GAMMA-IRRADIATION OF 2'-DEOXYADENOSINE IN OXYGEN-FREE AQUEOUS-SOLUTIONS - IDENTIFICATION AND CONFORMATIONAL FEATURES OF FORMAMIDOPYRIMIDINE NUCLEOSIDE DERIVATIVES

The two major radiation-induced decomposition products of 2'-deoxyadenosine in oxygen-free aqueous solution have been isolated by reverse-phase HPLC. The H-1 and C-13 NMR features of the two modified nucleosides obtained in DMSO-d(6) are indicative of a similar formamidopyrimidine structure for the base residue (the ring-opened form of a C-8 hydroxylated purine). Interestingly, the sugar moiety exhibits a pyranose configuration, the two nucleosides being a pair of alpha and beta anomers. One-bond and long-range H-1-C-13 2D NMR experiments have allowed the complete assignment of the carbon atoms. Confirmation of the base structure was obtained by H-1-N-15 sealar-correlated 2D NMR experiments. Attempts were made to characterize the expected furanose form of the initially generated formamidopyrimidine derivative. In this respect, isomerization reaction of the sugar moiety of the latter compound takes place rapidly after gamma-irradiation as inferred from H-1 NMR analysis. The conformational study of the sugar moiety of the two pyranose anomers was inferred from detailed 600.13 MHz H-1 NMR analysis in D2O. The alpha anomer exhibits a predominant C-1(4) conformation whereas the beta anomer adopts preferentially a C-4(1) conformation. In addition, the dynamic study of the restricted rotation of the formamido bond has revealed a 1/5 ratio in favor of the s-cis rotamer for both nucleosides. The energy barrier at coalescence was determined to be Delta G(#) = 75.5 kJ . mol(-1) (T-c = 370 K).