Journal of the Chemical Society Perkin Transactions 2 · 1991 · 49 citations · 31 references
Life SciencesChemistryChemical KineticsEnzyme MechanismEnzymologyCatalytic MechanismsCholinergic NeurochemistryEnzyme ActivationEnzyme InhibitionEnzyme KineticsBrønsted CorrelationsEnzyme Activation KineticsEnzyme Inhibition KineticsEnzyme Kinetic AnalysisEnzyme ReactivityLevellingNucleophilic Reactivity
A kinetic study of the reactivity of a series of pyridinium carbaldoximate ions (pKa= 7.13–9.02), which are all potential reactivators of acetylcholinesterase inhibited by organophosphorus poisons, towards p-nitrophenyl acetate in aqueous solution is reported. The corresponding Brønsted plot is non-linear, defining a plateau at pKa 8 which fits very well the data previously obtained for a number of structurally different oximate ions. This phenomenon appears to be typical for the behaviour of these bases since Brønsted plots for reactions of oximate ions with other electrophiles show a similar levelling off. These observations support an explanation in terms of a requirement for desolvation of the oximate ion prior to nucleophilic attack which becomes more difficult with increasing basicity. Possible implications of the rapid levelling off in reactivity of oximate ions on their chemical ability to act as efficient reactivators are discussed.
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The Pharmacological Basis of Therapeutics
Frank W. Newell · American Journal of Ophthalmology · 1966 · 428 citations