Catalytic recruitment in the inactivation of acetylcholinesterase by soman: temperature dependence of the solvent isotope effect
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), Vol. 110:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
ACETYLCHOLINE
CATALYTIC EFFECTS
CHEMICAL REACTIONS
SOLVENT PROPERTIES
THERMODYNAMIC PROPERTIES
CHOLINESTERASE
DEUTERIUM
ISOTOPE EFFECTS
ORGANIC PHOSPHORUS COMPOUNDS
ACTIVATION ENERGY
CATALYSTS
CHEMICAL REACTION KINETICS
EXPERIMENTAL DATA
HEAVY WATER
TEMPERATURE DEPENDENCE
AMINES
AMMONIUM COMPOUNDS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARBOXYLESTERASES
DATA
DRUGS
ENERGY
ENZYMES
ESTERASES
ESTERS
HYDROGEN COMPOUNDS
HYDROGEN ISOTOPES
HYDROLASES
INFORMATION
ISOTOPES
KINETICS
LIGHT NUCLEI
NEUROREGULATORS
NUCLEI
NUMERICAL DATA
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PARASYMPATHOMIMETICS
PHYSICAL PROPERTIES
QUATERNARY COMPOUNDS
REACTION KINETICS
STABLE ISOTOPES
WATER
400202* - Isotope Effects
Isotope Exchange
& Isotope Separation