Pentafluorobenzyl-substituted benzimidazolium salts: Synthesis, characterization, crystal structures, computational studies and inhibitory properties of some metabolic enzymes

Abstract

This work contains the synthesis and characterization of the pentafluorobenzyl-substituted benzimidazolium salts which N-heterocyclic carbene (NHC) precursors. All compounds were characterized by using 1H, 13C, and 19F NMR, FT-IR spectroscopy, and elemental analysis techniques. All the spectroscopy and elemental analysis data fully confirm the proposed formulas. In the synthesized compounds, the molecular structures of compounds 1-(2-methylbenzyl)-3-(2,3,4,5,6-pentafluorobenzyl)benzimidazolium bromide (1b), 1-(4-methylbenzyl)-3-(2,3,4,5,6-pentafluorobenzyl)benzimidazolium bromide (1d) and 1-(4-trifluoromethylbenzyl)-3-(2,3,4,5,6-pentafluorobenzyl)benzimidazolium bromide (1f) were enlightened by single crystal X-ray diffraction studies. After enzyme inhibition study, a new series of pentafluorobenzyl-substituted NHC precursors were determined to be highly potent inhibitors for acetylcholinesterase (AChE) enzyme and carbonic anhydrases (hCAs) isoenzymes. Ki values were found in the range of 7.20±1.31 to 28.26±5.72 nM for AChE , 10.25±0.93 to 40.93±3.89 nM toward hCA I as pervasive metal containing enzymes present in prokaryotes and eukaryotes, and 3.33±0.15 to 58.22±6.99 nM for hCA II as the key enzyme promising strategy for the treatment of neurological disorders such as Alzheimer's disease. The molecular docking study performed for compounds had higher potential inhibitory properties involved in a novel series of pentafluorobenzyl-substituted NHC precursors based on the binding energy and interaction types against AChE and hCAs.