Metal ion coordination to azole nucleosides

Abstract

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 (10.85Å). © 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.