Cytosine, photohydration

Two types of addition to pyrimidine bases appear to exist. The first, the formation of pyrimidine photohydrates, has been the subject of a detailed review.251 Results suggest that two reactive species may be involved in the photohydration of 1,3-dimethyluracil.252 A recent example of this type of addition is to be found in 6-azacytosine (308) which forms a photohydration product (309) analogous to that found in cytosine.253 The second type of addition proceeds via radical intermediates and is illustrated by the addition of propan-2-ol to the trimethylcytosine 310 to give the alcohol 311 and the dihydro derivative 312.254 The same adduct is formed by a di-tert-butyl peroxide-initiated free radical reaction. Numerous other photoreactions involving the formation by hydrogen abstraction of hydroxyalkyl radicals and their subsequent addition to heterocycles have been reported. Systems studied include 3-aminopyrido[4,3-c]us-triazine,255 02,2 -anhydrouri-dine,256 and sym-triazolo[4,3-fe]pyridazine.257 The photoaddition of alcohols to purines is also a well-documented transformation. The stereospecific addition of methanol to the purine 313, for example, is an important step in the synthesis of coformycin.258 These reactions are frequently more... 

Setlow and Carrier57 report that 5-hydroxymethyl cytosine does not form a photohydrate. 

Becker et al.174 find that the photoproduct of cytidine-3 -phosphate is the photohydrate. The quantum yield is dependent on the pH, and is higher for the neutral form than for the acidic form. Albert176 has published a review article on nonphotolytic hydration of the C=N bond in many heteroaromatic substances, a reaction similar in many respects to photohydration of the pyrimidines. Shapiro and Klein175 report that cytidine and cytosine are deaminated at 95°C by a variety of aqueous buffers. The reaction is pH sensitive. 

All these bases absorb around 260 nm. Thymine and cytosine are most sensitive to irradiation. Two most important types of photochemical reactions that have been observed for these pyrimidine bases are photohydration and photodimerization. In vivo systems, interactions between protons and nucleic acids can also be initiated by radiations of wavelength dlorter than 300 nm. 

The pyrimidine nucleobases have the highest quantum yields for photoreactivity, with thymine uracil > cytosine. The purine nucleobases have much lower quantum yields for photochemistry, but can be quite reactive in the presence of oxygen. As can be seen from Figure 9-3, thymine forms primarily cyclobutyl photodimers (ToT) via a [2ir + 2tt cycloaddition, with the cis-syn photodimer most prevalent in DNA. This is the lesion which is found most often in DNA and has been directly-linked to the suntan response in humans [65]. A [2Tr + 2Tr] cycloaddition reaction between the double bond in thymine and the carbonyl or the imino of an adjacent pyrimidine nucleobase can eventually yield the pyrimidine pyrimidinone [6 1]-photoproduct via spontaneous rearrangement of the initially formed oxetane or azetidine. This photoproduct has a much lower quantum yield than the photodimer in both dinucleoside monophosphates and in DNA. Finally, thymine can also form the photohydrate via photocatalytic addition of water across the C5 = C6 bond. 

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