Computational and Experimental Exploration of Di‐Iodo‐Based Schiff Bases as Esterase Inhibitors: Single Crystal and Spectral Insights

ABSTRACT The current study was aimed at synthesizing ( E )‐2‐(((3‐hydroxy‐4‐methylphenyl)imino)methyl)‐4,6‐diiodophenol ( 1 ) and ( E )‐3‐((2‐hydroxy‐3,5‐diiodobenzylidene)amino)‐4‐methylbenzoate ( 2 ). The modern spectral tools like UV–Vis, FTIR, and NMR were used to determine the structures, while a single X‐ray diffraction approach was employed to prove that Compound 2 is orthorhombic and Compound 1 is triclinic. The 6‐31G(d,p) basis set along B3LYP (hybrid functional) was used for the optimisation of synthesized compounds. The energy gaps between various orbitals were estimated using DFT calculations, and a comparative study in terms of different structural parameters was also conducted, which confirmed the correlation between XRD and DFT measurements. Two‐dimensional fingerprint plots and Hirshfeld surface analysis were used to further elucidate the different interactions that stabilize the crystal. In vitro and in silico studies were employed to assess the biological potential of these molecules in terms of enzyme inhibition. Compound 2 depicted 74.17 ± 1.4% and 69.11 ± 1.3% inhibition against AChE and BChE, respectively. The docking score, as well as in vitro studies, demonstrated that Compound 2 is more potent than Compound 1 against acetylcholine esterase and butyrylcholine esterase.