Synthesis, characterization, computational studies and biological activities of novel NHC precursor and its silver (I) and selenium compounds

Abstract

The potential applications of fluorine in drug design are expanding rapidly. The evolution of synthetic methodologies has engendered the conception of novel fluorinated motifs. In the present study, the effective use of N-heterocyclic carbenes (NHCs) in pharmaceutical chemistry was combined with the enhancing role of fluorine groups in bioactivity, and the synthesis of a new NHC precursor (1) containing 2,6-difluorobenzyl group was achieved. Respective Ag-NHC (2) and Se-NHC (3) compounds were prepared from the synthesized NHC precursor. Structural characterization of each compound (1-3) was conducted by ¹H, ¹³C and ¹⁹F NMR, FT-IR, UV-visible spectroscopy, and elemental analysis methods. The antioxidant activity of these compounds was evaluated by using ABTS and DPPH radical scavenging assays as well as their ability to inhibit the acetylcholine esterase (AChE) enzyme. Besides, density functional theory (DFT) computations were performed in order to comparatively peruse the molecular structures, electronic properties, reactivity tendencies, donor-acceptor interactions, and electrostatic surface properties of compounds 1-3 for both vacuum and CHCl₃ phase. The reactivity ranking for the gas phase was clearly determined to be 3 < 2 < 1, based on the calculated energy gap values. The excited state characteristics of 1-3 in CHCl₃ were calculated by the TD-DFT method. The antioxidant activity showed that the compounds, particularly compound 3 displayed effective antioxidant activities. According to the enzyme inhibition outcomes, compound 2 (IC₅₀ value 8.43 ± 0.71 μM) had the most effective AChE inhibition among the synthesized compounds. Taken together, this investigation revealed the synthesis, characterization of various novel compounds (1-3) with, antioxidant potentials, AChE inhibitory activities, and quantum chemical calculations.