Substituent effect in protein binding, optical, electrochemical, and antimicrobial properties of dipyrazinylpyridine ligands

A series of 2,6-di(pyrazine-2-yl)pyridine (dppy) ligands <b>1</b>–<b>4</b> of varying substituents of different electronic nature (-NMe₂, -OMe,–Me, and -Cl) in the 4-position of the pyridine moiety has been designed and synthesized to study the binding behavior of the dppy ligands towards Bovine Serum Albumin (BSA), a low-cost serum albumin protein. The interaction between ligands <b>1–4</b> and BSA has been studied using UV-Visible and fluorescence spectroscopy and molecular docking studies. The fluorescence of BSA was found to be quenched in the presence of all the ligands <b>1–4</b>, in which ligand <b>1</b>, having the most electron donating group NMe_2, exhibits the maximum binding affinity towards BSA. The interaction between ligands <b>1–4</b> and BSA was found to be static and spontaneous in nature. Further, the effect of substituents on the photophysical, thermal, and electrochemical properties of the dppy ligands has also been studied. Structure optimization and theoretical studies have been conducted to acquire a deeper understanding of the ligands’ nature. The trend of the energy gaps between the HOMO and the LUMO of the synthesized ligands <b>1–4</b>, calculated from the electrochemical analysis, has been reflected in the theoretical observations. Moreover, the ligands were also tested against different bacterial and fungal strains, and ligands containing electron-donating–NMe₂ and–OMe groups were quite active in both bacterial and fungal studies. The ligand <b>4</b>, having the–CH₃ group, showed moderate activity against fungal strains.