Salicylic acid active species

It has been shown that in some compounds the active species is the non-ionized molecule while the ion is inactive (benzoic acid, phenols, nitrophenols, salicylic acid, acetic acid). Thus, conditions of pH which favour the formation of the ions of these compounds will also reduce their activity. The effect of pH on the ability of acetic acid and phenol to inhibit the growth of a mould is shown in Fig. 11.4. 

An efficient and selective Cu-assisted ortho-hydroxylation procedure for the conversion of benzoate to salicylate has been described, involving trimethylamine N-oxide (TMAO) as the oxidant [191,192]. The reaction was assumed to proceed via oxidation of a Cu carboxylate complex by TMAO to produce the active species (postulated to be a Cu hydroxo complex, but with only circumstantial evidence), followed by oxygen transfer to the benzoate group (Scheme 14). Using a set of different amide derivatives of benzoic acid, Comba and co-workers gained additional mechanistic hints in support of a reactive Cu-oxo or Cu-hydroxo intermediate that is stabilized by a five-membered chelate [193]. A pre-equilibrium involving Cu the ligand, and TMAO was proposed, but details of the reaction are far from clear. 

Another active principle soon extracted from plants was salicylic acid. Salicin, extracted from the willow tree, has been launched in 1876 by a Scottish physician, Thomas John McLogan It was in extensive competition with Cinchona bark and quinine and never became a very popular treatment for fever or rheumatic symptoms. The Italian chemist Raffaele Piria, after having isolated salicylalde-hyde (1839) in Spireae species, prepared salicylic acid from salicin in Dumas laboratory in the Sorbonne, Paris. This acid was easier to use and was an ideal step before future syntheses. Its structure was closely related to benzoic acid, an effective preservative useful as an intestinal antiseptic for instance in typhoid fever. Acetylsalicylic acid has been first synthesized by Charles Frederic Gerhardt in 1853 and then, in a purer form, by Johann Kraut (1869). Acetylsalicylic acid synthesis with carbolic acid and carbon dioxide was improved by Hermann Kolbe in1874, but in fact nobody noticed its pharmacological interest. 

Kawano T, Muto S. Mechanism of peroxidase actions for salicylic acid-induced generation of active oxygen species and an increase in cytosolic calcium in tobacco suspension culture. J Experi Bot2000 51 685-693. 

Drugs are known that are only active because they are metabolized to bioactive chemical species. An intrinsically active drug is frequently converted to an active metabolite. Well-known examples are the hydrolysis of aspirin to salicylic acid by esterase enzymes, the cleavage of the ethyl ether group of phenacetin to acetaminophen, the demethylation of imipramine to desipramine, and the oxidation of phenylbutazone to oxyphenbutazone. In some cases the precursor drug and its metabolite are both used therapeutically. 

Significant antioxidant activity has also been observed in the hexane extracts of different cashew products (Table 10.3). The antioxidant activity was determined in the hypoxanthine/xanthine oxidase assay and expressed as inhibition of reactive oxygen species (ROS) attack on salicylic acid (%). CNSL has the highest antioxidant activity, followed by cashew fiber, cashew apple, raw cashew nut,... 

The kinetics of the reaction of cobalt(II) and nickel(II) with salicylic acid, and of the latter metal with 5-chloro-, 5-sulfo-, and 5-nitrosalicylic acids (H2L) have been interpreted in terms of there being two reactive metal species, the normal ion Maq and the deprotonated species MOH. While MOH reacts with rates which are consistent with the Id mechanism (and the bound OH" ligand produces no remarkable labilization of the metal-bound waters), the unhydrolyzed cations show rates which are two to three orders of magnitude below the normal values. This is thought to be attributable to the need to break the internal hydrogen bond in the active form of the ligand, HL". 

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