The applicants propose a novel and innovative method for the generation of activated oxygen species in biological systems, which may have utility in the field of photodynamic therapy. Specifically, they plan the development of redox-inert iron(III) chelate complexes that maintain coordinative saturation at physiological pH (and so are essentially unreactive under such conditions) but which undergo photodissociation upon irradiation to generate coordinatively unsaturated complexes that participate in Fenton-type oxidation reactions. Such systems are capable of forming hydroxyl radical species and thus act via the well established Type I mechanism for photodynamic activity. The novel iron(III) chelates prepared will be evaluated for oxidative potential using three systems: a) oxidation of D-ribose (to demonstrate potential); b) membrane peroxidation (to further demonstrate potential and possible mechanisms of oxidative damage; c) cell uptake and photodynamic activity using the RIF cell line (to extend studies to cell lines and to evaluate dark and light toxicity). Completion of these studies should allow an evaluation of the potential for photo-Fenton reagents to act as photodynamic agents.
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