The nucleobase 5-methylcytosine (I) is a minor component of eukaryotic DNA thought to be important in regulation of gene expression. The photochemical reactions of this nucleobase and its 2'-deoxyribonucleoside, 5-methyl-2'-deoxycytidine (II), in water have been studied. These reactions lead, respectively, to 3-amino-2-methylacrylamidine (Ib) and 3-(2-erythro-D-pentopyranos-1-yl)amino-2-methylacrylamidine (IIb) as the main photoproducts. The structure of the photoproducts was established by spectroscopic methods (1H and 13C NMR, UV spectroscopy, electron impact and liquid secondary ion mass spectrometry); in the case of Ib, confirmatory evidence was obtained by chemical methods (photolysis of 5-methyl[2-13C]cytosine, hydrolysis of N-carbomethoxy-3-amino-2-methylacrylamidine and reaction of Ib with 1,1'-carbonyldiimidazole to give I). The quantum yield for formation of Ib was determined to be 1.8 x 10(-3) at pH 7.5 while the quantum yield for formation of IIb has a lower value of 0.2 x 10(-3) at pH 7.5. These quantum yields depend strongly on pH and reach maximum values of 2.0 x 10(-3) at pH 7.0 (Ib) and 0.6 x 10(-3) at pH 5.0 (IIb). The mechanism of formation of Ib (or IIb) is proposed to involve nucleophilic attack of water on the C-2 position of photoexcited I (or II), followed by ring opening and decarboxylation of an intermediate carbamic acid.
The photochemistry of the dinucleoside monophosphate thymidylyl-(3'-5')-5-methyl-2'-deoxycytidine (Tpm5dC) has been studied in aqueous solution using both 254 nm and UV-B radiation. A variety of dinucleotide photoproducts containing 5-methylcytosine (m5C) have been isolated and characterized. These include two cyclobutane dimers (CBD) (the cis-syn [c,s]and trans-syn forms), a (6-4) adduct and its related Dewar isomer, and two isomers of a product in which the m5C moiety was converted into an acrylamidine. Small amounts of thymidylyl-(3'-5')-thymidine (TpT) were also formed, presumably as a secondary photoreaction product. In addition, a photoproduct was characterized in which the m5C moiety was lost, thus generating 3'-thymidylic acid esterified with 2'-deoxyribose at the 5-hydroxyl on the sugar moiety. The c,s CBD of Tpm5dC readily undergoes deamination to form the corresponding CBD of TpT. The kinetics of this deamination process has been studied; the corresponding enthalpy and entropy of activation for the reaction have been evaluated at pH 7.4 as being, respectively, 73.4 kJ/mol and -103.5 J/K mol. Deamination was not observed for the other characterized photoproducts of Tpm5dC.
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