Differential reactivity of alpha and beta 2'-deoxyribonucleosides towards protonation and metalation.
The reactivity of artificial 2'-deoxyribonucleosides, designed as nucleoside surrogates in metal-mediated base pairs, towards protonation and metalation has been shown to be dependent on the choice of the anomer. The alpha nucleosides comprising the aglycones imidazole, 1,2,4-triazole, benzimidazole and imidazo[4,5-b]pyridine are more basic than the respective beta nucleosides as was shown by a combined experimental and theoretical approach. The DeltapK(a) values observed experimentally are in the range of 0.19+/-0.03 to 0.41+/-0.07 (with the error representing three times the standard deviation of the mean value). An independent confirmation of this differential reactivity was obtained from density functional theory (DFT) calculations using 1,2,4-triazole nucleoside as an example. The result of these calculations is in good agreement with the experimental data (DeltapK(a)=0.16 vs. 0.21+/-0.07). The stability of the respective metal ion complexes of the anomeric 1,2,4-triazole nucleosides follows the same trend as that of the respective protonated nucleosides: Those of the alpha nucleoside are more stable than those of the beta nucleoside (Deltalogbeta(2)=0.6+/-0.2 for the 2:1 complex with Ag(+); Deltalogbeta(1)=0.51+/-0.07 for the 1:1 complex with Hg(2+)). These slightly different reactivities will be useful for fine-tuning the metal-ion binding behavior of oligonucleotides containing metal-mediated base pairs.
Müller
Jens
J
University of Dortmund, Department of Chemistry, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany. jens.mueller@uni-dortmund.de
Böhme
Dominik
D
Düpre
Nicole
N
Mehring
Michael
M
Polonius
Fabian-Alexander
FA
D001393:Azoles / Q000737:chemistry*; D003853:Deoxyribonucleosides / Q000737:chemistry*; D006860:Hydrogen Bonding; D006865:Hydrogenation; D008670:Metals / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*
D001393:Azoles; D003853:Deoxyribonucleosides; D008670:Metals; D009705:Nucleosides