Vibrational Optical Activity: Principles and Applications

Book Preface

During the years surrounding the new millennium, the field of vibrational optical activity (VOA), comprised principally of vibrational circular dichroism (VCD) and vibrational Raman optical activity (ROA), underwent a transition from a specialized area of research that had been practiced by a handful of pioneers into an important newfield of spectroscopy practiced by an increasing number of scientists worldwide. This transition was made possible by the development of commercial instrumentation and software for the routine measurement and quantum chemical calculation ofVOA. This development in turn was fueled by the growing focus among chemists for controlling and characterizing molecular chirality in synthesis, dynamics, analysis, and natural product isolation. The emphasis on chirality was particularly important in the pharmaceutical industry, where the most effective new drugs were single enantiomers and where new federal regulations required specifying proof of absolute configuration and enantiomeric purity for each newdrug molecule developed. Today, more than a decade beyond the start of this renaissance, chemists and spectroscopists are discovering the power of VOA to provide, directly, the stereo specific information needed to further enhance the ongoing revolution in the application of chirality across all fields of molecular science.

The impact of VOA has not been restricted to applications centered on molecular chirality. A concurrent revolution is currently taking place in the field of biotechnology. All biological molecules are chiral, where the chirality is specified by the homochirality of our biosphere, for example L-amino acids and D-sugars. The role of chirality here is not with the specification of absolute configuration but with the specification of the solution-state conformation of biological molecules in native environments. VOA has been found to be hypersensitive to the conformational state in all classes of biological molecules, including amino acids, peptides, proteins, sugars, nucleic acids, glycoprotiens, in addition to fibrils, viruses, and bacteria. Now that the human genome has been coded, emphasis has shifted to understanding what proteins and related molecules are specified in the genetic code. What is their structure and function? Thus VOA is particularly useful as a sensitive new probe of the solution structure of these new protein molecules by classification of their folding family in solution.

What is it aboutVOAthat allows it to determine absolute configuration and molecular conformation in new ways? It is simply that the field of VOA is fulfilling its promise of combining the detailed structural sensitivity of vibrational spectroscopy with the three-dimensional stereo-sensitivity of traditional forms of optical activity. The actual realization of the foreseen potential of VOA has been delivered by sweeping advances in the last two decades of both instrumentation for the measurement of VOA, and software for its calculation and accurate spectral simulation. As will be seen in the chapters of this book, VOA spectra are accompanied by their parent normal vibrational spectra, vibrational absorption, and Raman scattering, and the additional VOA spectrum, linked to a traditional spectrum, is what confers the specific new spectral information.