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Highly conducting, mixed-valence, multi-component nickel bis(diselenolene) salts were obtained by electrocrystallization of the monoanionic species [Ni(Me-thiazds)2]-1 (Me-thiazds: N-methyl-1,3-thiazoline-2-thione-4,5-diselenolate), with 1:2 and 1:3 stoichiometries depending of the counter ion used (Et4N+ and nBu4N+ vs Ph4P+, respectively). This behavior strongly differs from that of the corresponding monoanionic dithiolene complexes whose oxidation afforded the single component neutral species. This provides additional rare examples of mixed-valence conducting salts of nickel diselenolene complexes, only known in two examples with the dsit (1,3-dithiole-2-thione-4,5-diselenolate) and dsise (1,3-dithiole-2-selone-4,5-diselenolate) ligands. The mixed-valence salts form highly dimerized or trimerized bi- and trimetallic units, rarely seen with such nickel complexes. Transport measurements under a high pressure (up to 10 GPa) and band structure calculations confirm the semiconducting character of [Ph4P][Ni(Me-thiazds)2]3 and the quasi metallic character of [Et4N][Ni(Me-thiazds)2]2 and [NBu4]x[Ni(Me-thiazds)2]2 salts (0 < x < 1)., This work was supported in part by Université de Rennes 1 (Ph.D. grant to H.H.) and by the JSPS KAKENHI (grant JP16H06346). The stay of H.H. to RIKEN was supported in part by the RIKEN International Program Associate and by Rennes Métropole. We thank Takaaki Minamidate (RIKEN) and Thierry Guizouarn (Rennes) for the magnetic susceptibility (SQUID) measurements. Work in Spain was supported by MINECO through Grants PGC2018-096955-B-C44 and PID2021-128217NB-I00, Generalitat de Catalunya (2017SGR1506 and 2017SGR1289). E.C. acknowledges the support of the Spanish MINECO through the Severo Ochoa FUNFUTURE (CEX2019-000917-S) Excellence Centre distinction and P.A. acknowledges the support from the Maria de Maeztu Units of Excellence Program (MDM-2017-0767). Their support is gratefully acknowledged., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

Funding: This work was supported by the Biotechnology and Biological Sciences Research Council (REF: BB/S000313/1 to MFW), Medical Research Council (REF: MR/S021647/1 to RS) and the China Scholarship Council (REF: 202008060345 to QS). Type I CRISPR systems are the most common CRISPR type found in bacteria. They use a multisubunit effector, guided by crRNA, to detect and bind dsDNA targets, forming an R-loop and recruiting the Cas3 enzyme to facilitate target DNA destruction, thus providing immunity against mobile genetic elements. Subtypes have been classified into families A-G, with type I-G being the least well understood. Here, we report the composition, structure and function of the type I-G Cascade CRISPR effector from Thioalkalivibrio sulfidiphilus, revealing key new molecular details. The unique Csb2 subunit processes pre-crRNA, remaining bound to the 3′ end of the mature crRNA, and seven Cas7 subunits form the backbone of the effector. Cas3 associates stably with the effector complex via the Cas8g subunit and is important for target DNA recognition. Structural analysis by cryo-Electron Microscopy reveals a strikingly curved backbone conformation with Cas8g spanning the belly of the structure. These biochemical and structural insights shed new light on the diversity of type I systems and open the way to applications in genome engineering. Publisher PDF

YMgNi4-based alloys exhibit reversible hydrogen absorption and desorption reactions at near room temperature. Here, we report that Co-substituted YMgNi4-based alloys exhibited higher hydrogen contents and lower hydrogen absorption and desorption reaction pressures than unsubstituted alloys. The effects of Co-substitution viewed from atomic arrangements were particularly clarified by synchrotron radiation powder X-ray diffraction, neutron diffraction, and inelastic neutron scattering. Powder neutron diffraction of the Co-substituted alloy at 5 MPa of D-2 pressure suggested the formation of gamma-phase deuteride (higher deuterium content) from beta-phase deuteride (lower deuterium content). However, no gamma-phase deuteride was observed in the unsubstituted alloys at 5 MPa. Therefore, the gamma-phase deuteride formation of the Co-substituted alloy at lower pressure led to higher hydrogen contents than the unsubstituted alloys. The combined results of powder neutron diffraction and inelastic neutron scattering suggested that the gamma-phase hydride of the Co-substituted alloy was continuously generated due to additional H atoms at the H atom sites in the beta-phase hydride because of the disordered H atomic arrangement involving H-H interactions. As a result, hydrogen absorption and desorption reaction pressures for the gamma-phase deuteride formation with higher hydrogen storage capacity were lowered.

