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

Yinghong Sheng, Heather D. Bean, Irena Mamajanov, Nicholas V. Hud, Jerzy Leszczynski

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The problem of β-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 Mg2+ ion on the reaction mechanism is also investigated. Our calculations demonstrate that a Mg2+ 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.

Original languageEnglish (US)
Pages (from-to)16088-16095
Number of pages8
JournalJournal of the American Chemical Society
Volume131
Issue number44
DOIs
StatePublished - Nov 27 2009
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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