Journal of Computational Chemistry最新文献

This study investigates the Beckmann rearrangement of 1-phenyl-2-propanone oxime derivatives, focusing on the reaction path bifurcation behavior from the perspective of electron movement. The previous work reported that electron-withdrawing substituents drove the reaction toward the rearrangement pathway, while electron-donating substituents favored the fragmentation pathway. Through natural reaction orbital (NRO) analysis, this research demonstrates how electrons move at critical branching points, specifically in the directions of the intrinsic reaction coordinate (IRC) and the projected vibrational mode associated with the branching behavior. The NRO approach, which complements traditional IRC and ab initio molecular dynamics methods, not only provides valuable quantitative insights for predicting product distributions but also aids in the strategic design of substituents for desired products. These findings extend our understanding of reaction mechanisms and byproduct formation, offering fresh perspectives on complex chemical transformations.

Conditional-based molecule generation techniques help to provide molecules with specific conditions for practical applications. As the SMILES string is represented as a sequence of strings, it can be processed using a language model that gradually generates its complete sequence by employing a loop to generate the next token. The efficient parallelism and efficient reasoning ability of RWKV indicate its potential for success in the field of natural language processing. Therefore, we proposed the MolRWKV de novo conditional molecule generation model, which integrates CNN and GCN based on the RWKV model, combining the ability of CNN to extract local information of SMILES sequences and the ability of GCN to obtain topological structure information of molecular graphs. Experiments show that MolRWKV can achieve comparable results to existing models in both unconditional and conditional generation, improve the accuracy of conditional generation, generate diverse molecules while retaining scaffold information, and generate molecules with affinity for specific target proteins.

The Diels–Alder (DA) reaction between hexachlorocyclopentadiene and 1,2-dichloroethylene has been studied using the Molecular Electron Density Theory (MEDT) through Density Functional Theory (DFT) calculations at the B3LYP/6−31G(d) level. The electronic structure of the reagents has been characterized through the electron localization function (ELF) and the conceptual DFT (CDFT). The DA reaction of hexachlorocyclopentadiene with 1,2-dichloroethylene proceeds via a synchronous or low asynchronous one-step mechanism. Based on the conducted research, a two-step mechanism with a biradical intermediate was completely ruled out. Bonding Evolution Theory (BET) study of the DA reaction shows that this reaction is topologically characterized by nine different phases. The reaction begins with the rupture of the double bonds in substrate molecules. Formation of the first CC single bond takes place in phase VII, while the second CC single bond takes place in phase IX. Formation of these two single bonds takes place by sharing the nonbonding electron densities of the two pairs of pseudoradical centers. In addition, this study evaluates some ligands as potential HIV-1 inhibitors. Docking results identified 5 and 5-F as the most promising candidates, surpassing AZT in theoretical affinity. ADME analysis revealed limitations in solubility and absorption for compounds 3, 4, and 5, while 5-F showed better solubility but low absorption. Toxicity concerns around 5-F suggest the need for risk management, while the other compounds require further safety assessment.

Balancing computational efficiency and precision, MM/P(G)BSA methods have been widely employed in the estimation of binding free energies within biological systems. However, the entropy contribution to the binding free energy is often neglected in MM/P(G)BSA calculations, due to the computational cost of conventional methods such as normal mode analysis (NMA). In this work, the entropy effect using a formulaic entropy can be computed from one single structure according to variations in the polar and non-polar solvents accessible surface areas and the count of rotatable bonds in ligands. It was incorporated into MM/P(G)BSA methods to enhance their performance. Extensive benchmarking reveals that the integration of formulaic entropy systematically elevates the performance of both MM/PBSA and MM/GBSA without incurring additional computational expenses. In addition, we found the inclusion of dispersion can deteriorate the correlation performance (R_p) but reduce the root mean square error (RMSE) of both MM/PBSA and MM/GBSA. Notably, MM/PBSA_S, including the formulaic entropy but excluding the dispersion, surpasses all other MM/P(G)BSA methods across a spectrum of datasets. Our investigation furnishes a valuable and practical MM/P(G)BSA method, optimizing binding free energy calculations for a variety of biological systems.

