Laurence D. Barron

Ultrasensitive detection and characterization of biomolecules using superchiral fields.

The spectroscopic analysis of large biomolecules is important in applications such as biomedical diagnostics and pathogen detection, and spectroscopic techniques can detect such molecules at the nanogram level or lower. However, spectroscopic techniques have not been able to probe the structure of large biomolecules with similar levels of sensitivity. Here, we show that superchiral electromagnetic fields, generated by the optical excitation of plasmonic planar chiral metamaterials, are highly sensitive probes of chiral supramolecular structure. The differences in the effective refractive indices of chiral samples exposed to left- and right-handed superchiral fields are found to be up to 10(6) times greater than those observed in optical polarimetry measurements, thus allowing picogram quantities of adsorbed molecules to be characterized. The largest differences are observed for biomolecules that have chiral planar sheets, such as proteins with high β-sheet content, which suggests that this approach could form the basis for assaying technologies capable of detecting amyloid diseases and certain types of viruses.

Rayleigh and Raman scattering from optically active molecules

The intensity of Rayleigh and Raman scattering from optically active molecules is shown to be slightly different in right and left circularly polarized incident light. The circular intensity differential of the Rayleigh line is dependent on components of the optical activity tensor, and that of the Raman lines is a function of the variation of the optical activity with the vibrational coordinates. This circular intensity differential might be of the order of 10-3 times that of the Rayleigh or Raman intensity.

Solution structure and dynamics of biomolecules from Raman optical activity

Raman optical activity (ROA) 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 laser light. The ROA spectra of a wide range of biomolecules in aqueous solution can now be measured routinely. Because of its sensitivity to the chiral elements of biomolecular structure, ROA provides new information about solution structure and dynamics complementary to that supplied by conventional spectroscopic techniques. This article provides a brief introduction to the theory and practice of ROA spectroscopy followed by a review of recent ROA results on polypeptides, proteins, carbohydrates, nucleic acids and viruses which illustrate how new insight into current problems of structure, folding and function may be obtained from ROA studies.

Magneto-chiral birefringence and dichroism

It was pointed out recently that the absorption coefficient of a chiral molecule should be shifted slightly in a magnetic field parallel to a light beam in any polarization state. This suggestion is developed further by considering an analogous refractive index shift and by discussing these magneto-chiral phenomena in the unified context of effects generated by the ‘magnetic’ (time-odd) parts of the complex optical activity tensors. Explicit expressions, in terms of molecular property tensors, are derived for the difference in refractive index and absorption coefficient of a chiral molecule in a magnetic field parallel and antiparallel to the light beam, and magneto-chiral analogues of the Faraday A-, B- and C-terms introduced. A rough estimate of the magneto-chiral birefringence indicates that it should be observable using a modified Rayleigh refractometer. The feasibility of observing magneto-chiral dichroism A-, B- and C-terms in different types of chiral molecules is also considered. The magneto-chira...

Raman optical activity comes of age

The theory 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. Thanks to new developments in instrumentation, ROA may be applied to a wide range of chiral molecular species. 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 great promise for the determination of the three-dimensional structure and conformational distribution in unprecedented detail. The many structure-sensitive bands in the 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 such as helix and sheet. ROA studies of unfolded and partially folded proteins are providing 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 most intact viruses, from which information about the folds of the major coat proteins and the structure of the nucleic acid core may be obtained. Hopefully this review will stimulate interest in the molecular physics aspects of the subject, and will encourage further theoretical work aimed at extracting maximum information from the plethora of structure-sensitive bands in typical ROA spectra.

Rayleigh scattering of polarized photons by molecules

The scattering of polarized light by molecules is discussed in terms of a polarization density matrix. Particular attention is paid to scattering out of the direction of the incident beam, and the formalism enables the polarization characteristics of the non-forward scattered beam to be predicted for any polarization condition of the incident beam. Both Rayleigh and Raman scattering processes are contained in the formalism, although most attention is given to the former. Explicit expressions for the polarization of the scattered beams are obtained in terms of the polarizability and gyration tensors of the molecules by the application of diagrammatic perturbation theory, and it is demonstrated that a determination of the precise polarization state of the scattered beam can provide useful molecular information which is additional to that obtained from depolarization ratios alone. This is because the depolarization ratio depends on only the diagonal elements of the polarization density matrix and so does not...

Unfolded proteins studied by raman optical activity

Publisher Summary To understand the behavior of unfolded proteins it is necessary to employ experimental techniques able to discriminate between the dynamic true random coil state and more static types of disorder, including situations in which some ordered secondary structure might be present. One such technique is a novel chiroptical spectroscopy called Raman optical activity (ROA). This chapter reviews the application of ROA to studies of unfolded proteins. Because many discrete structure-sensitive bands are present in protein ROA spectra, the technique provides a fresh perspective on the structure and behavior of unfolded proteins and of unfolded sequences in proteins such as A-gliadin and prions that contain distinct structured and unstructured domains. It also provides new insight into the complexity of order in molten globule and reduced protein states and of the more mobile sequences in fully folded proteins such as β-lactoglobulin. The power of ROA in this area derives from the fact that, like the complementary technique of vibrational circular dichroism (VCD), it is a form of vibrational optical activity and so is sensitive to chirality associated with all the 3N−6 fundamental molecular vibrational transitions, where N is the number of atoms.

Chemistry: Chirality, magnetism and light

The importance of left- and right-handedness in nature is such that scientists have often wondered about its origins. The first use of a magnetic field to bias a chemical reaction in favour of one mirror-image product provides a possible explanation.

Vibrational Raman optical activity of proteins, nucleic acids, and viruses

Due to its sensitivity to chirality, Raman optical activity (ROA), which may be measured as a small difference in vibrational Raman scattering from chiral molecules in right- and left-circularly polarized incident light, is a powerful probe of biomolecular structure in solution. Protein ROA spectra provide information on the secondary and tertiary structures of the polypeptide backbone, hydration, side-chain conformation, and structural elements present in denatured states. Nucleic acid ROA spectra yield information on the sugar ring conformation, the base stacking arrangement, and the mutual orientation of the sugar and base rings around the C-N glycosidic linkage. ROA is able to simultaneously probe the structures of both the protein and the nucleic acid components of intact viruses. This article gives a brief account of the theory and measurement of ROA and presents the ROA spectra of a selection of proteins, nucleic acids, and viruses which illustrate the applications of ROA spectroscopy in biomolecular research.

Chiral electromagnetic fields generated by arrays of nanoslits

Using a modal matching theory, we demonstrate the generation of short-range, chiral electromagnetic fields via the excitation of arrays of staggered nanoslits that are chiral in two dimensions. The electromagnetic near fields, which exhibit a chiral density greater than that of circularly polarized light, can enhance the chiroptical interactions in the vicinity of the nanoslits. We discuss the features of nanostructure symmetry required to obtain the chiral fields and explicitly show how these structures can give rise to detection and characterization of materials with chiral symmetry.