Acid dissociation constants of bilirubin and related carboxylic acid compounds in bile salt solutions

Bilirubin, the yellow-orange tetrapyrrole pigment of jaundice, is essential ly insoluble in pure water, but is much more soluble in solutions of bile s alts such as sodium taurocholate, The biophysical chemistry of bilirubin in bile salt solutions is affected by changes in the pH of the solution in th e range 5-9, suggesting that interactions with bile salt molecules and mice lles may alter the acidity of the pigment. We have examined this possibilit y by determining the apparent pK(alpha) values for a series of carboxyl C-1 3-enriched model compounds, including the bilirubin analog mesobilirubin XI II alpha, in solutions of sodium taurocholate and sodium taurodeoxycholate. Apparent pK(alpha) values were determined by C-13 NMR titrations in dimeth yl sulfoxide-water mixtures. The results show that the acidity of all compo unds is decreased, or pK(alpha) increased, in micellar bile salt solution r elative to pure water and that the effect is greatest for the larger, less water-soluble compounds. We have proposed a model to explain these results and discussed the implications of these findings for the biophysical chemis try of bilirubin in bile. (C) 2000 Academic