Catalytic recruitment in the inactivation of acetylcholinesterase by soman: temperature dependence of the solvent isotope effect

Journal Article · Wed Jan 20 04:00:00 UTC 1988 · J. Am. Chem. Soc.; (United States)

DOI:https://doi.org/10.1021/ja00210a046· OSTI ID:5413470

Kovach, I M; Huber, J H.A.; Schowen, R L

3,3-Dimethyl-2-butyl methylphosphonofluoridate (soman) recruits at least 60-70% of the catalytic power of acetylcholinesterase during phosphonylation of the active-site serine, as compared with the acetylation by acetylcholine. The solvent isotope effect is 1.34 +/- 0.11 and is temperature independent within experimental error between 5 and 45/sup 0/C. This observation is quite similar to what has been found for the reactions of aryl acetates and anilides. Average activation parameters for the same temperature range are ..delta..H* = 7.3 +/- 0.6 kcal/mol and ..delta..S* = -4 +/- 2 eu (H/sub 2/O) and ..delta..H* = 7.1 +/- 0.4 kcal/mol and ..delta..S* = -6 +/- 1 eu (D/sub 2/O). A rate-limiting process with <50% contribution of general-base-catalyzed heavy-atom reorganization and >50% contribution of an induced-fit conformational change is supported by the data.

• Research Organization: Univ. of Kansas, Lawrence
• OSTI ID: 5413470
• Journal Information: J. Am. Chem. Soc.; (United States), Journal Name: J. Am. Chem. Soc.; (United States) Vol. 110:2; ISSN JACSA
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400202* -- Isotope Effects
Isotope Exchange
&amp; Isotope Separation
ACETYLCHOLINE
ACTIVATION ENERGY
AMINES
AMMONIUM COMPOUNDS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARBOXYLESTERASES
CATALYSTS
CATALYTIC EFFECTS
CHEMICAL REACTION KINETICS
CHEMICAL REACTIONS
CHOLINESTERASE
DATA
DEUTERIUM
DRUGS
ENERGY
ENZYMES
ESTERASES
ESTERS
EXPERIMENTAL DATA
HEAVY WATER
HYDROGEN COMPOUNDS
HYDROGEN ISOTOPES
HYDROLASES
INFORMATION
ISOTOPE EFFECTS
ISOTOPES
KINETICS
LIGHT NUCLEI
NEUROREGULATORS
NUCLEI
NUMERICAL DATA
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
OXYGEN COMPOUNDS
PARASYMPATHOMIMETICS
PHYSICAL PROPERTIES
QUATERNARY COMPOUNDS
REACTION KINETICS
SOLVENT PROPERTIES
STABLE ISOTOPES
TEMPERATURE DEPENDENCE
THERMODYNAMIC PROPERTIES
WATER