α-Tocopherol phosphate as a photosensitizer in the reaction of nucleosides with UV light: formation of 5,6-dihydrothymidine

INTRODUCTION: α-Tocopherol phosphate, a natural water-soluble α-tocopherol analog, exists in biological tissues and fluids. Synthesized α-tocopherol phosphate is used as an ingredient of cosmetics. FINDINGS: When a neutral mixed solution of 2′-deoxycytidine, 2′-deoxyguanosine, thymidine, and 2′-deoxyadenosine was irradiated with UV light at wavelengths longer than 300 nm in the presence of α-tocopherol phosphate, thymidine was markedly consumed in an α-tocopherol phosphate dose-dependent manner, whereas other nucleosides only slightly decreased. Two major product peaks were detected in an HPLC chromatogram. The products were identified as diastereomers of 5,6-dihydrothymidine. The addition of radical scavengers had almost no effects on the generation of 5,6-dihydrothymidine, whereas the reactions of nucleosides other than thymidine were suppressed. Trolox, another water-soluble α-tocopherol analog, did not generate 5,6-dihydrothymidine, although all nucleosides were slightly consumed. When UV irradiation of thymidine with α-tocopherol phosphate was conducted in D(2)O, two deuterium atoms were added to 5 and 6 positions of thymidine with both syn and anti configurations. The ratio of syn and anti configurations alternated depending on pD of the solution. CONCLUSIONS: The results indicate that α-tocopherol phosphate is a photosensitizer of nucleosides, especially thymidine, and that it introduces two hydrogen atoms to thymidine from H(2)O, generating 5,6-dihydrothymidine.