Intermolecular Hydrogen Bonding and Dimeric Structures in Bilirubin Esters from 1H-NMR Spectroscopy

Analysis of the N-H ¹H-NMR chemical shifts of various bilirubin dimethyl esters indicates intermolecularly H-bonded dimers in CDCl₃ solution with pairwise pyrromethenone associations. The presence of an exo (C-2 or C-18) vinyl or ethyl group on the lactam ring leads to relatively weaker H-bonding as compared with an endo (C-3 or C-17) vinyl or ethyl group. Consequently, in a non-symmetric bilirubin, e.g. IXα, the endo-vinylpyrromethenone to endo-vinylpyrromethenone intermolecular H-bonding becomes much stronger (with more deshielded N-H proton chemical shifts) than in corresponding symmetric isomers, e.g. XIIIα or IIIα.