Exploring the conformation of bilirubins with natural and unnatural analogues: Use of positional and bridged isomers of bilirubin IX alpha.

Unlike bilirubin IX alpha (1), the isomers bilirubin IX delta (2) and neobi lirubin IX beta (3) do not require conjugation with glucuronic acid in orde r to be excreted. A conformational analysis employing an optimized Monte Ca rlo method and a mixed Monte Carlo/stochastic dynamics reveals that isomer 2 exhibits a structure more closed than the well known 'ridge-tile' conform ation 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, the change in the configuration of the distal dipyrrinone and the blockage of the lactam ic 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 th is region is obliterated. The resulting molecular models for these compound s are consistent with H-1 NMR, UV-vis, and TLC data. (C) 1999 Elsevier Scie nce Ltd. All rights reserved.