1-THIOPSORALEN, A NEW PHOTOBIOLOGICALLY ACTIVE HETEROPSORALEN - PHOTOPHYSICAL, PHOTOCHEMICAL AND COMPUTER-AIDED STUDIES

1-Thiopsoralen (7H-thieno[3,2-g]benzofuran-7-one) I, a lead compound o f a series of heteropsoralens, was investigated. The electronic transi tions involved were studied. Fluorescence quantum yield is very low, w hile laser flash photolysis showed that the triplet state is practical ly the sole transient of 1. Fluorescence quantum yield (phi(F)) and tr iplet lifetime (tau(F)) as well as triplet quantum yield (phi(T)) and lifetime (tau(T)) were determined. The production of singlet oxygen wa s also evaluated by photophysical measurements. Photophysical data sug gest that DNA photobinding of 1, owing to short fluorescence lifetime value and high triplet quantum yield, occurs likely through triplet me chanism. Interactions between 1 and DNA were studied both in the groun d and the excited state. In the ground state 1 undergoes intercalation inside duplex DNA. This fact is also supported by molecular modeling studies. By UVA-light activation 1 photobinds covalently to DNA formin g mono and diadducts. The furan side l-thymine monoadduct, isolated fr om DNA photomodified by thiopsoralen, shows a cis-syn stereochemistry, in agreement with quantum mechanics studies. Compound 1 photobinds al so with linolenic acid, component of lecithins, giving a C-4-cycloaddi tion, and supporting that this compound also induces photolesions at t he level of cell membrane, like psoralen. Compound 1 exhibits strong s kin-phototoxicity.