Vibrational and Electronic Circular Dichroism of Dimethyl Mesobilirubins-XIIIα

Abstract

The vibrational circular dichroism (VCD) spectra of (αR,α'R)-, (αS,α'S)-, (βR,β'R)-, and (βS,β'S)-dimethylmesobilirubin-XIIIα have been recorded in the range of 1800-900 cm(-1) in CDCl3 solution and in mixed DMSO-d6/CDCl3 solutions. Ab initio density functional theory (DFT) calculations predict IR vibrational absorption (VA) and VCD spectra in excellent to good correspondence with observed data. The same calculations confirmed the ridge-tile conformation that has been known for a long time. Assignment of vibrational normal modes (NMs) sheds light on the relative importance of local moieties and groups in determining conformational properties of the molecules, as well as their interaction with solvent molecules. Time-dependent DFT (TDDFT) calculations were also performed to provide an understanding of electronic circular dichroism (ECD) spectra and confirm the well-known interpretation based on the exciton model.

On the aggregation of bilirubinoids in solution as evidenced by VCD and ECD spectroscopy and DFT calculations

“…This agrees with experiment, while DFT calculations for the monomer predict a more intense negative doublet with a positive feature at higher frequency. The presence of active VCD features for the monomer in this region is similar to what was observed and calculated for compound 4 . From the calculated structures of the dimer and monomer for molecule 2 , one may see that, in line with what had been anticipated, some 20 years ago, intermolecular HB are favored.…”

“…We report in Figure the experimental IR spectra in CDCl 3 at 3 concentration values (25, 10, and 5 mM) of 1 to 4 . The spectra of 4 were reported previously at the highest concentration . We repeated them at lower concentration and found no appreciable concentration dependence and show the data for 4 here for comparison.…”

“…The monomer, even with no OH, still has the shape of a ridge‐tile, with a more closed‐up appearance in the case of “closed” monomer (θ = 70° instead of 90°), as compared to the “open” monomer and as in molecule 4 . This may be better appreciated looking at the data of Table , where we compare the torsion angles φ1, φ2, and the dihedral angle θ (Figure C and E) for the dimer and monomer models of 2 with the value of the interplanar angle (θ) found previously for 4 . In the same table, we also compare the hydrogen bond length of NH···O═distances.…”

“…To understand the importance of intramolecular hydrogen bonding, synthetic analogs of bilirubin possessing stereogenic centers of known absolute configuration were prepared and examined by electronic circular dichroism (ECD) some 25 years ago and more recently by vibrational circular dichroism (VCD) . Typically, the stereogenic centers were located on the propionic acid chains, either at the α‐ or the β‐carbons, generally by attaching a methyl group at such sites.…”

“…Using VCD and ECD spectroscopy, coupled with density functional theory (DFT) calculations, we examined 3 bilirubinoids of known absolute configuration ( 1 , 2 , and 3 of Figure ). We further compare the spectroscopic behavior of these dimer‐forming pigments to that of monomeric dicarboxylic acid β S , β' S ‐dimethylmesobilirubin‐XIIIα ( 4 ); for the latter compound, some VCD measurements have been repeated at different concentrations. The VCD conjoined with DFT analysis has been established through the years as a reliable technique for the assignment of absolute configuration (AC) for a large variety of molecules .…”