Novel derivatives of the antibiotic NHC–Ag(I) drug candidate SBC3: Synthesis, biological evaluation and 109Ag NMR studies

Abstract

The synthesis of six novel N-heterocyclic carbene silver(I) acetate complexes, three symmetrical and three non-symmetrical, were achieved using 4,5-diphenylimidazole to produce intermediate imidazolium salts and then obtain the corresponding silver(I) complexes through complexation with silver acetate via the Youngs' method. In vitro biological testing, using the Kirby-Bauer disk diffusion method, was conducted against Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli, with a NHC-silver(I) acetate compound, SBC3, and Tetracycline as standards. Silver(I) acetate complex 7 resulted in a 4 mm clearance against MRSA, showing the highest antibiotic activity of the novel derivatives. Crystallographic data revealed similar bond lengths and angles to previously reported NHC-silver(I) acetate complexes, with complex 8 showing interesting g 2-coordination between the silver atom and acetate oxygens. 109 Ag NMR studies were conducted, highlighting the effects of the substituents of the imidazole ring on the silver atom shown by the corresponding shifts in the 109 Ag NMR spectra. The incorporation of isopropyl groups to several of the novel complexes resulted in larger upfield 109 Ag NMR shift values compared to all other substituents.

Synthesis, in vitro anticancer activities, and quantum chemical investigations on 1,3-bis-(2-methyl-2-propenyl)benzimidazolium chloride and its Ag(I) complex

“…49 In a recent study, it was reported that the carbon atom chemical shifts for benzimidazole complexes were reported in the range of 142.6-149.5 ppm. 48 As expected, the unsaturated ring 13 C shifts (atom nos. 1-6 and13) for compounds 1 and 2 occurred in the ranges of 116.1-137.4 and 116.1-137.5 ppm, whereas they were simulated in the ranges of 118.1-140.4 and 118.4-142.5 ppm in CHCl 3 .…”

“…As reported in the literature, [42][43][44] this peak was not observed for the Agcarbene because of the fluxional behavior of the NHC complexes. [45][46][47] Furthermore, the chemical shifts of the acidic NCHN proton of the benzimidazolium ligand derivative has been reported at 11.04 48 and 11.25 ppm. 49 In a recent study, it was reported that the carbon atom chemical shifts for benzimidazole complexes were reported in the range of 142.6-149.5 ppm.…”

In vitro anti-bacterial and time kill evaluation of binuclear tricyclohexylphosphanesilver(I) dithiocarbamates, {Cy3PAg(S2CNRR′)}2

“…In the refinement of 4, the C11cyclohexyl ring was disordered over two positions. Anisotropic refinement but, with the displacement ellipsoids constrained to be nearly isotropic, led to a site occupancy factor = 0.571 (11) for the major component. The maximum and minimum residual electron density peaks of 1.15 and 1.32 eÅ −3 , respectively, were located 0.98 and 0.75 Å from the H26c and Ag1 atoms, respectively.…”

“…myocrisin and auranofin, are used for the treatment of rheumatoid arthritis [5]. Notably, silver and its compounds [6,7] and silver-based nanoparticles [8] have long been known to possess strong inhibitory and bactericidal effects as well as a broad spectrum of anti-microbial activities for bacteria, fungi and viruses, and continue to attract significant attention [9][10][11][12]. Silver generally exhibits higher toxicity to microorganisms with lower toxicity to mammalian cells compared with other metals [13].…”

Coinage Metal N‐Heterocyclic Carbene Complexes: Recent Synthetic Strategies and Medicinal Applications

“…These salts 91 were stirred with silver acetate in dichloromethane for 3 days to get desired complexes 92 in moderate yield in the range of 12–55 % (Scheme 21). [59] …”