Raman optical activity: An incisive probe of chirality, and of biomolecular structure and behaviour

The theory, instrumentation and applications of Raman optical activity (ROA), which measures vibrational optical activity by means of a small difference in the intensity of Raman scattering from chiral molecules in right- and left-circularly polarized incident light or, equivalently, a small circularly polarized component in the scattered light, are briefly reviewed. As well as providing the absolute configuration of small chiral molecules, the application of ab initio methods to the analysis of experimental ROA spectra holds promise for the determination of the three-dimensional structure and conformational distribution in unprecedented detail. The rich ROA spectra of aqueous solutions of biomolecules provide detailed structural information including, in the case of proteins, the tertiary fold in addition to secondary structure elements. ROA studies of unfolded and partially folded proteins provide new insight into the residual structure in denatured proteins and the aberrant behaviour of proteins responsible for misfolding diseases. It is even possible to measure the ROA spectra of intact viruses, from which information about the fold of the major coat proteins and the structure of the nucleic acid core may be obtained.