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 beta 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 beta2 values of >10), only Ag+ is able to reach this coordination pattern in the case of triazole nucleoside (log beta2 = 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 Angstroms) resembling those in idealized B-DNA (10.85 Angstroms).
Müller
Jens
J
Department of Chemistry, University of Dortmund, Germany. mueller@muellerlab.org
Böhme
Dominik
D
Lax
Patrick
P
Morell Cerdà
Marta
M
Roitzsch
Michael
M
D001393:Azoles / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009705:Nucleosides / Q000737:chemistry*
D001393:Azoles; D007202:Indicators and Reagents; D008024:Ligands; D008670:Metals; D009705:Nucleosides