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Chemical reactivity of some isothiazolone biocides
Author(s) -
Collier P.J.,
Ramsey A.,
Waigh R.D.,
Douglas K.T.,
Austin P.,
Gilbert P.
Publication year - 1990
Publication title -
journal of applied bacteriology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 156
eISSN - 1365-2672
pISSN - 0021-8847
DOI - 10.1111/j.1365-2672.1990.tb01551.x
Subject(s) - chemistry , biocide , glutathione , medicinal chemistry , protonation , cysteine , thio , thiol , organic chemistry , stereochemistry , enzyme , ion
C ollier , P.J., R amsey , A., W aigh , R.D., D ouglas , K.T., A ustin , P. & G ilbert , P. 1990. Chemical reactivity of some isothiazolone biocides. Journal of Applied Bacteriology 69 , 578–584. Chemical reactions between the isothiazolone biocides, N‐methylisothiazol‐3‐one (MIT), benzisothiazol‐3‐one (BIT) and 5‐chloro‐N‐methylisothiazol‐3‐one (CMIT) with cysteine have been investigated by u.v. and NMR spectroscopy. At physiological pH all three agents interacted oxidatively with thiols to form disulphides. Further interaction with thiols caused the release of cystine and formation of a reduced, ring‐opened form of the biocide (mercaptoacrylamide). In an analogous fashion to the initial reaction the mercaptoacrylamide reacted with another molecule of biocide to give biocide dimers. NMR spectral studies indicated that for CMIT the mercaptoacrylamide form is capable of tautomerization to a highly reactive thio‐acyl chloride. Formation of mercaptoacrylamide was in all cases highly pH‐dependent. Alcohol dehydrogenase was insensitive to all three agents but was highly sensitive to CMIT when co‐administered with dithiothreitol. Capacity to form a thioacyl chloride from the mercaptoacrylamide is suggested to account for much of this enhanced activity. Stopped‐flow spectroscopic studies showed rates of reaction with glutathione (GSH) to directly parallel antimicrobial activity. Additionally, CMIT was able to react directly with both ionization states of GSH (pH 7–10) whilst BIT and MIT appeared only to interact when the glutamyl‐nitrogen of GSH was charged (pH 8.5).