Our technique of selective DNA radical generation under mild conditions makes it possible to detect labile reaction products of single-stranded DNA radicals and to gain further insight into their cleavage reactions. In cases where a radical pair is formed, the shielding effect protects the DNA radical from external attack so that cleavage of the single strand competes successfully with trapping by O2. This shielding effect might be of general importance if the DNA radicals are generated by reagents that bind to the DNA.

Antitumor antibiotics like bleomycin or neocarzinostatin induce damage of the DNA strand mainly by H-abstraction of the 4'and/or S'-position of a deoxyribose unit.1 2Recently we have shown that a single-stranded 4'-oligonucleotide radical like 2 can be generated by photoinduced C-Se bond cleavage of the modified oligonucleotide l.2a In the absence of added traps the 4'-deoxyribosyl radical 2 yields oligonucleotide phosphates 3 and 4 as main products. The reaction starts with a heterolytic cleavage of the secondary phosphate group at C-3'. This leads to oligonucleotide fragment 4 and radical cation 6, which reacts with H20 and generates radical 7. Now the slower C-O bond cleavage of the primary phosphate group26 at C-5' can occur, which leads to fragment 3. The presence of the intermediate radicals 2 and 7 could be proven by trapping experiments with glutathione that yielded oligonucleotides 5 and 8 as further reaction products (Scheme 1).

Two synthetic pathways towards 4′‐C‐acylthymidines are presented. These modified mononucleosides are precursors of the 2′‐deoxyribonucleotide 4′‐C‐radical. They were converted into their corresponding 3′‐O‐[(2‐cyanoethyl) N,N‐diisopropylphosphoramidites] 3a–c and incorporated in oligonucleotides by solid‐phase synthesis. The structure of some modified nucleosides was revealed by X‐ray crystal‐structure analysis.

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