Synthesis and Antimicrobial Properties of Silver(I) N-Heterocyclic Carbene Complexes

New symmetric and asymmetric types of N-heterocyclic carbene (NHC) precursors, grouped into mono-dentate, bi-dentate and tri-dentate chelating ligands, were synthesized.

The reaction of the carbene precursors with silver(I) oxide in methanol at room temperature affords the silver(I) N-heterocyclic carbene complexes. The solubility and stability of silver(I) NHC complexes in water depends on the ligand and counter anion. In-vitro test of water soluble silver(I) NHC complex, [AgC₁₇N₅O₂H₂₁]⁺ [OH]^- 3a shows antimicrobial activity as good as 0.5 % AgNO3 using the same amount of silver on pathogenic bacteria and fungi of clinical importance.

The encapsulation of Ag(I) NHC complexes, [Ag₂C₃₄N₁₀O₄H]²⁺ 2[OH]^-, 6 and [Ag₃C₅₄N₁₂O₂H]³⁺[Br]^-2[OH]^-, 8a respectively by electrospinning technique, delivers bioactive nanosilver ions which improved the antimicrobial activity of the Ag(I) NHC over the un-encapsulated forms. The electrospun mat of 6 sustained the release of bioactive nanosilver ions for at least seven days.

Electrospun fiber mat containing 75 % of 6 showed improved antimicrobial efficacies in-vitro over silver sulfadiazine cream (SSD), with the rate of bactericidal activity six fold faster than SSD and ca. the same rate as 0.5 % AgNO₃. The amount of silver in the fiber mat is six times lower than SSD and 8 fold lower than 0.5 % AgNO₃. The size of the nanosilver ions of electrospun mat of 6 is <20 nm, while that of 8a is in the range of 50-100 nm.

Electrospun fiber of 8a is lower in bactericidal activity than that of 6. The NHC precursors also showed antimicrobial activity at higher concentrations than corresponding Ag(I) NHC complex. The thermal stability of NHC precursor salt C₂₆H₂₃Br₃N₆O, 7a is ca. 304 °C. This is relatively higher than most Ag(I) NHC complexes and imidazolium salts reported. Toxicity assessment of the NHC precursor 5 shows an LD50 of 100 mg/Kg in the rat.