Phenylsulfonylethyl‐Substituted Benzimidazolium Salts: Synthesis, Characterization, Crystal Structure, Molecular Docking, and Inhibitory Properties Against Various Enzymes

ABSTRACT N ‐heterocyclic carbenes (NHCs) are chemical structures called heterocyclic structures that contain one or more nitrogen atoms. N ‐heterocyclic compounds are the basic building blocks of many drugs and biologically active molecules. One of these compounds is benzimidazolium salts. Herein, we present the synthesis of a series of phenylsulfonylethyl‐substituted benzimidazolium salts. These compounds were characterized using NMR ( 1 H‐ and 13 C‐) and FTIR spectroscopic techniques. Compound 1b exhibits a U‐shaped benzimidazolium cation paired with a chloride anion. A hierarchical supramolecular architecture arises from C–H⋯Cl chains, C–H⋯π layers, and π⋯π stacking, demonstrating cooperative non‐covalent stabilization of the crystal structure. The synthesized benzimidazolium derivatives exhibited notable inhibitory effect against human carbonic anhydrases (hCA I, hCA II)and acetylcholinesterase (AChE), with several compounds showing markedly lower K i values than the clinical standards. Molecular docking of the NHCs with different receptors showed excellent binding capability with the active site of the target receptors. Moreover, the physicochemical and ADME analysis of the compounds were performed with SwissADME software. Overall examined compounds were found with very good oral bioavailability determined by Lipinski and Verber's rule. The compounds showed Pgp susceptibility with reasonable blood brain barrier permeability.