Ligand substitution reactions and cytotoxic properties of [Au(L)Cl<inf>2</inf>]⁺ and [AuCl<inf>2</inf>(DMSO)<inf>2</inf>]⁺ complexes (L=ethylenediamine and S-methyl-l-cysteine)

Abstract

We have studied the kinetics of the complex formation of gold(III) complexes, [AuCl2(en)]+ (dichlorido(ethylenediamine)aurate(III)-ion) and [AuCl2(SMC)] (dichlorido (S-methyl-l-cysteine)aurate(III)) with four biologically N-donor nucleophiles. It was shown that studied ligands have a high affinity for gold(III) complex, which may have important biological implications, since the interactions of Au(III) with DNA is thought to be responsible for the anti-tumour activity. The [AuCl2(SMC)] complex is more reactive than [AuCl2(en)]+. L-His reacts faster than the other N-donor nucleophiles in the reaction with [AuCl2(en)]+, but in the reaction with [AuCl2(SMC)] 5'-GMP is the best nucleophile. Gold(III) complexes are much more reactive than Pt(II) complexes with the same nucleophiles. The activation parameters for all studied reactions suggest an associative substitution mechanism. The cytotoxicity of gold(III) complexes, [AuCl2(en)]+, [AuCl2(SMC)] and [AuCl2(DMSO)2]+ was evaluated in vitro against chronic lymphocytic leukemia cells, obtained from blood of patients with chronic lymphocytic leukemia (CLL). The [AuCl2(en)]+ complex show comparable cytotoxicity profiles compared to cisplatin. © 2010 Elsevier Inc.