Reactivity and Transformation of Antimetastatic and Cytotoxic Rhodium(III)–Dimethyl Sulfoxide Complexes in Biological Fluids: An XAS Speciation Study

Rhodium(III) anticancer drugs can exert preferential antimetastatic or cytotoxic activities, which are dependent on subtle structural changes. In order to delineate factors affecting the biotransformations and speciation, mer,cis-[RhCl3(S-dmso)2(O-dmso)] (A1) and mer,cis-[RhCl3(S-dmso)2(2N-indazole)] (A2) have been studied by X-ray absorption spectroscopy (XAS). Interactions of these complexes with saline buffer, cell culture media, serum proteins (albumin and apo-transferrin), native and chemically degraded collagen gels, and A549 cells have been studied using linear combination fitting (LCF) and 3D scatter plots of XAS data. Following initial aquation and hydrolysis reactions involving stepwise displacement of Cl– and S-/O-dmso ligands, the Rh(III) complexes underwent further ligand substitution reactions with biological nucleophiles (e.g., amino acid residues of serum proteins). The reaction of A1 with chemically degraded collagen gel was postulated to be a key reason for its antimetastatic activity. A...