title: Transesterification thio effects of phosphate diesters: free energy barriers and kinetic and equilibrium isotope effects from density-functional theory.
abstract: Primary and secondary kinetic and equilibrium isotope effects are calculated with density-functional methods for the in-line dianionic methanolysis of the native (unsubstituted) and thio-substituted cyclic phosphates. These reactions represent reverse reaction models for RNA transesterification under alkaline conditions. The effect of solvent is treated with explicit (single and double) water molecules and self-consistently with an implicit (continuum) solvation model. Singly substituted reactions at the nonbridging O(P1) position and bridging O(2)('), O(3)('), and O(5)(') positions and a doubly substituted reaction at the O(P1) and O(P2) positions were considered. Aqueous free energy barriers are calculated, and the structures and bond orders of the rate-controlling transition states are characterized. The results are consistent with available experimental data and provide useful information for the interpretation of measured isotope and thio effects used to probe mechanism in phosphoryl transfer reactions catalyzed by enzymes and ribozymes.
authors.affiliation: Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455-0431, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Brent A
authors.initials: BA
authors.lastname: Gregersen
authors.forename: Alvan
authors.initials: A
authors.lastname: Hengge
authors.forename: Darrin M
authors.initials: DM
authors.lastname: York
mesh_terms: D002384:Catalysis; D004951:Esterification; D007700:Kinetics; D008956:Models, Chemical; D010755:Organophosphates / Q000737:chemistry*; D010103:Oxygen Isotopes / Q000737:chemistry*; D010766:Phosphorylation; D012313:RNA / Q000737:chemistry; D016337:RNA, Catalytic / Q000378:metabolism; D012997:Solvents / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D010755:Organophosphates; D010103:Oxygen Isotopes; D016337:RNA, Catalytic; D012997:Solvents; D014867:Water; D012313:RNA