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Keywords:

  • azole;
  • bioinorganic chemistry;
  • coordination chemistry;
  • ligand design;
  • 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 <−3, respectively. This decrease in basicity results in a decreasing ability to form 2:1 complexes with linearly coordinating metal ions such as Ag+ and Hg2+. In all cases, the Ag+ complexes are of higher stability than the corresponding Hg2+ complexes. Whereas imidazole nucleoside forms highly stable 2:1 complexes with both metal ions (estimated log β2 values of >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).