RNase P is a ribonucleoprotein (RNP) that catalyzes removal of the 5 ' leader from precursor tRNAs in all domains of life. A recent cryo-EM study of Methanocaldococcus jannaschii (Mja) RNase P produced a model at 4.6-angstrom resolution in a dimeric configuration, with each holoenzyme monomer containing one RNase P RNA (RPR) and one copy each of five RNase P proteins (RPPs; POP5, RPP30, RPP21, RPP29, L7Ae). Here, we used native mass spectrometry (MS), mass photometry (MP), and biochemical experiments that (i) validate the oligomeric state of the Mja RNase P holoenzyme in vitro, (ii) find a different stoichiometry for each holoenzyme monomer with up to two copies of L7Ae, and (iii) assess whether both L7Ae copies are necessary for optimal cleavage activity. By mutating all kink-turns in the RPR, we made the discovery that abolishing the canonical L7Ae-RPR interactions was not detrimental for RNase P assembly and function due to the redundancy provided by protein-protein interactions between L7Ae and other RPPs. Our results provide new insights into the architecture and evolution of RNase P, and highlight the utility of native MS and MP in integrated structural biology approaches that seek to augment the information obtained from low/medium-resolution cryo-EM models. NIH [GM-120582, P41 GM128577, S10OD023582]; NASA [NNX13AI05G]; Virginia Tech Agricultural Experiment Station Hatch Program [CRIS project] [VA160021]; OSU Comprehensive Cancer Center for a Pelotonia Pre-doctoral Fellowship; Virginia Tech Genetics, Bioinformatics, and Computational Biology Doctoral Program Fellowship Published version NIH [GM-120582 to M.P.F., V.H.W., V.G., P41 GM128577 to V.H.W., S10OD023582 to J.E.J.]; NASA [NNX13AI05G to B.M.]; Virginia Tech Agricultural Experiment Station Hatch Program [CRIS project VA160021 to B.M.]; OSU Comprehensive Cancer Center for a Pelotonia Pre-doctoral Fellowship (to H.D.P.); Virginia Tech Genetics, Bioinformatics, and Computational Biology Doctoral Program Fellowship (to B.K.). Funding for open access charge: University funds.

beta-Ureidopropionase is the third enzyme of the pyrimidine degradation pathway and catalyses the conversion of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid to beta-alanine and beta-aminoisobutyric acid, ammonia and CO2. To date, only a limited number of genetically confirmed patients with a complete beta-ureidopropionase deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 10 newly identified beta-ureidopropionase deficient individuals. Patients presented mainly with neurological abnormalities and markedly elevated levels of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid in urine. Analysis of UPB1, encoding beta-ureidopropionase, showed 5 novel missense variants and two novel splice-site variants. Functional expression of the UPB1 variants in mammalian cells showed that recombinant beta-ureidopropionase carrying the p.Ala120Ser, p.Thr129Met, p.Ser300Leu and p.Asn345Ile variant yielded no or significantly decreased beta-ureidopropionase activity. Analysis of the crystal structure of human beta-ureidopropionase indicated that the point mutations affect substrate binding or prevent the proper subunit association to larger oligomers and thus a fully functional beta-ureidopropionase. A minigene approach showed that the intronic variants c.[364 + 6 T > G] and c.[916 + 1_916 + 2dup] led to skipping of exon 3 and 8, respectively, in the process of UPB1 pre-mRNA splicing. The c.[899C > T] (p.Ser300Leu) variant was identified in two unrelated Swedish beta-ureidopropionase patients, indicating that beta-ureidopropionase deficiency may be more common than anticipated.

The scattering pattern of a crystal obeys the symmetry of the crystal structure through the corresponding Laue group. This is usually also true for the diffuse scattering, containing information about disorder, but here a case is reported where the diffuse scattering is of lower symmetry than the parent crystal structure. The mineral bixbyite has been studied by X-ray and neutron scattering techniques since 1928 with some of the most recent studies characterizing the low-temperature transition to a magnetically disordered spin-glass state. However, bixbyite also exhibits structural disorder, and here single-crystal X-ray and neutron scattering is used to characterize the different modes of disorder present. One-dimensional rods of diffuse scattering are observed in the cubic mineral bixbyite, which break the expected symmetry of the scattering pattern. It is shown that this scattering arises from epitaxial intergrowths of the related mineral, braunite. The presence of this disorder mode is found to be directly observable as well-defined residuals in the average structure refined against the Bragg diffraction. An additional three-dimensional diffuse scattering component is observed in neutron scattering data, which is shown to originate from the substitutional disorder on the Fe/Mn sites. This occupational disorder gives rise to local relaxations of the oxide sublattice, and the pattern of oxide displacements can be rationalized based on crystal-field theory. The combined use of neutron and X-ray single-crystal scattering techniques highlights their great complementarity. In particular, the large sample requirements for neutron scattering experiments prove to be an obstacle in solving the intergrowth disorder due to several growth orientations, whereas for X-ray scattering the one-dimensional nature of the intergrowth disorder renders solving this a more tractable task. On the other hand, the oxide relaxations cannot be resolved using X-rays due to the low Mn/Fe contrast. By combining the two approaches both types of disorder have been characterized.

