Metal Ion Coordination to Azole Nucleosides

To evaluate the possibility of introducing azole nucleosides as building blocks for metal‐mediated base pairs in artificial oligonucleotides, imidazole nucleoside, 1,2,4‐triazole nucleoside and tetrazole nucleoside have been synthesized and characterized. The X‐ray crystal structures of p‐toluoyl‐protected 1,2,4‐triazole and tetrazole nucleosides are reported. Contrary to the situation primarily found for deoxyribonucleosides, the sugar moieties adopt C3′‐endo conformations. The acidity of the β nucleosides increases with increasing number of nitrogen ring atoms, giving pKa values of 6.01±0.05, 1.32±0.05 and 10), only Ag+ is able to reach this coordination pattern in the case of triazole nucleoside (log β2 = 4.3±0.1). Tetrazole nucleoside does not form 2:1 complexes at all under the experimental conditions used. These data suggest that imidazole nucleoside, and to a lesser extent 1,2,4‐triazole nucleoside, are likely candidates for successful incorporation as ligands in oligonucleotides based on metal‐mediated base pairs. DFT calculations further corroborate this idea, providing model complexes for such base pairs with glycosidic bond distances (10.8–11.0 Å) resembling those in idealized B‐DNA (10.85 Å). Likely candidate ligands for incorporation into oligonucleotides: The metal ion coordination behavior of azole nucleosides (see picture) as potential nucleobase surrogates in artificial DNA based on metal‐modified base pairs has been determined. As a result, imidazole nucleoside and, to a lesser extent, 1,2,4‐triazole nucleoside are promising candidates for incorporation into oligonucleotides.