From phoshines to carbens: synthesis of new coinage metal complexes with applications in bioinorganic chemistry

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, NHCs begun to replace phosphines in the development of novel complexes showing cytotoxic properties. In particular, our research group has synthesized new Ag(I) carbene complexes from the precursors {[HB(RImH)3]Br2} (R = Bn, Mes or tBu). 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 Au(I) complexes. We also reported the first discrete molecules with bis(triazolylidene)borate carbene ligands, Ag2[H2B(BnTz)2]2 and the homoleptic Au2[H2B(BnTz)2]2. These complexes have been recently studied for their antitumor properties. Following this line of research we are recently developing new ligands, modulating the steric and/or electronic properties, and the hydrophilic/lypophilic balance by variation of the azole ring substituents. We have also reported the synthesis of hydrophilic bimetallic complexes of general formula {Na2[H2C(AzR)2]2Ag2} (Az = Im or Tz; R = PrSO3 or EtCOO). Another evolution of this research line involves the chemistry of new water soluble zwitterionic mono-NHC ligands functionalized with hydrophilic side arms. We have synthesized the water soluble carbene ligand precursors{Im1R,3R} (R = PrSO3, CH2COOEt or CH2CONEt2) and the related Cu(I), Ag(I) and Au(I) carbene complexes. They were evaluated for their cytotoxic activity towards a panel of several human tumour cell lines.