Electronic Circular Dichroism Measurements

Over the past decade two forms of vibrational optical activity have become established. One is called vibrational circular dichroism (VCD), the extension of electronic circular dichroism into the infrared vibrational region of the spec-tram. The first measurements of VCD were reported by George Holzwarth and co-workers at the University of Chicago in 1973 for crystals (3) and 1974 for neat liquids (4). In VCD one measures the small difference in the absorption of a sample for left versus right circularly polarized incident infrared radiation. The early stages of the development of VCD have been reviewed from several perspectives (5-8). 

For our purpose, it is convenient to classify the measurements according to the format of the data produced. Sensors provide scalar valued quantities of the bulk fluid i. e. density p(t), refractive index n(t), viscosity dielectric constant e(t) and speed of sound Vj(t). Spectrometers provide vector valued quantities of the bulk fluid. Good examples include absorption spectra A t) associated with (1) far-, mid- and near-infrared FIR, MIR, NIR, (2) ultraviolet and visible UV-VIS, (3) nuclear magnetic resonance NMR, (4) electron paramagnetic resonance EPR, (5) vibrational circular dichroism VCD and (6) electronic circular dichroism ECD. Vector valued quantities are also obtained from fluorescence I t) and the Raman effect /(t). Some spectrometers produce matrix valued quantities M(t) of the bulk fluid. Here 2D-NMR spectra, 2D-EPR and 2D-flourescence spectra are noteworthy. A schematic representation of a very general experimental configuration is shown in Figure 4.1 where r is the recycle time for the system. 

If two different three-dimensional arrangements in space of the atoms in a molecule are interconvertible merely by free rotation about bonds, they are called conformations if not, configurations.l85 Configurations represent isomers that can be separated, as previously discussed in this chapter. Conformations represent conformers, which are rapidly interconvertible and thus nonseparable. The terms conformational isomer and rotamer are sometimes used instead of conformer. A number of methods have been used to determine conformations.186 These include x-ray and electron diffraction, ir, Raman, uv, nmr,187 and microwave spectra,188 photoelectron spectroscopy,189 supersonic molecular jet spectroscopy,190 and optical rotatory dispersion and circular dichroism measurements.191 Some of these methods are useful only for solids. It must be kept in mind that the conformation of a molecule in the solid state is not necessarily the same as in solution.192 Conformations can be calculated by a method called molecular mechanics (p. 149). 

Nuclease behaves like a typical globular protein in aqueous solution when examined by classic hydrodynamic methods (40) or by measurements of rotational relaxation times for the dimethylaminonaphth-alene sulfonyl derivative (48)- Its intrinsic viscosity, approximately 0.025 dl/g is also consistent with such a conformation. Measurements of its optical rotatory properties, either by estimation of the Moffitt parameter b , or the mean residue rotation at 233 nin, indicate that approximately 15-18% of the polypeptide backbone is in the -helical conformation (47, 48). A similar value is calculated from circular dichroism measurements (48). These estimations agree very closely with the amount of helix actually observed in the electron density map of nuclease, which is discussed in Chapter 7 by Cotton and Hazen, this volume, and Arnone et al. (49). One can state with some assurance, therefore, that the structure of the average molecule of nuclease in neutral, aqueous solution is at least grossly similar to that in the crystalline state. As will be discussed below, this similarity extends to the unique sensitivity to tryptic digestion of a region of the sequence in the presence of ligands (47, 48), which can easily be seen in the solid state as a rather anomalous protrusion from the body of the molecule (19, 49). 

Several theoretical studies concluded that the two bands originate from electronic transitions from one ground state to two excited states [47-51,55], The D3-symmetry conformation was confirmed by an X-ray diffraction study of crystal samples [56], resonance Raman studies [46,51,57], and magnetic circular dichroism measurements [55], Yet, no C2-symmetry conformation has been identified yet. 

Electronic Circular Dichroism In contrast to most organic compounds in which CD measurements are limited to the ultraviolet region, most metal complexes possess d-d absorption bands in the more accessible visible and near-infrared regions, allowing for relatively easier application of electronic circular dichroism (ECD) measurements. In fact, the first observation by Cotton of optical rotation measurements through an absorption band and interpretation in terms of differential absorption of the circularly polarized beam was performed on solutions of L-tartrate chromium(III) and copper(II) complexes.100... 

