title: Non-enzymatic ribonucleotide reduction in the prebiotic context.
abstract: Model studies of prebiotic chemistry have revealed compelling routes for the formation of the building blocks of proteins and RNA, but not DNA. Today, deoxynucleotides required for the construction of DNA are produced by reduction of nucleotides catalysed by ribonucleotide reductases, which are radical enzymes. This study considers potential non-enzymatic routes via intermediate radicals for the ancient formation of deoxynucleotides. In this context, several mechanisms for ribonucleotide reduction, in a putative H2 S/HS(.) environment, are characterized using computational chemistry. A bio-inspired mechanistic cycle involving a keto intermediate and HSSH production is found to be potentially viable. An alternative pathway, proceeding through an enol intermediate is found to exhibit similar energetic requirements. Non-cyclical pathways, in which HSS(.) is generated in the final step instead of HS(.) , show a markedly increased thermodynamic driving force (ca. 70 kJ mol(-1) ) and thus warrant serious consideration in the context of the prebiotic ribonucleotide reduction.
authors.affiliation: Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb (Croatia); Department of Chemistry, Faculty of Science and Education, University of Mostar, Matice hrvatske bb, 88000 Mostar (Bosnia and Herzegovina).
authors.forename: Ivan
authors.initials: I
authors.lastname: Dragičević
authors.forename: Danijela
authors.initials: D
authors.lastname: Barić
authors.forename: Borislav
authors.initials: B
authors.lastname: Kovačević
authors.forename: Bernard T
authors.initials: BT
authors.lastname: Golding
authors.forename: David M
authors.initials: DM
authors.lastname: Smith
mesh_terms: D004247:DNA / Q000737:chemistry*; D003854:Deoxyribonucleotides / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry*; D006862:Hydrogen Sulfide / Q000737:chemistry; D008958:Models, Molecular; D000069497:Origin of Life; D010084:Oxidation-Reduction; D012313:RNA / Q000737:chemistry; D012265:Ribonucleotides / Q000737:chemistry*
chemical_list: D003854:Deoxyribonucleotides; D005609:Free Radicals; D012265:Ribonucleotides; D012313:RNA; D004247:DNA; D006862:Hydrogen Sulfide
keywords: DNA; computational chemistry; molecular evolution; prebiotic chemistry; radical reactions