Theoretical investigation of the cooperative effect of solvent: a case study.

The effect of solvent was investigated at the DFT level, M06-2X/6-31++G(d,p), for the implicit, namely the universal solvent model based on solute electron density (SMD) and hybrid solvation models, and a new pathway for the Markovnikov for the addition of HCl to 1-butene was suggested, incorporating the solvent in the reaction. The results showed that the use of implicit solvent brings greater stabilization for a large part of the reaction coordinates and for the charges of the transition states (TS). Studying the hybrid solvent model, it was shown by quantum mechanics and molecular simulations that although the first solvation shell is composed of approximately 30 solvent molecules, most of the effect comes from just eight solvent molecules explicitly added, with a variation in energy that tends to about -19.3 kJ mol-1. The reaction rates for the hydration of 1-butene were only able to achieve a reasonable accuracy with the addition of three explicit solvent molecules of 5.97 × 10-8 M-1 s-1 and 2.33 × 10-9 M-1 s-1 for the calculated and the experimental values, respectively. This indicates that not only hybrid solvation may be required, but also the number of explicit molecules added may heavily influence the calculated reaction rates. It was found that for the intermediary product of hydration the hydrogen bonds are stronger than average, suggesting a partial covalent characteristic.

Ammonia quantum tunneling in cold rare-gas He and Ar clusters and factorial design approach for methodology evaluation.

Quantum tunneling of the ammonia inversion motion and energy level splittings in He and Ar clusters were investigated. It was found that the double well potential (DWP) in He clusters is symmetrical and that the first layer of He atoms is able to model the system. The calculated tunneling splitting was in good agreement with the experimental, 36.4 and 24.6 cm[Formula: see text] respectively. For NH[Formula: see text] in Ar clusters, the DWP becomes slightly asymmetric, which is enough to decrease the resonance and make the symmetric DWP unable to model the system. An asymmetric potential was used and the result was in excellent agreement with the experimental splitting, of 9.0 and 10.6 cm[Formula: see text] respectively. Non-covalent interactions revealed that the asymmetry is caused by dissimilar interactions in each minimum of the double well potential. The effects of different methodologies were analyzed via a design of experiments approach. For the gas-phase NH[Formula: see text] molecule, only diffuse functions were statistically significant while for the NH[Formula: see text] embedded in He cluster both the MP2 method and polarization functions were significant. This tendency suggests higher order polarization functions may be essential to generate accurate barrier heights.

Potential activity of Linezolid against SARS-CoV-2 using electronic and molecular docking study.

The crescent evolution of a global pandemic COVID-19 and its respiratory syndrome (SARS-Cov-2) has been a constant concern (Ghosh 2021; Khan et al. 2021; Alazmi and Motwalli 2020; Vargas et al. 2020). The absence of a proven and effective medication has compelled all the scientific community to search for a new drug. The use of known drugs is a faster way to develop new therapies. Molecular docking is a powerful tool (Gao et al. J Mol Model 10: 44-54, 2004; Singh et al. J Mol Model 18: 39-51, 2012; Schulz-Gasch and Stahl J Mol Model 9:47-57, 2003) to study the interaction of potential drugs with SARS-CoV-2, Alsalme et al. (2020) and Sanders et al. (2020) spike protein as a consequence the main goal of this article is to present the result of the study of an interaction between (R and S)-Linezolid with receptor-binding domain (RBD) of SARS-Cov-2 spike protein complexed with human Angiostensin-converting enzyme 2 (ACE2) (6vW1 - from PDB). The Linezolid enantiomers were optimized at B3LYP/6-311++G(2d,p) level of theory. Molecular docking of the system (S)-Linezolid⋯RBD⋯ACE2 and (R)-Linezolid⋯RBD⋯ACE2 was performed, the analysis was made using LigPlot+ and NCIplot software packages, to understand the intermolecular interactions. The UV-Vis and ECD of the complexes - (R and S)-Linezolid⋯RBD⋯ACE2 were performed in two layers with DFT/6-311++G(3df,2p) and DFT/6-31G(d), respectively. The results showed that only the (S)-Linezolid had a stable interaction with - 8.05 kcal.mol- 1, whereas all the R-enantiomeric configurations had positive values of binding energy. The (S)-Linezolid had the same interactions as in the (S)-Linezolid ⋯ Haluarcula morismortui Ribosomal system, where it is well-known the fact that the latter has biological activity. A specific interaction on the fluorine ring justified an attenuation on the ECD signal, in comparison to isolated species. Therefore, some biological activity of (S)-Linezolid with SARS-CoV-2 RBD was expected, indicated by the modification of its ECD signal and justified by a similar interaction in the S-Linezolid⋯Haluarcula marismortui Ribosomal system.