Platinum(iv) dihydroxido diazido N-(heterocyclic)imine complexes are potently photocytotoxic when irradiated with visible light

Abstract

A series of trans-di-(N-heterocyclic)imine dihydroxido diazido Pt^IV complexes of the form trans,trans,trans-[Pt(N₃)₂(OH)₂(L₁)(L₂)] 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 (L₁ = py, L₂ = 3-pic) and 26 (L₁ = L₂ = 4-pic) were potently phototoxic following irradiation with visible light (420 nm), with IC₅₀ values of 4.0 μM and 2.1 μM respectively (A2780 cancer cell line), demonstrating greater potency than the previously reported complex 1 (L₁ = L₂ = py; 6.7 μM); whilst also being minimally toxic in the absence of irradiation. Complexes with mixed N-(heterocyclic)imine ligands 19 and 20 (L₁ = py, L₂ = 4-pic) were particularly photocytotoxic towards cisplatin resistant (A2780cis) cell lines. Complex 18 (L₁ = py, L₂ = 2-pic) was comparatively less photocytotoxic (IC₅₀ value 14.5 μM) than the other complexes, despite demonstrating the greatest absorbance at the irradiation wavelength and the fastest half-life for loss of the N₃ → Pt LMCT transition upon irradiation (λ_irr = 463 nm) in aqueous solution. Complex 29 (X₁ = X₂ = thiazole) although potently phototoxic (2.4 μM), was also toxic towards cells in the absence of irradiation.