bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure-based Discovery of a Series of NSD2-PWWP1 Inhibitor
Authors: Zhou Liwei , Yang Hong , Liu Ke , Huang Yuting , Cao Danyan , Li Yanlian , Sun Yaoliang , Yu Aisong , Du Zhiyan , Yu Feng , Zhang Ying , Wang Bingyang , Geng Meiyu , Li Jian , Liu Tongchao , Xu Shilin , Xiong Bing , Huang Xun
Published: February 2022

Overexpression, point mutations or translocations of protein lysine methyltransferase NSD2 was occurred in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we reported our efforts to develop a series of NSD2 PWWP1 inhibitors, and further structure-based optimization resulted a potent inhibitor 38, which has the high selectivity towards NSD2 PWWP1 domain. The detailed biological evaluation revealed that compound 38 can bind to NSD2-PWWP1 and then affect the expression of genes regulated by NSD2. We believe that the current discovery will provide a useful chemical probe to the future research in understanding the specific regulation mode of NSD2 by PWWP1 recognition.
Molecular sized Eu-oxide clusters in defining optical properties in crystalline ZnO nanosponges
Authors: Mukherjee Soham , Katea Sarmad , Rodrigues Emille , Segre Carlo , Hemmer Eva , Broqvist Peter , Rensmo Håkan , Westin Gunnar
Published: February 2022

The detailed structure of ZnO doped with 5 at.% (metal) of the large aliovalent Eu3+-ions was investigated using EXAFS to describe the local Eu and Zn coordination. The microstructure, crystalline phases, contents and ZnO unit-cell parameters for the ZnO:5%Eu sponges synthesised at 200 to 900 oC were obtained by XRD, SEM, and TEM analysis. XRD showed peaks solely of h-ZnO for the 600 oC sample, while heating at 700 oC and higher caused phase separation into h-ZnO:Eu and c-Eu2O3. XRD showed a close to zero increase in ZnO unit cell-volume of ca. 0.4 vol%, compared to un-doped ZnO for the non-phase separated, clean oxide made at 600 oC. The Zn EXAFS data showed an almost intact local ZnO structure. The Eu EXAFS showed an unusually low coordination number (CN) of ca. 5 for the 200-600 oC samples, while the CN increased for higher temperatures, in concert with the formation of c-Eu2O3. 23 DFT-generated theoretical ZnO structures containing Eu-clusters built from 1 to 4 Eu3+-Zn2+-vacancy- Eu3+ pairs were compared with the experimental data. The lowest formation energies and ZnO unit-cell volume increase versus un-doped ZnO (0.6-0.7 vol%), were obtained when combining two or four Eu3+-Zn2+-vacancy- Eu3+ pairs into Eu4 and Eu8 clusters showing an average Eu CN of ca. 5. These theoretically determined lowest energy structures were all in good agreement with the experimental results obtained by EXAFS and XRD. Photoluminescence excitation and emission spectra performed on the ZnO:5at%Eu sponges obtained at various temperatures, showed strong quenching of the characteristic Eu3+ transitions for samples obtained at 600 and 800 °C, most likely due to changes in the ZnO defect states, which are crucial for Eu3+ excitation, and due to self-quenching upon Eu clustering and c- Eu2O3 phase separation. Thus, the optical data further supported Eu clustering found by EXAFS, DFT and XRD techniques, corroborating structure-property relationships in these materials. Overall, as far as we can find, the findings reported herein point to a doping structure very different from those previously proposed in the literature. It demonstrates that the semiconductor ZnO can host molecular-sized clusters of metal-oxides, very dissimilar to ZnO.
Exponential Amplification by Redox Cross-Catalysis and Unmasking of Doubly Protected Molecular Probes
Authors: Pallu Justine , Rabin Charlie , Hui Pan , Moreira Thamires , Calvet Corentin , LIMOGES Benoît , Mavré François , Branca Mathieu
Published: February 2022

The strength of autocatalytic reactions lies in their ability to provide a powerful means of molecular amplification, which can be very useful for improving the analytical performances of a multitude of analytical and bioanalytical methods. However, one of the major difficulties in designing an efficient autocatalytic amplification system is the requirement for reactants that are both highly reactive and chemically stable in order to avoid limitations imposed by undesirable background amplifications. In the present work, we devised a reaction network based on a redox cross-catalysis principle, in which two catalytic loops activate each other. The first loop, catalyzed by H2O2, involves the oxi-dative deprotection of a naphthylboronate ester probe into a redox-active naphthohydroquinone, which in turn catalyzes the production of H2O2 by redox cycling in the presence of a reducing enzyme/substrate couple. We present here a set of new molecular probes with improved reactivity and stability, resulting in particularly steep sigmoidal kinetic traces and enhanced discrimination between specific and nonspecific responses. This translates into the sensitive de-tection of H2O2 down to a few nM in less than 10 minutes or a redox cycling compound such as the 2-amino-3-chloro-1,4-naphthoquinone H2O2 down to 50 pM in less than 30 minutes. The critical reason leading to these remarkably good performances is the extended stability stemming from the double masking of the naphthohydroquinone core by two boronate groups, a counterintuitive strategy if we consider the need for two equivalents of H2O2 for full deprotection. An in-depth study of the mechanism and dynamics of this complex reaction network is conducted in order to better understand, predict and optimize its functioning. From this investigation, the time response as well as detection limit are found highly dependent on pH, nature of buffer, and concentration of the reducing enzyme.
Electrocatalytic metal hydride generation using concerted proton electron transfer mediators
Authors: Dey Subal , Masero Fabio , Brack Enzo , Fontecave Marc , Mougel Victor
Published: February 2022

