Glycosidic bond cleavage in deoxynucleotides — A density functional study
| Autor: | Stacey D. Wetmore, Andrea L. Millen |
|---|---|
| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | Canadian Journal of Chemistry. 87:850-863 |
| ISSN: | 1480-3291 0008-4042 |
| DOI: | 10.1139/v09-024 |
| Popis: | Density functional theory was used to study the glycosidic bond cleavage in deoxynucleotides with the main goal to determine the effects of the nucleobase, hydrogen bonding with the nucleobase, and the (bulk) environment on the reaction energetics. Since direct glycosidic bond cleavage is a high-energy process, two nucleophile models were considered (HCOO–···H2O and HO–), which represent different stages of activation of a water nucleophile. The glycosidic bond cleavage barriers were found to decrease, while the reaction exothermicity increases, with an increase in the nucleobase acidity. The gas-phase barriers and reaction energies for bond cleavage in all deoxynucleotides were found to be significantly affected by hydrogen-bonding interactions with the nucleobase (by up to 30 kJ mol–1 depending on the nucleophile). Although the barriers increase and reaction energies become less exothermic in enzymatic and aqueous environments, the effects of the bulk environment are similar in the presence and absence of small molecules bound to the nucleobase. Therefore, the effects of hydrogen bonding with the bases are approximately the same in all environments. Our results suggest that hydrogen bonding with the nucleobase may play an important role in the glycosidic bond cleavage in both pyrimidine and purine nucleotides in a variety of environments. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|