Novel silver(I) complexes with fenamates: Insights into synthesis, spectral characterization, and bioactivity

Six new Ag(I) ions complexes with N-phenylanthranilic, mefenamic, and niflumic acids have been synthesized. Three of them are binary complexes with the [Ag(L)] formula (where L represents N-phenylanthranilate (nfa), mefenamate (mfa), or niflumate (nif) ions), and the other three complexes are ternary with the formula [Ag(L)(phen)₂]⋅nH₂O (where phen - 1,10-phenanthroline). The complexes were characterized by elemental analysis, differential scanning calorimetry (DSC), X-ray fluorescence, powder X-ray diffraction, and single-crystal X-ray structure analysis. Additionally, techniques such as ESI-MS spectrometry, ¹H NMR, UV-Vis, and FTIR spectroscopy were employed. The X-ray crystallography showed that in the solid [Ag(nif)] complex, the cation showed an unusual structure with coordination number 5, i.e. AgO₃NC. The silver cation interacts with three niflumate anions, forming a two-dimensional coordination polymer. Complexes have potential antibacterial efficacy with varied minimum inhibitory concentration values (MIC) between 45.96 and 800 μM against multidrug-resistant Pseudomonas aeruginosa. Antibacterial combination therapy of Ag(I) complexes with chloramphenicol (CHL) and kanamycin (KAN) showed a very strong synergistic impact against P. aeruginosa with no cytotoxic effect on normal human fibroblasts. Complexes [Ag(nif)] and [Ag(nfa)] inhibit protein denaturation, bind to BSA via static quenching (k_q = 0.65-1.08 × 10¹³ M^-1 s^-1). Furthermore, the formation of these complexes enhances the penetration of the drug across human membrane monolayers, which could improve bioavailability and therapeutic potential. The [Ag(nif)] complex demonstrates significant potential for topical dermal application due to its antimicrobial and anti-inflammatory properties. Notably, among all complexes evaluated, it displays the lowest BA/AB ratio (5.41), facilitating the most efficient transdermal permeation.