The electrochemical generation of metal hydride (M H) species remains one of the major hurdles for a wide range of catalytic reactions to be carried out electrochemically. We introduce here a new strategy for electrocatalytic M H generation using concerted proton electron transfer (CPET) mediators. We investigate the combination of a series of CPET mediators with the CO2 electroreduction catalyst [MnI(bpy)(CO)3Br] (bpy = 2,2’-bipyridine), probing the reversal of the product selectivity from CO to HCOOH to evaluate the efficiency of the M H generation step. We demonstrate the formation of the manganese-hydride by in-situ spectroscopic techniques and determine the thermodynamic boundary conditions for this mechanism to occur. A synthetic iron-sulfur cluster is identified as the best CPET-mediator for that system, enabling the preparation of a benchmark catalytic system for HCOOH generation.
New Application of Natural Language Processing（NLP）for Chemist Predicting Intermediate and Providing an Effective Direction for Mechanism Inference
Authors: Xu Jiangcheng , Zhang Yun , Han Jiale , Qiao Haoran , zhang Chengyun , Tang Jing , Xi Shen , Sun Bin , Zhai Silong , Wang Xinqiao , Wu Yejian , Su Weike , Duan Hongliang
Published: February 2022

Predicting and proposing the reaction mechanism, as well as speculating the reaction intermediates are great challenges among the development of modern organic chemistry. Herein, a model from Natural Language Processing (NLP) was firstly employed to learn and perform the task of intermediate prediction, which is served as a language translation task. Radical cascade cyclization is prevalently used in life science and pharmaceutical projects, while the regioselectivity of radical attack is difficult to predict. The model is trained on self-built dataset to tackle the challenge. And transfer learning was used to surmount the restriction of limited amounts of data. The NLP transformer model performs well with remarkable accuracy, providing an efficient instruction for mechanism understanding. Manual encoding of rules is not required, thus, providing a favorable tool towards solving the challenging problem of computational organic chemical mechanism inference.
Accessing Three Oxidation States of Cobalt in M6L3 Nanoprisms with Cobalt-Porphyrin Walls
Authors: Blackburn P. Thomas , Mansoor Iram F. , Dutton Kaitlyn G. , Tyryshkin Alexei M. , Lipke Mark C.
Published: February 2022

Nanocages with porphyrin walls are common, but studies of such structures hosting redox-active metals are rare. Pt-linked M6L3 nanoprisms with cobalt-porphyrin walls were prepared and their redox properties were evaluated electrochemically and chemically, leading to the first time that cobalt-porphyrin nanocages have been characterized in Co(I), Co(II), and Co(III) states.
Martini 3 Coarse-Grained Force Field: Small Molecules
Authors: Alessandri Riccardo , Barnoud Jonathan , Gertsen Anders S. , Patmanidis Ilias , de Vries Alex H. , Souza Paulo C. T. , Marrink Siewert J.
Published: February 2022

The recent re-parametrization of the Martini coarse-grained force field, Martini 3, improved the accuracy of the model in predicting molecular packing and interactions in molecular dynamics simulations. Here, we describe how small molecules can be accurately parametrized within the Martini 3 framework and present a database of validated small molecule models (available at https://github.com/ricalessandri/ Martini3-small-molecules and http://cgmartini.nl). We pay particular attention to the description of aliphatic and aromatic ring-like structures, which are ubiquitous in small molecules such as solvents and drugs or in building blocks constituting macromolecules such as proteins and synthetic polymers. In Martini 3, ring-like structures are described by models that use higher resolution coarse-grained particles (small and tiny particles). As such, the present database constitutes one of the cornerstones of the calibration of the new Martini 3 small and tiny particle sizes. The models show excellent partitioning behavior and solvent properties. Miscibility trends between different bulk phases are also captured, completing the set of thermodynamic properties considered during the parametrization. We also show how the new bead sizes allow for a good representation of molecular volume, which translates into better structural properties such as stacking distances. We further present design strategies to build Martini 3 models for small molecules of increased complexity. The present database, along with the outlined design strategies and the modularity of the Martini force field, constitute a resource of models that 1) can be used “as is” in (bio)molecular simulations; 2) gives reference points for the construction of other small molecule models; 3) provides guidelines and reference data for automated topology builders; and 4) can be used as building blocks for the construction of more complex (macro)molecules, hence enabling investigations of complex biomolecular and soft material systems.
Electrochemical Reduction of CO2 on Au Electrocatalysts in a Zero-Gap, Half-Cell Gas Diffusion Electrode Setup: a Systematic Performance Evaluation and Comparison to a H-cell Setup
Authors: Alinejad Shima , Quinson Jonathan , Wiberg Gustav K.H. , Schlegel Nicolas , Zhang Damin , Li Yao , Reichenberger Sven , Barcikowski Stephan , Arenz Matthias
Published: February 2022

