Structure and metabolism of natural and synthetic bilirubins.

The secondary structure of bilirubin, with a ridge-tile shape and six intramolecular hydrogen bonds, is more stable than any other conformation and perhaps the most important determinant of its solubility and properties in solution and its hepatic metabolism/excretion. Uncoupling the intramolecular hydrogen bonding, increasing the acidity of the propionic acid, or even increasing its length can decrease the pigment's hydrophobicity and permit its excretion intact across the liver into bile; less intuitively obvious, so can subtle modifications at C(10), the pivotal carbon in the ridge tile.