Hydroxybenzoic acid, conjugation

Ginkgo extract has no effect on the hepatic microsomal drug oxidation system, as measured by antipyrine elimination, even at doses of 400 mg per day (Duche et al. 1989). Ginkgo metabolites, the substituted benzoic acids (4-hydroxybenzoic acid conjugate, 4-hydroxyhippuric acid, 3-methoxy-4-hydroxyhippuric acid, 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, hippuric acid and 3-methoxy-4-hydroxybenzoic acid [vanillic acid]), are excreted in urine (Pietta et al. 1997). 

The inductive effect in 4-hydroxybenzoic acid is electron withdrawing, but this is a modest effect compared with the electron-donating resonance effect. This significantly destabilizes the conjugate base, and 4-hydroxybenzoic acid (p a 4.6) is less acidic than benzoic acid. The last example, 4-acetylbenzoic acid, is the most acidic of the group, and this is primarily the result of an electron-withdrawing resonance effect, though there is also a favourable inductive effect. 

In Section 9-3, we considered o- and p-hydroxybenzoic acids, designated HA. Now consider their conjugate bases. For example, the salt sodium o-hydroxybenzoate dissolves to give Na+ (which has no acid-base chemistry) and o-hydroxybenzoate. which is a weak base. The acid-base chemistry is the reaction of o-hydroxybenzoate with water ... 

Tian, Z. Wang, X.-B. Wang, L.-S. Kass, S. R. Are carboxyl groups the most acidic sites in amino acids Gas-phase acidities, photoelectron spectra, and computations on tyrosine, p-hydroxybenzoic acid, and their conjugate bases, J. Am. Chem. Soc. 2009, 131, 1174-1181. 

M37. Monti, J. P., Gallice, P., Crevat, A., et al. Identification by nuclear magnetic resonance and mass spectrometry of a glucuronic acid conjugate of o-hydroxybenzoic acid in normal urine and uremic plasma. Clin. Chem. (Winston-Salem, N.C.) 31, 1640-1643 (1985). 

The absence of p-coumaric and p-hydroxyphenylpropionic acids from normal urine of man and rabbit would indicate that the transformation of these acids into p-hydroxybenzoic acids (through P-oxidation) is more rapid in these species than in the rat. The same authors found also, in the urine of rats, coumaroylglycine and the ethereal sulfate of p-hydroxybenzoic acid, this conjugate being the only metabolite of p-hydroxybenzoic acid (B21). 

Great care must be taken over the interpretation this test. In particular, the isolation of 2,4,6-tribromophenol must not be taken as proof of the presence of phenol. The importance oS this is illustrated by the early claim of Baumann and Herter (8a) that phenol was formed as a metabolite of p-hydroxybenzoic acid by the dog because after distilling the acidified urine with steam they obtained a distillate from which 2,4,6-tribromophenol was isolated after addition of brcmine water. This is not valid proof of the presence of phenol in the urine dnce when p-hydroxybenzoic acid is treated with bromine water decarboxylation occurs and 2,4,6-tribromophenol is formed. (Some other phendic acids are also decarboxylated in tins way.) Subsequent work has, in fact, made it almost certain that the bulk, if not all, of Baumann and Herter s tribromophenol arose from p-hydroxybenzoic acid or its conjugates. 

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