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Deprotonation led to a new species with an [FeIII-(μ-O)-FeIII] core that could be further oxidized to its FeIIIFeIV analogue. Reactions with phenols suggest homolytic cleavage of the O-H bond to give products that are consistent with the initial formation of a phenoxyl radical─spectroscopic studies indicated that the electron is transferred to the FeIV center, and the proton is initially transferred to the more sterically hindered oxido ligand but then relocates to [poat]3-. These findings offer new mechanistic insights related to the stability of and the reactions performed by di-Fe enzymes.One strategy to improve the photovoltaic properties of nonfullerene acceptors (NFAs), employed in state-of-art organic solar cells, is the rational fluorination or chlorination of these molecules. Although this modification improves important acceptor properties, little is known about the effects on the triplet states. Here, we combine the polarizable continuum model with an optimally tuned range-separated hybrid functional to investigate this issue. We find that fluorination or chlorination of NFAs decreases the degree of the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) overlap along these molecules. Consequently, the energy gap between T1 and S1 states, ΔEST = ES1 - ET1, also decreases. This effect reduces the binding energy of triplet excitons, which favors their dissociation into free charges. Furthermore, the reduction of ΔEST can contribute to mitigating the losses produced by the nonradiative deactivation of the T1 excitons. Interestingly, although Cl has a lower electronegativity than F, chlorination is more effective to reduce ΔEST. [https://www.selleckchem.com/products/favipiravir-t-705.html T-705 chemical structure] Since the chlorination of NFAs is easier than fluorination, Cl substitution can be a useful approach to enhance solar energy harvesting using triplet excitons.We introduce a novel open-source software package QForte, a comprehensive development tool for new quantum simulation algorithms. QForte incorporates functionality for handling molecular Hamiltonians, Fermionic encoding, ansatz construction, time evolution, and state-vector emulation, requiring only a classical electronic structure package as a dependency. QForte also contains black-box implementations of a wide variety of quantum algorithms, including variational and projective quantum eigensolvers, adaptive eigensolvers, quantum imaginary time evolution, and quantum Krylov methods. We highlight two features of QForte (i) how the Python class structure of QForte enables the facile implementation of new algorithms, and (ii) how existing algorithms can be executed in just a few lines of code.A new method employing iron(III) acetylacetonate along with visible light is described to effect oxidative ring opening of cyclic ethers and acetals with unparalleled efficiency. The method allows for a photocatalytic radical chemistry approach to functionalize relatively inert cyclic ethers into useful synthetic intermediates. The methodology sheds further light on the use of underexplored iron complexes in visible-light photochemical contexts and illustrates that simple Fe(III) complexes can initiate redox processes from 4LMCT excited states.The analysis of chemical bonding in crystal structures and surfaces is an important research topic in theoretical chemistry. In this work, we present a PyMOL plugin, named LModeA-nano, as implementation of the local vibrational mode theory for periodic systems (Tao et al. J. Chem. Theory Comput. 2019, 15, 1761) assessing bond strength in terms of local stretching force constants in extended systems of one, two, and three dimensions. LModeA-nano can also analyze chemical bonds in isolated molecular systems thus enabling a head-to-head comparison of bond strength across systems with different dimensions in periodicity (0-3D). The new code is interfaced to the output generated by various solid-state modeling packages including VASP, CP2K, Quantum ESPRESSO, CASTEP, and CRYSTAL. LModeA-nano is cross-platform, open-source and freely available on GitHub https//github.com/smutao/LModeA-nano.The [1,2]-Meisenheimer rearrangement is well known as the [1,2]-migration of an O-substituted hydroxylamine from a tertiary amine N-oxide, and it is frequently employed in organic synthesis to enforce adjacent carbon oxidation or install a 1,2-oxazine core, which is a prevalent structural feature and pharmacophore of many bioactive natural products. Although the [1,2]-Meisenheimer rearrangement was proposed to occur in the biosynthesis of a number of 1,2-oxazine-containing natural products, it has never been proved biosynthetically. Here, we identified the biosynthetic gene cluster of an insecticidal natural product, paeciloxazine (1), from Penicillium janthinellum and characterized a flavin-dependent monooxygenase, PaxA, as the first example that mediates the formation of a 1,2-oxazine moiety via Meisenheimer rearrangement. In vitro biochemical assays, site-directed mutations, docking and molecular dynamics simulations, and density functional theory calculations support the mechanism that PaxA first catalyzes N-oxidation to form an N-oxide intermediate, which undergoes [1,2]-Meisenheimer rearrangement with the assistance of an amino acid with proton transfer property. This study expands the repertoire of rearrangement reactions during the biosynthesis of natural products and provides a new strategy for discovering natural products with N-O tethers by genome mining.NO2 and SO2, as valuable chemical feedstock, are worth being recycled from flue gases. The separation of NO2 and SO2 is a key process step to enable practical deployment. This work proposes SO2 separation from NO2 using chabazite zeolite (SSZ-13) membranes and