Bismuth Hybrid Halide with Dual Inhibition against α-amylase and Acetylcholinesterase Probed by Structural, Vibrational, and Theoretical Analysis

Abstract

This study presents the comprehensive synthesis, structural characterization, and biological evaluation of a novel zero-dimensional bismuth (III)-based hybrid material, (C7H10NO)4[BiCl6]·Cl·H2O. Single-crystal X-ray diffraction analysis confirmed its crystallization in the monoclinic centrosymmetric space group C2/c, revealing a structure composed of discrete [BiCl6]3- octahedra, protonated p-anisidinium cations, a free chloride ion, and a water molecule. Complementary SEM-EDS and PXRD analyses confirmed phase purity, distinct anisotropic needle-like morphology, and correct stoichiometry. The crystal packing is stabilized by an extensive network of strong N–H⋯Cl, N–H⋯O, and O–H⋯Cl hydrogen bonds, alongside weaker C–H⋯π and n→π interactions, as quantitatively decoded through Hirshfeld surface analysis. Combined experimental (FT-IR, Raman) and theoretical (DFT) vibrational studies provided unequivocal assignments of all characteristic modes, confirming the molecular structure and elucidating the distortion of the inorganic anion induced by the stereochemically active 6s2 lone pair on Bi (III) and external hydrogen-bonding forces. In addition, solution stability and structural integrity were investigated using UV–Visible spectroscopy and Liquid Chromatography–Mass Spectrometry, confirming the preservation of the hybrid framework over time. Most significantly, enzymatic inhibition assays demonstrated the compound's exceptional dual bioactivity. It exhibited potent inhibition against acetylcholinesterase (AChE, IC50 = 1.96 ± 0.1 mM) and α-amylase (IC50 = 0.27 ± 0.014 mM), outperforming its antimony (III) analogue by factors of 2 and 15, respectively, and the organic precursor p-anisidine by a factor of 14. This integrated study underscores the role of bismuth incorporation in enhancing functional properties, positioning this hybrid as a highly promising candidate for applications in optoelectronics, as a tailored functional material, and as a next-generation bioactive agent for therapeutic and agrochemical applications.