The conformational behaviour of the cardiac glycoside digoxin as indicated by NMR spectroscopy and molecular dynamics calculations.

The 1H- and 13C-NMR spectra of digoxin in solution in Me2SO-d6 have been assigned completely. Measurement of the 3JC,H values has enabled estimation of the torsional angles involving the bonds linking the digitoxose residues, between the inner digitoxose and the genin unit, and for the unsaturated gamma-lactone ring. These values have been supplemented by 1H-1H NOE data. In general, there is good agreement between the conformations in solution (NMR data) and the solid state (X-ray data), and that derived from theoretical modelling which shows evidence of conformational flexibility. The major difference occurs for the torsion between the genin and the innermost digitoxose residue where molecular dynamics predict the presence of two conformations, one similar to that seen by NMR and the other similar to the X-ray structure.