Chiroptical Spectroscopy of Surfactants

Three different chiroptical spectroscopic methods, namely, optical rotation, electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) have been evaluated for studying the aggregation of sodium dodecylsulfate (SDS), an achiral surfactant, using garcinia acid disodium salt (GADNa) as a chiral probe. The specific rotation and ECD of GADNa are found to be altered by the aggregation of SDS, suggesting for the first time that achiral surfactants can be characterized with chiroptical spectroscopy using appropriate chiral probes. In addition, a chiral compound, fluorenyl methyloxy carbonyl l-leucine sodium salt (FLNa) is found for the first time to behave as a surfactant in water, with 205 Ų surface area per molecule at the air–water interface, critical micelle concentration (CMC) of 0.18 M, and Gibbs energy of micellization of −14 kJ/mol. The specific rotation of FLNa in water is found to increase with concentration beyond CMC, suggesting the formation of chiral aggregates. Different conformations of FLNa amenable to micellization have been identified using quantum chemical conformational analysis and their specific rotations calculated. The formation of lamellar aggregates of FLNa in water is suggested to be the cause for increase in specific rotation with concentration beyond CMC

Similarity in Dissymmetry Factor Spectra: A Quantitative Measure of Comparison between Experimental and Predicted Vibrational Circular Dichroism

To quantitatively determine the agreement between experimental and calculated vibrational circular dichroism (VCD) spectra, a new approach, based on the similarity of dissymmetry factor spectra has been developed and implemented. This method, which places emphasis on robust regions both in the experimental and in the calculated spectra, has been tested with six chiral compounds of known absolute configurations, namely, (<i>R</i>)-(+)-3-chloro-1-butyne, (3<i>R</i>)-(+)-methylcyclopentanone, (3<i>R</i>)-(+)-methylcyclohexanone, (1<i>S</i>)-(−)-α-pinene, (1<i>R</i>)-(+)-camphor, and (<i>S</i>)-(+)-epichlorohydrin. The criterion of maximum overlap among experimental and calculated dissymmetry factor spectra is shown to have definite advantages over those using maximum overlap among VCD or absorption spectra individually. The new method provides a better assessment of the comparison between experimental observations and quantum chemical VCD predictions and improves the confidence in the assignment of absolute configurations

Determination of the Absolute Configurations Using Exciton Chirality Method for Vibrational Circular Dichroism: Right Answers for the Wrong Reasons?

Quantum chemical (QC) predictions of vibrational circular dichroism (VCD) spectra for the keto form of 3-benzoylcamphor and conformationally flexible diacetates of spiroindicumide A and B are presented. The exciton chirality (EC) model has been briefly reviewed, and a procedure to evaluate the relevance of the EC model has been presented. The QC results are compared with literature experimental VCD spectra as well as with those obtained using the EC model for VCD. These comparisons reveal that the EC contributions to bisignate VCD couplets associated with the CO stretching vibrations of benzoylcamphor, spiroindicumide A diacetate, and spiroindicumide B diacetate are only ∼30%, ∼3%, and ∼15%, respectively. With such meager EC contributions, the correct absolute configurations (ACs) suggested in the literature for spiroindicumide A diacetate and spiroindicumide B diacetate molecules using the EC concepts can be considered fortuitous. The possibilities for obtaining wrong AC predictions using the EC concepts for VCD are identified, and guidelines for the future use of this model are presented

Understanding Solvent Effects in Vibrational Circular Dichroism Spectra: [1,1′-Binaphthalene]-2,2′-diol in Dichloromethane, Acetonitrile, and Dimethyl Sulfoxide Solvents

We present a combined experimental and computational investigation of the vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra of [1,1′-binaphthalene]-2,2′-diol. First, the sensitive dependence of the experimental VA and VCD spectra on the solvent is demonstrated by comparing the experimental spectra measured in CH₂Cl₂, CD₃CN, and DMSO-<i>d</i>₆ solvents. Then, by comparing calculations performed for the isolated solute molecule to calculations performed for molecular complexes formed between solute and solvent molecules, we identify three main types of perturbations that affect the shape of the VA and VCD spectra when going from one solvent to another. These sources of perturbations are (1) perturbation of the Boltzmann populations, (2) perturbation of the electronic structure, and (3) perturbation of the normal modes

Unprecedented Relationship Between the Size of Spherical Chiral Micellar Aggregates and Their Specific Optical Rotations

Transmission electron microscopy (TEM) images and fluorescence quenching methods indicated that lauryl ester of L-phenylalanine (LEP) and lauryl ester of L-tyrosine (LET) form spherical chiral micelles in the 50–200 mM range and their size increases with concentration. The number of molecules present in these spherical chiral aggregates varied from 80 to 160 for LEP and 80–100 for LET. The specific optical rotation, representing circular birefringence, for LEP at 405 nm and 32 °C is found to increase linearly from 37 deg cc g^–1 dm^–1 for an isolated molecule to 56 deg cc g^–1 dm^–1 for ∼200 nm size aggregate. A similar trend was found for temperatures up to 70 °C and at other visible wavelengths. A linear relation between specific optical rotation and the size of aggregate is also observed for LET. Circular dichroism, as measured in both the visible and infrared wavelength regions, however did not reveal any concentration dependent changes. The unique sensitivity uncovered for specific optical rotation as a function of the size of spherical chiral aggregates is unprecedented and opens new areas of enquiry for physical chemists

Atropoisomerism in Biflavones: The Absolute Configuration of (−)-Agathisflavone via Chiroptical Spectroscopy

The first natural occurrence in optically active form of the dimeric flavonoid agathisflavone and definition of its axial chirality using chiroptical spectroscopic methods are described. The experimental electronic circular dichroism, electronic dissymmetry factor, optical rotatory dispersion, vibrational circular dichroism (VCD), and vibrational dissymmetry factor spectra of agathisflavone are presented and analyzed with their corresponding quantum chemical predictions to definitively assign the axial chirality of (−)-agathisflavone as (a<i>S</i>)

Structure and Stereochemical Determination of Hypogeamicins from a Cave-Derived Actinomycete

Culture extracts from the cave-derived actinomycete <i>Nonomuraea specus</i> were investigated, resulting in the discovery of a new S-bridged pyronaphthoquinone dimer and its monomeric progenitors designated hypogeamicins A–D (<b>1</b>–<b>4</b>). The structures were elucidated using NMR spectroscopy, and the relative stereochemistries of the pyrans were inferred using NOE and comparison to previously reported compounds. Absolute stereochemistry was determined using quantum chemical calculations of specific rotation and vibrational and electronic circular dichroism spectra, after an extensive conformational search and including solute–solvent polarization effects, and comparing with the corresponding experimental data for the monomeric congeners. Interestingly, the dimeric hypogeamicin A (<b>1</b>) was found to be cytotoxic to the colon cancer derived cell line TCT-1 at low micromolar ranges, but not bacteria, whereas the monomeric precursors possessed antibiotic activity but no significant TCT-1 cytotoxicity