Synthesis and Antimicrobial Activities of Gold(I) N-heterocyclic Carbene Complexes

Since 1991, when Arduengo isolated the first free carbene N-heterocyclic (NHC) [1], a wide variety of NHC complexes has been synthesized involving both transition and main group metals [2]. It is possible to modify the properties of these neutral ligands by introducing different substituents, for example, water-soluble functional groups. On the other hand, in the last two decades, the use of gold complexes has increased substantially due to its high efficiency in chemical transformations [3] as well as its proven antimicrobial and antitumor activity [4]. Because water is the biologically most relevant solvent, the synthesis of water-soluble metal-based drugs stable in water or physiological media is a matter of increasing interest. Herein, we report the synthesis and characterization of two water-soluble NHC gold(I) complexes, that is, [1-mesityl-3-(3-sodiumsulfonatopropyl)imidazol-2-ylidene] gold(I) chloro and [1,3-bis(2,6-diisopropyl-4-sodiumsulfonatophenyl)imidazol-2-ylidene] gold(I) chloro. Both were prepared, in high yield, by carbene transmetallation from the appropriate NHC silver complex with chloro tetrahydrothiophene gold ([AuCl(tht)]). The antimicrobial efficacy of both the gold (I) compounds and the respective ligands was assessed by agar diffusion assay and the broth macrodilution method against both gram positive and negative bacteria. MICs values (> 128 ug/ml) were superior to those displayed by the reference antibiotics penicillin G and streptomycin. [1] A.J. Arduengo III, R.L. Harlow, M. Kline, J. Am. Chem. Soc.1991, 113, 361. [2] N-Heterocyclic Carbenes; Diez-Gonzalez, S., Ed.; The Royal Society of Chemistry 2011. [3] a) H. Schmidbaur, A. Schier, Organometallic, 2010, 29, 2. [4] J. Coetzee,S. Cronje,L. Dobrzanska,H.G. Raubenheimer,G. Jooné,M.J. Nell, H.C. Hoppe, Dalton Trans. 2011, 40, 1471–1483.