Structure of bilirubin

Abstract

THE biological breakdown of haem proceeds through a series of intermediates of which the orange-yellow bile pigment, bilirubin, the chromophore responsible for coloration in the various forms of jaundice, is a key member. In the adult human, for example, erythrocytes have a lifetime of about 3 months and their destruction produces about 300 mg bilirubin each day^1,2. Although there were some early doubts (arising from the possibility of a cyclisation between the CIS vinyl group and the oxygen function at C19)³, the gross chemical structure (Fig. 1) for bilirubin has been beyond reasonable dispute for many years⁴. There remain, however, considerable structural uncertainties with respect to (1) stereochemistry, the geometry around bridges 5 and 15 being unknown, and represented variously as E or Z in the current literature. (The two configurations, E and Z, have been recognised in a model pyrromethanone system, however, (see ref. 5 and Fig. 2)); (2) tautomerism, although spectroscopic evidence favours the lactam formula for rings A and D (shown in Fig. 1) over the lactim^6–9; and (3) conformation, although several speculations, supported by spectroscopic evidence and model making, are available^10–17. We report the X-ray analysis of bilirubin—the first such analysis of a naturally occurring linear tetrapyrrole—which shows that bilirubin has the Z configuration at the C4–C5 and C15–C16 bonds, and possesses in the crystal a ridge tile conformation with considerable intramolecular hydrogen bonding.