(C^Npz^C)AuIII complexes of acyclic carbene ligands: synthesis and anticancer properties

Abstract

A series of cyclometallated gold(III) complexes supported by pyrazine-based (C^N^pz^C)-type pincer ligands were synthesized via two different pathways. Nucleophilic attack on the isocyanide complex [(C^N^pz^C)Au(CNC₆H₃Me₂-2,6)]SbF₆ (2) gave [(C^N^pz^C)Au(ACC)]SbF₆ complexes with aniline (4·SbF₆), 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^pz^C)AuNHPh followed by protonation with HBF₄·OEt₂ gave the acyclic carbene complex 4·BF₄. 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.