Use this URL to cite or link to this record in EThOS:
Title: Computational and experimental studies on the biological and chemical reactivity of the 3-isothiazolones
Author: Oliver, A. J.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 1999
Availability of Full Text:
Access from EThOS:
A series of eighteen structurally diverse 3-isothiazolones which were synthesised by Zeneca Specialities were evaluated for their potential biological activity, by identifying the minimum inhibitory concentrations required to inhibit an actively growing E. coli culture via agar diffusion techniques. These isothiazolones included fused ring, halogenated, long alkyl chain and aryl compounds. The physical effect on one biocide, 4,5-benzo-3-isothiazolone (BIT) on the cell surface of Gram-negative bacteria was investigated by Atomic Force Microscopy and the biological activity of BIT was found to be related to the ability of the compound to induce lysis of the cell wall. Semi-empirical molecular orbital methods were employed to explore the reactivity of five key isothiazolones with a model alkyl thiolate for a simple bimolecular reaction. The results obtained were not however consistent with the observed biological activity. Subsequent experimental studies were carried out to show that the reaction was second order in thiol suggesting that one molecule of 3-isothiazolone undergoes nucleophilic S-N bond cleavage by two molecules of cellular thiol, resulting in the formation of a disulphide species which in turn inhibits the attacking thiol species from performing its natural biological role and impairs the biological mechanisms of the bacterial cell. A QSAR study indicated that the biological activity of the isothiazolones both in the membrane and aqueous phases of the cell, is dependent on its molecular weight and a non-linear relationship with the permeability of the compound. Membrane phase activity is also dependent on dipole moment and the key CSN ring angle of the compound. The aqueous phase activity is further described by the presence of chlorine at the five position of the heterocyclic ring and subsequent thio-acyl chloride generation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available