Synthesis, antibacterial and computational studies of Halo Chalcone hybrids from 1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one

Abstract

In an endeavor to develop antibacterial agents, a series of six 1,4-benzodioxan-6-yl substituted chalcone derivatives were synthesized by the base-catalyzed Claisen-Schmidt reaction of the 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one with fluoro and chloro substituted aromatic aldehydes. The synthesized products were characterized by FT-IR, 1H NMR, and 13C NMR spectroscopic techniques. The density functional theory (DFT) calculations were performed using the B3LYP functional with the 6-31G(d,p) basis set for the optimization of molecular geometries and frequency calculations. The CAM-B3LYP functional with a 6-31G(d,p) basis set was used in time-dependent density functional theory (TD-DFT) calculations for the electronic absorption studies. Optimized geometries, frontier molecular orbitals, and global reactivity descriptors' specifications were computed and addressed. The simulated electronic absorption spectra were recorded in the gas phase and dichloromethane (DCM) solvent. The electronic configurations, oscillator strengths, and excited state energies were also discussed. The theoretical UV–Vis and IR vibrational analyses were equated with the experimental findings for the assignment of absorption bands. The synthesized chalcones were evaluated for in vitro antibacterial activities against two Gram positive bacteria (Bacillus subtilis and Staphylococcus aureus) and two Gram negative bacteria (Escherichiacoli and Proteus vulgaris). The DFT simulations were correlated with the antibacterial findings and it was discovered that they were highly helpful in the designing antibacterial agents and to establish the structure–activity relationship. Theoretical calculations are in good correlation with the in vitro antibacterial results.