Orthogonal Geometry Enhancing the Intersystem Crossing and Photosensitive Efficiency of Spiro Organoboron Compounds.

Based on the reported spiro organoboron compounds (PS1 and PS2 as potent 1O2 sensitizers), several new organoboron molecules (PS4-PS9) were constructed through structural modification, and their low-lying excited states and photophysical properties have been explored by density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. The predicted effective intersystem crossing (ISC) processes arise from the S1→T2 transition for PS4-PS6 and the S1→T4 transition for PS1, and corresponding KISC rate constants reach the order of magnitude of 109 (s-1). The organoboron compounds with a (N, N) chelate acceptor are predicted to exhibit relatively higher ISC efficiency than those bearing a (N, O) acceptor, and the planar C3NBN ring and the orthogonal configuration between the donor and acceptor moieties are responsible for the ISC rate enhancement. Importantly, the geometric features of the lowest singlet excited state (S1) for these compounds play a decisive role in their photosensitive efficiency. The present results provide a basis for better understanding of the photosensitivity of these spiro organoboron compounds and the structural modification effect.

A Dual-Focus Workflow for Simultaneously Engineering High Activity and Thermal Stability in Methyl Parathion Hydrolase.

Industrial fermentation applications typically require enzymes that exhibit high stability and activity at high temperatures. However, efforts to simultaneously improve these properties are usually limited by a trade-off between stability and activity. This report describes a computational strategy to enhance both activity and thermal stability of the mesophilic organophosphate-degrading enzyme, methyl parathion hydrolase (MPH). To predict hotspot mutation sites, we assembled a library of features associated with the target properties for each residue and then prioritized candidate sites by hierarchical clustering. Subsequent in silico screening with multiple algorithms to simulate selective pressures yielded a subset of 23 candidate mutations. Iterative parallel screening of mutations that improved thermal stability and activity yielded, MPHase-m5b, which exhibited 13.3 °C higher Tm and 4.2 times higher catalytic activity than wild-type (WT) MPH over a wide temperature range. Systematic analysis of crystal structures, molecular dynamics (MD) simulations, and Quantum Mechanics/Molecular Mechanics (QM/MM) calculations revealed a wider entrance to the active site that increased substrate access with an extensive network of interactions outside the active site that reinforced αß/ßα sandwich architecture to improve thermal stability. This study thus provides an advanced, rational design framework to improve efficiency in engineering highly active, thermostable biocatalysts for industrial applications.

THF-Assisted CO2 Reduction Catalyzed by Electride Mg2EP: Insight from DFT Calculations.

Hydroboration and hydrogenation reductions of CO2 catalyzed by a porphyrinoid-based dimagnesium(I) electride (Mg2EP) were investigated by density functional theory calculations. Herein, the presence of potentially excess electrons located at the Mg-Mg bond endows Mg2EP with the ability to activate small molecules such as CO2, HBpin, and H2, thus opening up the possibility for further CO2 conversion. The Mg2EP-catalyzed hydroboration of CO2 to HCOOBpin is predicted to have relatively higher activity in comparison to the hydrogenation reduction to formic acid (HCOOH). Interestingly, the common solvent molecule tetrahydrofuran as an auxiliary can coordinate with the Mg center to effectively weaken the bonding interaction between the dimagnesium center and the intermediate species from the CO2 conversion, thereby promoting the catalytic cycle for the CO2 hydroboration. The present results suggest that the electride Mg2EP is promising for the molecular catalyst in the CO2 transformation.

Subpocket-Based Analysis Approach for the Protein Pocket Dynamics.

Structural and dynamic characteristics of protein pockets remarkably influence their biological functions and are also important for enzyme engineering and new drug research and development. To date, several softwares have been developed to analyze the dynamic properties of protein pockets. However, due to the complexity and diversity of the pocket information during the kinetic relaxation, further improvement and capacity expansion of current tools are required. Here, we developed a platform software AlphaTraj in which a computational strategy that divides the whole protein pocket into subpockets and examines various properties of the subpockets such as survival time, stability, and correlation was proposed and implemented. We also proposed a scoring function for the subpockets as well as the whole pocket to visualize the quality of the pocket. Furthermore, we implemented automated conformational search functions for ligand docking and ligand optimization. These functions may help us to gain a deep understanding of the dynamic properties of protein pockets and accelerate the protein engineering and the design of inhibitors and small-molecule drugs. The software is freely available at https://github.com/dooo12332/AlphaTraj.git under the GNU GPL license.

Elucidating the Enzymatic Mechanism of Dihydrocoumarin Degradation: Insight into the Functional Evolution of Methyl-Parathion Hydrolase from QM/MM and MM MD Simulations.

Methyl-parathion hydrolase (MPH), which evolved from dihydrocoumarin hydrolase, offers one of the most efficient enzymes for the hydrolysis of methyl-parathion. Interestingly, the substrate preference of MPH shifts from the methyl-parathion to the lactone dihydrocoumarin (DHC) after its mutation of five specific residues (R72L, L273F, L258H, T271I, and S193Δ, m5-MPH). Here, extensive QM/MM calculations and MM MD simulations have been used to delve into the structure-function relationship of MPH enzymes and plausible mechanisms for the chemical and nonchemical steps, including the transportation and binding of the substrate DHC to the active site, the hydrolysis reaction, and the product release. The results reveal that the five mutations remodel the active pocket and reposition DHC within the active site, leading to stronger enzyme-substrate interactions. The MM/GBSA-estimated binding free energies are about -20.7 kcal/mol for m5-MPH and -17.1 kcal/mol for wild-type MPH. Furthermore, this conformational adjustment of the protein may facilitate the chemical step of DHC hydrolysis and the product release, although there is a certain influence on the substrate transport. The hydrolytic reaction begins with the nucleophilic attack of the bridging OH- with the energy barriers of 22.0 and 18.0 kcal/mol for the wild-type and m5-MPH enzymes, respectively, which is rate-determining for the entire process. Unraveling these mechanistic intricacies may help in the understanding of the natural evolution of enzymes for diverse substrates and establish the enzyme structure-function relationship.