Based on H-cell measurements, gold (Au) is one of the most selective catalysts for the CO2 reduction reaction (CO2RR) to CO. To ensure a high dispersion, typically Au small nanoparticles (NPs) are used as catalyst. However, the preparation of small Au NPs based on conventional synthesis methods often requires the use of surfactants such as polyvinylpyrrolidone (PVP). Here, we present a systematic evaluation of the performance of laser-generated, surfactant-free Au NPs for the CO2RR in a gas diffusion electrode (GDE) setup and compare the results to investigations in an H-cell configuration. The GDE setup supplies a continuous CO2 stream at the electrode−electrolyte interface to circumvent CO2 mass transport limitations encountered in conventional H-cells. We investigate the influence of the catalyst loading and the effect of PVP. Comparing the two screening methods, i.e. GDE and H-cell measurements, it is shown that the performance of the same catalyst can be substantially different in the two environments. In the GDE setup without liquid electrolyte-catalyst interface a higher reaction rate, but lower faradaic efficiendy is determined. Independent of the setup, the presence of PVP favours the hydrogen evolution reaction (HER), however, in the GDE setup PVP is more detrimental for the performance than in the H-cell.
Food phytochemicals, epigallocatechin gallate and myricetin, covalently bind to the active site of the coronavirus main protease in vitro
Authors: Kato Yoji , Higashiyama Akari , Takaoka Emi , Nishikawa Miyu , Ikushiro Shinichi
Published: February 2022

SARS-CoV-2 main protease is a possible target for protection against viral infection. This study examined the inhibitory effect of food phytochemicals on the main protease of SARS-CoV-2 by determining a cleaved product after chromatographic separation. First, 37 phytochemicals, including glycosides and metabolites, were screened at 20 µM; epigallocatechin gallate, myricetin, theaflavin, herbacetin, piceatannol, myricitrin, and isothiocyanates inhibited the enzyme in varying degrees. The IC50 values were estimated from 0.4 to 33.3 µM against the 0.5-µM enzyme. The dose-dependent adduction of epigallocatechin gallate and myricetin was confirmed by quinone staining of protein blotted onto a membrane. The enzyme activity was decreased by increasing the concentration of the two phytochemicals, accompanied by increasing the respective adducted molecule estimated by intact mass spectrometry. Reduced glutathione canceled the formation of conjugate and the inhibitory effect of epigallocatechin gallate or myricetin on the enzyme, suggesting that the formation of the quinone moiety in the phytochemicals is critical for the inhibition. The covalent binding of epigallocatechin gallate or myricetin to the cysteine residue at the active site was confirmed by analyzing peptides from the chymotrypsin-digested main protease.
Femtosecond X-ray Spectroscopy Directly Quantifies Transient Excited State Mixed Valency and Subsequent Vibronic Dynamics
Authors: Liekhus-Schmaltz Chelsea , Fox Zachary , Andersen Amity , Kjaer Kasper , Alonso-Mori Roberto , Biasin Elisa , Carlstad Julia , Chollet Matthieu , Gaynor James , Glownia James , Hong Kiryong , Kroll Thomas , Lee Jae Hyuk , Poulter Benjamin , Reinhard Marco , Sokaras Dimosthenis , Zhang Yu , Doumy Gilles , March Anne-Marie , Southworth Stephen , Mukamel Shaul , Cordones-Hahn Amy , Schoenlein Robert , Govind Niranjan , Khalil Munira
Published: February 2022

Quantifying charge delocalization and coupled nuclear motions on short-lived photoexcited states in solution remains experimentally challenging, requiring element specific femtosecond experimental probes of time-evolving electron transfer. Here, we use advanced X-ray spectroscopic probes and excited state calculations to measure the hole charge on the photoexcited charge transfer state of a prototypical mixed valence bimetallic (FeIIRuIII) complex in water. We find that the hole charge at the Fe atom is 0.75±0.18 on the metal-to-metal charge transfer excited state, which has a 58±10 fs lifetime. The X-ray emission data reveals that the rapid back electron transfer excites vibrations that modulate the Fe-Ru distance on the non-equilibrium ground state. Our combined experimental and computational approach provides a spectroscopic ruler to quantify excited state valency and sheds light on the low-frequency nuclear vibrations that are coupled to core level transitions
Binding methylarginines and methyllysines as free amino acids: a comparative study of multiple supramolecular host classes
Authors: Warmerdam Zoey , Kamba Bianca , Le My-Hue , Schrader Thomas , Isaacs Lyle , Bayer Peter , Hof Fraser
Published: February 2022

Methylated free amino acids are an important class of targets for host-guest chemistry that have recognition properties distinct from those of methylated peptides and proteins. We present comparative binding studies for three different host classes that are each studied with multiple methylated arginines and lysines to determine fundamental structure-function relationships. The hosts studied are all anionic and include three calixarenes, two acyclic cucurbiturils, and two cleft-like hosts. We determined the binding association constants for a panel of methylated amino acids using indicator displacement assays. The calixarene hosts show weak binding that favours the higher methylation states, with the strongest binding observed for trimethyllysine. The acyclic cucurbiturils display stronger binding to the methylated amino acids, and some unique patterns of selectivity. The cleft-like hosts follow two different trends, one shallow host following similar trends to the calixarenes, and the other more closed host binding certain less-methylated amino acids stronger than their per-methylated counterparts. Molecular modeling sheds some light on the different preferences of different hosts. The results identify hosts with selectivities that will be useful for certain biomedical applications. The overall selectivity patterns are explained by a common framework that considers the topology, depth of binding pockets, and functional group participation across all host classes.
Atomistic simulations of dopamine diffusion dynamics on a pristine graphene surface
Authors: Jia Qizhang , Yang Cheng , Venton B. Jill , DuBay Kateri H.
Published: February 2022

