These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Probing mechanism of metal catalyzed hydrolysis of Thymidylyl (3'-O, 5'-S) thymidine phosphodiester derivatives.
    Author: Rahimian M, Gejji SP.
    Journal: J Mol Model; 2013 Mar; 19(3):1027-37. PubMed ID: 23111685.
    Abstract:
    Hydrolysis of nucleic acids is of fundamental importance in biological sciences. Kinetic and theoretical studies on different substrates wherein the phosphodiester bond combined with alkyl or aryl groups and sugar moiety have been the focus of attention in recent literature. The present work focuses on understanding the mechanism and energetics of alkali metal (Li, Na, and K) catalyzed hydrolysis of phosphodiester bond in modeled substrates including Thymidylyl (3'-O, 5'-S) thymidine phosphodiester (Tp-ST) (1), 3'-Thymidylyl (1-trifluoroethyl) phosphodiester (Tp-OCH(2)CF(3)) (2), 3'-Thymidylyl (o-cholorophenyl) phosphodiester (Tp-OPh(o-Cl)) (3) and 3'-Thymidylyl(p-nitrophenyl) phosphodiester (Tp-OPh(p-NO(2))) (4) employing density functional theory. Theoretical calculations reveal that the reaction follows a single-step (A(N)D(N)) mechanism where nucleophile attack and leaving group departure take place simultaneously. Activation barrier for potassium catalyzed Tp-ST hydrolysis (12.0 kcal mol(-1)) has been nearly twice as large compared to that for hydrolysis incorporating lithium or sodium. Effect of solvent (water) on activation energies has further been analyzed by adding a water molecule to each metal ion of the substrate. It has been shown that activation barrier of phosphodiester hydrolysis correlates well with basicity of leaving group.
    [Abstract] [Full Text] [Related] [New Search]