Special Issue "Applications of Circular Dichroism"

Guest Editor
Prof. Dr. David Kliger
Department of Chemistry and Biochemistry; University of California, Santa Cruz, Santa Cruz, CA 95064, USA
E-Mail: kliger@ucsc.edu

Dear Colleagues,

Chiroptical phenomena have been known for two centuries.  However, new developments over the past 20 – 30 years have greatly expanded the capability and versatility of chiroptical spectroscopy, as evidenced by the articles in this special issue.

Biot first observed optical rotation, and he and Fresnel studied the phenomenon in the early 1800’s.  In the mid 1800’s Pasteur related the phenomenon to molecular asymmetry.  Since that time optical rotation (OR), and the related phenomenon of circular dichroism (CD), have been used in innumerable studies of molecular structures.

Early studies of chiroptical phenomena, of course, did not have the use of electronic devices that we now take for granted, so they involved measurements of optical rotation using null techniques detected visually. This situation changed as photoelectric light detectors were developed along with electronic devices to record light intensities in the twentieth century. With the advent of fast modulators of light polarization and phase sensitive measurement techniques, it became possible to measure differences in the absorption of left and right circularly polarized light with high sensitivity.  CD spectroscopy then became a more common tool for molecular structure determinations since  CD spectra can more easily be correlated with molecular structure than OR spectra and because instruments capable of producing sensitive measurements of visible and ultraviolet CD spectra, became commercially available.

The more recent developments of the past several decades have again expanded the capabilities of chiroptical spectroscopy by opening up access to spectral regions and higher order optical effects sensitive to additional features of molecular structure, by extending time resolution to the very fast time scales of fundamental molecular processes, and by advancing the theoretical understanding needed to interpret the structural implications of chiroptical spectra. Circularly polarized luminescence spectroscopy has increased the sensitivity of CD measurements of emitting chiral molecules.  Structural determinations have been improved by making CD measurements farther into the UV region and even extending CD measurements into the X-ray and IR regions. IR measurements of CD monitor anisotropies of vibrational transitions and are thus particularly sensitive to local structural features. Similar capabilities have also been introduced with the development of Raman optical activity measurements.  Highly sensitive measurements of local structural features around aromatic moieties have also been made possible with the development of magnetic circular dichroism. Techniques have also been developed to measure CD spectra with nanosecond or even picosecond or femtoseconds time resolution. These new developments, and improved theoretical analyses of CD spectra, have brought new capabilities to this old technique, thus made it useful for new applications.  This issue explores a variety of such new applications of CD spectroscopy.

Prof. Dr. David Kliger
Guest Editors

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• chiroptical phenomena
• circular dichroism
• magnetic circular dichroism
• optical activity
• Raman optical activity
• vibrational circular dichroism
• structure determination
• time-resolved circular dichroism

Feature Paper:

Type of Paper: Article
Title: Nanosecond T-jump Experiment in Poly(glutamic acid): a Circular Dichroism Study
Authors: Lucille Mendonça and François Hache
Affiliation: Laboratoire d'Optique et Biosciences, Ecole Polytechnique, CNRS, INSERM, 91128 Palaiseau, France; E-Mail: francois.hache@polytechnique.edu
Abstract: Poly(glutamic acid) has been studied with a nanosecond T-jump experiment. A new experimental set-up based on the frequency-quadrupling of an 82 MHz Titanium-Sapphire laser allows rapid CD measurements to be performed. Combining time-resolved absorption and circular dichroism at 205 and 220 nm, we are able to measure precisely the relaxation time as well as the helical fraction as a function of time. We show that only CD at 220 nm is relevant to observe the unfolding of an alpha helix whereas no change is observed for CD at 205 nm. Conversely, both absorptions yield information on the dynamics of the process.

General Papers:

Type of Paper: Review
Title: Protein Circular Dichroism for Wavelengths Less than 170 nm: What is Behind the Waterfall?
Author: John C. Sutherland ^1,2
Affiliations: ¹ Physics Department, East Carolina University, Greenville, NC 27858, USA; E-Mail: sutherlandj@ecu.edu
² Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA
Abstract: Ultraviolet (UV) radiation from synchrotron radiation sources have extended the short-wavelength limit of circular dichroism measurements (CD) to about 120 nm. The absorption of water, however, has limited measurement of the CD of proteins in an aqueous environment to wavelengths greater than about 170 nm. Intense synchrotron light sources have improved significantly the quality of CD spectra that can be obtained for wavelengths less than about 190 nm, thereby improving the reliability of predictions of protein structure and detection of conformational transitions. Opening an additional 40 to 50 nm of the UV to the observation of CD may be similarly advantageous provided proteins can be maintained in appropriately native environments. This paper reviews the instrumentation that makes possible CD measurements in this extended spectral region, the highly structured CD spectra of dehydrated protein films, approached to extending such measurements to hydrated samples and the nature of the spectral transitions at the shorter UV wavelengths.
Keywords: synchrotron radiation; vacuum ultraviolet; water absorption; peptide bands