Vibrational optical activity (VOA) is a relatively new area of natural optical activity. It consists of the measurement of optical activity in the spectral regions associated with vibrational transitions in chiral molecules. There are two basic manifestations of VOA. The first is simply the extension of electronic circular dichroism (CD) into the infrared region where fundamental one-photon vibrational transitions are located. This form of VOA is referred to as vibrational circular dichroism (VCD). It was first measured as a property of individual molecules in 1974 [1], and was independently confirmed in 1975 [2]. Within the past twelve years, VCD has been reviewed on a number of occasions from a variety of perspectives [3-15], and two more reviews are currently in press [16,17], The second form of VOA has no direct analog in classical forms of optical activity. Optical activity in Raman scattering, known simply as Raman optical activity (ROA), was measured successfully for the first time in 1973 [18], and confirmed independently in 1975 [19], ROA has been described in detail and reviewed several times in the past decade from several points of view [20-24], and two additional reviews [25,26], one with a view toward biological applications [25] and the other from a theoretical perspective [26], are currently in press. In addition, two articles of a pedagogical nature are in press that have been written for a general audience, one on infrared CD [27] and the other on ROA [28],... 

Since sarcophaginates and sepulchrates are relatively easy to crystallize, a great number of these compounds are studied by X-ray crystallography, which together with molecular geometry calculations makes it possible to establish their three-dimensional structures both in crystal and in solution. The optical activity of such clathrochelates enables one routinely to utilize circular dichroism measurements to investigate their structure. The spatial and electronic structures of sarcophaginates and sepulchrates are much more seldomly determined by alternative spectral techniques compared with clathrochelates of other types. 

Discussions of chiroptical properties of corresponding compounds in this series of The Chemistry of Functional Groups generally refer to the spectral range 589-190 nm, i.e. the emphasis is on optical (molar) rotations [O] J in the transparent region (optical rotatory dispersion, ORD) and rotations [0]J measured at the wavelength of the sodium-D-line (X = 589 nm) as well as electronic circular dichroism A e (CD) in the near ultraviolet region (X 190 nm) ... 

ORD measurements in the IR region never have played any role. The ORD method has to be applied in the UV/vis spectral region if a compound does not possess a suitable chromophore. But in order to avoid an ORD analysis, chromophore-free compounds will often be substituted with suitable absorbing groups (see section on Electronic circular dichroism for compounds without a chromophore). 

Synthesis and characterization of a new type of crown ethers (81)-(83) have been deseribed by Huszthy. The electronic circular dichroism (BCD) spectra of the ehiral crown ethers (i ,i )-(81) and (i ,i )-(82) eontaining an alkyl diarylphosphinate moiety, showed a strong exciton splitting in the Bb spectral region of the aromatic chromophores. In the case of the proton-ionizable ehiral derivative (i ,i )-(83) containing the phosphinic acid unit, the BCD speetrum measured in MeCN, suggested molecular dimerization or aggregation. 

The analogous reaction of 83 with phloroglucinol (1,3,5-trihydroxybenzene) led to the corresponding isomer of type 87 in 10 % yield. The racemic mixture of this compound was resolved by chiral HPLC on Chiralpak ADH stationary phase using propan-2-ol/hexane (2 98) as mobile phase. The absolute configuration of the two separated enantiomers was determined by the comparison of experimentally measured optical rotation dispersion and electronic circular dichroism with DFT calculations of these chiroptical properties [39]. 

The dispersion of the optical rotation was for a long time also the focus of much experimental attention through optical rotatory dispersion measmements. Even after it became customary to restrict the optical rotation measurements to a single frequency, ORD served as an important tool for determining excitation energies in chiral molecules, althoughit has now been surpassed by electronic circular dichroism for these purposes (see O section Circular Dichroism ). 

Snyder, P. A., Atanasova, S., 8c Hansen, R. W. C. (2004). Ethylene. Experimental evidence for new assignments of electronic transitions in the n 71 energy region. Absorption and magnetic circular dichroism measurements with synchrotron radiation. Journal of Physical Chemistry A, 10, 4194. 

The chiroptical methods include optical rotation (OR), optical rotatory dispersion (ORD), electronic circular dichroism (BCD), vibrational circular dichroism (VCD), and Raman optical activity (ROA). These are nondestructive methods that can be measured directly in solution and without the need for crystallization. The power of the above-mentioned methods for the stereochemical investigation of chiral organic compounds resides in the fact that the two mirror-image CPL beams interacting with an asymmetric molecule is a manifestation of diastereo-meric discrimination. ... 

It may be worthwhile to compare briefly the PECD phenomenon discussed here, which relates to randomly oriented chiral molecular targets, with the likely more familiar Circular Dichroism in the Angular Distribution (CDAD) that is observed with oriented, achiral species [44 7]. Both approaches measure a photoemission circular dichroism brought about by an asymmetry in the lab frame electron angular distribution. Both phenomena arise in the electric dipole approximation and so create exceptionally large asymmetries, but these similarities are perhaps a little superficial. 

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