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.
Kogan
M J
MJ
Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Mora
M E
ME
Awruch
J
J
Delfino
J M
JM
D001663:Bilirubin / Q000031:analogs & derivatives* / Q000737:chemistry; D002855:Chromatography, Thin Layer; D005965:Glucuronates; D020723:Glucuronic Acid; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009010:Monte Carlo Method; D011422:Propionates; D013056:Spectrophotometry, Ultraviolet
D005965:Glucuronates; D011422:Propionates; D020723:Glucuronic Acid; D001663:Bilirubin