8-Ethynyl-2'-deoxyisoguanosine with two tautomeric forms in the unit cell: crystal structure, packing and Hirshfeld surface analysis.

Isoguanine nucleosides constructed by different heterocyclic skeletons play a significant role in the context of genetic code expansion, as well as for purine-purine base pairing. However, with respect to structure analysis, only limited information is available on this class of nucleosides. In this study, the single-crystal X-ray structure of 8-ethynyl-2'-deoxyisoguanosine, C₁₂H₁₃N₅O₄·C₁₂H₁₃N₅O₄·2H₂O (1), has been investigated. In the crystal of 1, the N1-H and N3-H tautomers exist together. They are connected by O3'-H to O3' hydrogen bonds. The conformation at the glycosylic bond is syn for both tautomeric forms. This conformation is stabilized by intramolecular hydrogen bonds from N3 or N3-H of the pyrimidine ring to the 5'-OH group of the sugar residue. For both tautomers, the sugar conformation adopts a C2'-endo-C3'-exo twist (²T₃; S-type), with P = 165.0 and 163.9°. A synclinal orientation is observed around the C4-C5' bond. Crystal packing is controlled by a tridentate purine-purine pair of 8-ethynyl-2'-deoxyisoguanosine that is enabled by a tautomeric shift of the proton from N1 to N3 of the nucleobase. Additional stability to the 3D network is contributed by water molecules connecting different layers in the solid state. A Hirshfeld surface analysis was performed confirming the existence of the purine-purine pair and the impact of the water molecules on hydrogen bonding. To the best of our knowledge, this is the first X-ray analysis on a nucleoside with two different tautomeric forms in the crystal unit that form a purine-purine base pair.