Carbon microelectrodes enable in vivo detection of neurotransmitters, and new electrodes are being developed to optimize the carbon surface. However, the work is mainly empirical and there have not been corresponding theoretical studies using molecular-level simulations of the diffusion and orientation of neurotransmitters near these surfaces. Here, we employ molecular dynamics simulations to investigate in atomistic detail the surface diffusion of dopamine (DA), its oxidation product dopamine-o-quinone (DOQ), and their protonated forms on the pristine basal plane of flat graphene. All DA species rapidly adsorb to the surface and remain adsorbed for the full length of the equilibrium simulations, even without a holding potential or graphene surface defects. The diffusivities of the adsorbed and the fully solvated DA are similar, and all molecular diffusion on the surface is slower than that of an adatom of comparable molecular weight. The protonated species diffuse more slowly than their corresponding neutral forms, and the oxidized species diffuse more rapidly. The underlying hexagonal graphene structure has little influence over the molecular adsorbate's lateral position. The vertical placement of the amine group on dopamine is highly dependent upon its charge, and the protonated amine prefers to be above the surface near the solvating waters. Solvation has a large effect on surface diffusivities when diffusion is compared to that in a vacuum. These are the first results of molecular dynamics simulations of dopamine diffusion at the aqueous-graphene interface, and they show that dopamine diffuses quickly on graphene surfaces, even without an applied potential. These calculations provide a basis for future simulations to predict the behavior of neurotransmitter diffusion on advanced carbon materials electrodes.
Operando spectroelectrochemistry of redox state kinetics in water-oxidation IrOx electrocatalysts
Authors: Bozal-Ginesta Carlota , Rao Reshma R. , Mesa Camilo A. , Liu Xinyi , Hillman Sam A.J. , Stephens Ifan E.L. , Durrant James R.
Published: February 2022

Hydrous iridium oxides (IrOx) are the best oxygen evolution electrocatalysts available for operation in acidic environments. In this study, we employ time-resolved operando spectroelectrochemistry to investigate the redox states kinetics of IrOx electrocatalyst films for both water and hydrogen peroxide oxidation. Three different redox species involving Ir3+, Ir4+ and Ir4.x are identified spectroscopically and their concentrations are quantified as a function of applied potential. The generation of Ir4.x+ states is found to be the potential determining step for catalytic water oxidation, whilst H2O2 oxidation is observed to be driven by the generation of Ir4+ states. The reaction kinetics for water oxidation, determined from the optical signal decays at open circuit, accelerate from ~ 20 s to < 0.5 s with increasing applied potential above 1.3V vs. RHE (i.e. TOFs per active Ir state increasing from 0.05 to 2 s-1). In contrast, the reaction kinetics for H2O2 are found to be almost independent of the applied potential (increasing from 0.1-0.3 s-1 over a wider potential window), indicative of a first order reaction mechanism. These spectroelectrochemical data quantify the increase of both the density of active Ir4.x+ states and the TOFs of these states with applied positive potential, resulting in the observed sharp turn on of catalytic water oxidation current. We reconcile these data with the broader literature while providing a new kinetic insight into IrOx electrocatalytic reaction mechanisms, indicating a first order reaction mechanism for H2O2 oxidation driven by Ir4+ states, and a higher order reaction mechanism involving the co-operative interaction of multiple Ir4.x+ states for water oxidation.
Organic Lecture: Teaching the Fluidity of Covalent Bonds
Authors: Taber Douglass
Published: February 2022

Covalent bonds are fluid, not rigid, as with hand-held plastic models. Raspberry jam is an effective visual demonstration of this fluidity.
Investigating the Transfer of Drug Particulate onto Evidence Packaging During Routine Case Analysis
Authors: Sisco Edward , Robinson Elizabeth L. , Mead Rebecca , Miller IV Charles R.
Published: February 2022

The presence of drug residue and drug background in a forensic context continues to be of interest for a variety of reasons ranging from its potential use as a means for presumptive identification to ensuring the safety and well-being of drug chemists. While prior work has studied the presence of these residues on laboratory surfaces and on drug evidence, the contribution of residue on the exterior of drug packaging from the analysis process itself has not yet been studied. This work aims to qualitatively and quantitively identify what, if any, effect the analysis of drug evidence has on the drug residue levels on the exterior of the evidence packaging. Using wipe collection techniques, samples from the exterior of drug evidence packaging were taken prior to opening cases and after repackaging to measure changes in residue composition and mass. A total of 64 submissions were analyzed, and an increase in drug residue mass was observed 85.5 % of the time. After analysis and repackaging, 95 % of packages had detectable drug residue on their exterior even though some of the cases were repackaged into new bags. Drug residue masses on the exterior of drug packaging were found to be as high as tens of micrograms. The presence of drug residue on the exterior of drug evidence packaging is expected given the collection and analysis procedures, therefore potential ways to minimize these levels are currently being studied. The presence of these residues is an important factor to consider when developing protocols for the entire evidence handling process and its impact on personnel – from evidence handling technicians to crime scene technicians to submitting officers.
Cross-Electrophile Coupling of Alcohols with Aryl and Vinyl Halides
Authors: Chi Benjamin , Widness Jonas , Gilbert Michael , Salgueiro Daniel , Garcia Kevin , Weix Daniel
Published: February 2022

