Design, Synthesis, and X-Ray Structural Characterization of Silver(I) NHC Complexes: Correlating Coordination Geometry With Biological Activity

Abstract

A series of novel silver(I) complexes bearing N-heterocyclic carbene (NHC) ligands were successfully synthesized and characterized using spectroscopic methods, elemental analysis, and X-ray diffraction techniques. Single-crystal X-ray diffraction analysis establishes complex 2f as a neutral monomeric silver(I) complex [Ag(L)₂]Cl. The compound crystallizes in the monoclinic space group P2₁/n (Z = 4) with unit-cell parameters a = 12.698(3) Å, b = 9.872(2) Å, c = 24.428(5) Å, β = 91.149(9)°. Hirshfeld surface analysis reveals that crystal packing is governed by dispersion-dominated H⋯H contacts (47.3%), supplemented by nonclassical C–H⋯N (17.9%) and C–H⋯Cl (6%) hydrogen bonds, along with enriched π–π stacking interactions. Powder X-ray diffraction confirmed the phase purity of the bulk samples. The electronic structures of the complexes were further elucidated by elemental analysis and FT-IR spectroscopy, supporting coordination via carbene carbon atoms. In parallel, the antibacterial activity of the synthesized compounds was evaluated against representative Gram-positive and Gram-negative bacterial strains. Several silver–NHC complexes demonstrated pronounced antibacterial effects, with inhibition zone diameters ranging from 11.94 to 28.99 mm and minimum inhibitory concentration (MIC) values between 0.073 and > 10 mg/mL. Among these, complex 3g exhibited the highest antibacterial potency, particularly against Listeria monocytogenes (MIC = 0.073 ± 0.05 mg/mL), alongside significant activity against Staphylococcus aureus (MIC = 0.621 ± 0.05 mg/mL). By contrast, complex 3f showed strong activity against the two Gram-negative strains, respectively, Pseudomonas aeruginosa (MIC = 0.075 ± 0.05 mg/mL) and Salmonella enterica (MIC = 0.076 ± 0.05 mg/mL). Cytotoxicity study of the silver(I) complexes 3 was evaluated against the two human cancer cell lines MDA-MB-231 and MCF-7. These findings highlight the potential of NHC–silver complexes as versatile agents in medicinal chemistry and provide valuable insights into their structure–function correlations.