Eight polythiophene derivatives containing pyrazoline side groups were synthesized by a chemical oxidative coupling polymerization using FeCl3. The crystal structures of four monomers were determined which confirm the almost perpendicular orientation of the thiophene and pyrazoline rings, while the other substituents are more coplanar. Analyses of IR, 1H-NMR, Raman and UV-Vis spectra demonstrated that the suggested polymerization was successful to generate the synthesized polythiophenes with the expected structures. The morphology of the synthesized polythiophenes was studied by SEM. The different substituents attached to the 1- and 3-positions of the pyrazoline side chain led to differences in optical properties, electrical conductivity, and thermal stability of the synthesized polythiophenes. By adding a pyrazoline side chain to polythiophenes, some polymers achieve good solubility, electrical conductivity of about 1.3 × 10-6 S/cm, high fluorescence intensity (above 40,000 a.u.) at 505-550 nm and thermal stability up to 590°C in the air. ispartof: DESIGNED MONOMERS AND POLYMERS vol:25 issue:1 pages:136-147 ispartof: location:England status: published

James Barber, known to colleagues and friends as Jim, passed away in January 2020 after a long battle against cancer. During his long and distinguished career in photosynthesis research, Jim made many outstanding contributions with the pinnacle achieving his dream of determining the first detailed structure of the Mn cluster involved in photosynthetic water oxidation. Here, colleagues and friends remember Jim and reflect upon his scientific career and the impact he had on their lives and the scientific community.

Allium ampeloprasum L., elephant garlic, is a plant that is cultivated and notable for its usage for medical and nutritional purposes. From this point, the present work presents the phenolic profiles of methanol extracts from the flowers, leaves, and bulbs of A. ampeloprasum collected in the wild in Izmir, Turkey, using a liquid chromatography-mass spectrometry technique. Among the 30 quantified phenolic compounds, 3-hydroxybenzoic acid was the major component in A. ampeloprasum from Cambel (AA2) with a value of 3505 +/- 12.8 mu g/g extract, while the bioactive flavonols, quercetin (98.37 +/- 1.75 mu g/g extract), and kaempferol (173.20 +/- 1.3 mu g/g extract) were notable molecules in samples of A. ampeloprasum from Armutlu (AA1). Additionally, antioxidant activity by ferric-reducing antioxidant power and cupric ion-reducing assays, and the total phenolic, and flavonoid content were determined for all extracts. Finally, the samples' capacity to inhibit the enzymes acetylcholinesterase, butyrylcholinesterase, and tyrosinase was evaluated using a 96-well microplate reader, the flowers of both samples generally had stronger inhibitory activity. Furthermore, the relationship between enzyme inhibition potency and the main phenolic components was expounded by molecular modeling studies. Consequently, these experiments were achieved to investigate the prospective usage of A. ampeloprasum both in pharmaceutical and nutraceutical fields., Scientific and Technical Research Council of Turkey (TUBITAK) [217S341]; Pharmaceutical Science Research Centre (FABAL) in Ege University, Acknowledgments We thank the Scientific and Technical Research Council of Turkey (TUBITAK) grant no 217S341 and the Pharmaceutical Science Research Centre (FABAL) in Ege University for their financial and technical sup-port, respectively.

The integrity of a cell's proteome depends on correct folding of polypeptides by chaperonins. The chaperonin TCP-1 ring complex (TRiC) acts as obligate folder for >10% of cytosolic proteins, including he cytoskeletal proteins actin and tubulin. Although its architecture and how it recognizes folding substrates are emerging from structural studies, the subsequent fate of substrates inside the TRiC chamber is not defined. We trapped endogenous human TRiC with substrates (actin, tubulin) and cochaperone (PhLP2A) at different folding stages, for structure determination by cryo-EM. The already-folded regions of client proteins are anchored at the chamber wall, positioning unstructured regions toward the central space to achieve their native fold. Substrates engage with different sections of the chamber during the folding cycle, coupled to TRiC open-and-close transitions. Further, the cochaperone PhLP2A modulates folding, acting as a molecular strut between substrate and TRiC chamber. Our structural snapshots piece together an emerging model of client protein folding within TRiC. Tagging of the endogenous type II chaperonin TRiC complex using CRISPR knock-in enables its purification for cryo-EM. A series of structures reveal the fate of substrates and co-chaperones inside the TRiC chamber to uncover its inner workings.

