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. To study whether any bile pigment metal 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 350 m[mu] (Soret band) and 2 visible absorption bands at 595 m[mu] and 645 m[mu]. Infrared spectroscopy showed that this compound is a complex salt of bilirubin and Cu having an analogous structure to metalloporphyrins, in which bilirubin has a ring structure of tetrapyrroles and Cu is located in the center of N 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 Cu to sodium bilirubinate. The black pigments of the gallstone thus possibly include some metal-complexes of bile pigments.