of the total absorption), and as conventional optical elements may be used, the construction of the spectrometers is fairly straightforward. It was soon realized that utilizing a similar phenomenon in the vibrational region could provide more detailed and reliable stereochemical information, because the vibrational spectrum contains many more bands sensitive to minute features of the molecular structure. [7, 8] The vibrational region was successfully tackled in 1973 when the circular-polarization dependence of vibrational Raman scattering was first measured with visible laser light. [9] In 1974 this success was followed by a report on VCD. [10] Ever since then, VOA has been applied to a broad scale of problems ranging from small chiral molecules to proteins, nucleic acids, and viruses. [11–17] Nevertheless, the technique remained confined to specialized laboratories, predominantly in the United States, for a long time. As the light wavelength is much larger than the molecular dimensions, the VOA signal is very weak, typically mere 10 � 4 –10 � 5 of the total scattering or absorption. Accurate measurements required advanced instrumentation, high stability of the optics and light sources, and special detectors coupled with dedicated electronics, such as lockin amplifiers. First commercial attempts to sell the VCD instruments failed in the eighties. The instrumentation problems, however, were eventually solved and this vibrational optical activity was re-introduced to the market around 1997, this time successfully. A few years later, an ROA spectrometer became commercially available as well. Similar to conventional spectrometers, the new detection technique utilizes the familiar phenomenon of linearly polarized light being rotated and partially depolarized by an optically active medium, as shown diagrammatically in Figure 1. In a traditional VCD measurement, a piezoelectric photoelastic modulator is used to periodically yield the left- and rightcircularly polarized (LCP, RCP) light. This produces a varying signal at the detector, which is electronically weighted against the total (non-polarized) absorption. [18]
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