Relative steric size of SCH3, OCH3, and C-3 groups from circular dichroismmeasurements

The relative steric size of methyl, methoxy, and methylthio groups was dete rmined from circular dichroism (CD) spectroscopy using a sensitive system b ased on the bilirubin model. In the cyclohexane model, equatorial vs. axial orientation and conformational analysis led to quantitative measurements o f orientation preference or steric demand: conformational A-values CH3 > SC H3 > OCH3. A more sterically demanding model for assessing group size has b een found in bilirubin analogs, which are yellow pigments that adopt a ridg e-tile shape stabilized by a matrix of intramolecular hydrogen bonds. Optic ally active bilirubins have been shown to exhibit intense bisignate CD Cott on 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 intramole cular nonbonded steric interactions that arise when substituents are introd uced at equivalent sterically demanding sites, viz., the alpha or beta carb ons of the pigment's propionic acid chains. Such substituents shift the con formational equilibrium toward the M or the P-chirality conformer, dependin g only on the S or R stereochemistry at the alpha and beta sites, and the r esulting exciton CD for the similar to 430 nm transition(s) was used to eva luate the relative steric size, SCH3 > CH3 > OCH3. (C) 2000 Wiley-Liss. Inc .