Rosalivingston5760

Metallic glasses exhibit excellent properties such as ultrahigh strength and excellent wear and corrosion resistance, but there is limited understanding on the relationship between their atomic structure and mechanical properties as a function of their structural state. In this paper, we bridge the processing-structure-property gap by utilizing molecular dynamics simulation for a model binary metallic glass, namely Ni80P20. The structural statistics including the fraction of Voronoi index, the distribution of Voronoi volume, and medium-range ordering are calculated to explain the observed changes in mechanical behavior and strain localization upon relaxation and rejuvenation. Our findings demonstrate that the evolution of mechanical properties can be linked to the atomic structure change in terms of short- and medium-range ordering. With the help of structural statistics, the mechanical properties are determined based on simple Voronoi analysis.Research on small-molecule dissociation on plasmonic silver nanoparticles is on the rise. Herein, we investigate the effect of various parameters of light, i.e., field strength, polarization direction, and energy of oscillation, on the dynamics of oxygen upon photoexcitation of the O2@Ag8 composite using real-time time-dependent density functional theory calculations with Ehrenfest dynamics. From our excited-state dynamics calculations, we found that increasing the strength of the external electric field brings a significant contribution to the O-O dissociation. In addition, the polarization direction of the incident light becomes important, especially at weaker field strengths. The light that is polarized along the direction of charge transfer from the metal to adsorbate and the light that is polarized along the long axis of molecular oxygen were found to enhance the bond breaking of O2 significantly. We also found that at the weakest electric field strength, the oxygen molecule stays adsorbed to the silver cluster when the incident light resonates with low-energy excited states and desorbs away from the metal cluster with high-energy excitations. With strong electric fields, oxygen either desorbs or dissociates.A new methodology for classifying fragment combinations and characterizing pseudonatural products (PNPs) is described. The source code is based on open-source tools and is organized as a Python package. Tasks can be executed individually or within the context of scalable, robust workflows. First, structures are standardized and duplicate entries are filtered out. Then, molecules are probed for the presence of predefined fragments. For molecules with more than one match, fragment combinations are classified. The algorithm considers the pairwise relative position of fragments within the molecule (fused atoms, linkers, intermediary rings), resulting in 18 different possible fragment combination categories. Finally, all combinations for a given molecule are assembled into a fragment combination graph, with fragments as nodes and combination types as edges. This workflow was applied to characterize PNPs in the ChEMBL database via comparison of fragment combination graphs with natural product (NP) references, represented by the Dictionary of Natural Products. The Murcko fragments extracted from 2000 structures previously described were used to define NP fragments. Cyclopamine The results indicate that ca. 23% of the biologically relevant compounds listed in ChEMBL comply to the PNP definition and that, therefore, PNPs occur frequently among known biologically relevant small molecules. The majority (>95%) of PNPs contain two to four fragments, mainly (>95%) distributed in five different combination types. These findings may provide guidance for the design of new PNPs.Chromosome region maintenance 1 (CRM1) is a major nuclear export receptor protein and contributes to cell homeostasis by mediating the transport of cargo from the nucleus to the cytoplasm. CRM1 is a therapeutic target comprised of several tumor types, including osteosarcoma, multiple myeloma, gliomas, and pancreatic cancer. In the past decade, dozens of CRM1 inhibitors have been discovered and developed, including KPT-330, which received FDA approval for multiple myeloma (MM) and diffuse large B-cell lymphoma (DLBCL) in 2019 and 2020, respectively. This review summarizes the biological functions of CRM1, the current understanding of the role CRM1 plays in cancer, the discovery of CRM1 small-molecule inhibitors, preclinical and clinical studies on KPT-330, and other recently developed inhibitors. A new CRM1 inhibition mechanism and structural dynamics are discussed. Through this review, we hope to guide the future design and optimization of CRM1 inhibitors.A pair of chiral bis(amidine) [BAM] proton complexes provide reagent (catalyst)-controlled, highly diastereo- and enantioselective direct aza-Henry reactions leading to α-alkyl-substituted α,β-diamino esters. A C2-symmetric ligand provides high anti-selectivity, while a nonsymmetric congener exhibits syn-selectivity in this example of diastereodivergent, enantioselective catalysis. A detailed computational analysis is reported for the first time, one that supports distinct models for selectivity resulting from the more hindered binding cavity of the C1-symmetric ligand. Binding in this congested pocket accommodates four hydrogen bond contacts among ligands and substrates, ultimately favoring a pre-syn arrangement highlighted by pyridinium-azomethine activation and quinolinium-nitronate activation. The complementary transition states reveal a wide range of alternatives. Comparing the C1- and C2-symmetric catalysts highlights distinct electrophile binding orientations despite their common