Description

Isothiazoline (sometimes isothiazolone) is an organic compound with the formula (CH)2SN(H)CO. A white solid, structurally related to isothiazole. Isothiazolone itself is of limited interest, but several of its derivatives are widely used as preservatives and antimicrobials.
Biological effects

The significant biological effects observed for isothiazole-containing compounds have generated great interest in this scaffold for drug discovery and development programs, leading to a continuous increase in the number of related patent applications as well as the successful introduction of isothiazole-based derivatives to the market. .

Application

Among them, the most used for industrial applications and reactive intermediates, for the synthesis of various organic substances including pharmaceuticals and agricultural chemicals, are those based on isothiazoline-3 (isothiazolinone).

Their 3-isothiazolinones are known for their significant antifungal and antibacterial properties and are widely used as biocides in a variety of industrial water treatment applications to control microbial growth and biofouling. They are also recommended as preservatives to prevent fungal growth in a wide range of manufactured goods such as emulsion paints, wood varnishes, adhesives, and natural and synthetic leather.

Commercial use

The isothiazolinones most commonly found in commercial applications, alone or in combination, are methylisothiazolinone (MI), methylchloroisothiazolinone (MCI), benzisothiazolinone (BIT), octylisothiazolinone (OIT), and dichlorooctylisothiazolinone (DCOIT).

Methylisothiazolinone is commonly used in wastewater treatment processes, cosmetics, dyes and detergent raw materials and in combination with MCI (in a ratio of 3:1) as a commercial biocidal active ingredient, Kathon. Although BIT and OIT are prohibited for use in cosmetics, they are commonly used in cleaning and leather products, respectively, and as antifouling coating agents. DCOIT, the biocide in SeaNine 211, is an antifouling agent widely used to prevent undesirable biofouling phenomena.

Allergy to isothiazolin

Although the use of isothiazoline has increased in recent years, concerns about the potential for inherent sensitization and allergic contact dermatitis, which are often observed in consumers as well as workers in various industries, have been reported. Additionally, cross-reactivity between different isothiazolinones has been shown in animal assays, expanding the potential implications of sensitization to this type of compound.

As a result of the widespread use of this type of heterocycles and the renewed interest in this scaffold, this review provides an overview of the most widely used compounds containing the isothiazolinone ring. In-depth information on the synthesis of the most common isothiazolinone biocides used in consumer products and their biological/toxicity profile is provided. In addition, due to the increasing concern about possible unwanted side effects of isothiazolinones on human health and the environment, this review also covers chemical and photochemical stability issues and the analytical methods that are often used for their determination.