The design of proteins that bind to a specific site on the surface of a target protein using no information other than the three-dimensional structure of the target remains a challenge1–5. Here we describe a general solution to this problem that starts with a broad exploration of the vast space of possible binding modes to a selected region of a protein surface, and then intensifies the search in the vicinity of the most promising binding modes. We demonstrate the broad applicability of this approach through the de novo design of binding proteins to 12 diverse protein targets with different shapes and surface properties. Biophysical characterization shows that the binders, which are all smaller than 65 amino acids, are hyperstable and, following experimental optimization, bind their targets with nanomolar to picomolar affinities. We succeeded in solving crystal structures of five of the binder–target complexes, and all five closely match the corresponding computational design models. Experimental data on nearly half a million computational designs and hundreds of thousands of point mutants provide detailed feedback on the strengths and limitations of the method and of our current understanding of protein–protein interactions, and should guide improvements of both. Our approach enables the targeted design of binders to sites of interest on a wide variety of proteins for therapeutic and diagnostic applications.

Photosystem II (PSII) is the multi-subunit light-driven oxidoreductase that drives photosynthetic electron transport using electrons extracted from water. To investigate the initial steps of PSII assembly, we used strains of the cyanobacterium Synechocystis sp. PCC 6803 arrested at early stages of PSII biogenesis and expressing affinity-tagged PSII subunits to isolate PSII reaction center assembly (RCII) complexes and their precursor D1 and D2 modules (D1mod and D2mod). RCII preparations isolated using either a His-tagged D2 or a FLAG-tagged PsbI subunit contained the previously described RCIIa and RCII* complexes that differ with respect to the presence of the Ycf39 assembly factor and high light-inducible proteins (Hlips) and a larger complex consisting of RCIIa bound to monomeric PSI. All RCII complexes contained the PSII subunits D1, D2, PsbI, PsbE, and PsbF and the assembly factors rubredoxin A and Ycf48, but we also detected PsbN, Slr1470, and the Slr0575 proteins, which all have plant homologs. The RCII preparations also contained prohibitins/stomatins (Phbs) of unknown function and FtsH protease subunits. RCII complexes were active in light-induced primary charge separation and bound chlorophylls (Chls), pheophytins, beta-carotenes, and heme. The isolated D1mod consisted of D1/PsbI/Ycf48 with some Ycf39 and Phb3, while D2mod contained D2/cytochrome b559 with co-purifying PsbY, Phb1, Phb3, FtsH2/FtsH3, CyanoP, and Slr1470. As stably bound, Chl was detected in D1mod but not D2mod, formation of RCII appears to be important for stable binding of most of the Chls and both pheophytins. We suggest that Chl can be delivered to RCII from either monomeric Photosystem I or Ycf39/Hlips complexes.

Metal halide perovskites serving as one of the most promising photovoltaic materials are gaining considerable attention worldwide. For achieving high performance as well as long-term stability of the perovskite solar cells (PSCs), a good quality of perovskite film featuring in smooth, pinhole-free morphology, full coverage over substrates, good heterojunction contacts, and stable photoactive phase is of great importance. During solution fabrication for perovskite films, intermediate phase, which refers to the state of precursor composition before final annealing, plays an essential role in determining the film quality, especially in the state-of-theart PSCs. In this review, we summarize the research involving mechanism and applications of intermediate phase engineering (IPE) processes in various solution-processing technologies. The challenges of IPE are further discussed, and perspectives are provided for developing high-performance PSCs via IPE.

Catalysts consisting of highly dispersed copper on a mesoporous ZrO2 support were synthesised via a one-pot sol-gel synthesis and were tested for the selective catalytic reduction of NOx by NH3. The copper dispersion was investigated by XRD and TEM, which showed no discernible copper oxide particles up to 6 wt% Cu, while they were detected at 15 wt% Cu., NH3 adsorption and the SCR reaction were followed in situ by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) on mesoporous ZrO2 and on one-pot synthesized 3 wt% Cu/ZrO2. Cu was found to improve the NH3 adsorption capacity of the catalyst by enhancing the Lewis functionality., The catalysts were efficient for SCR at low temperature, at 150 degrees C 75% of NO was converted over 6 wt% Cu/ ZrO2 at water-free conditions. Increasing the copper loading while maintaining the dispersion improved NOx conversion.