provides insights into the feasibility and advantages of this process using molecular simulation. Grand canonical ensemble Monte Carlo and equilibrium molecular dynamics methods were respectively adopted to simulate the adsorption equilibria and diffusion of SO2, NO2, and N2O4 on SSZ-13 at varying Si/Al (1, 5, 11, 71, +∞), temperatures (248-348 K), and pressures (0-100 kPa). The adsorption capacity and affinity (SO2 &gt; N2O4 &gt; NO2) demonstrated strong competitive adsorption of SO2 based on dual-site interactions and significant reduction in NO2 adsorption due to dimerization in the ternary gas mixture. The simulated order of diffusivity (NO2 &gt; SO2 &gt; N2O4) on SSZ-13 demonstrated rapid transport of NO2, strong temperature dependence of SO2 diffusion, and the impermeability of SSZ-13 to N2O4. The membrane permeability of each component was simulated, rendering a SO2/NO2 membrane separation factor of 26.34 which is much higher than adsorption equilibrium (6.9) and kinetic (2.2) counterparts. The key role of NO2-N2O4 dimerization in molecular sieving of SO2 from NO2 was addressed, providing a facile membrane separation strategy at room temperature.Rising antimicrobial resistance challenges our ability to combat bacterial infections. The problem is acute for tuberculosis (TB), the leading cause of death from infection before COVID-19. Here, we developed a framework for multiple pharmaceutical companies to share proprietary information and compounds with multiple laboratories in the academic and government sectors for a broad examination of the ability of β-lactams to kill Mycobacterium tuberculosis (Mtb). In the TB Drug Accelerator (TBDA), a consortium organized by the Bill &amp; Melinda Gates Foundation, individual pharmaceutical companies collaborate with academic screening laboratories. We developed a higher order consortium within the TBDA in which four pharmaceutical companies (GlaxoSmithKline, Sanofi, MSD, and Lilly) collectively collaborated with screeners at Weill Cornell Medicine, the Infectious Disease Research Institute (IDRI), and the National Institute of Allergy and Infectious Diseases (NIAID), pharmacologists at Rutgers University, and medicinal chemists at the University of North Carolina to screen ∼8900 β-lactams, predominantly cephalosporins, and characterize active compounds. In a striking contrast to historical expectation, 18% of β-lactams screened were active against Mtb, many without a β-lactamase inhibitor. One potent cephaloporin was active in Mtb-infected mice. The steps outlined here can serve as a blueprint for multiparty, intra- and intersector collaboration in the development of anti-infective agents.Excitatory amino acid transporters (EAATs) are glutamate transporters that belong to the solute carrier 1A (SLC1A) family. They couple glutamate transport to the cotransport of three sodium (Na+) ions and one proton (H+) and the counter-transport of one potassium (K+) ion. In addition to this coupled transport, binding of cotransported species to EAATs activates a thermodynamically uncoupled chloride (Cl-) conductance. Structures of SLC1A family members have revealed that these transporters use a twisting elevator mechanism of transport, where a mobile transport domain carries substrate and coupled ions across the membrane, while a static scaffold domain anchors the transporter in the membrane. We recently demonstrated that the uncoupled Cl- conductance is activated by the formation of an aqueous pore at the domain interface during the transport cycle in archaeal GltPh. However, a pathway for the uncoupled Cl- conductance has not been reported for the EAATs, and it is unclear if such a pathway is conserved. Here, we employ all-atom molecular dynamics (MD) simulations combined with enhanced sampling, free-energy calculations, and experimental mutagenesis to approximate large-scale conformational changes during the transport process and identified a Cl--conducting conformation in human EAAT1 (hEAAT1). Sampling the large-scale structural transitions in hEAAT1 allowed us to capture an intermediate conformation formed during the transport cycle with a continuous aqueous pore at the domain interface. The free-energy calculations performed for the conduction of Cl- and Na+ ions through the captured conformation highlight the presence of two hydrophobic gates that control low-barrier movement of Cl- through the aqueous pathway. Overall, our findings provide insights into the mechanism by which a human neurotransmitter transporter supports functional duality of active transport and passive Cl- permeation and confirm the commonality of this mechanism in different members of the SLC1A family.Cells sense and respond to a variety of physical cues from their surrounding microenvironment, and these are interpreted through mechanotransductive processes to inform their behavior. These mechanisms have particular relevance to stem cells, where control of stem cell proliferation, potency, and differentiation is key to their successful application in regenerative medicine. It is increasingly recognized that surface micro- and nanotopographies influence stem cell behavior and may represent a powerful tool with which to direct the morphology and fate of stem cells. Current progress toward this goal has been driven by combined advances in fabrication technologies and cell biology. Here, the capacity to generate precisely defined micro- and nanoscale topographies has facilitated the studies that provide knowledge of the mechanotransducive processes that govern the cellular response as well as knowledge of the specific features that can drive cells toward a defined differentiation outcome. However, the path forward is not fully defined, and the "bumpy road" that lays ahead must be crossed before the full potential of these approaches can be fully exploited.