On Bilirubin-metal Complex Compounds in Relation to Black Pigments of Gallstones

Abstract

Gallstones occasionally contain black pigments which consist mostly of polymers of bilirubin derivatives. In order to study whether any bile pigmentmetal complex is also concerned with such black pigments of the gallstone, attempts were made at synthesis of bilirubin-Cu complexes. When free bilirubin and cupric chloride were mixed in a solvent mixture of chloroform and ethanol, a dark blue or black substance was formed. This pigment was soluble in ethanol and showed a characteristic absorption at 350mμ (Soret band) and two visible absorption bands at 595mμ and 645mμ. Infrared spectroscopy has revealed that this compound is a complex salt of bilirubin and copper having an analogous structure to metalloporphyrins, in which bilirubin has a ring structure of tetrapyrroles and copper is located in the center of nitrogen atoms of pyrroles. On the other hand, addition of cupric chloride to bilirubin in sodium hydroxide solution resulted in sedimentation of a black substance. This pigment has proved spectrometrically to be a bilirubin-Na-Cu complex formed by coordination of copper to sodium bilirubinate. Thus, it seems to be possible that the black pigments of the gallstone include some metal-complexes of bile pigments.