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Photoactive platinum azide anticancer complexes
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Photoactive platinum compounds have the potential to reduce some of the debilitating side-effects associated with conventional chemotherapeutics, such as cisplatin. Stable, inert platinum(IV) compounds which are reduced to active platinum(II) species only upon irradiation, could provide a site-specific treatment. The PtIV azide complexes, cis, trans, cis-[Pt(N3)2(OH)2(NH3)2] and cis, trans-[Pt(en)(N3)2, have previously been shown to be stable in the dark but reduced to PtII upon irradiation. The synthesis and characterisation of new platinum azide compounds, designed to improve important properties such as solubility and wavelength of absorbance are described here. Complexes which have azide ligands in a trans position were synthesised, the general formula is trans, trans, trans-[Pt(N3)2(OH)2(NH3)R] where R is NH3, pyridine, methylamine, ethylamine, thiazole, 2-picoline, 3-picoline, 4-picoline or cyclohexylamine. Several PtIV diazido compounds containing chelating aromatic ligands, such as 2,2’-bipyridine and 1,10-phenanthroline were also prepared. Many of the novel compounds synthesised were characterised by X-ray structure determination. The complexes with trans azides generally showed improved water solubility as well as a shift of the main absorbance band towards the visible region, compared to their cis analogues. A transcription mapping study of a fragment of pSP73KB plasmid DNA treated with cis, trans-[Pt(en)(N3)2(OH)2] and visible light, has shown that platination mainly occurs at consecutive guanine bases. The major binding sites were similar to those of cisplatin. No platination was seen in an identical sample which was not irradiated.
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