Chloranilic acid–Gabapentin proton transfer complexes: Synthesis, spectroscopic, antimicrobial, computational, and molecular docking studies

Abstract

The behavior of Gabapentin (Gab) towards Chloranilic acid (CLA) in solution is checked using UV–visible spectroscopy in three different solvents: methanol, ethanol, and acetonitrile. Applying Job's continuous variation method, the reaction is proved to proceed as a 1:1 molar composition in solution. On the other hand, two nanocrystalline solid products are isolated from the reaction of Gabapentin (Gab) with chloranilic acid (CLA), depending on the initial mole ratio (G1CLA and G2CLA). The isolated solid products are characterized by physicochemical tools (UV–vis., FT-IR, 1HNMR), proving the existence of proton transfer interaction. The semi-crystalline G2CLA (1CLA: 2Gab) product was investigated using powder x-ray diffraction, whereas the crystallized G1CLA (1CLA: 1Gab) product was analyzed by SXRD. The determined crystallite sizes for G1CLA and G2CLA were 30.02 nm and 40.17 nm, respectively. G1CLA was optimized in ethanol and gas phase, using DFT computational study, with basis sets B3LYP/6–31+G(d,p). The calculations showed the occurrence of charge transfer and hydrogen bonding in gas phase whereas proton transfer took place in ethanol. NBO charge calculations, reactivity parameters, and MEP maps indicated that CLA exhibits e-accepting ability, while Gab demonstrates e-donating properties. The main electronic transition states were determined by TD-DFT method. Moreover, the isolated solids were subjected to biological activity study, against six pathogens: two fungi, two gram-positive, and two gram-negative bacteria. Molecular docking simulation of G1CLA was performed on the crystal structure of proteus vulgaris HigA antitoxin (6CF1), revealing a total binding energy of -74.8704 Kcal/mole.