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 of a series of heteropsoralens, was investigated. The electronic transitions involved were studied. Fluorescence quantum yield is very low, while laser flash photolysis showed that the triplet state is practically the sole transient of 1. Fluorescence quantum yield (phi(F)) and triplet lifetime (tau(F)) as well as triplet quantum yield (phi(T)) and lifetime (tau(T)) were determined. The production of singlet oxygen was also evaluated by photophysical measurements. Photophysical data suggest that DNA photobinding of 1, owing to short fluorescence lifetime value and high triplet quantum yield, occurs likely through triplet mechanism. Interactions between 1 and DNA were studied both in the ground 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 forming mono and diadducts. The furan side l-thymine monoadduct, isolated from DNA photomodified by thiopsoralen, shows a cis-syn stereochemistry, in agreement with quantum mechanics studies. Compound 1 photobinds also with linolenic acid, component of lecithins, giving a C-4-cycloaddition, and supporting that this compound also induces photolesions at the level of cell membrane, like psoralen. Compound 1 exhibits strong skin-phototoxicity.