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

Abstract

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 D2O, 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 H2O, generating 5,6-dihydrothymidine.

Effects of additives on reaction of nucleosides with UV light in presence of uric acid and salicylic acid

“…(14) Recently, we reported that α-tocopherol phosphate induces the UV reaction of nucleosides, especially dT, generating 5,6dihydrothymidine as the major product. (15) Trolox slightly decreased dC, dG, and dT. Trolox is another water-soluble αtocopherol analog, substituting a hydrocarbon chain for a carboxy group.…”

“…(16) Reportedly, Trolox induces the reaction of nucleosides by UV irradiation, although 5,6-dihydrothymidine is not generated. (15) Tryptophan reduced the dT concentration. It has been reported that tryptophan reacts with thymine to generate photoadducts by UV irradiation.…”

“…α-Tocopherol phosphate is a naturally occurring water-soluble α-tocopherol analog detected in biological tissues and fluids.‍ ( 13 ) α-Tocopherol phosphate is used as an ingredient of cosmetics due to its more favorable hydrophilicity and stability than α-tocopherol.‍ ( 14 ) Recently, we reported that α-tocopherol phosphate induces the UV reaction of nucleosides, especially dT, generating 5,6-dihydrothymidine as the major product.‍ ( 15 ) Trolox slightly decreased dC, dG, and dT. Trolox is another water-soluble α-tocopherol analog, substituting a hydrocarbon chain for a carboxy group.‍ ( 16 ) Reportedly, Trolox induces the reaction of nucleosides by UV irradiation, although 5,6-dihydrothymidine is not generated.‍ ( 15 ) Tryptophan reduced the dT concentration. It has been reported that tryptophan reacts with thymine to generate photoadducts by UV irradiation.‍ ( 17 ) l -DOPA, dopamine, noradrenaline, and adrenaline mainly induced the consumption of dT.…”

“…(53) Compounds showing no or little effects were α-tocopherol phosphate, glycine, allantoin, urea, NaF, NaCl, NaNO 3 , and NaHCO 3 . Although αtocopherol phosphate induced decrease of dT concentration almost exclusively in the absence of uric acid probably due to hydrogenation of dT (Table 1), (15) the consumption of dT was reduced in the presence of uric acid (Table 2). Uric acid may suppress the hydrogenation of dT by α-tocopherol phosphate.…”

“…For the reaction of dC, N 4 ,5-cyclic amide-2'-deoxycytidine was formed by cycloaddition of an amide group from uric acid. When a 15 Nlabeled uric acid, having two 14 N and two 15 N atoms in the molecule, was used, N 4 ,5-cyclic amide-2'-deoxycytidine containing both 14 N and 15 N atoms was generated. For both the UV reactions of dG and dA acetylated on their ribose moiety, several products are generated.…”