Synthesis, crystal structures, in vitro DNA binding, antibacterial and cytotoxic activities of new di- and polynuclear silver(I) saccharinate complexes with tertiary monophosphanes

Abstract

Four new silver(I) saccharinate (sac) complexes, [Ag(mu-sac)(PPh3)](2) (1), [Ag(mu-sac)(PPh2CY)](2) (2), [Ag(mu-sac)(PPhCy2)](2) (3) and [Ag(mu-sac)(PCy3)](n) (4), where PPh3 = triphenylphosphane, PPh2Cy = cyclohexyldiphenylphosphane, PPhCy2 = dicyclohexylphenylphosphane and PCy3 = tricyclohexylphosphane, have been synthesized and fully characterized by elemental analysis, IR, NMR, ESI-MS and single crystal X-ray diffraction. Fluorescence ethidium bromide displacement indicate that all complexes bind to fish sperm (FS) DNA by intercalation with binding constants (K-A) of 29.1 +/- 0.26 x 10(5) M-1 for 1, 2.54 +/- 0.12 x 10(5) M-1 for 2, 2.42 +/- 0.08 x 10(5) M-1 for 3, 0.19 +/- 0.03 x 10(5) M-1 for 4. The relative viscosities of the FS-DNA solutions increase with increasing of the complex concentration, providing strong evidence for the intercalation mode. The gel electrophoresis assay further confirms their binding with the pBR322 plasmid DNA. The MIC values of the silver(I) complexes are generally higher than those of AgNO3 and silver sulfadiazine, but 1 presents a promising activity against Salmonella typhimurium and Staphylococcus aureus. All complexes are highly cytotoxic on human lung carcinoma (A549) and human breast adenocarcinoma (MCF-7) cell lines with IC50 values ranging from 0.82 to 3.13 mu M.