In vitro anti-bacterial and time kill evaluation of binuclear tricyclohexylphosphanesilver(I) dithiocarbamates, {Cy 3 PAg(S 2 CNRR')} 2 .

Four binuclear phosphanesilver(I) dithiocarbamates, {cyclohexyl ₃ PAg(S ₂ CNRR')} ₂ for R = R' = Et (1), CH ₂ CH ₂ (2), CH ₂ CH ₂ OH (3) and R = Me, R' = CH ₂ CH ₂ OH (4) have been synthesised and characterised by spectroscopy and crystallography, and feature tri-connective, μ ₂ -bridging dithiocarbamate ligands and distorted tetrahedral geometries based on PS ₃ donor sets. The compounds were evaluated for anti-bacterial activity against a total of 12 clinically important pathogens. Based on minimum inhibitory concentration (MIC) and cell viability tests (human embryonic kidney cells, HEK 293), 1-4 are specifically active against Gram-positive bacteria while demonstrating low toxicity; 3 and 4 are active against methicillin resistant S. aureus (MRSA). Across the series, 4 was most effective and was more active than the standard anti-biotic chloramphenicol. Time kill assays reveal 1-4 to exhibit both time- and concentration-dependent pharmacokinetics against susceptible bacteria. Compound 4 demonstrates rapid (within 2 h) bactericidal activity at 1 and 2 × MIC to reach a maximum decrease of 5.2 log ₁₀  CFU/mL against S. aureus (MRSA).
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