competing immobile defects; and second, that any increase in lithium defect concentration gives a corresponding increase in ionic conductivity. To evaluate the effectiveness of aliovalent doping in Li3OCl, we have performed a hybrid density-functional theory study of the defect chemistry of Li3OCl and the response to supervalent and subvalent doping. In nominally stoichiometric Li3OCl the dominant native defects are predicted to be VLi, OCl, and VCl. Supervalent doping increases VLi and OCl concentrations, with the preferentially formed defect species dependent on synthesis conditions. Subvalent doping increases the concentration of VCl more than the concentration of Lii under all accessible synthesis conditions. While supervalent doping is predicted to be effective at increasing ionic conductivity, particularly under Li-poor synthesis conditions, subvalent doping is predicted to decrease room-temperature ionic conductivities at low-to-moderate doping levels. This effect is due to a reduction in the number of lithium vacancies formed during synthesis, and increased [VLi + Lii] Frenkel-pair recombination upon cooling to room temperature. The strongly asymmetric doping response of Li3OCl with respect to supervalent versus subvalent doping is explained as a consequence of the low [VLi + VCl] Schottky pair formation energy, suggesting analogous behaviour should be expected in other Schottky-disordered solid electrolytes.
Serendipitous One-Step Synthesis of Cyclopentene Derivatives from 5′-Deoxy-5′-Heteroarylsulfonylnucleosides as Nucleoside-Derived Julia–Kocienski Reagents
Authors: Oka Natsuhisa , Kanda Mayuka , Furuzawa Minami , Arai Wakaba , Ando Kaori
Published: February 2022

A serendipitous one-step transformation of 5′-deoxy-5′-heteroarylsulfonylnucleosides into cyclopentene derivatives is reported. This unique transformation likely proceeds via a domino reaction initiated by α-deprotonation of the heteroaryl sulfone and subsequent elimination reaction to generate a nucleobase and an α,β-unsaturated sulfone that contains a formyl group. The Michael addition of the nucleobase to the α,β-unsaturated sulfone and subsequent intramolecular Julia–Kocienski reaction eventually generate the cyclopentene ring. Heteroarylthio and acylthio groups can be incorporated into the cyclopentene core in place of the nucleobase by conducting this reaction in the presence of a heteroarylthiol and a thiocarboxylic acid, respectively. Cis,cis-trisubstituted cyclopentene derivatives are obtained as a single stereoisomer from ribonucleoside-derived Julia–Kocienski sulfones.
Evaluation and Data Analysis of Sol-Gel Method with Acids to Determine Most Effective Sol-Gel Method
Authors: Moore Joshua , Ramsay Aniska
Published: February 2022

Synthesizing nanocomposite materials using sol-gel methodology is a cheap and effective method for creating quality U3O8 particles. To some degree acids can influence the synthesis of the nanoparticles by catalyzing the reaction. This paper presents important details comparing different acids used as catalysts in nanocomposite synthesis versus time manipulation to determine if an acid catalyst is necessary for the synthesis of U3O8/SiO2 nanocomposites.
Data-driven machine learning models for the quick and accurate prediction of Tg and Td of OLED materials
Authors: Zhao Yihuan , Fu Caixia , Fu Ling , Lu Zhiyun , Pu Xuemei
Published: February 2022

Organic light-emitting-diode (OLED) materials have exhibited a wide range of applications. However, further development and commercialization of OLEDs requires higher-quality OLED materials, including high thermal stability associated with the glass transition temperature (Tg) and decomposition temperature (Td). Experimental determinations of the two important properties genernally involve a time-consuming and laborious process. Thus, it is highly desired to develop a quick and accurate prediction tool. Motivated by the changelle, we explored machine learning based framework by constructing new dataset with more than one thousand samples collected from a wide range of literaturesm, throngh which ensemble learning models were explored. Models trained with the LightGBM algorithm exhibit the best prediction performance, where the values of MAE, RMSE, and R2 are 17.15 K, 24.63 K, and 0.77 for Tg prediction, 24.91 K, 33.88 K, and 0.78 for Td prediction. The prediction performance and the generalization of the machine learning models are further tested by out-of-sample dataset, also exhibiting satisfactory results. Experimental verification further demonstrates the reliability and the practical potential of the ML-based model. In order to extend the practice application of the ML-based models, an online prediction platform was constructed, including the optimal predition models and all the thermal stability data under study, which are freely available at http://oledtppxmpugroup.com. We expect that they will become a useful tool for experimental investigations on Tg and Td, in turn accelerating the design of the OLED materials with high performance.
On the electro-oxidation of small organic molecules: towards a fuel cell catalyst testing platform
Authors: Zhang Damin , Du Jia , Quinson Jonathan , Arenz Matthias
Published: February 2022

