Structure-property correlation in gallic acid and 4-cyanopyridine cocrystal and binding studies with drug efflux pump in bacteria

Abstract This work focuses on the self-assembled gallic acid (GA) and 4-cyanopyridine (4-CNpy) (1:1) adduct, GA-CNpy (1), constructed from various non-covalent interactions. The cocrystal was characterized by X-ray crystallography, FT-IR and NMR spectroscopy. In the crystal lattice of 1, GA and 4-CNpy molecules are connected with each other through O H⋅⋅⋅O and N H⋅⋅⋅O hydrogen bonding interactions involving hydroxyl groups, carboxylic acid groups and 4-CNpy molecules to form a 3-D supramolecular assembly. QTAIM and NCI analyses of the optimized geometries confirm the existence of hydrogen bonds between the molecules. Further, calculations on hydrogen bonding motifs indicate that proton transfer from –OH (carboxylic acid) to N (pyridine base) is unfavorable due to high activation energy barrier. Special attention was paid to the in vitro antioxidant and antibacterial studies of 1. Our findings indicate that the GA-CNpy adduct, in its binary form, can enhance these properties to a greater extent relative to their individual counter parts. The mechanism of antibacterial activity in molecular docking study also suggests inhibitory role of the cocrystal against drug efflux pump AcrB in E. coli.