(C^N^C)Au complexes of acyclic carbene ligands: synthesis and anticancer properties.

A series of cyclometallated gold(iii) complexes supported by pyrazine-based (C^N^C)-type pincer ligands were synthesized via two different pathways. Nucleophilic attack on the isocyanide complex [(C^N^C)Au(C[triple bond, length as m-dash]NCHMe-2,6)]SbF (2) gave [(C^N^C)Au(ACC)]SbF complexes with aniline (4·SbF), adamantylamine (5), glycine ethyl ester (6), alanine methyl ester (7), valine methyl ester (8), phenylglycine methyl ester (9) and methionine methyl ester (10) substituents (ACC = acyclic carbene). The pathway via isocyanide insertion into gold-amide bonds was also investigated; e.g. the reaction of xylyl isocyanide with (C^N^C)AuNHPh followed by protonation with HBF·OEt gave the acyclic carbene complex 4·BF. To the best of our knowledge compounds 6-10 represent the first examples of gold(iii) acyclic carbene complexes bearing amino acid functions. The compounds provide a versatile platform for the study of the anti-proliferative properties of gold(iii) complexes. Tests against human adenoma-type lung cancer cells identified 5, 6, 7 and 10 as particularly promising and demonstrate the synthetic flexibility of acyclic carbene complexes and the potential of that class of compounds for anticancer applications. Compared to cisplatin, amino ester-containing ACC complexes showed improved selectivity for MCF-7 breast cancer cells over that for healthy fibroblasts.