In Vitro Evaluation of Rhodium and Osmium RAPTA Analogues:  The Case for Organometallic Anticancer Drugs Not Based on Ruthenium

Reaction of the dimer [(η 5 -C 5 Me 5 )RhCl(μ 2 -Cl)] 2 with 2 or 4 equiv of the water-soluble phosphine 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (pta) affords [Rh(η 5 -C 5 Me 5 )(pta)Cl 2 ] and [Rh(η 5 -C 5 Me 5 )(pta) 2 Cl]Cl, respectively. Both complexes have been characterized in solution by NMR spectroscopy and in the solid state by single-crystal X-ray diffraction, the latter as the chloride and BPh 4 - salts. In addition, the rhodium(I) complexes [Rh(η 5 -C 5 Me 5 )(CO)(pta)] and [Rh(η 5 -C 5 H 5 )(pta) 2 ] have been prepared from [Rh(η 5 -C 5 Me 5 )(CO) 2 ] and [Rh(η 5 -C 5 H 5 )(PPh 3 ) 2 ], respectively, by reaction with pta. An in vitro evaluation of these compounds, together with [Os(η 6 -C 10 H 14 )(pta)Cl 2 ] and the well-characterized antimetastasis drug [Ru(η 6 -C 10 H 14 )(pta)Cl 2 ], RAPTA-C, was undertaken using HT29 colon carcinoma, A549 lung carcinoma, and T47D breast carcinoma cells. In the HT29 cell line, the two nearest congeners to [Ru(η 6 -C 10 H 14 )(pta)Cl 2 ], viz., [Rh(η 5 -C 5 Me 5 )(pta)Cl 2 ] and [Os(η 6 -C 10 H 14 )(pta)Cl 2 ], demonstrated very similar cytotoxicity profiles. [Rh(η 5 -C 5 Me 5 )(pta)Cl 2 ] proved significantly more cytotoxic in A549 cells and [Rh(η 5 -C 5 Me 5 )(pta) 2 Cl]Cl 3-fold more cytotoxic in T47D cells, both relative to RAPTA-C. These data suggest that the development of organometallic anticancer drugs based on the neighboring elements to ruthenium should not be overlooked.