Access to benzofuran-2(3H)-one derivatives from readily available substrates under mild conditions is crucial in the pharmaceutical and plastics industries. We identified (Z)-3-(2-phenylhydrazineylidene)benzofuran-2(3H)-one (P) during the recrystallization of (E)-2-(2,2-dichloro-1-(phenyldiazenyl)vinyl)phenol using a 96% ethanol solution. The mechanism of the unexpected substrate conversion leading to P is investigated using density functional calculations. The computations revealed that ethanol is required to initiate the reaction via TS1E, which involves a concerted deprotonation of ethanol by the basic diaza group of the substrate and an ethoxy group attacking the electrophilic center (Cl₂C), with an energy barrier of 28.3 kcal/mol. The resulting intermediate (I1E) is calculated to be unstable and can yield a cyclic chloroacetal adduct with a lower energy barrier of 2.2 kcal/mol via the ring-closure transition state (TS2E). In the absence of water, the next steps are impossible because water is required to cleave the ether bond, yielding P. A small amount of water (4% of the recrystallization solvent) can promote further transformation of I2E via the transition states TS3E (∆G^‡ = 11.1 kcal/mol) and TS4E (∆G^‡ = 10.5 kcal/mol). A comparison of the ethanol/water- and only water-promoted free energy profiles shows that the presence of ethanol is crucial for lowering the energy barriers (by about 5 kcal/mol) for the initial two steps leading to the cyclic chloroacetal (I2E), whereas water is then required to initiate product formation.

The analysis and interpretation of theoretical results remain significant challenges for researchers in computational chemistry, particularly when working with molecules containing a large number of atoms. The manual selection, organization, and interpretation of desired parameters from output files generated by computational tools can be error-prone, tedious, and time-intensive, often taking days to complete. This study introduces the Computational Chemistry Parameter (CCPE), providing extraction, formatting, and presentation of the computational data obtained from Gaussian and VEDA programs. By integrating outputs from the widely used GAUSSIAN and VEDA programs, CCPE provides an efficient, user-friendly solution for extracting and organizing key data such as vibrational modes, frequency assignments, optimization parameters, and molecular orbital data. This tool significantly reduces the time required for these tasks from several days to a matter of minutes, while minimizing the likelihood of errors. The CCPE software, developed using the C# programming language, emphasizes reliability and adaptability, offering researchers a practical means of handling complex computational data. Through its ability to generate publication-ready outputs in widely accepted formats, CCPE aims to enhance productivity and data accuracy, presenting a transformative step in the field of computational chemistry.

Quantum chemical simulations were utilized to investigate the nature of the bonding of N³⁻, P³⁻, As³⁻, O²⁻, S²⁻, Se²⁻, F⁻, Cl⁻, and Br⁻ anions with the designed anion receptor cyclopenta-2,4-diene-1,1-diylbis(borane) abbreviated as CPDB and consecutive hyperconjugative aromaticity in its cyclopentadiene ring. Various analytical tools, including quantum theory of atoms in molecules (QTAIM), Electron Localization function (ELF), and reduced density gradient (RDG) were employed to explore the interaction between the selected anions and the CPDB structure. Moreover, the changes in the bond lengths (∆BL), harmonic oscillator model of aromaticity (HOMA), and localized orbital locator purely contributed by π-orbitals (LOL-π) analyses were performed to study the hyperconjugative aromaticity upon anion accepting. The findings indicate that the anions are connected to the CPDB structure through the electron deficiency of the B atoms and can induce the aromaticity via Schleyer's hyperconjugative aromaticity to the CPBD's ring. The nature of the interactions and hyperconjugative aromaticity effect of each anion is discussed in detail.

We perform a computational investigation to unravel the mechanisms of intramolecular thiol proton transfer and triplet formation in dithiotropolone. The S₁ and S₂ states are dipole-forbidden, whereas S₃ and S₄ are dipole-allowed states in this molecule. Upon initiating the nuclear wavepacket on S₃, this molecule exhibits simultaneous S₃ to S₂/S₁ internal conversion and S₃-T₄ intersystem crossing. Further simulations reveal that the molecule shows ultrafast internal conversion in the triplet manifold, similar to its singlet dynamics. Apart from these decay processes in the Franck-Condon region, this molecule can display thiol proton transfer via multiple singlet states due to low barrier energies along the reaction coordinate. The S₁-T₄ and S₃-T₅/T₆ crossings upon the S-H coordinate's elongation illustrate that the molecule can also show the triplet formation outside the Franck-Condon region.