Photochemistry of 5,7- dimethoxycoumarin, a skin senitizing agent

Abstract

The photoreaction of 5, 7-dimethoxycoumarin (DMC) with pyrimidine bases has been studied as a model reaction in order to elucidate the molecular basis of skin-photosensitization. 1, 3-Dimethylthymine is the most reactive pyrimidine base with respect to photoaddition with DMC among the pyrimidines tested. The major photoaddition product was isolated by column chromatography and purified by recrystallization after photolysis of DMC-thymine mixture at 365nm. The best condition for the formation of DMC-thymine photoadduct was found to be irradiation to two reactants in a frozen solution with an excess of pyrimidine. The characterization of isolated photoadduct was carried out to elucidate the chemical mechanism of interactions between DNA and skinsensitizing coumaryl compounds under UV irradiation. The structure of obtained photoadduct was identified as a $C_4$-cycloaddition product of DMC and thymine. The structure of this adduct was confirmed by the characteristics in their UV, IR, NMR, mass spectra and by elemental analysis. The isolated photoadduct was very easily photodissociated into DMC and thymine when irradiated with 254nm UV light and also photosplit into initial compounds at 300nm UV light in lower efficiency. The triplet sensitizers such as tryptophan and chloranil also photosplit the photoadduct in lower efficiency than direct photosplitting when 300nm UV light was used. It is quite phobable that this sensitized photosplitting of photoadduct involves an electron transfer methanism. DMC had no self-quenching effect and fluroescence of DMC was not quenched by thymine in contrast ot tetramethlethylene. Similar results were obtained in case of 8-methoxypsoralen. The photocycloaddition reaction of DMC to thymine occurs probably via single state, since DMC shows very low efficiency in populating triplet state and the photodimerization of DMC proceeds exclusively via singlet state in direct irradiation. The lethality and mutability of excision deficient $...