Photolysis of an iodoplatinum(IV) diamine complex to cytotoxic species by visible light.

The feasibility of photolyzing the Pt(IV) complex trans,cis-[PtCl2I2(en)] to cytotoxic species by visible light was evaluated. The synthesis of trans, cis-[PtCl2I2(en)] was achieved by the oxidation of [PtI2(en)] with PCl5 in tetrahydrofuran at room temperature for 30 min in the dark. The UV-Vis spectrum of trans, cis-[PtCl2I2(en)] in water showed a broad ligand-to-metal charge-transfer (LMCT) band with lambda(max) = 396 nm (epsilon = 1191/M/cm). Although trans,cis-[PtCl2I2(en)] was relatively stable in water in the dark, irradiation at lambda(irr) = 410 nm brought about its rapid decomposition. A detailed analysis of the photodecomposition products was not carried out, but two lines of evidence suggest that I2 and [PtCl2(en)], a known antitumor agent, may be formed as a result of a reductive-elimination type reaction: (i) irradiation of trans, cis-[PtCl2I2(en)] in water at lambda(irr) = 410 nm led to the same spectral changes as when [PtCl2(en)] and I2 together were irradiated at the same wavelength; (ii) the photoinduced loss of trans,cis-[PtCl2I2(en)] was accompanied by the covalent binding of Pt to DNA at a rate comparable to that of [PtCl2(en)] at 37 degrees C, and the presence of 100 mM chloride suppressed this DNA platination. On the other hand, the combined photolysis products, formed when trans,cis-[PtCl2I2(en)] was irradiated in culture medium at lambda(irr) > 375 nm for 60 min, were less potent than [PtCl2(en)] at inhibiting the growth of two human cancer cell lines. Two limitations make the use of trans,cis-[PtCl2I2(en)] in the therapy of cancer impractical: (i) trans,cis- [PtCl2I2(en)] was relatively unstable in the presence of serum: however, [PtI2(en)] did not appear to be a product of the reaction; (ii) the LMCT band extends only weakly into the region of the electromagnetic spectrum (i.e. lambda > 600 nm) where maximal tissue penetration would be expected. In conclusion, these investigations demonstrate that iodo-Pt(IV) diamines can be photolyzed to cytotoxic species by visible light, but the aforementioned limitations must be overcome before this new class of Pt(IV) complexes can be used as antitumor agents.