Photochemistry of 6-amino-2-azido, 2-amino-6-azido and 2,6-diazido analogues of purine ribonucleosides in aqueous solutions

Abstract

The photochemistry of 6-amino-2-azidopurine, 2-amino-6-azidopurine and 2,6-diazidopurine ribonucleosides has been investigated in aqueous solutions under aerobic and anaerobic conditions. Near UV irradiation of 6-amino-2-azido-9-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)purine and 2-amino-6-azido-9-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)purine in the presence of oxygen leads to efficient formation of 6-amino-2-nitro-9-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)purine and 2-amino-6-nitro-9-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)purine. Under anaerobic conditions, both azidopurine ribonucleosides preferentially undergo photoreduction to 2,6-diamino-9-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)purine. The structures of the photoproducts formed were confirmed by UV, NMR and HR ESI-TOF MS spectral data. The photoproducts observed in this study for the aminoazidopurines are distinctly different from those observed previously for 6-azidopurine. When no amino group is present, the photochemistry of 6-azidopurine leads to the formation of a 1,3,5-triazepinone nucleoside. The energetics of the 6-nitreno moiety along both oxidation and ring expansion pathways was calculated using the nudged elastic band (NEB) method based on density functional theory (DFT) using DMol3. The role of the 2-amino group in regulating the competition between these pathways was elucidated in order to explain how the striking difference in reactivity under irradiation arises from the greater spin density on the 6-nitreno-9-methyl-9H-purin-2-amine, which essentially eliminates the barrier to oxidation observed in 6-nitreno-9-methyl-9H-purine. Finally, the importance of tetrazolyl intermediates for the photochemical activation of azide bond cleavage to release N₂ and form the 6-nitreno group was also corroborated using the DFT methods.