Platinum(Iv) Dihydroxido Diazido N-(Heterocyclic)Imine Complexes Are Potently Photocytotoxic When Irradiated With Visible Light

A series of trans-di-(N-heterocyclic)imine dihydroxido diazido Pt-IV complexes of the form trans,trans,trans-[Pt(N-3)(2)(OH)(2)(L-1)(L-2)] where L = pyridine, 2-picoline, 3-picoline, 4-picoline, thiazole and 1-methylimidazole have been synthesised and characterised, and their photochemical and photobiological activity evaluated. Notably, complexes 19 (L-1 = py, L-2 = 3-pic) and 26 (L-1 = L-2 = 4-pic) were potently phototoxic following irradiation with visible light (420 nm), with IC50 values of 4.0 mu M and 2.1 mu M respectively (A2780 cancer cell line), demonstrating greater potency than the previously reported complex 1 (L-1 = L-2 = py; 6.7 mu M); whilst also being minimally toxic in the absence of irradiation. Complexes with mixed N-(heterocyclic)imine ligands 19 and 20 (L-1 = py, L-2 = 4-pic) were particularly photocytotoxic towards cisplatin resistant (A2780cis) cell lines. Complex 18 (L-1 = py, L-2 = 2-pic) was comparatively less photocytotoxic (IC50 value 14.5 mu M) than the other complexes, despite demonstrating the greatest absorbance at the irradiation wavelength and the fastest half-life for loss of the N-3 -> Pt LMCT transition upon irradiation (lambda(irr) = 463 nm) in aqueous solution. Complex 29 (X-1 = X-2 = thiazole) although potently phototoxic (2.4 mu M), was also toxic towards cells in the absence of irradiation.