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

Abstract

Complexes trans,trans,trans-[Pt(N₃)₂(OH)(OCOR)(py)₂] where py = pyridine and where OCOR = succinate (1); 4-oxo-4-propoxybutanoate (2) and N-methylisatoate (3) have been synthesized by derivation of trans,trans,trans-[Pt(OH)₂(N₃)₂(py)₂] (4) and characterised by NMR and EPR spectroscopy, ESI-MS and X-ray crystallography. Irradiation of 1–3 with green (517 nm) light initiated photoreduction to Pt(II) and release of the axial ligands at a 3-fold faster rate than for 4. TD-DFT calculations showed dissociative transitions at longer wavelengths for 1 compared to 4. Complexes 1 and 2 showed greater photocytotoxicity than 4 when irradiated with 420 nm light (A2780 cell line IC₅₀ values: 2.7 and 3.7 μM) and complex 2 was particularly active towards the cisplatin-resistant cell line A2780cis (IC₅₀ 3.7 μM). Unlike 4, complexes 1–3 were phototoxic under green light irradiation (517 nm), with minimal toxicity in the dark. A pK_a(H₂O) of 5.13 for the free carboxylate group was determined for 1, corresponding to an overall negative charge during biological experiments, which crucially, did not appear to impede cellular accumulation and photocytotoxicity.