Sulfoxides as chiral complexation agents. Conformational enantiomer resolution and induced circular dichroism of bilirubins

Bilirubin-IX, the end product of porphyrin metabolism in mammals and the neurotoxic yellow-orange pigment of jaundice, exhibits a strong tendency to fold like a book into either of two interconverting enantiomeric conformations, which are further stabilized by intramolecular hydrogen bonding. Bilirubin exhibits optical activity in R-(-)-ethylmethylsulfoxide solvent, as seen by moderately strong bisignate circular dichroism Cotton effects (Δε^max₄₅₂=+10.9,Δε^max₄₀₄=-4.5), and in dichloromethane solution in the presence of 2M R-(+)-methyl-p-tolylsulfoxide its circular dichroism spectrum (Δε₄₆₃^max=+11.2,Δε₄₁₂^max=-7.1) is comparably strong. As observed earlier for chiral recognition of bilirubin by optically active amines and serum albumins, the optically active sulfoxide acts as a chiral complexation agent to induce an asymmetric transformation of bilirubin, whose bisignate circular dichroism spectra are characteristic of an exciton splitting arising from interaction of the two component dipyrrinone chromophores.