7-Iodo-5-aza-7-deazaguanine ribonucleoside: crystal structure, physical properties, base-pair stability and functionalization

Abstract

The positional change of nitrogen-7 of the RNA constituent guanosine to the bridgehead position-5 leads to the base-modified nucleoside 5-aza-7-deazaguanosine. Contrary to guanosine, this molecule cannot form Hoogsteen base pairs and the Watson–Crick proton donor site N3—H becomes a proton-acceptor site. This causes changes in nucleobase recognition in nucleic acids and has been used to construct stable `all-purine' DNA and DNA with silver-mediated base pairs. The present work reports the single-crystal X-ray structure of 7-iodo-5-aza-7-deazaguanosine, C10H12IN5O5 (1). The iodinated nucleoside shows an anti conformation at the glycosylic bond and an N conformation (O4′-endo) for the ribose moiety, with an antiperiplanar orientation of the 5′-hydroxy group. Crystal packing is controlled by interactions between nucleobase and sugar moieties. The 7-iodo substituent forms a contact to oxygen-2′ of the ribose moiety. Self-pairing of the nucleobases does not take place. A Hirshfeld surface analysis of 1 highlights the contacts of the nucleobase and sugar moiety (O—H...O and N—H...O). The concept of pK-value differences to evaluate base-pair stability was applied to purine–purine base pairing and stable base pairs were predicted for the construction of `all-purine' RNA. Furthermore, the 7-iodo substituent of 1 was functionalized with benzofuran to detect motional constraints by fluorescence spectroscopy.