Synthesis and SAR of group 11 N-heterocyclic carbene complexes

N-Heterocyclic Carbene (NHC) complexes constitute a recent and important field of research as potential anticancer drugs. Their key features are the easy tuning and design of the ligand structure that allow the modulation of the hydro-/lipo-philicity balance, responsible for the selectivity against the target tissue. Our research group, during the last 5 years, have developed different classes of coinage metal-NHC complexes obtained from the precursors {[HB(RImH)3]Br2} (R = Benzyl, Mesityl and t-Butyl), {[H2B(BnTzH)2]Br}, {[H2B(pNO2BnTzH)2]Br}4, {H2C(HTzR)2} and {H2C(HImR)2} (HTz = 1,2,4-triazole; HIm = imidazole; R = (CH2)3SO3- or (CH2)2COO-)5 (Figure 1). Recently we have focused the research work on the development of new 11th group metal-NHCs complexes obtained from the water soluble ligands Him1R,3RCl (R = COOCH3, COOCH2CH3 or CON(CH2CH3)2)6 or the zwitterionic water soluble precursor NaHIm1R,3R (R = (CH2)3SO3-)7. Here we report the synthesis and the cytotoxic activity of these ligands and the related coinage metal complexes. We also present the synthesis of the novel zwitteronic symmetrical NHC ligands NaHIm1R,3R,4R’’ (R = (CH2)3SO3-, R’’ = H, CH3 or NO2), NaHBzim1R,3R (R = (CH2)3SO3-) and non-symmetrical NHC ligands NaHIm1R,3R’,4R’’ (R = (CH2)3SO3-, R’ = CH2C6H5, R’’ = H, CH3 or NO2), {[HBzim1R,3R’]Br} (R = (CH2)3SO3Na, R’ = CH2C6H5) and the SAR study of the related water soluble metal-NHC complexes.