Itaconic acid, or methylidenesuccinic acid, is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

. This

dicarboxylic acid In organic chemistry, a dicarboxylic acid is an organic compound containing two carboxyl groups (). The general molecular formula for dicarboxylic acids can be written as , where R can be aliphatic or aromatic. In general, dicarboxylic acids show ...

is a white solid that is soluble in water, ethanol, and acetone. Historically, itaconic acid was obtained by the distillation of

citric acid Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in t ...

, but currently it is produced by fermentation. The name ''itaconic acid'' was devised as an anagram of

aconitic acid Aconitic acid is an organic acid. The two isomers are ''cis''-aconitic acid and ''trans''-aconitic acid. The conjugate base of ''cis''-aconitic acid, ''cis''-aconitate is an intermediate in the isomerization of citrate to isocitrate in the citric ...

, another derivative of citric acid.

Production

Since the 1960s, it is produced industrially by the fermentation of

carbohydrate In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...

s such as

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...

molasses Molasses () is a viscous substance resulting from refining sugarcane or sugar beets into sugar. Molasses varies in the amount of sugar, method of extraction and age of the plant. Sugarcane molasses is primarily used to sweeten and flavour foods ...

using fungi such as '' Aspergillus itaconicus'' or ''

Aspergillus terreus ''Aspergillus terreus'', also known as ''Aspergillus terrestris'', is a fungus (mold) found worldwide in soil. Although thought to be strictly asexual until recently, ''A. terreus'' is now known to be capable of sexual reproduction. This saprotr ...

''. For ''A. terreus'' the itaconate pathway is mostly elucidated. The generally accepted route for itaconate is via glycolysis, tricarboxylic acid cycle, and a decarboxylation of ''cis''-aconitate to itaconate via ''cis''-aconitate-decarboxylase. The smut fungus ''

Ustilago maydis Corn smut is a plant disease caused by the pathogenic fungus ''Ustilago maydis'' that causes smut on maize and teosinte. The fungus forms galls on all above-ground parts of corn species. It is edible, and is known in Mexico as the delicacy ''h ...

'' uses an alternative route. ''Cis''-aconitate is converted to the thermodynamically favoured ''trans''-aconitate via aconitate-Δ-isomerase (Adi1). ''trans''-Aconitate is further decarboxylated to itaconate by ''trans''-aconitate-decarboxylase (Tad1). Itaconic acid is also produced in cells of macrophage lineage. It was shown that itaconate is a

covalent A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atoms ...

inhibitor of the enzyme

isocitrate lyase Isocitrate lyase (), or ICL, is an enzyme in the glyoxylate cycle that catalyzes the cleavage of isocitrate to succinate and glyoxylate. Together with malate synthase, it bypasses the two decarboxylation steps of the tricarboxylic acid cycle (TC ...

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

''. As such, itaconate may possess antibacterial activities against bacteria expressing isocitrate lyase (such as ''

Salmonella enterica ''Salmonella enterica'' (formerly ''Salmonella choleraesuis'') is a rod-headed, flagellate, facultative anaerobic, Gram-negative bacterium and a species of the genus ''Salmonella''. A number of its serovars are serious human pathogens. Epidemi ...

'' and ''

Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its c ...

''). However, cells of macrophage lineage have to "pay the price" for making itaconate, and they lose the ability to perform mitochondrial substrate-level phosphorylation.

Laboratory synthesis

Dry distillation Dry distillation is the heating of solid materials to produce gaseous products (which may condense into liquids or solids). The method may involve pyrolysis or thermolysis, or it may not (for instance, a simple mixture of ice and glass could be se ...

of citric acid affords

itaconic anhydride Itaconic anhydride is the cyclic Organic acid anhydride, anhydride of itaconic acid (an unsaturated, dicarboxylic acid) and is obtained by the pyrolysis of citric acid. It is a colourless, crystalline solid, which dissolves in many polar organic s ...

, which undergoes hydrolysis to itaconic acid.

Reactions

Upon heating, itaconic anhydride isomerizes to

citraconic acid Citraconic acid is an organic compound with the formula CH3C2H(CO2H)2. It is a white solid. It is the ''cis''- isomer of mesaconic acid. It is one of the pyrocitric acids formed upon the heating of citric acid. Citraconic acid can be produced, ...

anhydride, which can be hydrolyzed to

(2-methylmaleic acid). CitricToCitraconic

Partial

hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a Catalysis, catalyst such as nickel, palladium or platinum. The process is commonly employed to redox, reduce or S ...

of itaconic acid over Raney nickel affords

2-methylsuccinic acid 2-Methylsuccinic acid is an organic compound with the formula HO2CCH(CH3)CH2CO2H. A white solid, it is the simplest chiral dicarboxylic acid. It is a recurring component of urban aerosols. Salts and esters of 2-methylsuccinic acid are called 2-m ...

. Itaconic acid is primarily used as a co-monomer in the production of

acrylonitrile butadiene styrene Acrylonitrile butadiene styrene (ABS) (chemical formula (C8H8)''x''·(C4H6)''y''·(C3H3N)''z'' is a common thermoplastic polymer. Its glass transition temperature is approximately . ABS is amorphous and therefore has no true melting point. A ...

and

acrylate Acrylates (IUPAC: prop-2-enoates) are the salts, esters, and conjugate bases of acrylic acid. The acrylate ion is the anion C H2=CHC OO−. Often, acrylate refers to esters of acrylic acid, the most common member being methyl acrylate. These acry ...

latex Latex is an emulsion (stable dispersion) of polymer microparticles in water. Latexes are found in nature, but synthetic latexes are common as well. In nature, latex is found as a milky fluid found in 10% of all flowering plants (angiosperms ...

es with applications in the paper and architectural coating industry.

References

{{Authority control Enoic acids Dicarboxylic acids Monomers Vinylidene compounds