Colloidal nanocrystals (NCs) of fully inorganic lead halide perovskites (LHPs) are the latest generation of quantum-dot materials with compelling optical characteristics. Favored by the nearly regular cubic shape of NCs, they readily self-organize into highly ordered supercrystals (SCs) that have been stimulating in-depth investigation of uncommon collective properties at the fundamental level. Herein, we explore LHP NC SCs formed in colloidal suspensions and as solid materials, without any prior rigorous NC size-selection process. The spontaneous self-organization manifests itself in synchrotron wide-angle X-ray total scattering (WAXTS) measurements of randomly oriented ensembles of SCs by virtue of the substructure in the 100(c) peak (in cubic notation). By developing atomistic models of SCs, we find an evidence that, in spite of the initial NCs size polydispersity (up to 20%), SCs of CsPbBr3 and CsPbBr1.5I1.5 NCs form through a size segregation process. The SCs exhibit high spatial structural coherence, that is, crystallographic alignment between NCs, along two and three directions, a degree of orientational order (the SCs mosaicity) below 2 degrees, and coherent sizes on the order of tens of nanometers. In situ coupled photoluminescence (PL) and WAXTS experiments evidence pronounced electronic coupling between NCs in SCs, seen as an ca. 50-70 meV red-shifted emission in dried samples compared to the corresponding dilute solution of NCs. ISSN:0897-4756

In this study, a total of 13 compounds (5-17) were synthesized starting from oleanolic acid (OA), a natural triterpenoid. Five new compounds (10, 11, 12, 15 and 17), are the main targets of the study, which were synthesized for the first time in this work as oxime, imine and hydrazone derivatives of OA. Other compounds were previously obtained as natural or semi-synthetically. NMR and HRMS analyses were carried out to determine of structures of all the synthesized molecules. The inhibitory effects of the synthesized compounds on acetylcholinesterase (AChE), human carbonic anhydrase I (hCA I) and II (hCA II) were evaluated. Compounds 13 and 15 showed better inhibitory activity than the other compounds against both hCA I and hCA II isoenzymes, which are competing with AZA. In addition, compound 15 showed the strongest AChE inhibitory activity among all the tested compounds, with an IC50 value of 34.46 mu M.

Receptor avidity through multivalency is a highly sought-after property of ligands. While readily available in nature in the form of bivalent antibodies, this property remains challenging to engineer in synthetic molecules. The discovery of several bivalent venom peptides containing two homologous and independently folded domains (in a tandem repeat arrangement) has provided a unique opportunity to better understand the underpinning design of multivalency in multimeric biomolecules, as well as how naturally occurring multivalent ligands can be identified. In previous work, we classified these molecules as a larger class termed secreted cysteine-rich repeat-proteins (SCREPs). Here, we present an online resource; ScrepYard, designed to assist researchers in identification of SCREP sequences of interest and to aid in characterizing this emerging class of biomolecules. Analysis of sequences within the ScrepYard reveals that two-domain tandem repeats constitute the most abundant SCREP domain architecture, while the interdomain "linker" regions connecting the functional domains are found to be abundant in amino acids with short or polar sidechains and contain an unusually high abundance of proline residues. Finally, we demonstrate the utility of ScrepYard as a virtual screening tool for discovery of putatively multivalent peptides, by using it as a resource to identify a previously uncharacterized serine protease inhibitor and confirm its predicted activity using an enzyme assay. ispartof: PROTEIN SCIENCE vol:32 issue:2 ispartof: location:United States status: published

A novel cadmium complex, [Cd(L)2](NO3)2(H2O)2, (hereinafter simply designated as Cd IIL2) has been syn-thesized by reacting a hydrazone-oxime ligand, (2E,3E)-3-(2-(6-chloropyridin-2-yl)hydrazono)butan-2-one oxime ( L ), with cadmium nitrate tetrahydrate. The ligand L and Cd IIL2 were characterized by LC/MS-MS, FT-IR, elemental analysis, NMR, molar conductivity, UV-Vis spectroscopy and thermal analysis. The struc-ture of the Cd IIL2 was also elucidated by the single-crystal X-ray diffraction technique. The X-ray powder diffraction pattern of Cd IIL2 was then performed to confirm the purity of the crystalline compound. Addi-tionally, as a result of analytical and spectroscopic data suggested that the metal in Cd IIL2 exhibits a dis-torted octahedral geometry. Hirshfeld surface analysis (HSA) was used in conjunction with 2D fingerprint plots to evaluate intermolecular forces, involving hydrogen bonds, in the crystal lattice of Cd IIL2. Thermal and kinetic studies of the synthesized compounds were performed between 30 and 10 0 0 degrees C using dif-ferent heating rates of 5, 10, and 15 degrees C/min under two different atmosphere (N 2 and O 2 ). The Kissinger-Akahira-Sunose (KAS) and Flynn-Wall-Ozawa (FWO) integral methods have been selected to determine the values of the reaction activation energies ( Ea ). According to the Ea values, FWO was selected to in-vestigate the thermodynamic parameters, i.e., the free energy change ( AG), entropy ( AS) and enthalpy (AH) changes. The ligand and its complex exhibited better thermal stability and higher thermodynamic values in O 2 atmosphere than in N 2 atmosphere. (c) 2022 Elsevier B.V. All rights reserved.

