Comprehensive investigation of the energetics of pyrimidine nucleoside formation in a model prebiotic reaction.

TitleComprehensive investigation of the energetics of pyrimidine nucleoside formation in a model prebiotic reaction.
Publication TypeJournal Article
Year of Publication2009
AuthorsSheng, Y, Bean, HD, Mamajanov, I, Hud, NV, Leszczynski, J
JournalJ Am Chem Soc
Volume131
Issue44
Pagination16088-95
Date Published2009 Nov 11
ISSN1520-5126
KeywordsGlycosylation, Magnesium, Models, Chemical, Pyrimidine Nucleosides, Solvents, Water
Abstract

The problem of beta-nucleoside formation under prebiotic conditions represents one of the most significant challenges to the "RNA world" hypothesis. The possibility exists that alternative bases may have come before the contemporary bases (i.e., A, G, C, and U), including bases that more readily form nucleosides. We previously reported the first successful synthesis of a pyrimidine nucleoside from a free base and a nonactivated sugar in a plausible prebiotic reaction. Here we present a detailed computational study on the reaction at the density functional theory (DFT) level. The catalytic role of a Mg(2+) ion on the reaction mechanism is also investigated. Our calculations demonstrate that a Mg(2+) ion, serving as a Lewis acid, can afford the necessary stabilization to the base and leaving water molecule during glycoside bond formation. The solvent effect is considered by the Onsager solvation model and also by an extended model with the addition of explicit water molecules within the SCRF solvation model. In addition, predictions regarding the formation of nucleosides from other pyrimidine bases are also addressed, providing valuable insights into what chemical features of the bases facilitate glycoside formation in drying-heating reactions.

DOI10.1021/ja900807m
Alternate JournalJ. Am. Chem. Soc.
PubMed ID19839590