Synthesis, quantum chemical studies, molecular docking, molecular dynamics simulation and ADMET studies on 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1, 4,5-triphenyl-1H-imidazole derivatives

Abstract

A novel 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,4,5-triphenyl-1H-imidazole (DDTI) molecule was synthesised and characterised by FT-IR and NMR (1H and 13C) spectral techniques. The molecular structure was optimised using the density functional theory (DFT) method with B3LYP/6-311 G (d, p) basis set. Natural bonding orbital (NBO) analysis was used to determine the electron densities of donor (i) and acceptor (j) bonds as well as the hyperconjugative interaction energy (E ( 2) ). In highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) calculations, the smaller energy gap value was discovered. Molecular electrostatic potential has been analysed. The Mulliken atomic charges of the carbon, nitrogen and oxygen atoms were calculated at the same level of theory. The dipole moment, polarizability and first-order hyperpolarizability demonstrate the good nonlinear optical (NLO) feature of the title molecule. Molecular docking studies are implemented to analyse the binding energy of the DDTI compound against standard drugs such as the crystal structure of ADP ribose phosphatase of NSP3 from SARS-CoV-2 in complex with MES, SARS-CoV-2 main protease with an unliganded active site (2019-nCoV, corona virus disease 2019, COVID-19) and the crystal structure of COVID-19 main protease in complex with an inhibitor N3 found to be considered having better antiviral agent. Molecular dynamics simulation was performed for COVID-19 main protease (Mpro: 6WCF/6Y84/6LU7) to understand the elements governing the inhibitory effect and the stability of interactions under dynamic conditions. Virtual ADMET studies were carried out as well and a relationship between biological, electronic and physicochemical qualifications of the target compound was determined. Toxicity prediction by computational technique for the title compound was also carried out.