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 /?-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 pK a 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 β 2 = 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 A) resembling those in idealized B-DNA (10.85 A).