Stefan E. Boiadjiev

Bicamphor: A Prototypic Molecular System to Investigate Vibrational Excitons

Vibrational circular dichroism (VCD) and IR spectra have been recorded in the fingerprint and carbonyl stretching regions for endo,endo-bicamphor (1), exo,exo-bicamphor (2), endo,exo-bicamphor (3), 3,3-bicamphorylidene (4), and exo,exo-bis-thiocamphor (5). The C2 symmetry possessed by these molecular systems (except in one case), as well as their limited conformational mobility associated with well-defined degrees of freedom, allow for optimal test of the vibrational circular dichroism exciton chirality (VCDEC) rule introduced by Taniguchi and Monde. Density functional theory calculations are employed not only to predict the entire aspect of the VCD and IR spectra but also to study how the VCDEC rule may be impacted by the coupling between C═O stretchings and from C═O stretchings with other vibrational modes and by the rotation about the C-C bond connecting the two camphors. Comments are provided about the limitations and potentialities of the VCDEC method and about the manifestation of different vibrational excitons in other regions of the VCD spectra, either in the mid-IR or in the CH-stretching regions.

Observation of Vibrational Circular Dichroism for Overtone Transitions with Commercially Available CD Spectrometers

It is demonstrated that some commercially available circular dichroism spectrometers can be used to gather vibrational circular dichroism data associated with overtone transitions. By way of specific example, the circular dichroism spectra of neat S−(−)−limonene and R-(+)-limonene are measured in the region 800–600 nm. The observed spectral features correspond to the overtone bands Δv = 5 and 6 for CH-stretching motions. A discussion of the data is also given.

pH Dependent Chiroptical Properties of (1R,2R)- and (1S,2S)-trans-Cyclohexane Diesters and Diamides from VCD, ECD, and CPL Spectroscopy.

Diesters of (1R,2R)- and (1S,2S)-cyclohexanediols and diamides of (1R,2R)- and (1S,2S)-diaminocyclohexane with p-hydroxycinnamic acid have been known for some time to exhibit intense bisignate electronic circular dichroism (ECD) spectra in CH3OH. It was also known that added NaOH causes a bathochromic shift of ∼50 nm in CH3OH, and an even higher one in DMSO. We have measured vibrational circular dichroism (VCD) spectra both for neutral compounds and in the presence of NaOH and other bases. The VCD and IR spectra in the mid-IR region for CD3OD and DMSO-d6 solution exhibit high sensitivity to the charged state for the diesters. They possess two strong bisignate features in the presence of bases in the mid-IR, which are interpreted in terms of vibrational exciton couplets, while this phenomenon is less evident in diamides. VCD allied to density functional theory (DFT) calculations allows one to shed some light on the spectral differences of diesters and diamides by studying their conformational properties. Optical rotatory dispersion (ORD) curves confirm the ECD data. Circularly polarized luminescence (CPL) data have been also acquired, which are rather intense in basified solution: the CPL spectra are monosignate and are as intense in the diester and in the diamide case.

Vibrational and Electronic Circular Dichroism of Dimethyl Mesobilirubins-XIIIα

The vibrational circular dichroism (VCD) spectra of (αR,αR)-, (αS,αS)-, (βR,βR)-, and (βS,βS)-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.

Slipping Past UGT1A1 and Multidrug Resistance-Associated Protein 2 in the Liver: Effects of Steric Compression and Hydrogen Bonding on the Hepatobiliary Elimination of Synthetic Bilirubins

The hepatobiliary metabolism and excretion of three isomeric bilirubin analogs with propanoic replaced by benzoic acid side-chains were studied in the rat. Despite their isomeric relationship and similar constitutions, the three analogs were metabolized quite differently from each other and from bilirubin. In the di-o-benzoic compound, steric hindrance involving the phenyl groups reinforces intramolecular hydrogen bonding of the two carboxyl groups. This compound is considerably less polar than bilirubin on reverse-phase high-performance liquid chromatography and, like bilirubin, was not excreted in bile in UGT1-deficient (Gunn) rats. But, quite unlike bilirubin, it was not glucuronidated or excreted in bile in normal rats. In contrast to both bilirubin and the di-o-benzoic isomer, the more polar m- and p-isomers, in which intramolecular hydrogen bonding of carboxyl groups is sterically difficult, were excreted rapidly in bile in unchanged form in both normal and Gunn rats. However, only one of them, the di-m-isomer, was excreted rapidly and unchanged in bile in rats (TR- rats) congenitally deficient in the canalicular ATP-binding cassette transporter Mrp2. The marked differences in hepatobiliary metabolism of the three isomers studied can be rationalized on the basis of their computed three-dimensional structures and minimum-energy conformations and the remote effects of steric compression on intramolecular hydrogen bonding.

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

Vibrational and electronic circular dichroism (VCD and ECD) spectra of 3 optically active bilirubin analogs with propionic acid groups replaced by (1) 1-(S)-methylpropyl groups, (2) 3-acetoxy-1-(S)-methylpropyl groups, and (3) 1-(S)-2-(R)-dimethyl-2-(methoxycarbonyl)ethyl groups have been recorded at different concentrations in chloroform. The aliphatic chains attached to C-8 and C-12 of the 3 chosen mesobilirubins were modified so as to possess no OH group. The variation of the VCD spectra with concentration is consistent with the formation of dimers at high concentration. Density functional theory and time-dependent density functional theory calculations on monomeric and dimeric forms support such a conclusion. Comparing with previous VCD (ECD) and IR (UV) studies of other mesobilirubin molecules, it is concluded that here, the key feature for aggregation is the missing OH groups on the propionic acid chains. The latter, in synergy with the polar groups of lactam moieties, appear to be involved in intramolecular phenomena and thus favor monomeric forms. Investigation of ECD and UV spectra of the same compounds in mixed DMSO/chloroform solutions provide further clues to the proposed picture.