Computational Chemical Analysis of Unconjugated Bilirubin Anions and Insights into pKa Values Clarification

ESTEBAN G. VEGA HISSI; MARIO R. ESTRADA; MARTÍN J. LAVECCHIA; REINALDO PIS DIEZ

JOURNAL OF CHEMICAL PHYSICS

AMER INST PHYSICS

Lugar: New York; Año: 2013 vol. 138 p. 351011 - 3510110

0021-9606

The pKa, the negative logarithm of the acid dissociation equilibrium constant, of the carboxylicacid groups of unconjugated bilirubin in water is a discussed issue because there are quite dif-ferent experimental values reported. Using quantum mechanical calculations we have studied theconformational behavior of unconjugated bilirubin species (in gas phase and in solution modeledimplicitly and explicitly) to provide evidence that may clarify pKa values because of its pathophys-iological relevance. Our results show that rotation of carboxylate group, which is not restricted,settles it in a suitable place to establish stronger interactions that stabilizes the monoanion and thedianion to be properly solvated, demonstrating that the rationalization used to justify the high pKavalues of unconjugated bilirubin is inappropriate. Furthermore, low unconjugated bilirubin (UCB)pKa values were estimated from a linear regression analysis.