Although alcohols represent one of the largest pools of commercially available alkyl substrates, approaches to di-rectly utilize them in cross-coupling and cross-electrophile coupling are limited. We report the use of alcohols in cross-electrophile coupling with aryl and vinyl halides to form C(sp3)–C(sp2) bonds in a one-pot strategy. This strategy allows the use of primary and secondary alcohols through their very fast (<1 min) in situ conversion to the corre-sponding alkyl bromides with compatible phosphonium activating reagents. The utility of the reaction is exempli-fied by its simple reaction setup, scalability, and broad scope (41 examples, 57% ± 15% ave yield). The reaction can be performed on the benchtop without the need for electro-chemical or photochemical equipment. Finally, translation to standard parallel synthesis techniques is demonstrated by successfully coupling all combinations of 8 alcohols with 12 aryl cores in a 96-well plate using only one (99% cover-age) or two (100% coverage) sets of conditions.
Mixed-Halide Triphenyl Methyl Radicals for Site-Selective Functionalization and Polymerization
Authors: Chen Lisa , Arnold Mona , Blinder Rémi , Jelezko Fedor , Kuehne Alexander
Published: February 2022

Derivatives of the stable, luminescent tris-2,4,6-trichlorophenylmethyl (TTM) radical exhibit unique doublet spin properties that are of interest for applications in optoelectronics, spintronics, and energy storage. However, poor reactivity of the chlo-ride-moieties limits the yield of functionalization and thus the accessible variety of high performance luminescent radicals. Here, we present a pathway to obtain mixed-bromide and chloride derivatives of TTM by simple Friedel-Crafts alkylation. The re-sulting radical compounds show higher stability and site-specific reactivity in cross-coupling reactions, due to the better leaving group character of the para-bromide. The mixed halide radicals give access to complex, and so far inaccessible luminescent open-shell small molecules, as well as polymers carrying the radical centers in their backbone. The new mixed-halide triphenyl methyl radicals represent a powerful building block for customized design and synthesis of stable luminescent radicals.
Programmable zwitterionic droplets as biomolecular sorters and model of membraneless organelles
Authors: Capasso Palmiero Umberto , Paganini Carolina , Kopp Marie , Linsenmeier Miriam , Kuffner Andreas , Arosio Paolo
Published: February 2022

It is emerging that cells can regulate biochemical functions by generating open compartments with well-defined composition. One important mechanism underlying this control is simple coacervation driven by disordered proteins that encode multivalent interactions. Inspired by these observations, here we develop programmable droplets based on simple coacervation of synthetic responsive polymers that mimic the architecture of these biological disordered proteins. We have adopted a bottom-up approach starting from zwitterionic polymers, demonstrating that they can form liquid droplets that exclude most molecules. Starting from this reference material we have progressively introduced in the polymer architecture an increasing number of different intermolecular interactions. With this strategy, we can independently control multiple properties of the droplets, such as stimulus responsiveness, polarity, selective uptake of client molecules and miscibility. We demonstrate that these droplets can separate and enable the detection of target molecules even within complex mixtures, opening attractive applications in bioseparation and in diagnostics.
Chemodivergent Organolanthanide Catalyzed C-H a-Mono-1 Borylation of Azines
Authors: Rothbaum Jacob O. , Motta Alessandro , Kratish Yosi , Marks Tobin
Published: February 2022

C-H activation and functionalization of pyridinoid azines is a key transformation forthe synthesis of many natural products, pharmaceuticals, and materials. Reflecting the azinyl nitrogen lone-pair steric repulsion, tendency to irreversibly bind to metal ion catalysts, and the electron-deficient nature of pyridine, C-H functionalization at the important a-position remains challenging. Thus, the development of earth abundant catalysts for the a-selective mono-functionalization of azines is a crucial hurdle for modern chemical synthesis. Here, the selective organolanthanide catalyzed a-mono-borylation of a diverse series of pyridines is reported, affording a valuable precursor for cross-coupling reactions. Experimental and theoretical mechanistic evidence support the formation of a C-H activated η2-lanthanide-azine complex, followed by intermolecular a-mono-borylation via σ-bond metathesis. Notably, varying the lanthanide identity and substrate electronics promotes chemodivergence of the catalytic selectivity: smaller/more electrophilic lanthanide3+ ions and electron-rich substrates favor selective a-C-H functionalization, whereas larger/less electrophilic lanthanide3+ 1 ions and electron poor substrates favor selective B-N bond-forming 1,2-dearomatization. Such organolanthanide series catalytic chemodivergence is, to our knowledge, unprecedented.
Drug Repurposing for Candidate SARS-CoV-2 Papain-like protease (PLpro) Inhibitors by a combined in Silico Method
Authors: Sencanski Milan , Perovic Vladimir , Milicevic Jelena , Todorovic Tamara , Prodanovic Radivoje , Veljkovic Veljko , Paessler Slobodan , Glisic Sanja
Published: February 2022

