Theoretical studies of biliverdin: energetics of the reduction pathways to bilirubin.

Abstract

Geometries and energies of formation of bilirubin formed by reduction of biliverdin via three meso carbon sites, the beta, gamma and delta positions, have been calculated using semiempirical methods. It has been shown that gamma-bilirubin with a ridge-tile conformation forms six intramolecular hydrogen bonds and is the most stable of the three above mentioned positions by at least 22 kcal mol(-1). Reduction pathways for beta-, gamma- and delta-bilirubin formations from biliverdin are studied in detail. The roles of loss of conjugation and hydrogen bond formations in stability of different conformers have been discussed. Gamma-bilirubin was fully optimized by using ab initio methods. Fine refinements of calculated results show excellent agreement with experimental results.