Monensin metal complexes

Ionophores, or polyether (PET) antibiotics, produced by various species of Streptomyces, possess broad spectrum anticoccidial activities. They are chemically characterized by several cyclic esters, a single terminal carboxylic acid group, and several hydroxyl groups. Representative members of this class include salinomycin (SAL), monensin (MON), lasalocid (LAS), narasin (NAR), maduramicin (MAD), and semduramicin (SEM). The main chemical properties of interest in the extraction methodology are their low polarities and instability under acidic conditions. They are able to form stable complexes with alkaline cations. All of these compounds, with the exception of LAS, bind monovalent cations (e.g., Na+ and K+). Lasalocid has a tendency to form dimers and can form complexes with divalent cations such as Mg2+ and Ca2+. The formation of metal complexes results in all of these compounds adopting a quasi-cyclic formation consequent to head-to-tail hydrogen bonding. No MRLs have yet been set by the EU for any of the carboxylic acid PETs (98). 

Antibiotics form a large proportion of the remaining natural products which have been examined by X-t y analysis. The crystallographic interest in antibiotics centres both on the ability to form a variety of complexes with different metal ions, and also on the polarization of hydrophobic and hydrophilic properties within the moiecuies, since it has been suggested that both these features may be implicated in the biological functions of such molecules. One antibiotic, monensin (158), has been studied both as the free acid, and also as the silver(i) salt. In the metal complex, the... 

Gertenbach, P. G., and Popov, A. T., Solution chemistry of monensin and its alkali metal complexes. Potentiometric and spectroscopic studies, J. Am. Chem. Soc., 97, 4738, 1975. 

The alkali metal cation complexes of compounds of the nigeridn group (nigericin, monensin, grisorixin, X-206, X-537A, dianemycin) are electrically neutral. 

Both monensin (24) and nigericin (25) complex Na+ and K+ strongly but not selectively. The crystal structures of the Na+, Tl+ and Ag+ complexes all show the metal ion to be in an O-rich cavity. The carboxylate group is not involved however.97 With the antibiotics (26), (27) and (28) the thermodynamic stabilities (Table 9) are greater for the divalent than for the monovalent metal ions.98 The conformations adopted in these complexes axe very solvent dependent, and the implication of these to the biological transportation of the cations has been discussed.99... 

The antibiotics are compounds secreted by microbes that enhance the permeability of membranes to cations. One class functions by binding a metal to give a liposoluble complex that can then pass across the membrane. Examples are valinomycin, a cyclic peptide that binds K+ selectively, and monensin which binds Na+. These too are oxygen-donor ligands, and will be discussed in the following section. They function as antibiotics because they allow the concentrations of a cation across membranes to become equalized, and so cause the collapse of the membrane potential. 

Polyether metabolites are ionophoric antibiotics which have their major applications in the area of animal husbandry. The distribution of oxygen atoms in these structures predisposes them towards the complexation of alkali metal ions, and their mode of action is considered to depend upon the ability to disrupt the sodium-potassium ion balance across cell membranes. Monensin A from Streptomyces cinnamonensis and tetronasin from Streptomyces longisporoflavus are extensively studied examples of these metabolites. 

The conformational studies on the ferrichromes and on ferrioxamine B indicate that a number of intramolecular hydrogen bonds are formed in the process of metal-chelation and that these contribute to the overall stability of the coordinated conformation relative to that of the free species. Consistent with this view, it should be mentioned that extensive hydrogen bonding has also been observed in the low molecular weight monovalent cation complexes of the antibiotics monensin, nigericin, dianemycin, the enniatins and valinomycin by NMR spectroscopy (69, 70), X-ray crystallography (71, 72, 73), or both. Like the siderochromes, these compounds act by mediating cation fluxes across membranes. 

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