Mid-infrared and near-infrared vibrational circular dichroism: New methodologies for biological and pharmaceutical applications

Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)




Vibrational circular dichroism, Near-infrared spectroscopy, Infrared spectroscopy

Subject Categories

Analytical Chemistry | Chemistry | Physical Sciences and Mathematics


New methodologies have been developed at the cutting-edge of Fourier transform vibrational circular dichroism (FT-VCD) spectroscopy aimed at various pharmaceutical and biological applications. VCD spectra of a series of proteins with different secondary structures were obtained with a modified ChiralIR (BioTools, Jupiter, FL) FT-VCD spectrometer in the near-infrared (near-IR) region from 6000 to 4000 cm -1 and the mid-infrared (mid-IR) region from 2000 to 800 cm -1 . High quality mid-IR-VCD spectra were obtained to support accurate quantitative analysis based on VCD data. The NIR-VCD spectra of proteins show distinct spectral features for different protein structural motifs, indicating a new valuable method to study protein structures.

For the first time, VCD spectroscopy is applied to study the structures and associated formation dynamics of insulin and lysozyme proteins fibrils. Mid-IR VCD spectra show remarkable sensitivity to these protein fibrils which are β-rich structural fibrils developed under the conditions of heating native protein solutions at low pH, indicating that VCD is a powerful tool to study such complex systems. In addition, VCD shows successful results on monitoring the protein structural changes during fibrillation. The potential for new insight into the mechanism and dynamics of the fibril formation process is elucidated.

Two-dimensional correlation VCD spectroscopy (2D-COS VCD) is developed to enhance the applications of VCD. The pD-dependence of the VCD and IR spectra of Lalanine in D 2 O solution in the mid-IR CH-bending and CH-stretching regions, and near-IR region are presented. Analysis of the 2D correlation plots provide further insight into the relative sensitivities of structural changes that take place in L-alanine as a function of pD. Near-IR band assignments are facilitated by hetero-spectral-region 2D-COS spectra that correlate the combination band region to that of the underling fundamental modes. Furthermore, 2D COS VCD was applied to investigate structures of insulin fibrils during the formation process. New insight into the functional groups associated with the fibrillation process is thereby obtained.

Enhanced VCD and magnetic VCD (MVCD) in transition metal complexes are presented. Similar to previous VCD results, resonance-enhanced MVCD spectra are observed for a series of complexes with open-shell transition metals at coordination sites, further confirming that the resonance enhancement comes from low-lying excited electronic states (LLESs). Moreover, regular MVCD are obtained from several complexes without LLESs, suggesting a promising research method for structural determination of a wide range of molecules.

The structure of amylose tris-(dimethylphenylcarbamate) (ADMPC) and its conformational changes with respect to polar solvents were investigated by VCD for the first time. By providing rich information on a number of different functional groups, VCD was shown to be a powerful and innovative molecular-level probe to study the structures of this type of chiral polymer. In addition, the conformations of side chains and the backbone of ADMPC were monitored using VCD in the solid film state in the presence of different concentrations of alcohols. VCD results revealed new insight into the behavior of ADMPC in the presence of these polar solvents when in combination with nonpolar solvents such as hexane.


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