Typical linear and porphyrin-like structure representations of bilirubin give an incorrect impression of its actual shape and expected solution properties. Conformational analysis of bilirubin, assisted by molecular dynamics computations, indicates that (i) nonbonded intramolecular steric interactions are minimized in a ridge-tile shape conformation lying at a global energy minimum on the conformational energy map and (ii) considerable additional stabilization is achieved through a networkof intramolecular hydrogen bonds. The linear and porphyrin-like conformations arecomputed to lie some 37-48 kcal/mol above the isoenergetic global minimum energy conformations, which correspond to superimpsable (identical) or to nonsuperimposable (enantiomeric) mirror image intramolecularly hydrogen-bonded ridge-tile conformers. Two different low-energy (1 9.5 and 2 1.4 kcal/mol) transition states can be identified on pathways for interconverting these conformational enantiomers. The conformation of bilirubin may be determined experimentally by UV-visible and, especially, circular dichroism (CD) spectroscopy. Such conformation dependent spectra arise from exciton coupling between the two dipyrrinone chromophores of bilirubin. Theoretical analysis using the exciton coupled oscillator model allowed a mapping of CD Ae for each bilirubin conformation of the conformational energy surface. An intense bisignate CD spectrum is predicted for the global energy minimum conformation with Cotton effects A€ N 1200 L mol-' cm-1 for the long wavelength UV-visible absorption near 450 nm. Surprisingly, Cotton effect sign reversals without inversion of molecular absolute configuration are predicted when the ridge-tile conformations are flattened somewhat into higher energy structures.

No abstract

There are cases in which exciton coupling between two chromophores does not occur because the two electric transition moments which should interact are coplanar. This is seen with cyclohexane-1,4-diols (both ee or ea) and a wide variety of 3-hydroxy carotenoids, 3-hydroxyretinoids, etc. A general approach to deal with such cases is to acylate one of the hydroxyl groups with a chiral allenic acid substituted with a suitable chromophore, e.g., CHROM-CH = C = CH-COOH. The allenic bond introduces a 90 degrees twist at the italicized central carbon so that the allenic CHROM now couples with the second chromophore. This concept of introducing an auxiliary allenic center should be of general applicability in other similar cases.

No abstract

No abstract