Chemical radiation studies of 8-bromo-2'-deoxyinosine and 8-bromoinosine in aqueous solutions.

The reactions of hydrated electrons (eaq−) with 8-bromo-2′-deoxyinosine (8) and 8-bromoinosine (12) have been investigated by radiolytic methods coupled with product studies and have been addressed computationally by means of BB1K-HMDFT calculations. Pulse radiolysis revealed that one-electron reductive cleavage of the CBr bond gives the C8 radical 9 or 13 followed by a fast radical translocation to the sugar moiety. Selective generation of a C5′ radical occurs in the 2′-deoxyribo derivative, whereas in the ribo analogue the reaction is partitioned between the C5′ and C2′ positions with similar rates. Both C5′ radicals undergo cyclizations, 10→11 and 14→15, with rate constants of 1.4×105 and of 1.3×104 s−1, respectively. The redox properties of radicals 10 and 11 have also been investigated. A synthetically useful photoreaction has also been developed as a one-pot procedure that allows the conversion of 8 to 5′,8-cyclo-2′-deoxyinosine in a high yield and a diastereoisomeric ratio (5′R)/(5′S) of 4:1. The present results are compared with data previously obtained for 8-bromoadenine and 8-bromoguanine nucleosides. Theory suggests that the behavior of 8-bromopurine derivatives with respect to solvated electrons can be attributed to differences in the energy gap between the π*- and σ*-radical anions.