The electrocatalytic oxidation of small organic compounds such as methanol or formic acid has been the subject of numerous investigations in the last decades. The motivation for these studies is often their use as fuel in so-called direct methanol or direct formic acid fuel cells, promising alternatives to hydrogen-fueled proton exchange membrane fuel cells. The fundamental research spans from screening studies to identify the best performing catalyst materials to detailed mechanistic investigations of the reaction pathway. These investigations are commonly performed in standard three electrode electrochemical cells with a liquid supporting electrolyte to which the methanol or formic acid is added. In fuel cell devices, however, no liquid electrolyte will be present, instead membrane electrolytes are used. The question therefore arises, to which extend results from conventional electrochemical cells can be extrapolated to conditions found in fuel cells. We previously developed a gas diffusion electrode setup to mimic “real-life” reaction conditions and study electrocatalysts for oxygen gas reduction or water splitting. It is here demonstrated that the setup is also suitable to investigate the properties of catalysts for the electro-oxidation of small organic molecules. Using the gas diffusion electrode setup, it is seen that employing a catalyst - membrane electrolyte interface as compared to conventional electrochemical cells can lead to significantly different catalyst performances. Therefore, it is recommended to implement gas diffusion electrode setups for the investigation of the electro-oxidation of small organic molecules.
Pulsed Blue Laser Diode Thermal Desorption Microplasma Imag-ing Mass Spectrometry
Authors: Knodel Alexander , Marggraf Ulrich , Hoffmann-Posorske Edeltraut , Burhenn Sebastian , Brandt Sebastian , Ahlmann Norman , Foest Daniel , Lorenz Kristina , Franzke Joachim
Published: February 2022

An ambient air laser desorption, plasma ionization imaging method is developed and presented using a pulsed laser diode for desorption and the flexible microtube plasma for ionization of the neutral desorbate. Inherent parameters such as the laser pulse frequency and pulse width are optimized to the imaging application. For the desorption substrate, copper spots on a copper-glass sandwich structure are used. This novel design enables imaging without ablating the metal into the mass spectrometer. On this substrate, fixed calibration markers are used to decrease the positioning error in the imaging process, featuring a 3D offset correction within the experiment. The image is both screened spot-by-spot and per line scanning at a constant speed, which allows direct comparison. In spot-by-spot scanning, a novel algorithm is presented to unfold and to reconstruct the imaging data. This approach significantly decreases the time required for the imaging process, which allows imaging even at decreased sampling rates and thus higher mass resolution. After the experiment, the raw data is automatically converted and interpreted by a second algorithm, which allows direct visualization of the image from the data, even on low-intensity signals. Mouse liver microtome cuts have been screened for dehydrated cholesterol, proving good agreement of the unfolded data with the morphology of the tissue. The method optically resolves 30 µm, with 30 µm diameter copper spots and a 10 µm gap. No conventional chemical matrices or vacuum conditions are required.
Protonation States of Molecular Groups in the Chromophore-Binding Site Modulate Properties of the Reversibly Switchable Fluorescent Protein rsEGFP2
Authors: Grigorenko Bella , Domratcheva Tatiana , Polyakov Igor , Nemukhin Alexander
Published: February 2022

