The gem-dimethyl effect: amphiphilic bilirubins

Abstract

New bilirubin congeners ( 1a– 1d ) with the central C(10) CH 2 replaced by C(CH 3) 2 were smoothly synthesized by coupling two identical dipyrrinones with 2,2-dimethoxypropane under acid catalysis. The new yellow pigments, with acid chains varying from acetic ( n=1) to propionic ( n=2) to butyric ( n=3) to hexanoic ( n=5), exhibit unusual amphiphilicity relative to the parent mesobilirubins without the gem-dimethyls and have highly favorable solubility in organic solvents ranging from nonpolar (benzene) to polar (CH 3OH). Like the parent rubins, 1a– 1d can easily bend about the middle but unlike the parents they cannot form mesobiliverdin analogs. NMR spectroscopic analysis and molecular dynamics calculations indicate that, like the parents, 1a– 1d adopt ridge-tile shapes that are stabilized by intramolecular hydrogen bonding. Confirmation of the conformation in 1b comes from its X-ray crystallographic structure.