Exciton chirality of bilirubin homologs

Abstract

Bilirubin, the yellow pigment of jaundice, is a bichromophoric tetrapyrrole that readily adopts either of two enantiomeric, folded conformations shaped like ridge-tiles and stabilized by a network of six intramolecular hydrogen bonds. Interconversion of these M and P helical chirality conformational enantiomers is rapid at room temperature but may be displaced toward either enantiomer by intramolecular nonbonded steric interactions. Introduction of a methyl group at the β and β′ carbons of the propionic acid chains on the symmetric bilirubin analog, mesobilirubin-XIIIα, shifts the conformational equilibrium toward the M or the P-chirality intramolecularly hydrogen-bonded conformer, depending only on the S or R stereochemistry at β and β′, resulting in pigments with intense exciton coupling circular dichroism (CD) for the ∼430 nm transition(s). Optically active synthetic analogs of bilirubin with propionic acid groups lengthened systematically to heptanoic acid (1–5) were synthesized and examined by spectroscopy to explore the influence of alkanoic acid chain length on conformation and intramolecular hydrogen bonding. In these diacids and their dimethyl esters (6–10), strong exciton chirality CD spectra are observed, and the data are correlated with molecular helicity. Chirality 9:604–615, 1997. © 1997 Wiley-Liss, Inc.