Electrophilic active microbicides

The ambient medium impairs the effectiveness of microbicides also if its constituents include those capable of interacting with a microbicide in competition with the constituents of the microbe cell. This is true of electrophilically active microbicides in general as far as the ambient medium contains nucleophilically active constituents with which the microbicide can react in competition with the corresponding cell constituents. It is also true, however, of membrane-active microbicides if adsorption of the microbicide on organic matter competes with the adsorptive processes on the cytoplasmic membrane or if such microbicides, e.g. phenol derivatives, become incorporated in micelles that are formed in certain media at levels above the critical micelle concentration with the result that the incorporated active substance molecules are no longer available for the antimicrobial effect (see III. 16, Fig. 34). 

The effectiveness and efficiency of microbicides result from the interplay of the chemicophysical properties of the active substance molecule, which are determined by the molecule s constitution. Solubility, polarity, ionicity and reactivity are examples of properties that influence effectiveness. Taking the N-trihalo-methylthio derivative as examples, Paulus Kiihle (1986) drew attention to an important principle that evidently applies to electrophilically active microbicides in general, namely that the relationship shown in Fig. 11 exists between the antimicrobial effectiveness and reactivity of microbicide molecules. As the reactivity increases, so, too, does the effectiveness—until it peaks at a moderately high reactivity level. Thereafter the antimicrobial activity decreases as the reactivity continues to rise because at this stage competition reactions — interactions of the reactive microbicide molecules with constituents of the surrounding medium — predominate. 

Organometallic compounds such as phenylmercury acetate (PMA) and tributyl tin fluoride (TBTF) are classified as electrophilically active microbicides... 

The efficacy of a preservative and the concentration level of a microbicide to be added are very much dependent on the germ content of the material to be protected. This is in particular valid for electrophilic active microbicides which in general react irreversibly with nucleophilic components of the microbial cell, that means that they are used up by being effective. But membrane active microbicides which adsorptively coat microbial cell walls are also withdrawn from action at least temporarily if large numbers of microbial cells are present. The exponential growth profile of microbes (p. 2) always has to be taken into consideration. 

Another group of active ingredients to be used in slimicides and algicides for cooling waters belongs to the electrophilic active microbicides ... 

Bronopol, like the majority of electrophilic active ingredients, has a slow microbicidal effect Bronopol concentrations 2-4 times higher than the MIC in Table 18 take as long as 24 h to display bactericidal activity. 

The electrophilic active compound exhibits a broad spectrum of activity which covers bacteria, yeasts and fungi. It is used as a preservative for the in-can protection of water based functional fluids, e.g. paints. Due to its properties — irritant, moderate stability — the microbicide has been applied to a limited extent only. 

Also haloalkylthio amides, e.g. Ar,A dimethyl-A/ -phenyl-A/ -dichlorofluoromethyl-thiosulphamide (Section 14.5) or A-triahalomethylthio-phthalimides (Sections 14.1 and 14.2) are well-known microbicides. They are electrophilic active agents with an activated N-S bond their role as an important class of microbicides is described separately in Section 14 (A -haloalkylthio compounds). 

Also haloalkylthio amides are well-known microbicides they are electrophilic active agents disposing of an activated N-S bond. Their role as an important class of microbicides is described separately under 16. 

Microbicides of this kind are electrophilic active substances having at their disposal an activated halogen atom in the a-position and/or in the vinyl position to an electronegative group E (Figure 20). The antimicrobial activity of these substances arises from the fact that nucleophilic entities (H-Nu) of the microbial cell react with the carbon atom boasting an electron hole. It is apparent that a variety of modifications of both the electronegative... 

These electrophilic substances can react with nucleophilic compounds, for example, of the microbial cell, by way of an elimination reaction in the case of micro-bicides with an activated halogen in the a-position to an electronegative group, whereas microbicides with vinyl-activated halogen combine with nucleophiles by way of an addition-elimination reaction (Fig. 3). 

Active substances. Target specificity is a non-desired property of a technical microbicidal active molecule. The applied molecules are either classified as membrane-active substances or as reactive electrophiles. Some molecules can not be clearly assigned to one of the two categories while showing both modes of actions. See chapter 2. 

---