Isolation and characterization of psoralen photoadducts to DNA and related model compounds

The main products of the photoreaction of 3-carbethoxypsoralen and 8-methoxypsoralen with 2'-deoxyribonucleosides have been isolated and characterized by various spectroscopic measurements involving proton nuclear magnetic resonance and mass spectrometry (fast atom bombardment and 252Cf plasma desorption techniques). Near ultraviolet photolysis of frozen aqueous solutions of thymidine containing 3-carbethoxypsoralen gives rise to two furan-side photocycloadducts having cis-syn stereochemistry. The corresponding thymine mean value of 3-carbethoxy-psoralen monoadduct has been shown to be the major photoproduct in DNA. The main cis-syn diastereoisomeric [2+2] photocycloadducts which arise from the photoreaction of 8-methoxypsoralen and thymidine in frozen aqueous solutions were shown to involve either the 4',5' furan ring or the 3,4 pyrone moiety and the 5,6-pyrimidine bond. Photobinding of 8-methoxypsoralen to 2'-deoxyadenosine also occurs, with covalent bond formation between carbon 3 or 4 of the pyrone ring and the sugar moiety of the nucleoside.