Comprehensive investigation of the energetics of pyrimidine nucleoside formation in a model prebiotic reaction.
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.
Sheng
Yinghong
Y
Department of Chemistry and Mathematics & Whitaker Center, College of Arts & Sciences, Florida Gulf Coast University, 10501 FGCU Boulevard South, Fort Myers, Florida 33965, USA. ysheng@fgcu.edu
Bean
Heather D
HD
Mamajanov
Irena
I
Hud
Nicholas V
NV
Leszczynski
Jerzy
J
D006031:Glycosylation; D008274:Magnesium; D008956:Models, Chemical; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis*; D012997:Solvents; D014867:Water / Q000737:chemistry
D011741:Pyrimidine Nucleosides; D012997:Solvents; D014867:Water; D008274:Magnesium