[Mechanism of the reaction of N,N-dimethyl-2-phenylaziridinium with acetylcholinesterase in its active site].

Effect of temperature on the rate of the bond-breaking step of acetylcholinesterase modification with N,N-dimethylaziridinium ion was studied within 8 to 45 degrees C temperature interval. For this reaction measured by irreversible inhibition of the acetylcholinesterase-catalyzed hydrolysis of acetylthiocholine the activation parameters delta H not equal to = 94 kJ/mole and delta S not equal to (25 degrees C) = -9.4 J/mol X deg were obtained. Processing of these data together with our earlier results on spontaneous solvolysis of the aziridinium ion in various water-solvent mixtures showed that all these reactions form a common isokinetic series. That gave evidence of the SN1 mechanism of the alkylation reaction occurring at the acetylcholinesterase active centre. Kinetics of spontaneous decomposition of the covalent bond between the aziridinium reagent and protein molecule was studied. This reaction followed the first-order kinetics and lead to complete liberation of the label from the enzyme, thus suggesting that a single carboxylic or amide group in the active centre was modified by the aziridinium ion.