Molecular docking, expounding the chemo-, regio-selectivity, and the mechanism of [3 + 2] cycloloaddition reaction between nitrile-imine and (thio)-chalcone
摘要
The study explores the application of molecular electron density theory, focusing on the [2 + 3] cycloaddition mechanisms between nitrile-imine and chalcone or thiochalcone. Density Functional Theory (DFT) calculations employing the B3LYP/6–311(d,p) methodology are utilized to determine activation and reaction energies, as well as reactivity indices. Through investigation of conceptual DFT indices, nitrile-imine is identified as a nucleophile, while chalcone and thiochalcone act as electrophiles in the reaction. The reactions exhibit both chemo- and regiospecifics, as confirmed by Parr functions, Electron Localization Function (ELF) survey, and energetic analysis, consistent with experimental results. ELF analysis suggests a two-phase mechanism for these [2 + 3] cycloadditions. Furthermore, docking studies on the resultant products reveal enhanced interaction energies with proteins due to the presence of oxygen and sulfur atoms, in their interaction with the crystal structure of COVID-19 main protease (PDB ID: 6LU7) and paves a ways for manufacturing innovation.
Graphical abstract