Nucleic acids pyrimidine dimers

There is always interest in the photochemistry of the pyrimidine nucleic acid bases and related simple pyrimidinones, due to its importance in genetic mutation. In addition to damaging DNA, photo-induced reactions may also repair the damage, as in the reduction, by FADH, of the thymine glycol 64 back to thymine <06JACS10934>. Another report related to repair of DNA involved a model study, by means of the linked dimer 65, of the involvement of tryptophan in the electron-transfer leading to reversion of thymine oxetane adducts <06OBC291>. 

An unusual photochemical reaction of 2-pyridones, 2-aminopyridinium salts and pyran-2-ones is photodimerization to give the so-called butterfly dimers. These transformations are outlined in equations (13) and (14). Photodimerization by [2+2] cyclization is also a common and important reaction with these compounds. It has been the subject of particular study in pyrimidines, especially thymine, as irradiation of nucleic acids at ca. 260 nm effects photodimerization (e.g. equation 15) this in turn changes the regular hydrogen bonding pattern between bases on two chains and hence part of the double helix structure is disrupted. The dimerization is reversed if the DNA binds to an enzyme and this enzyme-DNA complex is irradiated at 300-500 nm. Many other examples of [2+2] photodimerization are known and it has recently been shown that 1,4-dithiin behaves similarly (equation 16) (82TL2651). 

An interesting and significant outcome is the finding that the pyrimidine bases of nucleic acids (uracil, thymine, and cytosine) are photoreactive and undergo [2 + 2] cycloadditions on irradiation with ultraviolet light. Thymine, for example, gives a dimer of structure 7 ... 

In summary, then, there is little quantitative information derived from ab initio calculations that pertain to the energetic contribution of CH- - -X bonds to nucleic acid structure. The best data available at present derives from the pyrimidine dimer [126] wherein a value on the order of 1.6 kcal/mol was suggested. However, this quantity pertains to angularly distorted CH- - -N bonds in vacuo, with no account taken of the surroundings. 

There is only one value in the literature that pertain to nucleic acids. The bent CH- - -N bonds in the pyrimidine dimer were estimated [126] to contribute roughly 1.6 kcal/mol each a larger value would be expected in the absence of this distortion. More information is available that relate to proteins. Although not present per se in polypeptides, the amidic CH appears to form H-bonds on the order of 1.9. 0 kcal/mol [137, 138]. 

Nucleic Acids. Efforts in this area have focused almost exclusively on the photosensitized splitting of pyrimidine dimers [140] (see Chart XXI, which shows the dimer D and the monomer M of dimethyluracil). Motivation of these studies has been to gain insight into the mechanism of photorepair of DNA by DNA photolyase. The operating principle of this enzyme is photoinduced electron transfer. However, the key question whether excited DNA photolyase donates or accepts the electron is still unresolved. 

Formation of such dimers in the nucleic acids of an organism or virus has been shown to be a probable cause for the inactivation of the organism (17) or virus. The intermediate responsible for formation of such dimers, at least in simple pyrimidines, is probably the triplet excited state of the pyrimidine, on the basis of the effects of known triplet sensitizers and quenchers (8, 10, 18). 

As an illustration of bimolecular reactions, the formation of pyrimidine nucleobase adducts in the excited state will be presented here (see Roca-Sanjudn et al. 2008b Serrano-P6rez et al. 2008d). Among the possible photoreactions that pyrimidine (Pyr) bases of nucleic acids may undergo upon ultraviolet (UV) irradiation, cyclobutane thymine dimers (ToT or CBT) formed by intrastrand adjacent thymine bases (see O Fig. 14-26) constitute one of the major photoinduced lesions, particularly in cellular DNA, in spite of the direct reparation by a light-activated mechanism (DNA photolyase) in which abnormal bonds are cleaved. Unrepaired or... 

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