The need for an effective drug against COVID-19, is, after almost 18 months since the global pandemics outburst, still very high. A very quick and safe approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 PLpro promotes vi-ral replication and modulates the host immune system, resulting in inhibition of the host antiviral innate immune response, and there-fore is an attractive drug target. In this study, we used a combined in silico virtual screening candidates for SARS-CoV-2 PLpro protease inhibitors. We used the Informational spectrum method applied for Small Molecules for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 44 drugs as potential SARS-CoV-2 PLpro inhibitors that we propose for further experimental testing.
Tetraphenylporphyrin Enters the Ring: First Example of a Complex Between Highly Bulky Porphyrins and a Protein
Authors: Shisaka Yuma , Sakakibara Erika , Suzuki Kazuto , Stanfield Joshua Kyle , Onoda Hiroki , Ueda Garyo , Hatano Miu , Sugimoto Hiroshi , Shoji Osami
Published: February 2022

Tetraphenylporphyrin (TPP) is a synthetic porphyrin whose properties can be readily modified, endowing it with significant benefits over naturally occurring porphyrins. Yet, their insolubility in water and/or steric bulk have rendered them incompatible with biological systems. Herein, we report the first example of a native biomolecule capturing TPP as well as its derivatives. The haemoprotein HasA, secreted by certain pathogens to scavenge haem from their hosts, can capture various metal- and meso-substituted TPPs. The rapid crystallisation of TPP derivatives captured by HasA revealed the binding mode of TPP at excellent resolutions. A single-site mutation (L85A) of HasA enlarged the binding pocket, allowing the incorporation of a bulkier derivative of TPP. HasA binding TPP derivatives was also demonstrated to inhibit proliferation of the opportunistic pathogen Pseudomonas aeruginosa. This study not only represents a simple method for the complexation of TPP derivatives with a native protein, but also opens the door for the future use of TPP derivatives as biological tools.
Aromatic, or Antiaromatic, That Is the Question:
Authors: Cuyacot Ben Joseph R , Foroutan-Nejad Cina
Published: February 2022

The term aromaticity in chemistry is reminiscent of symmetric, stable structures that have delocalized electrons and sustain diamagnetic ring currents in the presence of external magnetic fields. The two latter characteristics sometimes mistakenly are thought to be the same. In a groundbreaking discovery Liddle and co-workers synthesized a D3h complex with rare Th‒Th bonds. Studying the electronic structure of a neutral singlet model system, 3”, showed that the molecule has a delocalized HOMO between three Th atoms akin to a 2-electron 3-center bond. Employing nucleus independent chemical shift (NICS) computations and according to the pattern of the NICS scan plot on 3”, the authors suggested that the molecule is a σ-aromatic species as it is reflected also in the title of their paper. Unfortunately, NICS is an inappropriate tool for evaluation of the magnetic aromaticity among early and mid-transition metals (TM), the elements that share a characteristic with thorium; they all have low-energy unoccupied orbitals. In the following we explain why NICS fails to assess aromaticity of molecules containing TMs and prove that the Th3 ring is a weakly antiaromatic system. We introduce a simple protocol to examine the aromaticity of any molecule utilizing software packages, which have been used by the authors of the main article.
Understanding the reaction mechanism of Kolbe electrolysis on Pt anodes
Authors: Liu Sihang , Govindarajan Nitish , Prats Hector , Chan Karen
Published: February 2022

Kolbe electrolysis has been proposed an efficient electrooxidation process to synthesize (un)symmetrical dimers from biomass-based carboxylic acids. However, the reaction mechanism of Kolbe electrolysis remains controversial. In this work, we develop a DFT- based microkinetic model to study the reaction mechanism of Kolbe electrolysis of acetic acid (CH3COOH) on both pristine and partially oxidized Pt anodes. We show that the shift in the rate-determining step of oxygen evolution reaction (OER) on Pt(111)@α-PtO2 surface from OH* formation to H2O adsorption gives rise to the large Tafel slopes, i.e., the inflection zones, observed at high anodic potentials in experiments on Pt anodes. The activity passivation as a result of the inflection zone is further exacerbated in the presence of Kolbe species (i.e., CH3COO* and CH3*). Our simulations find the CH3COO* decarboxylation and CH3* dimerization steps determine the activity of Kolbe reaction during inflection zone. In contrast to the Pt(111)@α-PtO2 surface, Pt(111) shows no activity towards Kolbe products as the CH3COO* decarboxylation step is limiting throughout the considered potential range. This work resolves major controversies in the mechanistic analyses of Kolbe electrolysis on Pt anodes: the origin of the inflection zone, and the identity of the rate limiting step.
Covalent Functionalization of Nickel Phosphide Nanocrystals with Aryl-Diazonium Salts
Authors: Murphy Ian , Rice Peter , Monahan Madison , Zasada Leo , Miller Elisa , Raugei Simone , Cossairt Brandi
Published: February 2022

