Cyto- and genotoxic effects of coordination complexes of platinum, palladium and rhodium in vitro

Abstract

The growing industrial use of platinum group elements as catalysts, especially in automobile exhaust detoxification (trimetal catalytic converters), is causing increasing occupational and environmental pollution. The cytotoxic and mutagenic properties of industrially used coordination complexes of platinum, palladium and rhodium were investigated using the neutral red cytotoxicity assay on two established cell lines and the Salmonella typhimurium/microsome test system (Ames test). Cytotoxic effects of the platinum complexes, measured as ED50, occurred at test concentrations of 0.2 mM. The analogous palladium salts tested were 3 times less toxic with ED50 being 0.6 mM, while the rhodium salts proved to be 30 times less toxic (ED50 = 6 mM). Levels of toxicity of the different complexes of a particular metal did not differ significantly from each other, which indicates that the metal itself is responsible for the toxic effects. In the Ames test, the spontaneous mutation rates increased by factors of 3 to 20 when the four tester strains were exposed to the platinum complexes. The analogous rhodium compounds proved to be considerably less mutagenic, and palladium demonstrated no mutagenic potential. As all of the four tester strains contain different mutations, the mutagenic potential of platinum and rhodium complexes appears to be based on a variety of mechanisms that damage DNA. From these in vitro experiments, it can be concluded that water-soluble complex salts of rhodium are less toxic and have a smaller mutagenic potential than the analogous platinum complexes. For palladium there is no evidence of any mutagenic property. From this point of view, the development of a catalytic converter containing predominantly palladium may be a possible means of minimizing potential health risks from this exhaust detoxification technique.

C 2 ,N-dimethylbenzylamine cyclopalladated compounds: evaluation of cytotoxic, mutagenic and antitubercular activities

“…The Ames test, which is normally used to evaluate the mutagenic properties of new chemicals and drugs, can be also used to assess the ability of tested compounds to interact with DNA ( Mortelmans and Zeiger, 2000). Bünger et al (1996) have demonstrated that PdCl 2 , K 2 PdCl 4 and (NH 4 ) 2 PdCl 4 were non-mutagenic in the Ames test, contrary to their platinum analogues. Bünger et al (1996) have demonstrated that PdCl 2 , K 2 PdCl 4 and (NH 4 ) 2 PdCl 4 were non-mutagenic in the Ames test, contrary to their platinum analogues.…”

Synthesis, structural, physico-chemical and biological properties of new palladium(II) complexes with 2,6-dimethyl-4-nitropyridine

“…• It is possible to overcome the high labile-ligand exchange at Pd-center by designing high thermodynamic stabile and kinetically inert complexes [31]. • Some palladium compounds, contrary to platinum references, showed to be non-mutagenic, in the Ames test, and for this it seems possible to lower potential health risks by applying the palladium-based drugs [32]. • Palladium compounds might materialize a concept of tumor targeting which would result in drugs with other spectrum of activity and lack of cross-resistance as compared with platinum drugs [22].…”

“…• The trans-configuration of two leaving groups at square Pd center should not exclude their antiproliferative (or anticancer) activity because recently some very promising antitumor agents were found among the trans-Pt complexes [7,[27][28][29][30][31][32][33]. • It is possible to overcome the high labile-ligand exchange at Pd-center by designing high thermodynamic stabile and kinetically inert complexes [31].…”

Synthesis, characterization and in vitro cytotoxicity of homobimetallic complexes of palladium(II) with 2‐thiouracil ligands. Crystal structure of [Pd2(TU)(PPh3)3Cl2]

“…18 Palladium-based drugs, in contrast to platinum references, were non-mutagenic in the Ames test and therefore exhibit a lower potential health risk. 19,20 A number of mixed ligand complexes of phosphines/amines have been reported. 21 The coordination of metal ions to heterocyclic thiones is of current interest because these complexes are used in the synthesis of clinically useful drugs.…”