Microenvironment effects on the excited state properties of psoralens: a clue to their photobiological activity.

Abstract

The singlet and triplet excited state parameters (phi f, tau t and phi T) of psoralen (PSO) and derivatives 4,6,4'-trimethylangelicin (TMA) and 4,5',8-trimethylpsoralen (TMP) show an extreme sensitivity to solvation in dioxane/water mixtures. These effects are attributed to the variation of the S1-->S0 internal conversion rate constant kic, which is the nonradiative deactivation path dominating their photophysical behavior. Depending on the compound, kic is very high, (approximately 1 x 10(10) s-1) in nonpolar solvents and then decreases to a low value (3 x 10(8) s-1), with increasing solvent polarity. This work shows that dioxane/water mixtures display the same solvent-induced changes in the electronic structure of psoralens during solvation as those induced by the biological microenvironment sensed by the drug's localization. This mixture matches the photophysical parameters of psoralens observed in protic and aprotic pure solvents, in micelles, in liposomes and in human serum low-density lipoproteins (LDL). They can be used to probe the solvating ability of the interaction site in macrocyclic hosts. A particular localization site, i.e. the more (TMA and TMP) or less (PSO) lipophilic sites found when in interaction with LDL, determines the amount of the triplet reactive state of psoralens and the molecular mechanism available for photoreaction: oxic (type I and type II) or anoxic (type III) pathways.