Spectral, theoretical characterization and antifungal properties of two phenol derivative Schiff bases with an intramolecular hydrogen bond

Abstract

Schiff bases show a wide variety of applications of great importance in medicinal research due to their range of biological activities. In this article we describe the electronic structure, optical, redox and wide antifungal properties of (E)-2-{[(2-aminopyridin-3-yl)imino]-methyl}-4,6-di-tert-butyl-phenol (L1) and (E)-2-{[(3-aminopyridin-4-yl)imino]-methyl}-4,6-di-tert-butyl-phenol (L2), two isomer phenol derivative Schiff bases exhibiting a strong intramolecular hydrogen bond (O–H⋯N). These compounds were characterized by their ¹H, HHCOSY, ¹³C-NMR, FT-IR spectra, and by cyclic voltammetry. All the experimental results were complemented with theoretical calculations using density functional theory (DFT) and time-dependent DFT (TDDFT). The antimicrobial activity of the compounds described herein was assessed by determining the minimal inhibitory concentration (MIC) and by a modification of the Kirby–Bauer method. We tested Salmonella enterica serovar Typhi (S. Typhi, Gram-negative bacteria), Cryptococcus spp. (yeast), and Candida albicans (yeast). We found that neither L1 nor L2 showed antimicrobial activity against S. Typhi or Candida albicans. On the other hand, L2, in contrast to L1, exhibited antifungal activity against a clinical strain of Cryptococcus spp. (MIC: 4.468 μg ml⁻¹) even better than ketoconazole antifungal medicaments. We mentioned above that L1 and L2 are isomer species, because the amino group is in the ortho-position in L1 and in the para-position in L2, however no significant differences were detectable by UV-vis, FT-IR, oxidation potentials and TDDFT calculations, but importantly, the antifungal activity was clearly discriminated between these two isomers.