New Photo-Releasable Iron Complexes

This proposal concerns the development of iron complexes that collapse upon exposure to specific wavelengths of light to release iron at the illuminated surface. These novel chemical tools will be useful for studying biological processes believed to arise from the release of Fe (III) from their normal sequestered state. Such photo-collapsible complexes will offer precise control over the space, time and concentration Fe(III) released in a biological system under study by the remote-control of light. These chemical tools will specifically be used to model processes leading to blood coagulation or thrombosis. Fe (III) is widely used to induce thrombosis in models, but is currently administered in a very poorly controlled way by placing filter paper soaked in the iron solution onto the site under study. This proposal seeks to develop a more precise method of administering iron that may provide more detailed understanding of the mechanisms leading to thrombus formation. Blood coagulation is an important feature of the healthy organism, protecting against injury to the vasculature, but the formation of thrombosis and the resulting occlusion of blood vessels is a feature of aging and many disease states, often with fatal consequences. The mechanisms leading to this event are complex and are an important area of study since this understanding may be directly relevant to health and welfare. Fe (III) is often implicated in other tissue damage processes, such as arthritis, because it can catalyse the formation of radical species associated with oxidative stress. The precise control over iron levels offered the proposed chemical tool may therefore be attractive to a wide range of researchers.

This proposal concerns the development of photolabile-iron complexes that release Fe(III) when illuminated with a specific wavelength of light. Such chemical tools will offer precise control over iron release in biological systems which may be useful for the study of biological processes believed to arise from non-transferrin bound, such as oxidative damage. Poole has identified a need to control the concentration, space and time of the iron release in order to improve modelling of thrombus formation. Currently iron (III) chloride solution of various concentrations is administered to model vasculature via a soaked filter paper at a variety of concentrations. There is a clear need for new chemical tools with which to construct this model with improved resolution and clarity. This new collaboration will seek to develop complexes of iron (III) which, like the natural siderophore desferroxamine, are oxidatively silent when the metal is tightly bound to three hydroxamate motifs. The proposed novel chemical tools will be constructed to include a covalent bond that can be cleaved upon illumination with a specific wavelength of light, leading to destruction of the three-fold binding and thus release of Fe (III). The proposed research program outlines the design and synthesis of such caged-iron complexes, initial characterisation in vitro and evaluation in a relevant model for thrombosis.