Radiation-induced and photosensitized splitting of C5-C5 '-linked dihydrothymine dimers. 2. Conformational effects on the reductive splitting mechanism

Radiation-induced and photosensitized reductive splitting of stereoisomeric C5-C5'-linked dihydrothymine dimers (la,b [meso], meso compound of (5R,5'S )- and (5S,5'R)-bi-5,6-dihydrothymines; 1a,b [rac], racemic compound of (5R ,5'R)- and (5S,5'S)-bi-5, 6-dihydrothymines) in aqueous solution were studi ed to compare with the one-electron oxidative splitting mechanism and the p hotorepair reaction of cyclobutane pyrimidine photodimers. Reacting with ra diation-chemically and photochemically generated hydrated electrons or with photoexcited reduced form of flavin adenine dinucleotide (*FADH(-)), the C 5-C5'-linked dihydrothymine dimers la,b produced the corresponding 5,6-dihy drothymine derivatives (3a,b) along with the thymine monomers (2a,b) in min or yields. Both the product and laser flash photolysis studies indicated th at one-electron adducts of the C5-C5'-linked dimers la,b undergo C5-C5'-bon d cleavage to generate the 5,6-dihydrothymin-5-yl radicals (5a,b) and the 5 ,6-dihydrothymine CS-anions (6a,b) resulting in the formation of 3a,b by fa cile protonation at C5. In the reduction by *FADH-, splitting of the 5,6-di hydro-1-methylthymine dimer 1a[meso] into the monomer 2a was more efficient than that of the racemic isomer 1a[rac]. Conformational analysis by NMR of la[meso] and la[rac] in solution suggested that la[meso] may favor a "clos ed-shell" conformation and undergo one-electron reduction to Form 5a and 6a , whereas la[rac] may be in a "opened-shell" conformation and undergo succe ssive two-electron reduction by "FADH(-) to produce 2 equiv of 6a as a prec ursor of 3a.