Platinum(IV)-azido monocarboxylato complexes are photocytotoxic under irradiation with visible light
View/ Open
Date
2021-08-14Author
Shaili, Evyenia
Romero, Marίa J.
Salassa, Luca
Woods, Julie A.
Butler, Jennifer S.
Romero Canelón, Isolda
Clarkson, Guy
Habtemariam, Abraha
Sadler, Peter J.
Farrer, Nicola J.
Metadata
Show full item record
Dalton Transactions 50(30) : 10593-10607 (2021)
Abstract
Complexes trans,trans,trans-[Pt(N-3)(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)(N-3)(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 mu M) and complex 2 was particularly active towards the cisplatin-resistant cell line A2780cis (IC50 3.7 mu M). 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.