Hydrolysis of phosphotriesters: Determination of transition states in parallel reactions by heavy-atom isotope effects

M. A. Anderson, H. Shim, F. M. Raushel, W. W. Cleland

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

The remote label method was used to measure primary and secondary 18O isotope effects in the alkaline hydrolysis of O,O-diethylphosphorylcholine iodide (DEPC) and the primary 18O effect in the alkaline hydrolysis of O,O-diethyl-m-nitrobenzyl phosphate (DEmNBP). Both the leaving group of interest (choline or m-nitrobenzyl alcohol) and ethanol can be ejected during hydrolysis due to the similarity of their pK values. The heavy-atom isotope effects were measured by isotope ratio mass spectrometry. Parallel reaction and incomplete labeling corrections were made for both systems. DEPC has a primary 18O isotope effect of 1.041 ± 0.003 and a secondary 18O isotope effect of 1.033 ± 0.002. The primary 18O isotope effect for DEmNBP was 1.052 ± 0.003. These large effects suggest a highly associative transition state in which the nucleophile approaches very close to the phosphorus atom to eject the leaving group. The large values are also indicative of a large compression, or general movement, on the reaction coordinate.

Original languageEnglish
Pages (from-to)9246-9253
Number of pages8
JournalJournal of the American Chemical Society
Volume123
Issue number38
DOIs
StatePublished - 26 Sep 2001

Fingerprint

Dive into the research topics of 'Hydrolysis of phosphotriesters: Determination of transition states in parallel reactions by heavy-atom isotope effects'. Together they form a unique fingerprint.

Cite this