MICROENVIRONMENT EFFECTS ON THE EXCITED-STATE PROPERTIES OF PSORALENS- A CLUE TO THEIR PHOTOBIOLOGICAL ACTIVITY

The singlet and triplet excited state parameters (Phi(f), tau(f), and Phi(T)) of psoralen (PSO) and derivatives 4,6,4'-trimethylangelicin (T MA) and 4,5',8-trimethylpsoralen (TMP) show an extreme sensitivity to solvation in dioxane/water mixtures. These effects are attributed to t he variation of the S-1 --> S-0 internal conversion rate constant k(ic ), which is the nonradiative deactivation path dominating their photop hysical behavior. Depending on the compound, k(ic) is very high, (simi lar to 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 wo rk shows that dioxane/water mixtures display the same solvent-induced changes in the electronic structure of psoralens during solvation as t hose induced by the biological microenvironment sensed by the drug's l ocalization. This mixture matches the photophysical parameters of psor alens observed in protic and aprotic pure solvents, in micelles, in li posomes and in human serum low-density lipoproteins (LDL). They can be used to probe the solvating ability of the interaction site in macroc yclic hosts. A particular localization site, i.e. the more (TMA and TM P) or less (PSO) lipophilic sites found when in interaction with LDL, determines the amount of the triplet reactive state of psoralens and t he molecular mechanism available for photoreaction: oxic (type I and t ype II) or anoxic (type III) pathways.