BIOCHEMISTRY - Textbook - Ostapchenko L. I. - 2012

Chapter 1. STRUCTURE AND REACTIVITY OF BIOORGANIC COMPOUNDS

1.3. Selected classes of bioorganic compounds and their biological significance

1.3.3. Carboxylic acids

Members of another Class of bioorganic compounds—carboxylic acids (derived from carbonic acid, Acidum carbonicum, R-COOH)—are classified as monocarboxylic (monopasic), dicarboxylic (diphasic), and tricarboxylic (triphasic) depending on the number of carboxyl groups. Based on The Structure of their hydrocarbon radical, carboxylic acids are subdivided into aliphatic, aromatic, and alicyclic. Examples include H-COOH (methanoic or formic acid), H₃C-COOH (ethanoic or acetic acid), and 3-methylbutanoic (isovaleric) acid. Higher carboxylic (or higher fatty) acids include those with a carbon chain length exceeding 12 atoms (e.g., C₁₅H₃₁-COOH, palmitic acid, etc.).

The chemical properties of carboxylic acids are determined by the carboxyl group and its constituents: the carbonyl (-CO-) and hydroxyl (-OH) groups, along with the hydroxyl proton, whose dissociation accounts for the acidic properties of these substances. The hydrocarbon radical alters the degree of hydroxyl proton dissociation through inductive effects of substituents:

Substituents in the radical enhance acidic properties: the pK_a of acetic acid (CH₃-COOH) is 4.76, whereas that of chloroacetic acid (Cl-CH₂-COOH) is 2.85, and trichloroacetic acid (CCl₃-COOH) is 0.66.

Dissociated sodium and potassium salts of Higher Fatty acids exhibit an amphiphilic nature, granting them surface activity: they localize at the Water interface and reduce surface tension at phase boundaries, such as water-oil or water-air. These fatty acid salts possess distinct detergent properties.

Among Nucleophilic substitution reactions in biochemistry, Esterification leading to The formation of esters (R₁-COO-R₂)—which include numerous physiologically vital Biomolecules such as Lipids—is of primary importance. The interaction between a carboxylic acid and coenzyme A yields a thioester:

Esterification reactions in an acidic medium are reversible, whereas in an alkaline medium, esters undergo irreversible Hydrolysis to yield a salt and an alcohol. The hydrolysis of lipid esters proceeds via hydrolase Enzymes (lipases). In addition to esterification, amidation (replacing the carboxyl -OH group with an -NH₂ group to form amides) and anhydridization (replacing the same group with a phosphate or pyrophosphate group to form Acyl phosphates, such as acetyl phosphate) play crucial roles in biochemistry:

Carboxylic acid derivatives, particularly α-Amino Acids during Peptide Synthesis, participate in amidation reactions, while the formation of acyl phosphates serves as the molecular mechanism for the metabolic activation of biomolecules. Unsaturated carboxylic acids exhibit properties characteristic of alkenes, including addition, oxidation, and polymerization reactions. These are predominantly Hydration and reduction reactions of α- and β-unsaturated carboxylic acids. Polymerization reactions are utilized in the manufacturing of medical plastics (e.g., polyacrylates in dentistry).

Dicarboxylic acids display stronger acidic properties due to the electron-withdrawing inductive effect of the second carboxyl group. In biochemical systems, dicarboxylic acids form Two Types of salts: acid salts with one base equivalent (HOOC-COOH + NaOH → HOOC-COONa + H₂O) and normal (neutral) salts (NaOOC-COONa). Both saturated and unsaturated dicarboxylic acids function as metabolic intermediates (e.g., oxalic, succinic, and glutaric acids).

Biologically important representatives of tricarboxylic acids are their hydroxy derivatives: citric (1), isocitric (2), and cis-aconitic (3) acids:

These acids participate in The Citric Acid Cycle, alongside fumaric, malic, oxaloacetic, and α-ketoglutaric dicarboxylic acids. Sodium citrate is widely used as an anticoagulant to prevent extracorporeal Blood clotting.

Arene monocarboxylic acids (in which the -COOH group is attached directly to an aromatic ring) include benzoic acid and its derivatives, as well as phenylacetic acid. In the latter, the -COOH group is located in the side chain of the arene:

These acids are metabolic products or are generated in the body during the BIOTRANSFORMATION OF XENOBIOTICS (foreign compounds such as drugs and toxins). Representatives of arene dicarboxylic acids include phthalic (1,2-benzenedicarboxylic), isophthalic (1,3-benzenedicarboxylic), and terephthalic (1,4-benzenedicarboxylic) acids. The Chemical properties of arene dicarboxylic acids do not differ significantly from those of arene monocarboxylic acids. Their derivatives are utilized in the synthesis of insecticides and Pharmaceuticals, including laxatives (e.g., phenolphthalein precursors). A phthalic anhydride derivative Functions as an acid-base indicator (phenolphthalein):

Phenol acids, as derivatives of aromatic carboxylic acids, differ from the latter by having one or more hydrogen atoms replaced by an -OH group. Their simplest representative is salicylic acid. Its derivative, acetylsalicylic acid (aspirin), was synthesized in 1853 and remains widely used in medicine as an anti-inflammatory drug. The primary mechanism of this action involves the inhibition of prostaglandin Biosynthesis (derivatives of arachidonic acid) by aspirin.