Synthesis, characterization, quantum chemical calculation, Hirshfeld surface analysis and antibacterial activity of a co-crystal of 4-Aminopyridine: p-Hydroxybenzoic acid with a water molecule

Abstract

A novel co-crystal of 4-Aminopyridine with p-Hydroxybenzoic acid having a water molecule (4AP:PHBA·H2O) has been synthesized using solution technique. The three-dimensional structure of 4AP:PHBA·H2O has been confirmed by single-crystal X-ray diffraction (SCXRD) and the spectral characterization has been carried out using FT-IR, 1HNMR and 13CNMR spectroscopy. The structure analysis reveals that the O−H···N, N−H···O, O−H···O and C−H···π hydrogen bonds are mainly responsible for the stabilization of crystal packing. The strong O−H···N interactions play a vital role in the formation of the crystal structure of 4AP:PHBA·H2O. The quantum chemical calculations, HOMO – LUMO energy gap, Mulliken population analysis and molecular electrostatic potential map have been performed using Hartree Fock (HF) and density functional theory (DFT) methods with 6–311+G(d,p) basis set level. The non-covalent interactions present in the structure have been examined quantitatively using the Hirshfeld surface and fingerprint plot analysis. The water molecule connects the crystal structure by acting as a donor and acceptor. The contribution of C−H···π interactions is 35%, the maximum contribution, however, comes from H−H contacts (40%). The compound shows an encouraging antibacterial activity against the bacterial pathogens S. aureus, E. coli, P. aeruginosa, when compared with the standard antibiotic ciprofloxacin drug. © 2023 Elsevier B.V.