Complexation of Metal Ions by Monensin. Crystal and Molecular Structure of Hydrated and Anhydrous Crystal Forms of Sodium Monensin

The conformations of the sodium-monensin complex observed in anhydrous and dihydrate crystal forms are nearly identical with one another, with the previously reported Ag+ complex, and with a complex with sodium bromide. The dihydrate crystallizes in the orthorhombic space group P212121 (a = 16.387 (4) Å,b = 18.684 (4) Å, c = 12.792 (3) Å, Z = 4) and the anhydrous complex crystallizes in the monoclinic space group P2X [a = 9.218 (5) Å, b = 12.702 (1) Å, c = 16.274 (7) Å, β = 101.02 (1)°, Z = 2). The conformations of all of the metal complexes differ from that of the free acid in the carboxylic acid conformation, the heat-to-tail hydrogen bonding, and the conformation of one of the five-membered rings. Although individual torsion angle differences between uncomplexed and complexed monensin seldom exceed 15°, the positions of three of the coordinating oxygens are shifted by 1.0, 1.9, and 2.1 Å relative to the oxygens in the invariant part of the molecule. A comparison of the complexed and uncomplexed structures suggests that complexation could easily be initiated by association of a metal ion with an ether oxygen, O(7), which is near the surface of the free acid. Two other oxygen atoms, O(6) and O(4), in the invariant part of the molecule are then positioned to displace additional water of hydration from the ion. No change in the monesin conformation is necessary during this step, but a minor rearrangement of the intramolecular hydrogen bonds must take place. This rearrangement initiates a change in head-to-tail hydrogen bonding and the repositioning of the O(8), O(9), and O(11) atoms so that the remaining solvent is displaced from the metal ion completing the coordination. If the ability of monensin to complex metal ions is in part attributable to the flexibility of the five-membered C ring it may be possible to modify monensin by methyl substitutions on this ring, stabilizing a particular conformation.