Conformation and hydrogen-bonding study of an exploded bilirubin

ORGN 533

Sanjeev K. Dey, deys@unr.nevada.edu and David A. Lightner. Department of Chemistry, University of Nevada, 1664 North Virginia Street, Reno, NV 89557
Bilirubin IXα is the lipophilic, water insoluble, yellow-orange pigment of jaundice. It is produced in the body as the end product of heme metabolism. Bilirubin IXα is composed of two dipyrrinone units conjoined together through a -CH2- group, and each dipyrrinone contains a propionic acid side chain. Each dipyrrinone unit can rotate independently around the -CH2- in order to reach the lowest energy conformation. The most stable conformation is one with six intramolecular hydrogen bonds, from each dipyrrinone to a CO2H, causing the pigment to adopt a ridge-tile conformation. The shape of bilirubin IXα plays a major role in its physicochemical properties and metabolism, making it very important to study. Major perturbations at the center of the pigment (at the C(10) -CH2-) and the alkanoic acid group can exert a large influence on the intramolecular hydrogen bonding and hence on its conformation and properties in solution. The C(10) -CH2- group has now been homologated to -CH2-CH2- with expected folding up of the ridge-tile, and the propionic acid chain has been replaced with butanoic acid to better favor intramolecular hydrogen bonding. In the closed-up pigment conformation the stereochemical consequences of these alterations are studied by 1H NMR, NOE experiments, VPO measurements and UV-Vis spectroscopy.