ORGN 549 |
| Bilirubin-IXα is a water-insoluble, lipophilic, yellow-orange tetrapyrrole pigment formed from heme during normal metabolism in mammals. It is composed of two dipyrrinone units conjoined together at a -CH2- group, and each dipyrrinone contains a propionic acid side chain. The most stable conformation of the pigment has six intramolecular hydrogen bonds, from each dipyrrinone to a CO2H, securing the pigment in a ridge-tile conformation. Due to its unusual lipophilicity, it can cross blood-brain barrier and can cause irreversible neurological damage in the new born. However, the mechanism of its uptake and neurotoxicity is not known. The degree of ionization of carboxylic acid of bilirubin may be key determinant in these processes. Although bilirubin has two propionic acid groups, accurate determination of the pKa in water is difficult due to the aqueous insolubility of the pigment in water at pH< 10. Therefore, a water-soluble analog of bilirubin bearing sodium sulfonate moiety at C10 position has been synthesized, and the average pKa of the carboxylic acid groups has been measured by potentiometric titration. |
|
New Reactions and Methodology, Heterocycles and Aromatics, Bioorganic Chemistry
8:00 PM-10:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster
Division of Organic Chemistry |