Photohydration

In contrast, the photochemistry of uracil, thymine and related bases has a large and detailed literature because most of the adverse effects produced by UV irradiation of tissues seem to result from dimer formation involving adjacent thymine residues in DNA. Three types of reaction are recognizable (i) photohydration of uracil but not thymine (see Section 2.13.2.1.2), (ii) the oxidation of both bases during irradiation and (iii) photodimer formation. 

Little study has been undertaken on the photoreactions of hetero-aromatic cations however, the photohydration of the methylpyridinium ion (45) to yield 6-methylazabicyclo[3,l,0]hex-3-en-2-ea o-ol (46) has been reported (Kaplan et al., 1972). 

Photohydration was observed for biphenylalkenes 113 and 114 via biphenyl-quinone methides 115 and 116, respectively (Eqs. 1.31 and I32).31meta-Biphenylquinone methide 116 was detected on LFP of 114 in TFE and showed a strong and sharp absorption band at 425 nm, consistent with spectra of previously... 

Brousmiche, D. W. Xu, M. Lukeman, M. Wan, P. Photohydration and photosolvolysis of biphenyl alkenes and alcohols via biphenyl quinone methide-type intermediates and diarylmethyl carbocations. J. Am. Chem. Soc. 2003, 125, 12961-12970. 

This reaction has also been shown to occur in cytidine, cytidylic acid, uracil, uridine, and uridylic acid (found in RNA) but reportedly not in thymine, thymidine, or thymidylic acid/55 The photohydration has been found to be partially reversible, dehydration being nearly complete at extremes of temperature and pH. 

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... 

The antidepressant protriptyline (116) causes skin photosensitization in man. Jones and Sharpies irradiated an aqueous solution of the hydrochloride with a medium-pressure mercury lamp for 16 h and separated the products by preparative TLC. First formed was the epoxide (117) which photohydrated to the diol (118). Also isolated was the enol (119) [84], Earlier, Gasparro and Kochevar had shown that only the hydrochloride was photodegraded under nitrogen in water or ethanol. Three products were isolated and all lysed erythrocytes, but the structure of only one was suggested. This was a cyclobutyl dimer as shown by its mass spectrum and its photolysis back to protriptyline by light of 254 nm. Presumably, a [2 + 2] cycloaddition of the olefine bonds had occurred [85]. 

Only the most general remarks will be made here about the photohydration reaction because, as in the case of dimerization phenomena, most experimental observations have been made on only single compounds and cannot be safely generalized to other pyrimidines. These will therefore be discussed under the headings of individual compounds and any general aspects mentioned at that time. Existing information about the hydration of pyrimidines is summarized in Table I. 

Both the dimer and the photohydrate from photolysis of uracil have been isolated not only as spots on a chromatogram7 but also as crystalline or amorphous solids—the dimer by Smietanowska and Shugar45 and Swenson and Setlow48 and the hydrate by Gattner and Fahr.45 Many physical properties have not been recorded for these materials. The melting points of the principal dimer is 380°.34 The infrared spectrum is not reported. The elementary composition of the hydrate has been reported.45 ... 

The dimer has also been isolated from photolysis of dried uracil deposits on filter paper,33 and its elementary composition and molecular weight determined. It has an ultraviolet spectrum similar to that of thymine dimer (15). Uracil can be recovered by photolysis of the dimer in solution at 240 nm, but only to the extent of 75%. The photoreversal of dimer in solution gives, in part, the photohydrate.33 The thermal reversibility of the photolyzed aqueous solution ranges from 17 to 44% recovery of absorbance. 

The photohydration of uridylic acid53 is one of the earliest known photolytic reactions of a pyrimidine derivative and has been the subject... 

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

Little such information is at hand to support proposed mechanisms for the photohydration and photodimerization of the pyrimidine bases and their derivatives discussed in this chapter, and much of what is known is confusing or self-contradictory. 

The observed rates of photohydration for uridylic acid derivatives show constant quantum yields by this measure only at concentrations of 10 M , at higher concentrations7 (Fig. 38) more than one molecule of the uridylic acid is involved in the formation of the product. Even the... 

It has been mentioned that the rate constant for photohydration of uracil shows a sigmoid variation with increasing pH over the pH range of 1.5-8.64 The rate is independent of (UH ), is independent of neutral salt concentration (showing that one species in the reaction complex is neutral), and is, as shown, first order in water concentration. The point of inflection of the rate versus pH curve is about 4, compared... 

According to this mechanism, the x>K of a singlet excited uracil is about 4, and thus excitation of uracil greatly increases its proton affinity and reduces its hydrogen bond-forming capacity. Similar variations of photohydration rate were observed for 1-ethyluracil, and 1-cyclohexyl uracil but the concommittant reaction of neutral excited molecules with water was faster, and was the predominant reaction for uridine photohydration up to pH 10.64 The photohydration rates of the two uridine phosphates was fastest at low pH values, and showed two inflection points, one at pH 1.5 and one at pH 6.161 It is clear from these data that the different ionic species of uracil, and its derivatives have greatly different rates of photohydration, and that these reactions exhibit the characteristics of an electrophilic attack of the excited species on neutral water molecules. 

There is as yet insufficient evidence for proper evaluation of electron transfer reaction as the possible key process in the photohydration reactions (and perhaps in some of the dimerization processes). It has also been suggested that there is a distinct charge separation in the (overall) neutral excited pyrimidine molecule, and that the charge is sufficiently localized that reaction of the excited molecule with OH or H+ (or both successively) can become a competitive reaction pathway.116 Such a dipolar reactant species has also been specifically proposed by Wacker et al.60 (Chart 8). This is an electrophilic attack on water similar to that proposed above for uracil photohydration. 

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. 

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