Mechanisms for steroid-induced conformational enantiomerism of bilirubin in protic solvents

Abstract

CD spectroscopy has been applied to clarify the mechanism for the conformational enantiomerism of bilirubin (BR) upon complexation with bile salts in water. The BR dianion when bound to the deoxycholate (1), cholate (2), chenodeoxycholate (3), ursodeoxycholate (4) or taurodeoxycholate ion (6) shows a (+)-to-(–) bisignate CD Cotton effect in water at pH 10.8 (NaOH), indicating that BR bound to these bile salts selectively adopts a (R)-helix configuration. Solubilization of BR in bile salt micelles is not necessary to induce the conformational enantiomerism of BR. The CD spectroscopic results on complexation of BR with various bile acids and their derivatives in methanol indicate that the hydrogen-bonding interactions between the hydroxy groups of a steroid and the carboxy groups of BR promote the conformational enatiomerism of BR. The mechanism for the enantioselective complexation in water at pH 10.8 has been deduced from the results obtained in methanol as that hydrogen bonding between the carboxylate ions of BR and the hydroxy groups of bile salt, as well as van der Waals interactions between the host and the guest, dominates the enantioselectivity in the BR–bile salt complexation.