NDLI: DFT investigations of phosphotriesters hydrolysis in aqueous solution: a model for DNA single strand scission induced by N-nitrosoureas

Content Provider	Springer Nature Link
Author	Liu, Tingting Zhao, Lijiao Zhong, Rugang
Copyright Year	2012
Abstract	DNA phosphotriester adducts are common alkylation products of DNA phosphodiester moiety induced by N-nitrosoureas. The 2-hydroxyethyl phosphotriester was reported to hydrolyze more rapidly than other alkyl phosphotriesters both in neutral and in alkaline conditions, which can cause DNA single strand scission. In this work, DFT calculations have been employed to map out the four lowest activation free-energy profiles for neutral and alkaline hydrolysis of triethyl phosphate (TEP) and diethyl 2-hydroxyethyl phosphate (DEHEP). All the hydrolysis pathways were illuminated to be stepwise involving an acyclic or cyclic phosphorane intermediate for TEP or DEHEP, respectively. The rate-limiting step for all the hydrolysis reactions was found to be the formation of phosphorane intermediate, with the exception of DEHEP hydrolysis in alkaline conditions that the decomposition process turned out to be the rate-limiting step, owing to the extraordinary low formation barrier of cyclic phosphorane intermediate catalyzed by hydroxide. The rate-limiting barriers obtained for the four reactions are all consistent with the available experimental information concerning the corresponding hydrolysis reactions of phosphotriesters. Our calculations performed on the phosphate triesters hydrolysis predict that the lower formation barriers of cyclic phosphorane intermediates compared to its acyclic counter-part should be the dominant factor governing the hydrolysis rate enhancement of DEHEP relative to TEP both in neutral and in alkaline conditions. Figure DEHEP hydrolysis involved in DNA single strand scission induced by N-nitrosoureas
Starting Page	647
Ending Page	659
Page Count	13
File Format	PDF
ISSN	16102940
Journal	Journal of Molecular Modeling
Volume Number	19
Issue Number	2
e-ISSN	09485023
Language	English
Publisher	Springer-Verlag
Publisher Date	2012-09-22
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Acyclic phosphorane Cyclic phosphorane Diethyl 2-hydroxyethyl phosphate Hydrolysis mechanism Triethyl phosphate Computer Applications in Chemistry Molecular Medicine Computer Application in Life Sciences Characterization and Evaluation of Materials Theoretical and Computational Chemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Physical and Theoretical Chemistry Computational Theory and Mathematics Catalysis Inorganic Chemistry Computer Science Applications

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