Circular dichroism, enantiomeric

Figure 5.32 Circular dichroism spectra of tubules made from mixtures of opposite enantiomers of DCg.gPC in 80 20 methanol-water. Spectra shown correspond to mixtures of (a) 100 0, (b) 75 25, (c) 50 50, (d) 25 75, and (e) 0 100 L-/D-DC89PC. Inset shows dependence of peak molar ellipticity on enantiomeric excess along with linear fit of data. Reprinted with permission from Ref. 125. Copyright 1998 by the American Chemical Society.

A special mention in the field of enantioselective HPLC separations must be made of chiro-optical detection systems, such as circular dichroism (CD) and optical rotation (OR), which can be also used to circumvent the low UV detectability of chromophore-lacking samples [40, 61]. While sensitivity of chiro-optical detection is not always sufficient to perform enantiomeric trace analysis, the stereochemical information contained in the bisignate spectropolarimetric response is useful in establishing elution order for those compounds not available as single enantiomers of known configuration. An example of application of different online detection systems (UV and CD at 254 nm) in the enantioselective separation of a racemic sulfoxide on a commercially available TAG CSP is reported in Figure 2.12, under NP conditions. 

Enantiomeric pnrity assays have also been performed without chromatographic separation being conducted prior to detection, for example, with circular dichroism (CD) and MS. Bertncci et al. [110] developed a chiral assay for pulegone, oxazepam, and warfarin by combining simnltaneons UV, CD, and g factor detection on an achiral separation system with a Hypersil CN colnmn and a mobile phase of hexane 2-PrOH (90 10). The precision (RSD%) of the method ranged from 0.6% to 2.6%, and the LOQs were between 0.1% and 1% (0.2-2.2 j,g). For fnrther information concerning the application of CD and polarometric detection for chiral detection, see the review by Bobbitt and Linder [111]. 

At present, polarimetry and allied techniques such as circular dichroism, NMR spectroscopy (employing nonracemic solvents or shift reagents) and various types of chromatography (employing nonracemic stationary or mobile phases) are the most widely used techniques for the direct determination of enantiomeric purities, and only these techniques are discussed further (see Sections 3.1.3. to 3.1.5.). 

At least for 14 the usual methods for determining the enantiomeric purity (especially NMR-methods) failed. From 14 and 15 several optically active derivatives were prepared 40 441 and their chiroptical properties [especially the circular dichroism (CD) spectra of derivatives of 14]40) recorded. 

The vibrational circular dichroism(VCD) spectroscopy can be used to elucidate the stereochemistries of chiral molecules, including the accurate estimation of enantiomeric excess and their absolute configrations[20]. Optically pure samples as well as a racemic sample(c) were used as a reference to compare the VCD spectra. Three VCD spectra are shown in Fig. 7 a spectrum of 99 % ee R(-)-1-phenyl 1,2-ethanediol(a) and that of 99 % ee S(+ )-1-phenyl l,2-ethanediol(b) obtained from Aldrich Co., and the other is that of the product obtained on the Ti-MCM-41/chiral Co(HI) salen catalyst(d). 

It has also been reported from circular dichroism (CD) studies [36] that polysaccharide-based CSPs can induce chirality in enantiomeric guests such as (4Z,15Z)-bilirubin-Ixoc (BR) (Fig. 5). Although not optically active, BR has two enantiomeric helical conformations maintained by six intramolecular hydrogen bonds between two carboxylic acid moieties and two pyrromethenone — NH— protons. These (R)- and (5)-helical conformers are in dynamic equilibrium in an achiral solution [37], but some optically active compounds can enantioselectively bind to BR to induce CD spectra in solution [38-40]. A significant induced CD... 

As the time scale of the Raman scattering event ( 3.3 x 10 14 s for a vibration with a Stokes wave number shift of 1000 cm 1 excited in the visible) is much shorter than that of the fastest conformational fluctuations, an ROA spectrum is a superposition of snapshot spectra from all the distinct conformations present in a sample at equilibrium. Since ROA observables depend on absolute chirality, there is a cancellation of contributions from enantiomeric structures arising as a mobile structure explores the range of accessible conformations. Therefore, ROA exhibits an enhanced sensitivity to the dynamic aspects of biomolecular structure. In contrast, conventional Raman band intensities are blind to chirality and so are generally additive and therefore less sensitive to conformational mobility. Ultraviolet circular dichroism (UVCD) also demonstrates an enhanced sensitivity to the dynamics of chiral structures ... 

Enantiomeric resolution of the corresponding racemates was accomplished by HPLC on chiral stationary phases (CSP) [23]. Chiroptical studies by means of circular dichroism indicated that the chiral dendrimer core exerted some influence... 

Measurement of circular dichroism can even permit elucidation of relatively small structural changes. CD spectroscopy is also suitable for the solution of specific application-relevant questions. Studies of the sensor properties of chiral dendrimers make use of the fact that complexation of chiral guest molecules induces changes in the CD bands of the host dendrimers. Thus guest-selective chiroptical effects observed in titration experiments with enantiomeric guest molecules give an indication of the potential of the chiral dendrimer to act as an enantioselective sensor [87]. 

Yamamoto, C., Okamoto, Y., Schmidt. T., Jager, R., Vogtle, F. Enantiomeric resolution of cycloenantiomeric rotaxane, topologically chiral catenane, and pretzel-shaped molecules observation of pronounced circular dichroism, J. Am. Chem. Soc. 119 (1997), 10547-10548. 

The system shown in Scheme 2 is based on the fact that irradiation at 250 and 300 nm yielded photostationary states of slightly different composition. Irradiation of enantiomerically pure (M)-cis-10 or (P)-trans-10 at 250 nm resulted in a photostationary state consisting of 68% (M)-cis-10 and 32% (P)-trans-10, whereas irradiation at 300 nm yielded 64% (M)-cis-10 and 36% (P)-trans-10. Thanks to the thermal stability of these pseudoenantiomers— no (P)-cis or (M)-trans-10 were detected after irradiation—the small difference in composition of the photostationary states could be detected by circular dichroism (CD) spectroscopy. In this case, the photoinduced 180° rotation around the olefin results in a change in the helicity of the tetrahy-drophenanthrene unit. Similar behavior was observed for the structurally related benzoannulated bithioxanthylidene [28]. 

The interaction of polarized light with chiral compounds is of great interest since chiroptical techniques are extremely useful as methods of characterization. It is equally true that although most scientists are aware that enantiomerically rich solutions will rotate the plane of linearly polarized light, the origins of this effect are not as simple as might be imagined. In this first article, the phenomena of polarimetry and optical rotatory dispersion will be discussed. A subsequent note will concern the related phenomenon of circular dichroism. 

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