The role of protonation states of the chromophore and its neighboring amino acid side chains of the reversibly switching fluorescent protein rsEGFP2 upon photoswitching is characterized by molecular modeling methods. Numerous conformations of the chromophore-binding site in computationally derived model systems are obtained using the quantum chemistry and QM/MM approaches. Excitation energies are computed using the extended multiconfigurational quasidegenerate perturbation theory (XMCQDPT2). The obtained structures and absorption spectra allow us to provide interpretation of the observed structural and spectral properties of rsEGFP2 in the active ON- and inactive OFF-states. To identify intermediates along the routes of chromophore transformations between the ON- and OFF-states, molecular dynamics trajectories with the QM/MM potentials are examined. The results demonstrate that in addition to the dominating anionic and neutral forms of the chromophore, the cationic and zwitterionic forms may participate in the photoswitching of rsEGFP2. Conformations and protonation forms of the Glu223 and His149 side chains in the chromophore-binding site play an essential role in stabilizing specific protonation forms of the chromophore.
Membrane fusion mediated by non-covalent binding of re-engineered cholera toxin assemblies to glycolipids
Authors: Wehrum Sarah , Williamson Daniel J , Siukstaite Lina , Branson Thomas R , Sych Taras , Madl Josef , Wildsmith Gemma C , Dai Wenyue , Ross James F , Thomsen Maren , Webb Michael E , Römer Winfried , Turnbull W Bruce
Published: February 2022

Membrane fusion is essential for the transport of macromolecules and viruses across membranes. While glycan-binding proteins (lectins) often initiate cellular adhesion, subsequent fusion events require additional protein machinery. No mechanism for membrane fusion arising from simply a protein binding to membrane glycolipids has been described thus far. Herein we report that a biotinylated protein derived from cholera toxin, becomes a fusogenic lectin upon crosslinking with streptavidin. This novel reengineered protein brings about hemifusion and fusion of vesicles as demonstrated by mixing of fluorescently labelled lipids between vesicles as well as content mixing of liposomes filled with fluorescently labelled dextran. Exclusion of the complex at vesicle-vesicle interfaces could also be observed indicating the formation of hemifusion diaphragms. We propose that negative membrane curvature, caused by binding of the cholera toxin to the membrane surface, induces formation of a fusion stalk as a result of high bending energies building up between multiple inverted membrane dimples aligned on opposing membranes at the vesicle-vesicle interface. Discovery of this fusogenic lectin complex demonstrates that new emergent properties can arise from simple changes in protein architecture and provides insights towards new mechanisms of lipid-driven fusion
Synovial Fluid Profile Dictates Nanopracticle Uptake into Cartilage- Implications of the Protein Corona for Novel Arthitis Treatments
Authors: von Mentzer Ula , Selldén Tilia , Råberg Loise , Erensoy Gizem , Hultgård-Ekwall Anna-Karin , Stubelius Alexandra
Published: February 2022

A major obstacle for joint drug delivery is to penetrate the dense, negatively charged cartilage matrix. Previous studies have extensively investigated particle approaches to increase uptake efficiency into tissues but have neglected to address potential interactions with the synovial fluid. Here, we developed a nanoparticle (NP) panel with varying PEGylation and incubated them with synovial fluid from either osteoarthritic (OA) or rheumatoid arthritis (RA) patients, or fetal calf serum (FCS). Compared to nonprotein- covered NPs, the formed protein coronas majorly impacted NP uptake into cartilage tissue and dictated their uptake in chondrocytes and monocytes - a measure of targeting efficiency and clearance potential. Utilizing a quantitative proteomics approach, we identified certain families of proteins on all panel members irrespective of the NP modifications. Nonetheless, NP-, and protein-specific differences were also observed between the groups, and candidate proteins were identified that could account for the observed differences. This study is the first to demonstrate how protein coronas from different biological origins impact NP uptake into cartilage, emphasizing the importance of considering the several aspects of the biological microenvironment for successful translation of drug delivery vehicles into clinics.
Arylboronic Acids Catalyzed Upgrade of Glucosamines for Deoxyfructosazine and Insights on Reaction Mechanism
Authors: Wang Meifeng , Zhu Gan , Li Yiqun , Gu Liuqun
Published: February 2022

Chitin is the most abundant N-containing polysaccharides in nature and D-glucosamine is one of most successful commercial monomer products in current market. Here we reported an arylboronic acids catalyzed upgrade of glucosamines in aqueous solution for deoxyfructosazine which is an important high-value compound in pharmaceutical and food industries, as well as a promising bio-based platform molecule for speciality chemicals and sustainable functional materials. Such direct integration of deoxyfructosazine into development of renewable chemicals/functional materials might be a practical way for utilization of chitin as a renewable nitrogen source. A mechanism focusing on catalytic cycle of arylboronic acid via a boron transfer was also proposed.