Inhibition of Clostridium botulinum 62A by fumarates and maleates and relationship of activity to some physicochemical constants.

A series of n-monoalkyl maleates and n-mono-, di-, and methyl n-alkyl fumarates were prepared, 18 esters of each, with R = CH3 to C18H37. Their activity against Clostridium botulinum was determined in culture medium. The n-monoalkyl maleates and fumarates possessed significant activity, particularly those esterified with higher C13 to C18 alcohols. Somewhat lower activity was exhibited by methyl n-alkyl fumarates, while symmetrical esters, di-n-alkyl fumarates, were almost inactive. An attempt was made to correlate the activity of n-monoalkyl maleates and fumarates with chain length, solubility in water, apparent dissociation constant (pKa'), and infrared and UV absorption frequencies. The active esters may have potential as preservatives in foods.

Inhibition of Clostridium botulinum 62A by Saturated n-Aliphatic Acids, n-Alkyl Formates, Acetates, Propionates and Butyrates.

Saturated aliphatic acids (C1 to C20) and n-alkyl formate, acetate, propionate and butyrate esters (C1 to C20) were evaluated to determine the minimum inhibitory concentrations (MIC) necessary to inhibit the growth of Clostridium botulinum 62A in a bacteriological medium. The C1 to C7 and C16 to C20 acids and esters were relatively inactive (MIC > 200 µg/ml). The C8 to C15 acids exhibited some antibotulinal acitivity (MIC = 100 µg/ml), whereas C8 to C15 esters were substantially more inhibitory. The n-alkyl formates, acetates and propionates having C13 to C14 groups gave the highest inhibition, with MIC's of 3.1, 6.3 and 6.3 µg/ml, respectively. The maximum inhibition for the butyrates (MIC = 12.4 µg/ml) was associated with C11 to C12 alkyl groups. A mathematical relationship between activity and alkyl group chain length was derived.

Inhibition of Clostridium botulinum by p-hydroxybenzoic acid n-alkyl esters.

Twelve straight-chain esters, C(5) to C(14), C(16), and C(18), of p-hydroxybenzoic acid were prepared, and their melting points, solubilities in water at 25 degrees C, infrared spectra, dissociation constants (pK(a)), and activities against Clostridium botulinum were determined. These studies also included four commercial straight-chain esters, C(1) to C(4). The most potent activity was exhibited by undecyl and dodecyl esters, which are about 300 times as active as sodium nitrite. Quadratic and cubic equations were developed correlating the activity with pK(a) values and chain length of the esters, respectively.

Inhibition of Clostridium botulinum by 5-nitrothiazoles.

A number of 5-nitrothiazoles with various substituents in the 2-position were tested for inhibition of Clostridium botulinum in a culture medium. Thiazole itself or 2-bromo- or 2-methylthiazole at 30 mug/ml did not inhibit the organism. An amino group in the 2-position of thiazole inhibited at 10 mug/ml. Substitution of a nitro group in the 5-position of 2-aminothiazole increased the inhibitory level to 0.12 mug/ml; acetyl-, propionyl-, or butyroyl-2-amino-5-nitrothiazole inhibited at 0.04 mug/ml. Benzoyl-2-amino-5-nitrothiazole inhibited at 0.16 mug/ml; this increased to 0.01 mug/ml when the benzoyl group carried a nitro group in the m- or p-position; a nitro group in the o-position, on the other hand, inhibited at 0.04 mug/ml. Unsaturated aliphatic acyls decreased inhibition. The greatest activity was exhibited by 2-nonanoyl- and 2-lauroylamides, with minimum inhibitory concentrations of 0.005 and 0.0025 mug/ml, respectively.