Selective Generation and Reactivity of 5′‐Adenosinyl and 2′‐Adenosinyl Radicals

Abstract

The reaction of hydrated electrons (e(-)(aq) with 8-bromoadenosine 7 has been investigated by radiolytic methods coupled with product studies. Pulse radiolysis revealed that one-electron reductive cleavage of the C-Br bond gives the C8 radical 8 followed by a fast radical translocation to the sugar moiety. The reaction is partitioned between C5' and C2' positions in a 60:40 ratio leading to 5'-adenosinyl radical 9 and 2'-adenosinyl radical 11. This radical translocation from C8 to different sites of the sugar moiety has also been addressed computationally by means of DFT B3LYP calculations. In addition, ketone 21 was prepared and photolyzed providing an independent generation of C2' radical 11. Both C5' and C2' radicals undergo unimolecular reactions. Radical 9 attacks adenine with a rate constant of 1.0 x 10(4) s(-1) and gives the aromatic aminyl radical 10, whereas C2' radical 11 liberates adenine with a rate constant of 1.1 x 10(5) s(-1).

Chemical Radiation Studies of 8‐Bromo‐2′‐deoxyinosine and 8‐Bromoinosine in Aqueous Solutions

“…These values are very similar to the analogous reactions with 8-bromoadenine [2,3] and 8-bromoguanine [4,6] nucleosides. The reaction of an aqueous solution of 8 (1 mm) and tBuOH (0.25 m) at pH% 7 with e aq À in the absence of O 2 was complete within % 300 ns.…”

“…[3] Pulsing O 2 -free aqueous solutions of 12 (1 mm) containing tBuOH (0.25 m) and different concentrations of TMPD (30-120 mm) at pH% 7 led to the oxidation of TMPD. The rate constants for this oxidation and the associated formation of TMPDC + were measured at l = 565 nm (e = 1.25 10 4 m À1 cm…”

“…In the analogous reaction with 8-bromoadenosine, the intramolecular hydrogen abstraction by the initially formed C8 radical is partitioned between two channels to generate both the C5' and C2' radicals with similar rate constants. [3] On the other hand, 8-bromo-2'-deoxyguanosine (5) captures electrons with the formation of radical anion 6 that undergoes protonation at C8 to afford the one-electron oxidized 2'-deoxyguanosine 7.…”

“…The reactions of hydrated electrons (e aq À ) with 8-bromoadenine [1][2][3] and 8-bromoguanine nucleosides [4][5][6] have recently been investigated by radiolytic methods. It was found that 8-bromo-2'-deA C H T U N G T R E N N U N G oxyA C H T U N G T R E N N U N G adenosine (1) captures electrons and rapidly loses a bromide ion to give the corresponding C8 radical 2.…”

“…We suggest that the initially produced radical 13 partitioned its translocation step between two channels to afford the C5'-radical 14 and the C2'-radical 16 (Scheme 3), similar to the case of 8-bromoadenosine. [3] The rate constant for heterolytic cleavage of the glycosidic bond, which produces the radical cation 17 and hypoxanthine 18, is slightly smaller than the analogous reaction of the 2'-adenosinyl radical (k f = 1.1 10 5 s…”