Narrowband emission from fully-bridged triphenylamine derivatives: insights into effects of structure modification and pressure.

Triphenylamine derivatives with narrowband emission have attracted growing attention in purely organic thermally-activated fluorescence (TADF) materials owing to their enhanced color purity and flexible molecular design strategy. Combined time-dependent density functional theory (TD-DFT) and ONIOM (QM/MM) calculations indicate that the excellent planarity of the experimentally developed DQAO could result in gradually decreased intermolecular interactions in the aggregated state at ambient pressure and upon compression, which is unfavorable for suppressing structural relaxation and achieving narrowband emission in its non-doped practical application. Therefore, three structure-modified derivatives, DQAO-Cb, DQAO-Ph, and DQAO-PhCb, were theoretically designed by introducing the spherical o-carborane and dangling phenyl units positioned para to the N atom of the DQAO to provide additional geometrical distortion and steric hindrance. The explorations on the reported DQAO, OQAO, and SQAO found that small structural relaxations, suppressed low-frequency vibrations, and noticeable short-range charge-transfer (SR-CT) natures of DQAO and OQAO are responsible for their much narrower emission spectral full-width at half-maxima (FWHMs) compared to that of SQAO. Introducing the o-carborane unit directly at the para position of the N atom could result in additional scissoring and stretching vibrations of the corresponding DQAO-Cb while the presence of the phenyl unit in DQAO-Ph is beneficial for suppressing the high-frequency vibrations of the pristine DQAO. More importantly, the bridged phenyl unit incorporated in DQAO-PhCb is of particular importance to inhibit the undesired low-frequency scissoring and high-frequency stretching vibrations of the o-carborane unit, which is crucial to reduce the reorganization energy of DQAO-PhCb and achieve narrowband emission. Also, the phenyl unit in DQAO-Ph and DQAO-PhCb helps to shorten charge transfer distances and improve ISC and RISC processes. Since the o-carborane unit is an adopted building block to achieve piezochromic behaviors, the theoretically structure-modified DQAO-PhCb is expected to exhibit narrowband emission, TADF, and piezochromic features all together. Our findings will hopefully provide ideas for designing triphenylamine-based TADF emitters with narrowband emission and piezochromic behaviors.

Elucidating the degradation mechanism of the nerve agent A-234 using various detergents: a theoretical investigation.

A-234 (ethyl N-[1-(diethylamino)ethylidene]phosphoramidofluoridate) is one of the highly toxic Novichok nerve agents, and its efficient degradation is of significant importance. The possible degradation mechanisms of A-234 by H2O, H2O2, NH3, and their combinations have been extensively investigated by using density functional theory (DFT) calculations. According to the initial intermolecular interaction and the proton transfer patterns between the detergent and the substrate A-234, the A-234 degradation reaction is classified into three categories, denoted as A, B, and C. In modes A and B, the degradation of A-234 by H2O2, H2O, and NH3 is initiated by the nucleophilic attack of the O or N atom of the detergent on the P atom of A-234, coupled with the proton transfer from the detergent to the O or N atom of A-234, whereas in mode C, the direct interaction of H2N-H with the F-P bond of A-234 triggers ammonolysis through a one-step mechanism with the formation of H-F and N-P bonds. Perhydrolysis and hydrolysis of A-234 can be remarkably promoted by introducing the auxiliary NH3, and the timely formed hydrogen bond network among detergent, auxiliary, and substrate molecules is responsible for the enhancement of degradation efficiency.

Enhancing CO2 Hydrogenation Using a Heterogeneous Bimetal NiAl-Deposited Metal-Organic Framework NU-1000: Insights from First-Principles Calculations.

The hydrogenation of CO2 to high-value-added liquid fuels is crucial for greenhouse gas emission reduction and optimal utilization of carbon resources. Developing supported heterogeneous catalysts is a key strategy in this context, as they offer well-defined active sites for in-depth mechanistic studies and improved catalyst design. Here, we conducted extensive first-principles calculations to systematically explore the reaction mechanisms for CO2 hydrogenation on a heterogeneous bimetal NiAl-deposited metal-organic framework (MOF) NU-1000 and its catalytic performance as atomically dispersed catalysts for CO2 hydrogenation to formic acid (HCOOH), formaldehyde (H2CO), and methanol (CH3OH). The present results reveal that the presence of the NiAl-oxo cluster deposited on NU-1000 efficiently activates H2, and the facile heterolysis of H2 on Ni and adjacent O sites serves as a precursor to the hydrogenation of CO2 into various C1 products HCOOH, H2CO, and CH3OH. Generally, H2 activation is the rate-determining step in the entire CO2 hydrogenation process, the corresponding relatively low free energy barriers range from 14.5 to 15.9 kcal/mol, and the desorption of products on NiAl-deposited NU-1000 is relatively facile. Although the Al atom does not directly participate in the reaction, its presence provides exposed oxygen sites that facilitate the heterolytic cleavage of H2 and the hydrogenation of C1 intermediates, which plays an important role in enhancing the catalytic activity of the Ni site. The present study demonstrates that the catalytic performance of NU-1000 can be finely tuned by depositing heterometal-oxo clusters, and the porous MOF should be an attractive platform for the construction of atomically dispersed catalysts.