Synthesis of new multi-functionalized Schiff base derivatives based on vanillic acid: Antimicrobial activity, photophysical, DFT calculations and in-silico study

Abstract

The paper reports the synthesis of novel multi-functional Schiff base derivatives (S1-S7) via Steglich esterification, thoroughly characterized by standard spectroscopic methods (1H NMR, 13C NMR, FT-IR and Mass spectrometry) and elemental analysis technique. Density Functional Theory calculations (including FMOs’, MEP, IR and UV–Visible), photophysical, molecular docking simulations, and in-vitro antimicrobial assays were employed to study the structure and reactivity of synthesized compounds. The study highlights significant antimicrobial activity of certain derivatives, which aligns with computational predictions. UV–Visible study identifies various transitions like π→π*, n→π* occurring in the system aligning with the theoretical absorption spectra. Biological studies reveal that compounds S1, S2 and S5 exhibit significant potency for antimicrobial investigation correlating with the computational study. Further, the calculated HOMO-LUMO band gap for S1-S7 molecules (3.29 eV) suggest their insulating nature. Notably, MEP study shows negative electrostatic potential near nitro group and the positive potential near alkyl groups indicating preferable site for electrophilic and nucleophilic attack, respectively. Moreover, molecular docking was implemented to computationally screen the multi-functionalized Schiff base along with molecular dynamics simulation including MM-PBSA energy calculation in order to discover the reasonable physiological significance ensuring stability of binding interactions of relevant molecules.