Lectins from plants of the Diocleinae subtribe often exhibit specificity towards mannose/glucose and derived sugars, with some plants also displaying a second lectin specific to lactose/GalNAc. Here, we present a novel lectin from Collaea speciosa, named CsL, that displays specificity for GlcNAc/glucose. The lectin was extracted from Collaea speciosa seeds and purified by a single chromatographic step on a Sephadex G-50 matrix. In solution, the lectin appears as a dimeric protein composed of 25 kDa monomers. The protein is stable at pH 7–8 and dependent on divalent cations. CsL maintained its agglutination activity after heating to 90 °C for 1 h. Glycan array studies revealed that CsL binds to N-glycans with terminal GlcNAc residues, chitobiose and chitotriose moieties. The partial amino acid sequence of the lectin is similar to that of some lactose-specific lectins from the same subtribe. In contrast to other ConA-like lectins, CsL is not toxic to Artemia. Because of its remarkably different properties and specificity, this lectin could be the first member of a new group inside the Diocleinae lectins.

Metallo-beta-lactamases (MBLs) are significant threats to humans because they deteriorate many kinds of beta-lactam antibiotics and are key enzymes responsible for multi-drug resistance of bacterial pathogens. As a result of in vitro screening, two compounds were identified as potent inhibitors of two kinds of MBLs: imipenemase (IMP-I) and New Delhi metallo-beta-lactamase (NDM-1). The binding structure of one of the identified compounds was clarified by an X-ray crystal analysis in complex with IMP-1, in which two possible binding poses were observed. Molecular dynamics (MD) simulations were performed by building two calculation models from the respective binding poses. The compound was stably bound to the catalytic site during the simulation in one pose. The binding model between NDM-1 and the compound was constructed for MD simulation. Calculation results for NDM-1 were similar to those of IMP-1. The simulation suggested that the binding of the identified inhibitory compound was also durable in the catalytic site of NDM-1. The compound will be a sound basis for the development of the inhibitors for MBLs.

Elongated akaganéite (β-FeOOH) nanostructures were synthesized through a simple hydrothermal route, in which a careful selection of the experimental conditions allows for a tunable length and aspect ratio and concomitantly predetermines the magnetic response. An in-depth structural characterization using transmission electron microscopy, X-ray diffraction, and Raman spectroscopy, jointly with DC magnetic measurements, reveals a complex scenario where the interstitial Cl-content dictates the β-FeOOH thermal stability and leads to the formation of bulk uncompensated spins along the inner channels. The coexistence of different magnetic contributions is observed to result in a non-monotonic dependence of the coercivity and exchange bias field on both temperature and size, posing major limitations for the archetypical magnetic core-shell model generally assumed for nanostructured antiferromagnets. As a proof of concept, we further show how the β-FeOOH internal microstructure can be chemically manipulated through Cl-anion exchange, giving rise to a superparamagnetic component that comes along with an almost 20-fold increase in the coercivity at low temperature. The evaluation of these results reveals the potential of controlling the interplay between the crystal and magnetic structure via intercalation chemistry in antiferromagnets, expanding fundamental science knowledge and supporting practical applications, given their huge role in the technological fields of spintronics and magnonics., M.T.-A. and E.T. acknowledge financial support from Xunta de Galicia (Regional Government, Spain) under grants ED481A-2017/377 and ED481A-2019/244. V.S. acknowledges financial support from the Spanish Ministerio de Ciencia e Innovación under project PID2020-119242-I00 and from the European Union under project PEPSA-MATE-872233. This project has been partly funded by the European Union’s Horizon 2020 research and innovation program under grant agreement no. 823717 (ESTEEM3)., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

Several gold +I and +III complexes are investigated computationally and spectroscopically, focusing on the d-configuration and physical oxidation state of the metal center. Density functional theory calculations reveal the non-negligible electron-sharing covalent character of the metal-to-ligand σ-bonding framework. The bonding of gold(III) is shown to be isoelectronic to the formal CuIII complex [Cu(CF3)4]1- , in which the metal center tries to populate its formally unoccupied 3dx2-y2 orbital via σ-bonding, leading to a reduced d10 CuI description. However, Au L3-edge X-ray absorption spectroscopy reveals excitation into the d-orbital of the AuIII species is still possible, showing that a genuine d10 configuration is not achieved. We also find an increased electron-sharing nature of the σ-bonds in the AuI species, relative to their AgI and CuI analogues, due to the low-lying 6s orbital. We propose that gold +I and +III complexes form similar bonds with substrates, owing primarily to participation of the 5dx2-y2 or 6s orbital, respectively, in bonding, indicating why AuI and AuIII complexes often have similar reactivity.

