Platinum(iv)-azido monocarboxylato complexes are photocytotoxic under irradiation with visible light

Abstract

Complexestrans,trans,trans-[Pt(N3)2(OH)(OCOR)(py)2] where py = pyridine and where OCOR = succinate (1); 4-oxo-4-propoxybutanoate (2) andN-methylisatoate (3) have been synthesized by derivation oftrans,trans,trans-[Pt(OH)2(N3)2(py)2] (4) and characterised by NMR and EPR spectroscopy, ESI-MS and X-ray crystallography. Irradiation of1-3with green (517 nm) light initiated photoreduction to Pt(ii) and release of the axial ligands at a 3-fold faster rate than for4. TD-DFT calculations showed dissociative transitions at longer wavelengths for1compared to4. Complexes1and2showed greater photocytotoxicity than4when irradiated with 420 nm light (A2780 cell line IC50values: 2.7 and 3.7 μM) and complex2was particularly active towards the cisplatin-resistant cell line A2780cis (IC503.7 μM). Unlike4, complexes1-3were phototoxic under green light irradiation (517 nm), with minimal toxicity in the dark. A pKa(H2O) of 5.13 for the free carboxylate group was determined for1, corresponding to an overall negative charge during biological experiments, which crucially, did not appear to impede cellular accumulation and photocytotoxicity.