Novel hydrophilic Au(I) and Ag(I) NHCs complexes

Since their discoveries in 1991, N-heterocyclic carbenes (NHCs) have been extensively investigated for their similarities to phosphines as ligands. Because of their unique electron-donating ability, the lower toxicity and the possibility to tune their structure, N-heterocyclic carbenes ligand begun to replace phosphines in the development of novel complexes showing cytotoxic properties. In particular, our research group has synthesized new silver(I) carbene complexes from the precursors {[HB(RImH)3]Br2} (R = Bn, Mes or tBu) and {[HC(MeBImH)3](BF4)3}.[1] Stable trimetallic complexes were obtained with general formula {Ag3[HB(RIm)3]2}Br, which were successfully employed as carbene transfer reagents in the synthesis of related gold(I) complexes by transmetallation. We also reported the first discrete molecules with bis(triazolylidene)borate carbene scorpionate-type ligands, the silver(I) carbene complex Ag2[H2B(BnTz)2]2 and the homoleptic gold(I) complex Au2[H2B(BnTz)2]2.[2] A limit of such complexes for biological studies is the poor solubility and stability in water. In order to evaluate the cytotoxic activity of metal adducts, the need to substitute organic solvents with water, solvent cheap and non-toxic, has received attention; therefore, the typical strategy is to modify compounds by attaching phase tags. In particular, water soluble groups such as esters, sulfonates and carboxylates have been used for this purpose. New N-heterocyclic carbene ligand precursors {H2C(HTzR)2} and {H2C(HImR)2} (HTz = 1,2,4-triazole; HIm = imidazole; R = PrSO3 or EtCOO) were obtained starting from the compounds bis(1,2,4-triazol-1-yl)methane and bis(imidazol-1-yl)methane.[3] The related silver(I) carbene complexes were obtained resulting in well-characterized and water soluble bimetallic compounds of general formula {Na2[H2C(TzR)2]2Ag2} and {Na2[H2C(ImR)2]2Ag2}. We are now developing the chemistry of new water soluble zwitterionic mono-NHC ligands, where imidazolium rings have two alkylsulfonate or alkylcarboxylate side arms, synthesizing the hydrophilic carbene ligand precursors{HIm4R,5R} (R = PrSO3 or CH2COOEt) and the related silver(I) carbene complexes {(Im4R,5R)AgCl}. The silver(I) complexes and the homoleptic gold(I) compounds were evaluated for their cytotoxic activity towards a panel of several human tumour cell lines.