Chirality inversion in the bilirubin molecular exciton.

The bichromophoric pigment bilirubin acts as a molecular exciton in its UV-visible and circular dichroism (CD) spectroscopy. In both polar and nonpolar solvents, an optically active analog, (beta R,beta 'R)-dimethylmesobilirubin-XIII alpha (1), exhibits intense bisignate CD Cotton effects in the region of its long wavelength UV-vis absorption near 400 nm: Delta epsilon(434)(max) + 337, Delta epsilon(389)(max) - 186 (CHCl(3)), and Delta epsilon(431)(max) + 285, Delta epsilon(386)(max) - 177 (CH(3)OH). However, introduction of an amine into a CHCl(3) solution of 1 causes the Cotton effect signs to become inverted, e.g., after addition of NH(3), Delta epsilon(433)(max) - 345, Delta epsilon(389)(max) + 243, and after addition of ethylene diamine, Delta epsilon(435)(max) - 420, Delta epsilon(390)(max) + 299. The sign inversions imply inversion of molecular chirality of the bilirubin and the phenomenon appears to be general for amines, including alpha,omega-diamines. 1,8-Diaminooctane was found to be more effective than longer or shorter chain analogs in producing CD sign inversion.

Relative steric size of SCH(3), OCH(3), and CH(3) groups from circular dichroism measurements.

The relative steric size of methyl, methoxy, and methylthio groups was determined from circular dichroism (CD) spectroscopy using a sensitive system based on the bilirubin model. In the cyclohexane model, equatorial vs. axial orientation and conformational analysis led to quantitative measurements of orientation preference or steric demand: conformational A-values CH(3) > SCH(3) > OCH(3). A more sterically demanding model for assessing group size has been found in bilirubin analogs, which are yellow pigments that adopt a ridge-tile shape stabilized by a matrix of intramolecular hydrogen bonds. Optically active bilirubins have been shown to exhibit intense bisignate CD Cotton effects from exciton coupling of their two dipyrrinone chromophores held in either of two enantiomeric ridge-tile conformations. Interconversion of these M and P conformational enantiomers of helical chirality is rapid at room temperature but may be displaced toward either enantiomer by intramolecular nonbonded steric interactions that arise when substituents are introduced at equivalent sterically demanding sites, viz., the alpha or beta carbons of the pigment's propionic acid chains. Such substituents shift the conformational equilibrium toward the M or the P-chirality conformer, depending only on the S or R stereochemistry at the alpha and beta sites, and the resulting exciton CD for the approximately 430 nm transition(s) was used to evaluate the relative steric size, SCH(3) > CH(3) > OCH(3).

Exciton chirality of bilirubin homologs.

Bilirubin, the yellow pigment of jaundice, is a bichromophoric tetrapyrrole that readily adopts either of two enantiomeric, folded conformations shaped like ridge-tiles and stabilized by a network of six intramolecular hydrogen bonds. Interconversion of these M and P helical chirality conformational enantiomers is rapid at room temperature but may be displaced toward either enantiomer by intramolecular non-bonded steric interactions. Introduction of a methyl group at the beta and beta' carbons of the propionic acid chains on the symmetric bilirubin analog, mesobilirubin-XIII alpha, shifts the conformational equilibrium toward the M or the P-chirality intramolecularly hydrogen-bonded conformer, depending only on the S or R stereochemistry at beta and beta', resulting in pigments with intense exciton coupling circular dichroism (CD) for the approximately 430 nm transition(s). Optically active synthetic analogs of bilirubin with propionic acid groups lengthened systematically to heptanoic acid (1-5) were synthesized and examined by spectroscopy to explore the influence of alkanoic acid chain length on conformation and intramolecular hydrogen bonding. In these diacids and their dimethyl esters (6-10), strong exciton chirality CD spectra are observed, and the data are correlated with molecular helicity.