Cycloaddition reactions thymine dimers

Exposure of DNA to ultraviolet light induces a [2 + 2] cycloaddition reaction between the double bonds of adjacent thymines. The resulting thymine dimer, containing a cyclobutane ring, prevents DNA reproduction and can lead to the development of skin cancer. 

Exposure to ultraviolet light causes skin cancer. This is one of the reasons why many scientists are concerned about the thinning ozone layer. The ozone layer absorbs ultraviolet radiation high in the atmosphere, protecting organisms on Earth s surface (Section 9.9). One cause of skin cancer is the formation of thymine dimers. At any point in DNA where there are two adjacent thymine residues (Section 27.1), a [2 -f 2] cycloaddition reaction can occur, resulting in the formation of a thymine dimer. Because [2 -I- 2] cycloaddition reactions take place only under photochemical conditions, the reaction takes place only in the presence of ultraviolet light. 

Fortunately, there are enzymes that repair damaged DNA. When a repair enzyme recognizes a thymine dimer, it reverses the [2 + 2] cycloaddition reaction to regenerate the original T-T sequence. Repair enzymes, however, are not perfect, and some damage always remains uncorrected. People who do not have the repair enzyme (called DNA photolyase) that removes thymine dimers rarely live beyond the age of 20. Fortunately, this genetic defect is rare. 

Pyrimidine base, thymine 5 present in DNA, on exposure to UV light undergoes dimerization to give 6 and 7 by [2+2]-cycloaddition reaction [8]. 

This function was utilized to inhibit the photo[2 -i- 2]cycloaddition reaction of TpT that produces a cis-syn cyclobutane-type thymine dimer (T[c,i]T) that is a typical... 

Photochemical [2 + 2] cycloaddition reactions do occur. The process is usefiJ as a method to produce cyclobutanes. An important biochemical reaction that cross-links bases on the same strand of DNA by formation of thymine dimers also occurs by a photochemical [2 + 2] cycloaddition. We will consider this reaction at the end of this section. From stereochemical studies, we conclude that the reaction occurs suprafaciaUy. 

Formation of Thymine Dimers A [2 + 2] Photochemical Cycloaddition Reaction... 

Single crystals of thymine derivatives with long alkyl-chain substituents are photochemically reactive and undergo (2 + 2) photodimerisation to yield solely the trans-anti dimer. In solution, however, the photoreaction affords the usual four cycloadducts. Irradiation of the bis-thymine PNA dimer (142) brings about intramolecular cycloaddition to give the adduct (143) in 50% yield. The reaction is carried out in water using irradiation at 254 nm. The results from a study of the photochemical cycloaddition within the thymidilyl system (144) has been reported. Photoadducts have been obtained from the... 

Acetone-sensitized irradiation of uracil (107) with ethene affords the adduct (108) in 75% yield. This compound can be transformed into the cyclobutane derivative (109) in an overall yield of 52%. The intramolecular cyclization of the dinucleotide model (110) has been investigated. The reaction affords the cycloadduct (111) by irradiation using wavelengths > 300 nm. The use of an anionic template for photochemical dimerization of a thymine system has been demonstrated. The thymine forms an assembly (112) with pyrophosphate. Irradiation of this brings about syn- 2 + 2)-cycloaddition of the thymine units. ... 

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