RESUMO
The 2'-deoxy-beta-D-ribonucleosides of 1,3-deazapurine (benzimidazole (1)), 1-deazapurine (both 1H-imidazo[4,5-b]pyridine (2) and 3H-imidazo[4,5-b]pyridine (3)), and 6-benzoylamino-1-deazapurine (7-benzoylamino-3H-imidazo[4,5-b]pyridine (4)) have been prepared and structurally characterized by X-ray crystallography. Especially compounds 1-3 can serve as artificial nucleosides that may substitute 2'-deoxy adenosine because they lack the exocyclic amino group and one or two of the endocyclic nitrogen atoms and hence have a much smaller potential to engage in hydrogen bonds. In the latter respect, they are candidates for nucleosides in metal-ion mediated base pairs. The unit cell of compound 3 contains two crystallographically independent molecules. Compound 4 was crystallized from methanol and water, respectively, giving rise to two different solvates. Despite the closely related aglycones, the sugar conformations in 1-4 are found to be highly variable (1: (2)T(1); 2: (3)T(2); 3: (3)E and E(4); 4: (2)E and (2)T(3)). The structures reported here confirm that there is no simple correlation between the sugar conformation and the character of the nucleoside, and they will hopefully contribute to a better understanding of the complex interplay of different effects that are in control of the conformational equilibrium.
Assuntos
Desoxirribonucleosídeos/química , Cristalografia por Raios X , Estrutura Molecular , PurinasRESUMO
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.