Construction and Evaluation of a Step Scanning Interferometric Instrument for the Observation of Infrared Circular Dichroism

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The following proposal is aimed at developing a prototype instrument for the observation of infrared, or vibrational Circular Dichroism (VCD), using Step-Scanning Fourier transform (SS-FT) methodology. VCD is a spectroscopic technique, developed originally in the mid 1970's, in which the differential absorption of left and right circularly polarized indrared light by vibrational transitions is observed. This effect is very small, yet contains conformational and structural information which cannot be obtained easily by any other spectroscopic method. The lack of commercial instrumentation for its observation has restricted the wider application of VCD as a structural tool. This proposal is intended to produce a new generation of VCD instruments which could serve as blueprints for commercial VCD spectrometers. The proposed instrument is conceived as a VCD spectrometer, rather than a Fourier Transform infrared spectrometer to which VCD capabilities were added. A number of technical innovations will make this instrument very unique, and will extend its capabilities beyond the present limits of VCD spectroscopy. The applicant's laboratory has been in the forefront of the development of vibrational optical activity, and has extensive experience with both dispersive and interferomatic spectroscopic methods. Thus, this laboratory is ideally suited to take a leading role in development of a new generation of VCD spectrometers. The main thrust of the applicant's research is the determination of the solution conformation of biological model systems: peptides and small proteins, as well asoligonucleotides and their interactions with drugs. The SS- FT-VCD instrument described here will be used in these studies to further reduce VCD data acquisition time, improve spectral quality and permit spectra to be collected from more dilute aqueous solutions.