PHOTOREACTIVITY OF BIOLOGICALLY-ACTIVE COMPOUNDS, XIV - INFLUENCE OF OXYGEN ON LIGHT-INDUCED REACTIONS OF PRIMAQUINE

The influence of molecular oxygen and oxygen radicals on the photoreac tivity of the antimalarial drug primaquine (PQ) has been investigated, Oxygen is directly involved in photodecomposition of the drug. Flushi ng with helium gas prior to and during irradiation to suppress the oxy gen level of the medium, retards the degradation rate of PQ (followed by HPLC) and leads to the formation of only two degradation products ( identified by MS) compared to eight main-and several minor products un der normal atmospheric conditions. Flushing with oxygen gas prior to a nd during irradiation to increase the oxygen content of the medium acc elerates the degradation rate of PQ. PQ produces oxygen radicals (hydr oxyl and superoxide) during photolysis, while the photoproducts of PQ seem likely to induce singlet oxygen formation (detected by addition o f radical scavengers). Sensitization reactions involving singlet oxyge n lead to decomposition of PQ (followed by HPLC). On the basis of our results, photochemical reaction mechanisms of PQ are postulated and di scussed. At physiological conditions (aqueous, neutral pH, oxygen rich ) PQ has a large potential to decompose after light absorption. The ph otoreaction seems to be initiated at the quinoline nitrogen. The abili ty to form an intramolecular hydrogen bond seems to be essential for t he luminescence properties of the drug. Phosphorescence lifetime of PQ is about 5 mu s. Fast chemical reactions may occur from the short-liv ed triplet state of the drug, but the excited compound can diffuse onl y a limited distance prior to deexcitation. This can be important conc erning light-induced adverse effects Which may appear after medication with PQ.