Study of a delta-hydroxy ketone-hemiketal equilibrium by 2D-NMR exchange spectroscopy for the antibiotic grisorixin: involvement in cationic transport through membranes.

ABSTRACT

Study of a delta-hydroxyketone-hemiketal equilibrium in the polyether antibiotic grisorixin was performed with 2D-NMR spectroscopy. The efficiency of 13C chemical exchange spectroscopy for the assignment of 1H and 13C resonances, in the 2 forms, was shown, making possible a conformational investigation of both forms. This equilibrium was observed for grisorixin in solvents of varying polarity, such as CD2Cl2, CDCl3, CD3CN, or CD3OD, but not in C6D12 or C6D6. Other related antibiotics with the same terminal heterocycle were described only in the closed hemiacetalic structure. The low ionic fluxes measured in a bulk chloroformic membrane for grisorixin were explained by this equilibrium, which competed unfavorably with the cation capture process at the water-chloroform interface. This equilibrium would not be present in a phospholipidic bilayer membrane containing the ionophore, published experimental results are taken into account. The peculiar tautomeric equilibrium observed for grisorixin could be linked to the specific axial stereochemistry of the C7-C8 bond, which creates tension in the globular conformation.