Abstract
A series of (1H-benzimidazol-2-ylmethyl)-N-(4-phenyl)amine derivatives incorporating different electrondonating and withdrawing groups (X = 4-OCH3 (1), 4-CH3 (2), H (3), 4-Cl (4), and 4-Br (5)) on the para-position of the phenyl substituent was prepared, characterized and screened for their potential antimicrobial activity against some microbes. The substituent effect on the spectroscopic data (vibrational modes and NMR resonances) is well established by fitting with the Hammett constant. The unsubstituted derivative 4 exhibited comparable activity (MIC = 0.26 mu M) to the standard tetracycline (MIC = 0.18 mu M) against Staphylococcus aureus. Introduction of a substituent to the phenyl ring led to diminishing of the antibacterial activity. The substituent effect on the electron structure of 1-5 was investigated by TDDFT calculations. The acid dissociation constants of the ionizable NH group correlate well with Kubota's sigma parameter (R-2 = 0.9196). The solvatochromism behavior of 1-5, in solvents of different polarity and hydrogen-bond tendency, was investigated by linear solvation-energy relationship equation analysis. Correlation between various quantum chemical descriptors, and antibacterial activity was carried out to verify a structural activity relation for this series of benzimidazole derivatives. (C) 2020 Elsevier B.V. All rights reserved.