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

abstract

• The remote label method was used to measure primary and secondary (18)O isotope effects in the alkaline hydrolysis of O,O-diethylphosphorylcholine iodide (DEPC) and the primary (18)O 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 (18)O isotope effect of 1.041 +/- 0.003 and a secondary (18)O isotope effect of 1.033 +/- 0.002. The primary (18)O 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.

authors

• Raushel, Frank

published proceedings

• J Am Chem Soc

author list (cited authors)

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

citation count

• 47

complete list of authors

• Anderson, MA||Shim, H||Raushel, FM||Cleland, WW

publication date

• September 2001

publisher

• American Chemical Society (ACS)  Publisher

published in

• Journal of the American Chemical Society  Journal

keywords

• Choline
• Esters
• Ethanol
• Hydrolysis
• Isotope Labeling
• Kinetics
• Nitro Compounds
• Nitrogen Isotopes
• Organophosphorus Compounds
• Oxygen Isotopes
• Phosphorylcholine

PubMed Central ID

• 11562204

Digital Object Identifier (DOI)

• 10.1021/ja011025g

start page

• 9246

end page

• 9253

volume

• 123

issue

• 38

URL

• http://dx.doi.org/10.1021/ja011025g