Awards/Grants

Current Proposals

Proposal Title: Chiral Ionic Liquids as Selectors for Chiral Analysis by Regression Modeling of Spectral Data

Principal Investigator: Kenneth W. Busch, Ph.D.

Funding Agency: University Research Grant

Abstract: Many molecules possess a handedness known as chirality and can be envisioned as existing in left- and right-handed forms.  Although the chemical and physical properties of the left- and right-handed forms of a chiral molecule are identical in an achiral environment, the two forms of a chiral molecule (known as enantiomers) often behave quite differently physiologically, with one form being more active than another.  Because of this difference in activity, researchers are interested in being able to determine the enantiomeric composition of samples of chiral molecules (i.e., the relative amounts of left- and right-handed forms in a sample).

Over the last few years, we have been studying this problem and have developed a novel method, known as chiral analysis by regression modeling of spectral data (CARMSD), that permits the enantiomeric composition of samples to be determined from ordinary spectroscopic data.  In our original CARMSD work, cyclodextrins, a group of macrocyclic sugars, were used as chiral selectors to induce changes in enantiomeric pairs that could be monitored spectroscopically.  In this proposal, we intend to study the use of ionic liquids as chiral selectors.  Ionic liquids are a new class of chemical solvents, made up entirely of cations and anions, that are finding widespread use in a wide variety of applications.  For example, chiral ionic liquids (CILs), where the chirality has been introduced into either the cation or the anion, are being studied extensively as solvents for asymmetric synthesis.  Compared with other chiral selectors like cyclodextrins, which require inclusion complex formation for enantiodiscrimination, CILs may offer a more general means of enantiodiscrimination by providing a chiral environment for the analyte without the need for inclusion complex formation.

In this project, we propose to study the use of chiral ionic liquids as chiral selectors for CARMSD. To accomplish this study, we propose to synthesize a variety of CILs with different functionalities and molecular properties.  These CILs will then be used a chiral selectors with different chiral selectands having different shapes, sizes, and functional groups.  Spectroscopic data will then be collected with various selector/selectand combinations and chemometric procedures like partial-least-squares regression techniques will be used to develop regression models that correlate enantiomeric composition with the spectral data.  The predictive ability of the regression models developed will be validated with independently prepared test samples.

Past Proposals

Proposal Title: Enantiomeric discrimination by Rayleigh light scattering

Principal Investigator: Kenneth W. Busch, Ph.D.

Funding Agency: Baylor University Faculty Research Investment Program

Abstract: Enantiomers are mirror-image isomers of a molecule whose physical and chemical properties are indistinguishable under normal circumstances.  The phenomenon of enantiomeric discrimination, which permits a pair of optical isomers to be distinguished chemically or physically, is an active area of research from a fundamental as well as applied standpoint.    Enantiomeric discrimination can be conventionally accomplished chemically with molecules known as chiral auxiliaries, which react or interact with an enantiomeric pair to form products that break the mirror-image symmetry of the enantiomeric pair, resulting in the formation of diastereomeric pairs with distinctly different chemical and physical properties that can be differentiated with ordinary chemical probes like nuclear magnetic resonance. Alternatively, enantiomeric discrimination can be accomplished physically by means of chiroptical techniques such as polarimetry, optical rotatory dispersion, circular dichroism (electronic and vibrational), and Raman optical activity, all of which employ some form of polarized radiation probe.  This proposal concerns the study of a new form of enantiomeric discrimination based on Rayleigh light scattering.

Proposal Title: Near-Infrared Spectral Studies of Cyclodextrin Inclusion Complexes

Principal Investigator: Marianna A. Busch, Ph.D.

Funding Agency: Welch Foundation

Abstract: The near-infrared (NIR) spectra of the inclusion complexes of alpha-, beta-, gamma-, and delta-cyclodextrins with a variety of chiral molecules having different sizes and substituents will be studied with the goal of using the spectral data for enantiodifferentiation.  The ability to differentiate between enantiomers of a chiral molecule by near-infrared spectroscopy is based on the premise that the (+)-enantiomer will bind to a particular cyclodextrin molecule in a slightly different fashion than the (-)-enantiomer, and that this difference in inclusion complex formation will produce NIR spectral changes that can be detected and correlated with the presence of a given optical isomer by multivariate statistical analysis. 

A major goal of this research will be to determine whether NIR spectral data can be used to predict enantiomeric purity.  For a given chiral molecule, NIR spectra of inclusion complexes for different known enantiomeric compositions will be taken, and principal component regression and partial least squares techniques will be used to correlate the known enantiomeric composition with the NIR spectral data.  For a given chiral molecule, regression models will be prepared for different cyclodextrins (alpha, beta, gamma, delta) to study the effect of cavity size on the ability to predict enantiomeric composition.    If robust regression models can be developed with solutions containing only a single chiral molecule, the effect of the presence of other chiral molecules on the regression model will be studied.