Monensin A acid complexes as a model of electrogenic transport of sodium cation

Abstract

New Monensin A acid complexes with water molecule, sodium chloride and sodium perchlorate were obtained and studied by X-ray and (1)H, (13)C NMR and FT-IR methods as well as ab initio calculations. The crystal structure of the complexes indicates the complexation of the water molecule and Na(+) cation in the pseudo-cycle conformation of the Monensin acid molecule stabilised by intramolecular hydrogen bonds. Important for stabilisation of this structure is also the intermolecular hydrogen bonds with water molecule or the coordination bonds with Na(+) cation. It is demonstrated that the counterions forming intermolecular hydrogen bonds with OH groups influence the strength of the intramolecular hydrogen bonds, but they have no influence on the formation of pseudo-cyclic structure. Spectroscopic studies of the complexes in dichloromethane solution have shown that the pseudo-cyclic structure of the compounds is conserved. As follows from the ab initio calculations, the interactions between the Na(+) cation and the electronegative oxygen atoms of Monensin acid totally change the molecular electrostatic potential around the supramolecular Monensin acid-Na(+) cationic complex relative to that of the neutral Monensin acid molecule.

Electrogenic and nonelectrogenic ion fluxes across lipid and mitochondrial membranes mediated by monensin and monensin ethyl ester

“…The structural basis for this type of transport can be the crystal structure of a complex of acidic form of monensin with a sodium ion (I-COOH-M + , Fig. 2B) postulated by Huczyński et al [22,30]. A diffusion of the complex in one direction and a backward diffusion of I-COOH without the metal cation can be a mechanism of this type of electrogenic ion transport (Fig.…”

“…However, the experiments with planar lipid bilayers (BLM) [18,19] and liposomes [20,21] showed that monensin was able to transport sodium and potassium cations in an electrogenic manner, that is, generating electrical current on BLM and electrical potential on liposomes. The structural basis for this type of transport can be the structure of the acidic form of monensin with a sodium cation (I-COOH-M + ) present in crystal and in solutions, as has been proved by Huczyński et al [22]. Diffusion of I-COOH-M + complex in one direction and a backward diffusion of I-COOH without the metal cation can be a mechanism of this type of electrogenic ion transport (Fig.…”

Salinomycin Hydroxamic Acids: Synthesis, Structure, and Biological Activity of Polyether Ionophore Hybrids

“…Despite extensive experimentation, we were unable to crystallize 5a or its Na + or K + salts. Drawing on a report of a neutral NaClO 4 complex of monensin, however, 50,51 we were gratifyingly able to obtain single crystals of a neutral form of 5a binding a sodium atom with a noncoordinating PF 6 − counterion. On a general note, this result suggests that alkali metals with noncoordinating counterions may be of a broader utility for growing crystals of related compounds that are otherwise difficult to crystallize.…”

Monensin Inhibits Canonical Wnt Signaling in Human Colorectal Cancer Cells and Suppresses Tumor Growth in Multiple Intestinal Neoplasia Mice

“…The ionophoric antibiotics, the group currently includes more than 100 compounds, are studied mainly for their antibacterial, antifungal, and antiparasitic biologic activity (9). Monensin was approved by the U.S. Food and Drug Administration for use in veterinary practice as a coccidiostat in poultry and growth-promoting agent in cattle (New Animal Drug Application No.…”

“…We identified monensin, an antibiotic isolated from Streptomyces cinnamonensis bacteria (9), as a potent blocker of the Wnt-induced transcription in cells stimulated with Wnt ligands or GSK3 inhibitors. The suppressive effect of monensin on Wnt signaling was also observed in the tail fin regeneration assay in zebrafish and Xenopus body axis duplication experiment.…”