Nonactin is a member of a family of naturally occurring cyclic

ionophores In chemistry, an ionophore () is a chemical species that reversibly binds ions. Many ionophores are lipid-soluble entities that transport ions across the cell membrane. Ionophores catalyze ion transport across hydrophobic membranes, such as liq ...

known as the macrotetrolide

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...

. The other members of this 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 Ethyl acetate ( systematically ethyl ethanoate, commonly abbreviated EtOAc, ETAC or EA) is the organic compound with the formula , simplified to . This colorless liquid has a characteristic sweet smell (similar to pear drops) and is used in glues ...

and

DMSO Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula ( CH3)2. This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds ...

, but insoluble in water.

Sources

Nonactin is commercially available; as of 2006, these bacterial species produce nonactin: ''

Streptomyces tsukubensis ''Streptomyces tsukubensis'' is a bacterium species from the genus of '' Streptomyces'' which has been isolated from soil in Ibaraki in Japan.Deutsche Sammlung von Mikroorganismen und Zellkulturenbr>/ref> ''Streptomyces tsukubensis'' produces ...

'', ''

Streptomyces griseus ''Streptomyces griseus'' is a species of bacteria in the genus ''Streptomyces'' commonly found in soil. A few strains have been also reported from deep-sea sediments. It is a Gram-positive bacterium with high GC content. Along with most other ...

'', '' 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

tetrahydrofuran Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water- miscible organic liquid with low viscosity. It is ...

rings and four

esters In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

linked by saturated aliphatic chain sections. Nonactin has a 48-member ring, built from 40 carbon and 12 (8 on the ring, 4 as ketones) oxygen atoms. Despite the 16 stereogenic centers, Nonactin is a

meso compound A meso compound or meso isomer is a non-optically active member of a set of stereoisomers, at least two of which are optically active. This means that despite containing two or more stereocenters, the molecule is not chiral. A meso compound is "su ...

, and therefore achiral.

Liquid chromatography-mass spectrometry A liquid is a nearly incompressible fluid that conforms to the shape of its container but retains a (nearly) constant volume independent of pressure. As such, it is one of the four fundamental states of matter (the others being solid, gas, a ...

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 alkali

cations An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by con ...

, 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 In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...

s, such as the cyclic ionophore

valinomycin Valinomycin is a naturally occurring dodecadepsipeptide used in the transport of potassium and as an antibiotic. Valinomycin is obtained from the cells of several ''Streptomyces'' species, '' S. fulvissimus'' being a notable one. It is a member o ...

, which is also an antibiotic, and

crown ether In organic chemistry, crown ethers are cyclic chemical compounds that consist of a ring containing several ether groups (). The most common crown ethers are cyclic oligomers of ethylene oxide, the repeating unit being ethyleneoxy, i.e., . Impo ...

s. Although nonactin (and 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 A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many ...

, 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 In coordination chemistry, the first coordination sphere refers to the array of molecules and ions (the ligands) directly attached to the central metal atom. The second coordination sphere consists of molecules and ions that attached in various ...

around the ion. In this complex, all polar carbonyl groups point inwards and nonpolar moieties point outwards, thus building up a

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, t ...

exterior for the complex and making it soluble in

lipid membrane The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...

s. 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 phosphorylation 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.Notification
the

World Trade Organization The World Trade Organization (WTO) is an intergovernmental organization that regulates and facilitates international trade. With effective cooperation in the United Nations System, governments use the organization to establish, revise, and ...

's revocation of Polynactin agricultural usage, July 20, 2004.

Applications

Nactins have no known medical use. Ultrapure nonactin, practically free of other nactins, is used for ammonium-specific electrodes.

Sources

Structure and properties

Reactions

Biological effects

Applications

References

Further reading