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This work was carried out in 1948-9 and formed the subject of confidential reports to the Ministry of Supply. It was part of a search for simple compounds which would protect cholinesterases against inhibition by such compounds as Tabun (ethyl NN-dimethylphosphoramidocyanidate), Sarin (isopropyl P-methylphosphonofluoridate) and ethyl-Sarin (iopropyl P-ethylphosphonofluoridate). As with DFP (dii8opropyl phosphorofluoridate: Mackworth & Webb, 1948) inhibition by Tabun (Augustinsson, 1951, 1953) and Sarin (unpublished work of A. Todrick & L. T. D. Williams) is irreversible, and it is reasonable to suppose that inhibition by ethyl-Sarin is also irreversible. The starting point of our experiments was the supposition that since nothing definite was known about the active centre of cholinesterases, the catalytic activity was probably associated with the amino acid side chains. A number of amino acids were examined for their ability to protect cholinesterase in vitro; only dopa (3:4-dihydroxyphenylalanine) was effective, but in high concentration, and it was found that protective ability was a property of catechol derivatives. It appears that Augustinsson (1952), independently and about the same time, discovered the reaction of catechols with Tabun, and published his results almost simultaneously with those of Jandorf, Wagner-Jauregg, O'Neill & Stolberg (1952) on the reaction of phenols with DFP. The present paper deals mainly with the properties of Sarin, but sufficient data are also given to make it clear that the three groups of workers have studied different facets of the same phenomenon. A brief account of this work has been published (Berry, 1953). THEORETICAL One of us (A.T.) in earlier unpublished work on Sarin in collaboration with L. T. D. Williams considered the case of irreversible inhibition by a labile inhibitor. The gist of their treatment is as follows:

Under appropriate conditions, S-benzyl-L-cysteine-4'-nitroanilide is rapidly hydrolyzed by serum cystine aminopeptidase. The enzyme may be estimated kinetically by determining the rate of liberation of 4-nitroaniline. A simple automated procedure has been devised, and 50 samples of pregnancy sera can be analyzed per hour by use of the LKB 8600 Reaction Rate Analyzer. The correlation coefficient between results of this method and those obtained with L-cystine-di-4'-nitroanilide as substrate was 0.97.