Type of Paper: Review
Title: Probing Kinetic Mechanisms of Protein Function and Folding  with Time-Resolved Natural and Magnetic Chiroptical Spectroscopies
Authors: Dave Kliger, Bob Goldbeck and Eefei Chen
Affiliation: Department of Chemistry and Biochemistry; University of California, Santa Cruz, Santa Cruz, CA 95064, USA; E-Mail: kliger@ucsc.edu (D.K.)
Abstract: Recent and ongoing developments in time-resolved spectroscopy have made it possible to monitor circular dichroism, magnetic circular dichroism, optical rotatory dispersion, and magnetic optical rotatory dispersion with nanosecond time resolution. These techniques have been applied to determine structural changes associated with the function of several proteins as well as to determine the nature of early events in protein folding. These studies have required new approaches in triggering protein reactions as well as the development of time-resolved techniques for polarization spectroscopies with sufficient time resolution and sensitivity to probe protein structural changes.

Title: Chiral Vibrational Structures of Proteins at Interfaces
Authors: Li Fu, Zhuguang Wang and Elsa C. Y. Yan
Affiliation: Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT06520, USA; E-Mail: elsa.yan@yale.edu
Abstract: This review discusses the current proceedings of chiral vibrational studies of protein secondary structures at interfaces using chiral sum frequency generation (SFG) spectroscopy. It focuses on the chiral amide I and N-H stretch vibrational signals of peptide backbones that are highly characteristic for various secondary structures. Both theoretical and experimental aspects are reviewed. The molecular origins of chiral signals from protein are discussed, and quantitative descriptions of the chiral SFG response are provided. To demonstrate the capacity of chiral SFG to distinguish protein secondary structures at interfaces, studies on various model peptides and proteins are summarized. Advantages of chiral SFG and prospects of its future applications are also presented, supporting that chiral SFG spectroscopy can be a powerful tool to probe the conformational changes and dynamics in protein structures at interfaces.

Type of Paper: Review
Title: Conformational Changes in DNA upon Drugs Binding Monitored by Circular Dichroism
Author: Yu-Ming Chang ¹, Cammy K.-M. Chen ¹ and Ming-Hon Hou ²
Affiliations: ¹ Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; ² Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, 402, Taiwan; E-Mail: mhho@nchu.edu.tw
Abstract: Circular dichroism (CD) spectroscopy is an optical technique that measures the difference in the absorption of left and right circularly polarized light and employed in the studies of nucleic acids structures.  The use of CD spectroscopy to monitor conformational polymorphism of DNA has grown tremendously in the past few decades. DNA may undergo conformational changes to, B-form, A-form, Z-form, quadruplexes, triplexes and other structures as a result of the binding process to different compounds. Here we review the recent CD spectroscopic studies regarding induction of DNA conformational changes by different drugs. Moreover, we discuss the determination of thermodynamic parameters of DNA upon drugs binding using CD spectroscopy. It is clear that CD spectroscopy is extremely sensitive and relatively inexpensive, as compared with other techniques. The result from these studies shows that CD spectroscopy is a powerful technique for monitoring DNA conformational changes resulting from drug binding and also is a potential drug-screening platform in future.
Keywords: DNA structure; circular dichroism; conformational changes; DNA-binding drugs; thermodynamic parameters

Title: Introducing DInaMo: A Package for Calculating Protein Circular Dichroism Using Classical Electromagnetic Theory
Authors: Neville Y. Forlemu ^1,2, Boris A. Sango ¹, Sandeep Pothuganti ¹ and Kathryn A. Thomasson ¹
Affiliations: ¹ Univeristy of North Dakota, Chemistry Department, 151 Cornell St. Stop 9024, ND 58202, USA; E-Mail: kthomasson@chem.und.edu
² Shorter University, Department of Natural Sciences, School of Science and Mathematics, Rome Hall 303, 315 Shorter Ave., Rome, GA 30165, USA
Abstract: The dipole interaction model is a classical electromagnetic theory that has successfully been able to reproduce the experimental CD for the π-π* transitions for peptides and proteins. This theoretical model, pioneered by Jon B. Applequist, is assembled into a package DInaMo written in C and Fortran. DInaMo is capable of treating whole proteins at a relatively low computational cost. The program reads Protein Data Bank formatted files of structures generated by molecular mechanics and molecular dynamics. The energy minimization, molecular dynamics requirement on simple crystal structures is due to the absence of hydrogens in most crystal structures available in the Protein Data Bank. DInaMo reduces all the amide chromophores to points with anisotropic polarizability and all nonchromophoric aliphatic atoms to points with isotropic polarizability; all other atoms are ignored. By determining the interactions among the chromophoric and nonchromphoric parts of the molecule using empirically derived polarizabilities, the rotational and dipole strengths are determined leading to the calculation of the CD spectrum for each molecule. Theoretically predicted CD for a variety proteins (lysozyme, myoglobin, insulin, and collagen) are compared with synchrotron radiation CD data. Theory shows good correlation and agreement with with experiment, showing bands with similar morphology and absorption maxima for the π-π* transitions.