International audience; The low-valent rhenium(I) salt Na[Re(η5-Cp)(BDI)] (BDI = N,N′-bis(2,6-diisopropylphenyl)-3,5-dimethyl-β-diketiminate) was shown to react with various halide and chalcogenolate reagents, leading to the isolation of a series of rhenium(III)–halide and −pseudohalide complexes: Re(X)(η5-Cp)(BDI) (1-X, X = F, Cl, Br, I; 2, X = OTf) and Re(ER)(η5-Cp)(BDI) (3-ER, ER = SBn, SeBn, TePh). The 1H NMR spectra of these complexes displayed sharp resonances shifted several ppm from typical diamagnetic regions, as well as distinct chemical shift trends down both the halide (with the exception of F) and chalcogenolate series, with both Cp and BDI backbone peaks moving downfield with increasing atomic number. Subsequent magnetic susceptibility measurements of the rhenium(III) halides 1-Cl, 1-Br, and 1-I indicated that these complexes display temperature-independent paramagnetism (TIP), with χTIP values of 7.41(44) × 10–4 to 1.50(51) × 10–3 cm3 mol–1. Multireference complete active space self-consistent field (CASSCF) computations incorporating spin–orbit state mixing revealed small energy separations (1.7–3.0 kcal/mol) between thermally isolated ground states and the first excited spin–orbit states for the rhenium halides, confirming that low-lying excited states are responsible for the observed TIP behavior.

Xenobiotic nucleic acids (XNAs) offer tremendous potential for synthetic biology, biotechnology, and molecular medicine but their ability to mimic nucleic acids still needs to be explored. Here, to study the ability of XNA oligonucleotides to mimic tRNA, we synthesized three L-Ala-tXNAs analogs. These molecules were used in a non-ribosomal peptide synthesis involving a bacterial Fem transferase. We compared the ability of this enzyme to use amino-acyl tXNAs containing 1',5'-anhydrohexitol (HNA), 2'-fluoro ribose (2'F-RNA) and 2'-fluoro arabinose. L-Ala-tXNA containing HNA or 2'F-RNA were substrates of the Fem enzyme. The synthesis of peptidyl-XNA and the resolution of their structures in complex with the enzyme show the impact of the XNA on protein binding. For the first time we describe functional tXNA in an in vitro assay. These results invite to test tXNA also as substitute for tRNA in translation. ispartof: NUCLEIC ACIDS RESEARCH vol:50 issue:20 pages:11415-11425 ispartof: location:England status: published

Binding to the neonatal Fc receptor (FcRn) extends serum half-life of IgG, and antagonizing this interaction is a promising therapeutic approach in IgG-mediated autoimmune diseases. Fc-MST-HN, designed for enhanced FcRn binding capacity, has not been evaluated in the context of a full-length antibody, and the structural properties of the attached Fab regions might affect the FcRn-mediated intracellular trafficking pathway. Here we present a comprehensive comparative analysis of the IgG salvage pathway between two full-size IgG1 variants, containing wild type and MST-HN Fc fragments, and their Fc-only counterparts. We find no evidence of Fab-regions affecting FcRn binding in cell-free assays, however, cellular assays show impaired binding of full-size IgG to FcRn, which translates into improved intracellular FcRn occupancy and intracellular accumulation of Fc-MST-HN compared to full size IgG1-MST-HN. The crystal structure of Fc-MST-HN in complex with FcRn provides a plausible explanation why the Fab disrupts the interaction only in the context of membrane-associated FcRn. Importantly, we find that Fc-MST-HN outperforms full-size IgG1-MST-HN in reducing IgG levels in cynomolgus monkeys. Collectively, our findings identify the cellular membrane context as a critical factor in FcRn biology and therapeutic targeting.

