Singlet oxygen generation by 8-methoxypsoralen in deuterium oxide:: Relaxation rate constants and dependence of the generation efficacy on the oxygen partial pressure

The photoactivation of 8-methoxypsoralen (8-MOP) by ultraviolet light is widely used for the treatment of several skin diseases. The major mechanism is the intercalation of 8-MOP into nuclear DNA in the dark and subsequently the formation of monoadducts and potential cross links under UVA irradiation. In addition, the irradiation of 8-MOP leads to the generation of singlet oxygen by means of photodynamic action which has been shown to induce a critical oxidative damage of the DNA in vitro. To assess the role of singlet oxygen generated by photoactivated 8-MOP, its relaxation in solutions of deuterium oxide was studied in detail. Relaxation rates and rate constants of the involved 8-MOP triplet T-1 state and oxygen (1)Delta(g) state were determined by analyzing the rise and decay rates of the luminescence of singlet oxygen at 1.27 mum. The efficacy of singlet oxygen generation is described by the singlet oxygen quantum yield Phi(Delta), which depends on the efficacy of 8-MOP T, state deactivation by oxygen, P-T([O-2)]. P-T([O-2]) has been determined for different oxygen concentrations and decreased from 2% under aerated conditions (e.g., in vitro conditions, 130 Torr) to 0.5% for the in vivo situation inside the skin (similar to20 Torr). The efficacy of singlet oxygen generation and maybe therefore the role of singlet oxygen in the oxidative damage depends critically on the respective oxygen partial pressure. This must be considered when transferring results and conclusions from experiments in vitro or in solution to the situation in vivo.