Probing the conformation of bilirubins with monopropionic analogs: a biological, spectroscopic, and molecular modeling study.

The in vivo metabolism of a bilirubin analog substituted with a propionic acid chain in C8 (5) showed that it is excreted in bile conjugated with glucuronic acid, while a positional isomer substituted with a propionate in C7 (6) is excreted in bile without conjugation. A conformational analysis employing an optimized Monte Carlo method and a mixed Monte Carlo/stochastic dynamics reveals that isomer 5 adopts a 'ridge tile' conformation, stabilized by the presence of three intramolecular hydrogen bonds. On the contrary, isomer 6 exhibits a more closed structure, where impairment in the formation of at least one of the hydrogen bonds occurs. These theoretical predictions agree well with 1H NMR, UV-vis, and TLC data.