The first synthesis of 2,4-bis(3,4-dimethoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-disulfide (SAV-A1 reagent) was achieved. Seven oxo-alkyl esters (HLn) were synthesized thereof. Ni(II) complexes ([Ni(Ln)(2)]) of these ligands were prepared in ethanol. The structures were identified by spectral studies. Ni(II) complexes were unambiguously determined by X-ray crystallography. In addition, the ligands and their Ni(II) complexes were tested on two different human cancer cell lines, including liver and colon. Moreover, density functional theory (DFT) calculations of the Ni(II) complexes were performed, and the molecular docking studies of these compounds with liver cancer protein, PDB ID: 3WZE and colon cancer antigen proteins, ID 2HQ6 were presented to investigate and predict potential interactions.

In the biosynthesis of the iron-guanylylpyridinol (FeGP) cofactor, 6-carboxymethyl-5-methyl-4-hydroxy-2-pyridinol (1) is 3-methylated to form 2, then 4-guanylylated to form 3, and converted into the full cofactor. HcgA-G proteins catalyze the biosynthetic reactions. Herein, we report the function of two radical S-adenosyl methionine enzymes, HcgA and HcgG, as uncovered by in vitro complementation experiments and the use of purified enzymes. In vitro biosynthesis using the cell extract from the Methanococcus maripaludis Delta hcgA strain was complemented with HcgA or precursors 1, 2 or 3. The results suggested that HcgA catalyzes the biosynthetic reaction that forms 1. We demonstrated the formation of 1 by HcgA using the 3 kDa cell extract filtrate as the substrate. Biosynthesis in the Delta hcgG system was recovered by HcgG but not by 3, which indicated that HcgG catalyzes the reactions after the biosynthesis of 3. The data indicated that HcgG contributes to the formation of CO and completes biosynthesis of the FeGP cofactor.

An efficient five steps, the protection-deprotection synthetic a novel synthetic routes to(+/-) noruleine (f)-uleine, are reported starting from tetrahydrocarbazole fused monoalkyl nitrile at C-2 position that is prepared on mul-tigram scale from 2-(3-ethyl-1-oxo-2,3,4,9-tetrahydro-1H-carbazol-2-yl)acetonitrile (1) as well as the key azocino [4,3-b]indole skeleton is constructed via the tetrafluoro-1,4-benzoquinone (TFB)-mediated cyclization of a tet-rahydrocarbazole derivative possessing direct amide synthesis from nitrile. As a result, Total synthesis of nor-uleine and uleine has been developed, which is accomplished in 4 and 5-steps synthesis of the ABCD tetracyclic of the strychnos alkaloids with an overall yield of 44% and 39%, respectively. The DFT computations were per-formed with B3LYP/6-311g(d,p) level to determine inter and intramolecular interactions and reactivity features of the compound 3-6. Also, TD-DFT computations were performed to characterize the electronic absorption spectra of all compounds. Last, the interactions of compounds 3-6 with selected targets AChE, BuChE, and HSA were evaluated in light of the molecular dockings. The bioactivity and drug-likeness scores revealed that com-pound 6 3-6 can be proper candidate for future drug-design studies more than the other compounds. Scientific and Technological Research Council of Turkey [TUBITAK] [112T503] Nesimi Uludag was supported by Scientific and Technological Research Council of Turkey [TUBITAK Project No.112T503] .

A new family of oxofluorophoshates, AFe(PO 3F) 2(A = K, (NH 4) 2Cl, NH 4, Rb, and Cs), was synthesized via ionothermal methods using PF 6ionic liquids. Single-crystal and powder X-ray diffraction reveal that AFe(PO 3F) 2with A = (NH 4) 2Cl crystallizes in a trigonal structure, while AFe(PO 3F) 2with A = NH 4, Rb, and Cs crystallizes in a triclinic structure. Dimorphic KFe(PO 3F) 2crystallizes in both the trigonal and triclinic forms. The structures of all compounds feature Yavapaiite-like Fe(PO 3F) 2slabs, which are characterized by triangular Fe layers, planar in the case of the trigonal structure and undulated in the case of the triclinic one. Magnetization measurements reveal all compounds to order antiferromagnetically at low temperatures. The trigonal phases AFe(PO 3F) 2(A = K and (NH 4) 2Cl) display complex magnetic H-T phase diagrams. The observation of magnetization plateaus at M sat/3 (M sat= saturation magnetization) indicates the existence of the up-up-down (UUD) and V-phases at applied magnetic fields in the magnetically ordered state. Powder neutron diffraction measurements of KFe(PO 3F) 2confirm the 120° spin structure at zero fields. Along c, the magnetic moments form a commensurate spiral since the spins in each plane are rotated by 90° with respect to the adjacent one. To our knowledge, this is the first time such a non-centrosymmetric version of the 120° spin structure with a 90° rotation between nearest planes has been reported.

ispartof: RESULTS IN PHYSICS vol:49 status: accepted