Chromatography Scrutiny, Molecular Docking, Clarifying the Selectivities and the Mechanism of [3 + 2] Cycloloaddition...

Employing the Molecular Electron Density Theory, [3 + 2] cycloaddition processes between 4-chlorobenzenenitrileoxide and linalool, have been applied using the DFT/B3LYP/6-311(d,p) method, activation, reaction energies and the reactivity indices are calculated. In an investigation of conceptual DFT indices, LIL-1 will contribute to this reaction as a nucleophile, whilst NOX-2 will participate as an electrophile. This cyclization is regio, chemo and stereospecific, as demonstrated by the reaction and activation energies, in clear agreement with the experiment's results, in addition, ELF analysis revealed that the mechanism for this cycloaddition occurs in two steps. Furthermore, a docking study was conducted on the products studied, and the interaction with the protein protease COVID-19 (PDB ID: 6LU7), our results indicate that the presence of the -OH group increases the affinity of these products, moreover, adsorption study by chromatography was made on silica gel as support; our outcome reveals that the -OH group creates an intramolecular hydrogen bond in the product P₂, while in the product P₃ will create a hydrogen bond with the silica gel which makes the two products P₂ and P₃ are very easy to separate by chromatography, this result is in excellent agreement with the R_f retention value. The study might provide a fundamental for developing natural anti-viral compound in promoting human health.