title: Photolysis of an iodoplatinum(IV) diamine complex to cytotoxic species by visible light.
abstract: 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.
authors.affiliation: Institut für Pharmazie, Universität Regensburg, Germany.
authors.forename: N A
authors.initials: NA
authors.lastname: Kratochwil
authors.forename: P J
authors.initials: PJ
authors.lastname: Bednarski
authors.forename: H
authors.initials: H
authors.lastname: Mrozek
authors.forename: A
authors.initials: A
authors.lastname: Vogler
authors.forename: J K
authors.initials: JK
authors.lastname: Nagle
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism*; D004355:Drug Stability; D006801:Humans; D008027:Light; D009944:Organoplatinum Compounds / Q000378:metabolism*; D010782:Photolysis; D011355:Prodrugs / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011355:Prodrugs