Fluorinated benzimidazolium salts: Synthesis, characterization, molecular docking studies and inhibitory properties against some metabolic enzymes

•Fluorinated benzimidazolium salts were synthesised.•Spectroscopic techniques (NMR and FT-IR) and elemental analyses were used to characterize all compounds.•The inhibitory effects of the benzimidazolium salts bearing the 4-fluorobenzyl group against AChE and hCA enzymes were examined.•The XRD method was used to determine the crystal structure of 1f and 1 h.•Molecular docking studies of 1f and 1 h against AChE and hCAs were performed.•The ADME-Tox study was examined to determine the binding mechanisms of compounds 1 h and 1f. Here, a number of symmetric and unsymmetric N-heterocyclic carbene (NHC) precursors based on benzimidazol-2-ylidene are synthesized. The N-benzyl substituent in these compounds has an electron-withdrawing group (F) at the para position. The structure of these compounds was characterized using elemental analysis and various spectroscopic methods (FTIR and NMR). The molecular and crystal structures of compound 1f and compound 1h were unambiguously elucidated through single-crystal X-ray diffraction analysis. According to the X-ray studies, compound 1f exhibits the formation of a U-shaped molecule whereas compound 1h has a Z-shape formation. In addition, the enzyme inhibition activities of these compounds were investigated against acetylcholinesterase (AChE) and carbonic anhydrases (hCAs). They showed a highly potent inhibition effect on AChE and hCAs (Ki values are in the range of 14.84±1.91 to 174.80±23.60 nM for AChE, 22.41±1.93 to 188.67±27.05 nM for hCA I and 35.29±7.21 to 136.55±17.61 nM for hCA II). These results may contribute to the design and development of new drug candidates, particularly for treatment of some widespread disorders displayed in the world including Alzheimer's disease and glaucoma. This work contains the synthesis and characterization of the fluorinated benzimidazolium salts. All compounds were characterized by NMR, FT-IR spectroscopy, and elemental analysis techniques. The molecular structures of two compounds were enlightened by single crystal X-ray diffraction studies. After enzyme inhibition study, a new series of benzimidazolium salts were determined to be highly potent inhibitors for acetylcholinesterase (AChE) enzyme and carbonic anhydrases (hCAs) isoenzymes. The molecular docking and ADMET-Tox study was performed for compounds with higher potential inhibitory properties based on binding energy and interaction types against AChE and hCAs. [Display omitted]