hydrogen bond donor-acceptor features. Among the factors driving unusual high syn-diastereoselection are favorable dispersion forces that leverage the anthracenyl substituent of the C1-symmetric ligand.The role of pigment-protein coupling in the dynamics of photosynthetic energy transport in chromophoric complexes has not been fully understood. The excitation energy transfer in the photosynthetic system is tremendously efficient. In particular, we investigate the excitation energy transport in the Fenna-Matthews-Olson (FMO) complex. The exciton dynamics and excitation energy transfer (EET) depend on the interaction between the excited chromophores and their environment. Most theoretical models believe that all bacteriochlorophyll-a (BChla) sites are surrounded by the same local protein environment, which is contradicted by the structural analysis of the FMO complex. Based on different values of pigment-protein coupling for different sites, measured in the adiabatic limit, we have theoretically investigated the effect of the heterogeneous local protein environment on the EET process. By the realistic and site-dependent model of the system-bath couplings, the results show that this interaction may have a critical value for the coherent energy-transfer process. Furthermore, we verify that the two transport pathways are coherent and stable to the important parameter reorganization energy of environmental interactions. The quantum dynamical simulations show that the correlation fluctuation keeps the oscillation of the coherent excitation on a long timescale. In addition, due to the inhomogeneous pigment-protein coupling, different BChl sites have asymmetric excitation oscillation timescales.We describe Cu-catalyzed intermolecular alkynylation and allylation of unactivated C(sp3)-H bonds with singly occupied molecular orbital-philes (SOMO-philes) via hydrogen atom transfer (HAT). Employing N-fluoro-sulfonamide as a HAT reagent, a set of substituted alkene and alkyne compounds were synthesized in high yields with good regioselectivity and functional-group compatibility. Late-stage functionalization of natural products and drug molecules is also demonstrated.Recently, the discovery of superconductivity in compressed electrides offers a promising route toward searching for high superconductivity in a high-pressure community. However, only a few superconducting electrides have been successfully found thus far, thereby limiting the variety of superconducting electride examples. In this work, we performed extensive structure searches on a high-pressure Y-Si system by using CALYPSO structure prediction methodology. Our simulations identified several stable stoichiometries of YSi, YSi2, YSi3, Y5Si3, Y2Si, and Y3Si under high pressure. These structures contain a diversity of structure configurations, including silicon chains, Si3 trilaterals, Si4 quadrilaterals, Si6 hexagons, Si8 rings, a Si4-Si6-Si8 frame, as well as a silicon layer. Remarkably, Y3Si is predicted to be an electride with a superconducting critical temperature (Tc) of ∼11.2 and 14.5 K at 30 and 50 GPa, respectively. These results highlight the role of the electrons at the Fermi surface in determining the superconductivity of predicted structures.With the rapid developments in mass spectrometry (MS)-based proteomics methods, label-free semiquantitative proteomics has become an increasingly popular tool for profiling global protein abundances in an unbiased manner. However, the reproducibility of these data across time and LC-MS platforms is not well characterized. Here, we evaluate the performance of three LC-MS platforms (Orbitrap Elite, Q Exactive HF, and Orbitrap Fusion) in label-free semiquantitative analysis of cell surface proteins over a six-year period. Sucrose gradient ultracentrifugation was used for surfaceome enrichment, following gel separation for in-depth protein identification. With our established workflow, we consistently detected and reproducibly quantified >2300 putative cell surface proteins in a human acute myeloid leukemia (AML) cell line on all three platforms. To our knowledge this is the first study reporting highly reproducible semiquantitative proteomic data collection of biological replicates across multiple years and LC-MS platforms. These data provide experimental justification for semiquantitative proteomic study designs that are executed over multiyear time intervals and on different platforms. Multiyear and multiplatform experimental designs will likely enable larger scale proteomic studies and facilitate longitudinal proteomic studies by investigators lacking access to high throughput MS facilities. Data are available via ProteomeXchange with identifier PXD022721.Here we report that a palladium(0) complex can mediate the unprecedented intermolecular coupling reaction of 1,3-enynes and N-sulfonylimines regio- and stereoselectively, and the resultant palladium(II) species undergo a cascade Suzuki reaction with organoboronic reagents. The substrate scope is substantial for the asymmetric three-component process, and the enantioenriched all-carbon tetra-substituted alkene derivatives are efficiently constructed in a modular and cis-difunctionalized manner. Control experiments and density functional theory (DFT) calculations support the idea that the palladium(0) acts as a π-Lewis base catalyst by chemoselectively forming η2-complexes with the alkene moiety of 1,3-enynes, thus increasing the nucleophilicity of the alkyne group based on the principle of vinylogy, to attack imines enantioselectively. The preferable formation of aza-palladacyclopentene intermediates, via a 90° single bond rotation from the resultant π-allyl complex, guarantees the formal cis-carbopalladation of alkyne group.