Nonactin

Nonactin is a member of a family of naturally occurring cyclic ionophores known as the macrotetrolide antibiotics. 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.

It was isolated by Corbaz et al. in 1955 from bacterial strains. It is composed of four tetrahydrofuran rings and four carbonylic esters linked by saturated hydrocarbon moieties. Nonactin has a 48-member ring, built from 40 carbon and 12 (8 on the ring, 4 as ketones) oxygen atoms.

As of 2006, there are three bacterial species that produce Nonactin: Streptomyces tsukubaensis, Streptomyces griseus, Streptomyces werraensis.

Nonactin is known for its ability to form complexes with alkali cations, most notably potassium and sodium. It also displays a marked binding preference for potassium ion over sodium ion. 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 ligands such as the cyclic ionophore valinomycin which is also an antibiotic. Ion selectivity is also observed in crown ethers which also exhibit a discriminatory preference of some ions over others. Although nonactin (and in fact, all nactins) exhibits an especially high cation selectivity for potassium ion over sodium and rubidium ion, it exhibits the highest selectivity for ammonium ion and thallium ion.

During complexation, the nonactin backbone convolutes into a pattern resembling the seam of a tennis ball. In the K+-nonactin complex, the K+ ion is entirely surrounded by four carbonyl oxygen atoms and the four oxygen atoms of the tetrahydrofuran ring. These eight oxygen atoms that surround 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 K+ ions across lipid membranes.

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.

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.

Nonactin is soluble in Methanol, Dichloromethane, Ethyl Acetate and DMSO (dimethyl sulfoxide). It is insoluble in water.

Nonactin is a very powerful chelate and must therefore be used with plenty of caution. It is toxic and suspected as eye irritant.

Use of Nonactin
There is no known medical use of nactins. Ultrapure Nonactin, practically free of other nactins, is used for ammonium specific electrodes.