Photoinduced transformation of iron chelator deferiprone: Possible implications in drug metabolism and toxicity

•Deferiprone and its Fe(III) complexes undergo fast decomposition under UV light.•Iron complexes of deferiprone are stable under visible light.•Deferiprone exhibits both electron accepting and electron donating abilities.•Free radical intermediates of deferiprone have been detected under direct and photosensitized UV irradiation.

Deferiprone (L1) is an effective iron chelating drug which is widely used for the treatment of iron overload diseases. Although L1 itself does not absorb visible light, the absorption spectra of its Fe(III) complexes exhibit intensive absorption bands between 300 and 800 nm. It was found that L1–Fe(III) complex is stable under irradiation with visible light but undergoes fast decomposition under UV irradiation (with quantum yield more than 0.7). Decomposition of L1 has been observed in the presence of Fe(II) in a dark process. Free, non iron bound L1 exhibits both electron accepting and electron donating abilities. Free radicals of L1 were detected by the chemically induced dynamic nuclear polarization (CIDNP) method during irradiation of its aqueous solution in the presence of quinones, amino acids and NADH. It indicates the ability of deferiprone to produce free radicals not only by direct UV irradiation, but also in photosensitized electron transfer reactions with various biomolecules. Phototransformation of L1 was elucidated by using CIDNP, UV–vis, NMR and mass-spectroscopy techniques. The structures of the products of L1 photolysis include 1,2-dihydro-2,3,4-trihydroxy-1,2-dimethylpyridine. It appears that the metabolism of drugs with iron binding properties can be affected by sunlight, as shown by the iron complexes of L1 and such changes may cause phototoxic and pharmacological effects in patients undergoing treatment.

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