Benzoic acid biological activities

Biological. Benzoic acid may degrade to catechol if it is the central metabolite whereas, if protocatechuic acid (3,4-dihydroxybenzoic acid) is the central metabolite, the precursor is 3-hydroxybenzoic acid (Chapman, 1972). Other compounds identified following degradation of benzoic acid to catechol include cis,c/5-muconic acid, (+)-muconolactone, 3-oxoadipate enol lactone, and 3-oxoadipate (quoted, Verschueren, 1983). Pure microbial cultures hydroxylated benzoic acid to 3,4-dihydroxybenzoic acid, 2- and 4-hydroxybenzoic acid (Smith and Rosazza, 1974). In activated sludge, 65.5% mineralized to carbon dioxide after 5 d (Freitag et al., 1985). 

The sodinm salt of benzoic acid, sodinm benzoate, is a very commonly employed preservative. Let s pause here for a moment to re-emphasize an important point biological activity is a sensitive fnnction of chemical structure. Benzene, the parent molecule of benzoic acid, is a serions toxin in contrast, the sodium salt of benzoic acid is sufficiently safe to be added, in modest amounts, to a great many foodstnffs. The addition of the carboxyl gronp to benzene has created a far safer molecnle. 

Benzoic and hydroxybiphenyl carboxylic acids are widely used in the synthesis of drugs, biologically active compounds, and heat-resistant polymers. The known methods for preparation of aromatic hydroxy carboxylic acids include many stages, require not easily accessible starting compounds, and provide poor summary yields of the target products. 

The search for an influence of steric effects on biological activity results from their well-established effects in chemical systems. As far back as 1894 (85), "steric hindrance" was invoked to account for the difficult esterification of 2,6-disub-stituted benzoic acids. However, inspection of equation 53 suggests that the substitutent constant, Eg, should include contributions from electronic effects as well. Indeed, acidic hydrolysis of esters of benzoic acids (4) have p values in the range -0.2 to +0.5. These p values are small and lie on both sides of zero, leading to the conclusion that electronic contributions to E are negligible (90). Proof for the existence of electronic effects in Es comes from Hancock s work (15) in which the electronic effects were attributed to a hyperconjugative effect of a-hydrogen atoms. 

Through a comparison of the insecticidal and toxicological data, structure-activity theories were developed which provided a means for the synthesis of safer compounds. A similar approach was used in the 2,4-D area. All manner of substituted phenoxy and benzoic acids and their derivatives were prepared. As a result, much was learned about the structural relationships for the auxin type action. This analog synthesis procedure has often been called "me too chemistry". The patent literature abounds with examples of such a strategy tried on almost everything that has shown a modicum of biological activity. 

In addition to many early examples, biological response has been found to be quantitatively linearly dependent on log P or it in the inhibition of the Hill reaction >activity of penicillins, toxicity of benzoic acids to mosquito larvae , phenol coefficients , cholinesterase inhibitors , and catechol-amine activity . 

In 1962, Hansen [14] derived a first Hammett-type relationship between the toxicities of substituted benzoic acids and the electronic a constants of their substituents. However, later, it turned out that this was a chance correlation that only resulted from a close interrelationship between the Hammett a parameter and the lipophilicity constant % (Sec. 4 Eqs. (42) and (43)). In the same year, for the very first time, a nonlinear multiparameter equation (Eq. 6) [15] was used to describe biological activity values ... 

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