Covalent functionalization of Ni2P nanocrystals was demonstrated using aryl-diazonium salts. Spontaneous adsorption of aryl functional groups was observed, with surface coverages ranging from 20-96% depending on the native reactivity of the salt as determined by the aryl substitution pattern. Increased coverage was possible for low reactivity species using a sacrificial reductant. Functionalization was confirmed using thermogravimetric analysis, FTIR and X-ray photoelectron spectroscopy. The structure and energetics of this nanocrystal electrocatalyst system, as a function of ligand coverage, was explored with density functional theory calculations. The Hammett parameter of the surface functional group was found to linearly correlate with the change in Ni and P core-electron binding energies and the nanocrystal’s experimentally and computationally determined work-function. The electrocatalytic activity and stability of the functionalized nanocrystals for hydrogen evolution were also improved when compared to the unfunctionalized material, but a simple trend based on electrostatics was not evident. Density functional theory was used to understand this discrepancy, revealing that H adsorption energies on the covalently functionalized Ni2P also do not follow the electrostatic trend and are predictive descriptors of the experimental results.
Crystals versus Electrochromic Films: Pathway-Dependent Coordination Networks
Authors: van der Boom Milko , Malik Naveen , Singh Vivek , Shimon Linda , Houben Lothar , Lahav Michal
Published: February 2022

We demonstrate the formation of metal-organic frameworks (MOFs) and thin-film coatings that have entirely different compositions and structures, distinct by cation exchange, despite using the same set of starting materials. The reaction of an iron polypyridyl complex with a copper salt by diffusion of one solution into another resulted in iron-to-copper exchange, concurrent ligand rearrangement and the formation of MOFs. This observation shows that polypyridyl complexes can be used as expendable precursors for the growth of MOFs. In contrast, alternative depositions of the iron polypyridyl complex with a copper salt by automated spin-coating on conductive metal-oxides resulted in the formation of electrochromic coatings, and the structure and redox properties of the iron complex were retained. The possibility to form such different networks by “in solution” versus "on surface” coordination chemistry from the same set of molecular building blocks broadens the synthetic space to design functional materials.
Assignment-free chirality detection in unknown samples via microwave three-wave mixing
Authors: Koumarianou Greta , Wang Irene , Satterhwaite Lincoln , Patterson David
Published: February 2022

Straightforward identification of chiral molecules in multi-component mixtures of unknown composition is extremely challenging. Current spectrometric and chromatographic methods cannot unambiguously identify components while the state of the art spectroscopic methods are limited by the difficult and time-consuming task of spectral assignment. Here, we introduce a highly sensitive generalized version of microwave three-wave mixing that uses broad-spectrum fields to detect chiral molecules in enantiomeric excess without any prior chemical knowledge of the sample. This method does not require spectral assignment as a necessary step to extract information out of a spectrum. We demonstrate our method by recording three-wave mixing spectra of multi-component samples that provide direct evidence of enantiomeric excess. Our method opens up new capabilities in ultrasensitive phase-coherent spectroscopic detection that can be applied for chiral detection in real-life mixtures, raw products of chemical reactions and difficult to assign novel exotic species.
Unprecedented and Readily Tunable Photoluminescence from Aliphatic Quaternary Ammonium Salts
Authors: Tang Saixing , Zhao Zihao , Yang Tianjia , Wang Yunzhong , Chen Xiaohong , Yuan Wang Zhang
Published: February 2022

Compounds bearing aliphatic amines could be emissive under proper conditions. Their ionized counterparts, quaternary ammonium salts (QASs), which are widely used as phase-transfer catalysts, ionic liquids, disinfectants and surfactants, however, are known as luminescence quenchers and thought to be nonemissive. Here we report the unprecedented intrinsic fluorescence-phosphorescence dual emission from a diversity of QASs, which can also be finely regulated by excitation wavelength, alkyl chain length, counter ions, mechanical stimuli, etc. The bright photoluminescence along with distinct afterglow and tunable multicolor emissions enables advanced multimode anticounterfeiting for QAS solids. This finding refreshes the cognition of QASs and would inspire emerging applications by utilizing their intrinsic luminescence. Furthermore, it opens opportunities for the investigation of QAS related processes and functions in a photophysical approach and affords strong implications for the fabrication of novel nonconventional luminophores.
The DNA–carbon nanotube binding mode determines the efficiency of carbon nanotube-mediated DNA delivery to intact plants
Authors: Ali Zahir , Serag Maged , Demirer Gozde , Torre Bruno , Fabrizio Enzo di , Landry Markita , Habuchi Satoshi , Mahfouz Magdy
Published: February 2022

Efficient delivery of DNA, RNA, and genome engineering machinery to plant cells will enable efforts to genetically modify plants for global food security, sustainable energy production, synthetic biology applications, and climate change resilience. For the delivery of functional genetic units into plant cells, charged nanoparticles, particularly carbon nanotubes (CNT), have attracted considerable interest. Although some success has been achieved using CNT-based approaches, the efficiency, batch reproducibility, and the limits of their applicability remain to be assessed. Here, we provide a mechanistic understanding of plasmid DNA-loaded CNTs based transfection of plant cells, and factors affecting the expression of the transformed plasmid. We show that transfection is inherently limited by the presence of the cell wall, Coulomb interactions between DNA and polymer coated CNT, and DNA size, whereas expression of the transformed plasmid is limited by relative gene-to-plasmid size and the intracellular accessibility of DNA. We further show that the formation of partially condensed DNA on the CNT surface is a prerequisite for successful transfection and expression. Furthermore, DNA does not detach completely from the CNT, so the accessibility of the transcription machinery to DNA is the key for transformation efficiency. This irreversible DNA plasmid binding and partial condensation limit the length of DNA that can be expressed, thus negatively affecting efficiency and reproducibility. Understanding the underlying mechanisms and limitations of CNT-mediated delivery of DNA through the plant cell wall is of considerable importance in guiding efforts to design nanomaterials for efficient transformation, trait engineering, and synthetic biology applications.
High performance ambipolar organic mixed ionic-electronic conductor for adaptive logic circuits and neuromorphic electronics
Authors: Zhang Yanxi , van Doremaele Eveline , Ye Gang , Stevens Tim , Song Jun , Chiechi Ryan , van de Burgt Yoeri
Published: February 2022

