Exploring the conformation of bilirubins with natural and unnatural analogues: use of positional and bridged isomers of bilirubin IXalpha

KOGAN MJ; MORA ME; BARI SE; ITURRASPE J; AWRUCH J; DELFINO JM

BIOORGANIC & MEDICINAL CHEMISTRY.

Año: 1999 vol. 7 p. 1309 - 1319

0968-0896

Unlike bilirubin IXalpha (1), the isomers bilirubin IXdelta (2) and neobilirubin IXbeta (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 Monte Carlo 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, the change 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. The resulting molecular models for these compounds are consistent with 1H NM R, UV-vis, and TLC data.