Magnesium and calcium reveal different chelating effects in a steroid compound: A model study of prednisolone using NMR spectroscopy.

In this work, we used high resolution NMR spectroscopy to investigate metal cation chelation by the steroidal drug 1,4-pregnadiene-11β,17α,21-triol-3,20-dione (Prednisolone; abbreviated as Prd). Prd/MgCl and Prd/CaCl mixtures were prepared at eight different molar ratios. Using two-dimensional H/C heteronuclear correlation spectroscopy, we were able to resolve most of the H signals, except those at 1.4-1.55 ppm, where signals for H15β, H16α and Me-19 are superimposed. The chelation sites were determined by the cation concentration-dependent C signals. Both ring A and ring D of Prd were found to be involved in Mg chelation, whereas only ring A was involved in Ca chelation. The dihedral angles deduced from the J coupling constants indicated that ring D of Prd might undergo rather small, but different, distortions in the presence of Mg and Ca. Additionally, using the continuous variation method, we deduced that the stoichiometric ratios of the Prd/Mg and Prd/Ca complexes were 1:1 and 2:1, respectively. All of the evidence led us to conclude that the Prd/Mg and Prd/Ca complexes are mediated by different chelating mechanisms.