Organic mixed ionic-electronic conductors (OMIECs) are central to bioelectronic applications such as biosensors, health monitoring devices and neural interfaces, and have facilitated efficient next-generation brain-inspired computing and biohybrid systems. Most OMIECs are hole-conducting (p-type) materials, while complimentary logic circuits and various biosensors require electron-conducting (n-type) materials too. Here we show an ambipolar mixed ionic-electronic polymer that achieves high on/off ratios with high ambient p- and n- type stability. We highlight the versatility of the material by demonstrating its use as a neuromorphic memory element, an adaptable ambipolar complementary logic inverter, and a neurotransmitter sensor. The ambipolar operation of this material allows for straightforward monolithic fabrication and integration, and opens a route towards more sophisticated complex logic and adaptive circuits.
Capturing the Most Active State of a Palladium(0) Cross-Coupling Catalyst
Authors: Lau Sii Hong , Chen Liye , Kevlishvili Illia , Davis Katherine , Liu Peng , Carrow Brad
Published: February 2022

Zerovalent palladium complexes are ubiquitous active species in modern cross-coupling reactions that comprise many premier methods for the construction of C–C and C–heteroatom bonds in organic synthesis. While palladium(0) complexes stabilized by two or more dative ligands are widely known, the most active form of Pd(0) coordinated by a single ancillary ligand (“monoligated Pd(0)”) has long eluded direct characterization. We report the synthesis and unambiguous solution- and solid-state characterization of functionally 12-electron Pd(0) complexes coordinated by a single tri(1-adamantyl)phosphine (PAd3) ligand. Access to these fleeting intermediates was achieved by enabling B-to-Pd transmetalation reactions that occur at cryogenic temperature. This work opens new avenues to experimentally interrogate highly reactive on-cycle Pd(0) catalysts and their structure-dependent reactivity and speciation, which should be broadly informative in continuing studies of catalytic processes featuring the prevalent Pd(0)/Pd(II) redox couple.
Decisive Role of Spin-States and Spin-Coupling in Dictating Selective O2 Adsorption in Chromium(II) Metal-Organic Framework
Authors: Rajaraman Gopalan , Jose Reshma , Kancharlapalli Srinivasu , Ghanty Tapan , Pal Sourav
Published: February 2022

By computing and analyzing the magnetic exchange coupling, binding energies, the partial density of states (pDOS), and adsorption isotherms for the pristine and gas bound MOFs [(Cr4(X)4Cl)3(BTT)8]3- (X=O2, N2, and H2), we unequivocally establish the role of spin-states and spin-coupling in controlling the gas selectivity. The computed geometries and gas adsorption isotherms are consistent with the earlier experiments. The O2 binding to the MOF follows an electron-transfer mechanism resulting in a Cr(III) superoxo species (O2-•) with a very strong antiferromagnetic coupling between the two centers, while N2/H2 found to only weakly perturb the metal center. Although the gas bound and unbound MOFs have S =0 ground state (GS), the nature of spin configurations and the associated magnetic exchanges are dramatically different. This study offers a hitherto unknown strategy of utilizing spin-state/spin-couplings to control gas adsorption selectivity in MOFs.
Enhancing Cysteine Chemoproteomic Coverage Through Systematic Assessment of Click Chemistry Product Fragmentation
Authors: Yan Tianyang , Palmer Andrew , Geiszler Daniel , Polansky Dan , Armenta Ernest , Nesvizhskii Alexey , Backus Keriann
Published: February 2022

Mass spectrometry-based chemoproteomics has enabled functional analysis and small molecule screening at thousands of cysteine residues in parallel. Widely adopted chemoproteomic sample preparation workflows rely on the use of pan-cysteine reactive probes such as iodoacetamide alkyne combined with biotinylation via copper-catalyzed azide–alkyne cycloaddition (CuAAC) or ‘click chemistry’ for cysteine capture. Despite considerable advances in both sample preparation and analytical platforms, current techniques only sample a small fraction of all cysteines encoded in the human proteome. Extending the recently introduced labile mode of the MSFragger search engine, here we report an in-depth analysis of cysteine biotinylation via click chemistry (CBCC) reagent gas-phase fragmentation during MS/MS analysis. We find that CBCC conjugates produce both known and novel diagnostic fragments and peptide remainder ions. Among these species, we identified a candidate signature ion for CBCC peptides, the oxonium-biotin fragment ion that is generated upon fragmentation of the N(triazole)–C(alkyl) bond together with cyclization. Guided by our empirical comparison of the fragmentation patterns of five CBCC reagent combinations, we achieved enhanced coverage of cysteine labeled peptides. For larger, fragmentation-prone biotinylation reagents, implementation of labile search afforded unique PSMs and provides a roadmap for the utility of such searches in enhancing chemoproteomic peptide coverage.