Nonactin
Encyclopedia
Nonactin is a member of a family of naturally occurring cyclic ionophores known as the macrotetrolide antibiotics. The other members of nactins homologous family are monactin, dinactin, trinactin and tetranactin which are all neutral ionophoric substances and higher homologs of nonactin. Collectively, this class is known as the nactins. Nonactin is soluble in methanol
, dichloromethane
, ethyl acetate
and DMSO
, but insoluble in water.
, Streptomyces griseus
, Streptomyces chrysomallus and Streptomyces werraensis. Total syntheses have been reported.
rings and four esters linked by saturated aliphatic chain sections. Nonactin has a 48-member ring, built from 40 carbon and 12 (8 on the ring, 4 as ketone
s) oxygen atoms. Liquid chromatography-mass spectrometry
(LC-MS) offers a modern approach to obtain more detailed process control data than the spectrophotometric and chromatographic measurements used in the past.
cations, most notably potassium and sodium. In general, nonactin (and other members of the nactin family) exhibits binding preferences for some ions over others. This ion selectivity is seen in other macrocyclic ligand
s such as the cyclic ionophore valinomycin
, which is also an antibiotic, and crown ether
s. Although nonactin (and in fact, all nactins) exhibits an especially high cation selectivity for potassium ions over sodium ions or rubidium ions, it exhibits the highest selectivity for ammonium ions and thallium ions.
Due to this property, Nonactin is also called "Ammonium ionophore"
During complexation, the nonactin backbone convolutes into a pattern resembling the seam of a tennis ball. In the potassium-nonactin complex, the potassium ion is entirely surrounded by four carbonyl oxygen atoms and the four oxygen atoms of the tetrahydrofuran ring. These eight oxygen atoms surrounding the ion are nearly equidistant from it and adopt a nearly cubic coordination sphere
around the ion. In this complex, all polar carbonyl groups point inwards and nonpolar moieties point outwards, thus building up a hydrophobic exterior for the complex and making it soluble in lipid membranes. This is how nonactin is able to transport potassium ions across lipid membranes.
of mitochondria of rat liver in a low concentration, and can also carry cations across biological and artificial membranes.
A nactins mixture, purposely enriched in tetranactin and poor in nonactin, known as Polynactin(c), was used as a pesticide, but since 2004 is not used any more, presumably because its residuals appeared in food.
Methanol
Methanol, also known as methyl alcohol, wood alcohol, wood naphtha or wood spirits, is a chemical with the formula CH3OH . It is the simplest alcohol, and is a light, volatile, colorless, flammable liquid with a distinctive odor very similar to, but slightly sweeter than, ethanol...
, dichloromethane
Dichloromethane
Dichloromethane is an organic compound with the formula CH2Cl2. This colorless, volatile liquid with a moderately sweet aroma is widely used as a solvent. Although it is not miscible with water, it is miscible with many organic solvents...
, ethyl acetate
Ethyl acetate
Ethyl acetate is the organic compound with the formula CH3COOCH2CH3. This colorless liquid has a characteristic sweet smell and is used in glues, nail polish removers, and cigarettes...
and DMSO
Dimethyl sulfoxide
Dimethyl sulfoxide is an organosulfur compound with the formula 2SO. This colorless liquid is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water...
, but insoluble in water.
Sources
Nonactin is commercially available; as of 2006, there are three bacterial species that produce nonactin: Streptomyces tsukubaensisStreptomyces tsukubaensis
Streptomyces tsukubaensis is a species of actinobacteria. It produces the immunosuppressive drug tacrolimus....
, Streptomyces griseus
Streptomyces griseus
Streptomyces griseus is a member bacterial species of the genus Streptomyces and are commonly found in soil. A few strains have been also reported from deep sea sediments. These are Gram positive bacterium with high GC content. Along with most other streptomycetes S...
, Streptomyces chrysomallus and Streptomyces werraensis. Total syntheses have been reported.
Structure and properties
Nonactin was isolated by Corbaz et al. in 1955 from bacterial strains. It is composed of four tetrahydrofuranTetrahydrofuran
Tetrahydrofuran is a colorless, water-miscible organic liquid with low viscosity at standard temperature and pressure. This heterocyclic compound has the chemical formula 4O. As one of the most polar ethers with a wide liquid range, it is a useful solvent. Its main use, however, is as a precursor...
rings and four esters linked by saturated aliphatic chain sections. Nonactin has a 48-member ring, built from 40 carbon and 12 (8 on the ring, 4 as ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
s) oxygen atoms. Liquid chromatography-mass spectrometry
Liquid chromatography-mass spectrometry
Liquid chromatography–mass spectrometry is an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography with the mass analysis capabilities of mass spectrometry. LC-MS is a powerful technique used for many applications which has very high...
(LC-MS) offers a modern approach to obtain more detailed process control data than the spectrophotometric and chromatographic measurements used in the past.
Reactions
Nonactin is known for its ability to form complexes with alkaliAlkali
In chemistry, an alkali is a basic, ionic salt of an alkali metal or alkaline earth metal element. Some authors also define an alkali as a base that dissolves in water. A solution of a soluble base has a pH greater than 7. The adjective alkaline is commonly used in English as a synonym for base,...
cations, most notably potassium and sodium. In general, nonactin (and other members of the nactin family) exhibits binding preferences for some ions over others. This ion selectivity is seen in other macrocyclic ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
s such as the cyclic ionophore valinomycin
Valinomycin
Valinomycin is a dodecadepsipeptide antibiotic.Valinomycin is obtained from the cells of several Streptomyces strains, among which "S. tsusimaensis" and S. fulvissimus....
, which is also an antibiotic, and crown ether
Crown ether
Crown ethers are cyclic chemical compounds that consist of a ring containing several ether groups. The most common crown ethers are oligomers of ethylene oxide, the repeating unit being ethyleneoxy, i.e., -CH2CH2O-. Important members of this series are the tetramer , the pentamer , and the hexamer...
s. Although nonactin (and in fact, all nactins) exhibits an especially high cation selectivity for potassium ions over sodium ions or rubidium ions, it exhibits the highest selectivity for ammonium ions and thallium ions.
Due to this property, Nonactin is also called "Ammonium ionophore"
During complexation, the nonactin backbone convolutes into a pattern resembling the seam of a tennis ball. In the potassium-nonactin complex, the potassium ion is entirely surrounded by four carbonyl oxygen atoms and the four oxygen atoms of the tetrahydrofuran ring. These eight oxygen atoms surrounding the ion are nearly equidistant from it and adopt a nearly cubic coordination sphere
Coordination sphere
In coordination chemistry, the coordination sphere refers to a central atom or ion and an array of molecules or anions, the ligands, around.Molecules that are attached noncovalently to the ligands are called the second coordination sphere....
around the ion. In this complex, all polar carbonyl groups point inwards and nonpolar moieties point outwards, thus building up a hydrophobic exterior for the complex and making it soluble in lipid membranes. This is how nonactin is able to transport potassium ions across lipid membranes.
Biological effects
Nonactin has been reported to specifically inhibit the processing of cytoplasmic precursor proteins destined for the mitochondria. It is able to uncouple the oxidative phosphorylationPhosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
of mitochondria of rat liver in a low concentration, and can also carry cations across biological and artificial membranes.
A nactins mixture, purposely enriched in tetranactin and poor in nonactin, known as Polynactin(c), was used as a pesticide, but since 2004 is not used any more, presumably because its residuals appeared in food.