Water soluble coinage metal N-Heterocyclic Carbene complexes: synthesis and anticancer studies

N-heterocyclic carbenes (NHCs) are an interesting class of ligands with donor properties similar to phosphanes. Their chemical versatility not only implies a wide variety of structural diversity and coordination modes, but also a capability to form stable complexes with a large number of transition metals with different oxidation states. In particular, NHC complexes of coinage metals have recently showed to be good candidates as an alternative to cisplatin, exhibiting encouraging results in the field of anticancer drugs research. In the last years, we have developed several classes of coinage metal-NHC complexes obtained from the precursors {[HB(HImR)3]Br2} (R = Bn, Mes and t-Bu), {H2C(HTzR)2} and {H2C(HImR)2} (R = (CH2)3SO3 - or (CH2)2COO-). Recently we have focused the research work on 11th group metal-NHCs complexes obtained from hydrosoluble 1,3-symmetrically and 1,3-unsymmetrically substituted NHCs precursors based on imidazole and benzimidazole scaffolds. More recently we have synthesized and investigated the cytotoxic activity of the novel NHC ligand precursor [HTz(pNO2Bn)2]Br, and the corresponding metal complexes M[Tz(pNO2Bn)2]Br (M = Cu(I), Ag(I) or Au(I)). In addition, novel water-soluble bis(NHCSO3)CuCl complexes (NHCSO3 = HImBn,PrSO3, Na(4-Me)ImPrSO3 and NaBzimPrSO3), derived by the sulfonated N-heterocyclic carbene precursors HImBn,PrSO3 (3-(1-benzyl-1H-imidazol-3-ium-3-yl)propane-1-sulfonate), Na(4-Me)HImPrSO3 (sodium 3,3'-(4-methyl-1Himidazole- 3-ium-1,3-diyl)dipropane-1-sulfonate) and NaHBzimPrSO3 (sodium 3,3'-(1H-benzo[d]imidazole-3- ium-1,3-diyl)dipropane-1-sulfonate), have been synthesized. The in vitro antitumor effects of the complexes and the corresponding free ligands were evaluated on a panel of various human tumour cell lines. Their cytotoxic properties were also evaluated against non-transformed human cells and on a cellular model of cisplatin-resistance.