Nonactin potassium complexes

Figure 30 The nonactin potassium complex and the schematic representation of this molecule (reproduced with...

Fig. 8. The nonactin (VI) potassium complex viewed along the two-fold axis (after (58)). The bonds marked A and B have torsion angles in the macrocyclic ring of about 63° and 150° respectively...

Fig. 9. The nonactin (FT) potassium complex viewed normal to the two-fold axis which is indicated by an arrow. Representation of atoms and of bonds A and B is the same as in Fig. 8...

Fig. 4.5. Structure of the potassium complex with nonactin (redrawn from B.T. Kilboum et al., J. Molec. Biol.

It was the first naturally occurring crown ether, and the earliest for which the antibiotic activity could be traced to its ionophoric properties (4). The actins give one-to-one complexes with many alkali and alkaline earth metal ions, with nonactin showing selectivity in the order NH4+ > K+ = Rb+ > Cs+ > Na+ > Ba2+ (5). The first X-ray crystal structure of an ionophore-metal complex was obtained from the nonactin-potassium thiocyanate complex (6). The potassium is bound by coordination to all four tetrahydrofuran oxygens and to the four ester carbonyl oxygens, which creates overall a "tennis ball seam" conformation to the carbon framework as it wraps around the metal. 

Nonactin (Fig. 2 is a macrotetrolide antibiotic comprised of four nonactic acid groups that have alternating chirality. Nonactin is of historical interest, as its potassium complex was the first solid-state structure of an ionophore complex to be resolved.The resulting structural insights were valuable in explaining the formation of such... 

It had been shown by Dunitz and co-workers in 1967 that the structure of the potassium complex of nonactin (la) is as shown in Figure 1. The 32-membered ring can be described as resembling the seam of a tennis ball with the K+ ion at the centre of the ball and the methyl substituents and methylene groups of the furan rings on the outside. More recently, the structure of the K+ complex of another macrocyclic antibiotic with potassium transport properties, enniatin B (2), has been determined. In this case, the carrier-K+ complex is in the form of a charged disc with a lipophilic exterior. The authors point out that both molecules are sufficiently large and impenetrable that any counter-ion or polar molecule in... 

Neutral carriers are organic complexing agents which are capable of sequestering and transporting ionic species in a hydrophobic organic phase. The antibiotics, valino-mycin and nonactin were the first neutral carriers to be incorporated in an ISE These macrocyclic neutral carriers contain a polar internal cavity and an outer hydro-phobic shell. The excellent selectivity exhibited by valinomycin for potassium ions is... 

Because the potassium ions are bound in the interior of the nonactin, this host-guest complex becomes hydrocarbonlike on its surface and passes readily through the interior of the membrane. 

Nonactin, isolated from actinomyces, is a macrotetrolide, (VI), which complexes alkali metal salts in the sequence Li < < Na+, Cs+< Rb+< K+. The crystal structures of its complex with potassium thiocyanate and of the uncomplexed molecule have been determined. 

The polyether nonactin (174) is an antibiotic tetralide produced by the Streptomyces family of microorganisms. From a biological point of view, nonactin and the other compounds in this family of tetrameric lactones have the ablility to strongly complex potassium ion and to facilitate the transport of potassium across membranes by providing a lipophilic shell. Ion transport has been shown to have a strong influence on important biological functions such as oxidative phosphorylation and mitochondrial respiration. 

Before leaving the subject of the mechanism of metal-ion transport across membranes, a cautionary result and a by-product of these investigations might be reported. Hall has found that the antibiotic monamycin forms complexes in solution with K+, Rb+, and Cs+, but not with Na+ or Li+. However, it seems that their antibacterial action is due to their lytic effects on cell membranes rather than to any ion-transporting properties they may possess. The metal-ion selectivity of nonactin and valino-mycin has been put to use in the design of potassium-selective membrane electrodes. These contain the antibiotics as components of the membrane, and can be used to estimate K+ in the presence of Na+, for example in human serum. 

In the enniatin B (2)-potassium iodide complex the disordered anions could not be located, but the potassium was found in a position of 3-fold symmetry with the carbonyl oxygen atoms octahedrally disposed at 2.6— 2.8 A. Like nonactin, this depsipeptide has no hydrogen bonds. 

---