Synthesis, theoretical calculations, X-ray, HS and energy framework analysis, molecular docking of amino pyrazole containing azo dye and its inhibition activity of COVID-19 main protease

Abstract

The synthesis and characterization of 5-Amino-4-Phenylazo-3-Methyl-1-(2-hydroxyethyl) Pyrazole (AD2a) were investigated in our study. The novel synthesized pyrazole-based disperse diazo dye has been elucidated by using UV–Vis, FT-IR, elemental analysis, LC/MS-MS, NMR and X-ray analysis. The AD2a molecule containing pyrazole and phenyl rings, hydroxy‑ethyl and azo group moieties crystallized in the orthorhombic space group Pbca. The crystal structures of AD2a are consolidated by N(3)-H(3A)⋯O(1) and O(1)-H(1)⋯N(5) intermolecular hydrogen bonds. The geometry of AD2a has been optimized with the DFT calculation B3LYP/6–31G(d,p) level and it has been observed that the obtained results give very good results with the X-ray diffraction data. The theoretical vibrational analysis, frontier orbital energies, electronic absorption spectrum, electronic properties, global reactivity descriptors and other theoretical parameters were obtained by using the same DFT method. Additionally, Hirshfeld surface analysis (HSA) with 2D fingerprint plots (FP) was performed to estimate contacts and the energy framework diagrams of AD2a (Eele, Edis and Etot) were determined. The inhibitor-receptor relationship established by the molecular docking study confirmed the inhibition activity of the AD2a construct against COVID-19. It showed that the AD2a molecule, shown as a drug candidate, binds strongly to SARS-CoV-2 (Mpro) (-6.5 kcal/mol) receptors.