Crystal Structure, Hirshfeld Surface Analysis, Computational Study and Molecular Docking Simulation of 4-Aminoantipyrine Derivative

Abstract

Herein, a new derivative (4APSA) has been synthesized by treating 4-aminoantipyrine with succinic anhydride at 25 degrees C employing glacial acetic acid as a solvent. The molecular structure of 4APSA is investigated via single crystal X-ray diffraction (XRD) analysis. Cambridge structure database CSD 2023.3.1 (updated March 2024) was used for comparison of 4APSA with the associated reported structures. The supramolecular assemblage was alleviated by several intermolecular connections. Hirshfeld surface analysis was conducted for further assessment of intermolecular interactions with respect to interatomic contacts for 4APSA and a closely associated structure having a reference code of HOMDUI. Interaction energy calculations were performed at B3LYP/6-31G(d,p) electron density level to find the type of interaction energy that had the highest contribution to the supramolecular assembly. Moreover, in-depth DFT calculations were studied at B3LYP/6-311++g(d,p) level to obtain molecular structure, Mulliken charge analysis, MEP surface, electronic properties, quantum chemical reactivity, and DOS spectrum. Strong correlations are found between theoretical and experimental structures. The ADME-T prediction was applied for the 4APSA, 4AP, and SA compounds utilizing OSIRIS DataWarrior. Docking simulation demonstrates the high tendency of 4APSA to bind with the active sites of Cannabinoid Receptor Subtype 2 (CB2R) compared to JWH-018. This finding suggested that the synthesized compound has a positive effect on the CB2R protein.