SYNTHESIS AND PROPERTIES OF BILIRUBIN ANALOGS WITH N,N-METHYLENE BRIDGES

Bilirubin analogs have been prepared with a methylene group forming an N to N bridge. When the bridge is in the same dipyrrinone, only one p ropionic acid can hydrogen bond intramolecularly (to the unbridged dip yrrinone), but the pigment still adopts a ridge-tile conformation. Mol ecular dynamics calculations predict global energy minima for two enan tiomeric ridge-tile conformations separated by an energy barrier of si milar to 14.5 kcal/mole. In contrast, when the bridge connects two dip yrrinones through their lactam nitrogens, that pigment is held in a po rphyrin-like shape, neither propionic acid groups can participate in i ntramolecular hydrogen bonding, and the pigment is much more polar and hydrophilic than bilirubin. Molecular dynamics calculations predict a n interconversion barrier of similar to 25 kcal/mole for this isomer.