γ Irradiation of 2'-deoxyadenosine in oxygen-free aqueous solutions: Identification and conformational features of formamidopyrimidine nucleoside derivatives

Article abstract of DOI:10.1021/tx00049a005

The two major radiation-induced decomposition products of 2'- deoxyadenosine in oxygen-free aqueous solution have been isolated by reverse- phase HPLC. The ¹H and ¹³C NMR features of the two modified nucleosides obtained in DMSO-d₆ 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 α and β anomers. One-bond and long- range ¹H-¹³C 2D NMR experiments have allowed the complete assignment of the carbon atoms. Confirmation of the base structure was obtained by ¹H- ¹⁵N scalar-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 γ- irradiation as inferred from ¹H NMR analysis. The conformational study of the sugar moiety of the two pyranose anomers was inferred from detailed 600.13 MHz ¹H NMR analysis in D₂O. The α anomer exhibits a predominant ¹C₄ conformation whereas the β anomer adopts preferentially a ⁴C₁ 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 ΔG = 75.5 kJ · mol^-1 (T(c) = 370 K).