Molecular properties and In silico bioactivity evaluation of (4-fluorophenyl)[5)-3-phen-(4-nitrophenyl yl-4,5-dihydro-1H-pyrazol-1- yl]methanone derivatives: DFT and molecular docking approaches

Abstract

Objectives: Molecular structures, spectroscopic properties, charge distributions, frontier orbital energies, nonlinear optical (NLO) properties and molecular docking simulations were analyzed to examine the biousefulness of a series of (4-fluorophenyl)[5-(4- nitrophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl] methanone derivatives. Methods: The compounds were studied through computational methods. Equilibrium optimization of the compounds was performed at the B3LYP/6-31G(d,p) level of theory, and geometric parameters, frequency vibration, UVevis spectroscopy and reactivity properties were predicted on the basis of density functional theory (DFT) calculations. Results: The energy gap (DEg), electron donating/ accepting power (u /uþ) and electron density response toward electrophiles/nucleophiles calculated for M1 and M2 revealed the importance of substituent positioning on compound chemical behavior. In addition, u /uþ and DEn/DEe indicated that M6 is more electrophilic because of the presence of two NO2 groups, which enhanced its NLO properties. The hyperpolarizability (b0) of the compounds ranged from 5.21 10 30 to 7.26 10 30 esu and was greater than that of urea; thus, M1eM6 were considered possible candidates for NLO applications. Docking simulation was also performed on the studied compounds and targets (PDB ID: 5ADH and 1RO6), and the calculated binding affinity and non-bonding interactions are reported. Conclusion: The calculated u and u þ indicated the electrophilic nature of the compounds; M6, a compound with two NO2 groups, showed enhanced effects. Molecular electrostatic potential (MEP) analysis indicated that amide and nitro groups on the compounds were centers of electrophilic attacks. The magnitude of the molecular hyperpolarizability suggested that the entire compound had good NLO properties and therefore could be explored as a candidate NLO material. The docking results indicated that these compounds have excellent antioxidant and anti-inflammatory properties.