Exploring the Conformation of Bilirubins with Natural and Unnatural Analogues: Use of Positional and Bridged Isomers of Bilirubin IX

KOGAN, MARCELO; MORA, MARÍA EUGENIA; BARI, SARA E. ; ITURRASPE, JOSÉ B.I. ; AWRUCH, JOSEFINA; DELFINO, JOSÉ MARÍA

BIOORGANIC & MEDICINAL CHEMISTRY.

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 1999 vol. 7 p. 1309 - 1319

0968-0896

Unlike bilirubin IXa (1), the isomers bilirubin IXd (2) and neobilirubin IXb (3) do not require conjugation with glucuronic acid in order to be excreted. A conformational analysis employing an optimized Monte Carlo method and a mixed MonteCarlo/stochastic dynamics reveals that isomer 2 exhibits a structure more closed than the well known `ridge-tile´ conformation of 1.The change in the position of both propionic acid chains causes the loss of at least four hydrogen bonds. On the other hand, thechange in the configuration of the distal dipyrrinone and the blockage of the lactamic nitrogen by the presence of a bridge in isomer 3 results in an open and more elongated structure, where the chance of hydrogen bond formation in this region is obliterated. Theresulting molecular models for these compounds are consistent with 1H NMR, UV±vis, and TLC data.