Synthesis, structural peculiarities, theoretical study and biological evaluation of newly designed O-Vanillin based azomethines

Abstract

Two azomethines: (E)-2-(((2-hydroxyethyl)imino)methyl)-6-methoxyphenol (1) and (E)-3-(((2-hydroxyethyl)imino)methyl)benzene-1,2-diol (2) were synthesized and characterized in solid state by FT-IR spectroscopy and single crystal X-ray crystallography, whereas in solution state by NMR (1H, 13C) and GC-MS. The titled compounds exist in a zwitter ionic form with a strong intramolecular N–H⋯O hydrogen bond between the NH+ and the phenolate O− as observed both in solution states as well as in solid state. Both the compounds are stabilized in 3D network due to C–H⋯O, N–H⋯O and O–H⋯O types of hydrogen bondings. The optimized molecular geometries were calculated by DFT (density functional theory) with B3LYP functional with 6–31G(d,p) basis set was used using GAUSSIAN 09 program package. The simulated geometries showed excellent correlation with experimentally found structures. The synthesized compounds were investigated for DNA binding interactions using UV–visible spectroscopy and viscometery giving the intercalative mode of interaction with SS-DNA (Salmon sperm DNA). In order to explore the binding modes of compounds with DNA, docking simulations were further performed, that also support the aforementioned results. The compounds were also screened for their in vitro antimicrobial activities and the results showed that their antibacterial activity is even higher than that of the standard drug, Cefixime while their antifungal activity is lower than the standard drug, Terbinafine. The interaction of the titled compounds with cetyl trimethy lammonium bromide (CTAB) was investigated by conductometric method to know the critical micelle concentration (CMC) of CTAB in the absence and presence of compounds. The conductivity measurements revealed higher CMC value in the presence of compounds (For compound 1 CMC = 0.003 M while for compound 2 CMC = 0.0031 M), proposing a stable compound-CTAB system.