Chiroptical changes

Goto, H., Okamoto, Y., and Yashrma, E., Solvent-induced chiroptical changes in supramolecular assemblies of an optically active, regioregular polythiophene. Macromolecules 35, 4590-4601, 2002. 

Bouchet A, Brotin T, Cavagnat D, Buffeteau T (2010) Induced chiroptical changes of a water-soluble cryptophane by encapsulation of guest molecules and counterion effects. Chem Eur J 16 4507 518... 

Xanthan is reported to undergo a chiroptically detected temperature or salt-driven conformational change from an ordered conformation at high salt and low temperature to a disordered conformation either associated with lowering the salt concentration, or with increasing the temperature (2-5). The primary structure of xanthan has been known for about a decade (6,7), but different structures have been suggested both for the ordered and disordered conformation. Some workers (8-13) conclude that the ordered conformation is double-stranded or double-helix, whereas others (14-17) claim that a single stranded description can account for the observed data under... 

The conformational mobility of a chromophoric main-chain polymer is often connected to its electronic structure. Therefore, changes in the UV-visible absorption spectra and/or chiroptical properties are spectroscopically observable as thermo-, solvato-, piezo-, or electrochromisms. It is widely reported that o-conjugating polysilanes exhibit these phenomena remarkably clearly.34 However, their structural origins were controversial until recently, since limited information was available on the correlation between the conformational properties of the main chain, electronic state, and (chir)optical characteristics. In 1996, we reported that in various polysilanes in tetrahydrofuran (THF) at 30°C, the main-chain peak intensity per silicon repeat unit, e (Si repeat unit)-1 dm3 cm-1, increases exponentially as the viscosity index, a, increases.41 Although conventional viscometric measurements often requires a wide range of low-dispersity molecular-weight polymer samples, a size exclusion chromatography (SEC) machine equipped with a viscometric detector can afford... 

Online CD detectors are now commercially available for use with HPLC that are inherently more sensitive than corresponding OR detectors and not affected by solvent changes to the same extent and are thus more gradient compatible [121]. Provided Ae and the concentration of an analyte are known with good precision/accuracy, the measurement of CD will allow the determination of enantiomeric purity. In addition, with CD-based detection systems, both chiroptical and ordinary absorbance can be determined simultaneously allowing the measurement of the g-factor (or dissymmetry factor), which is defined as the ratio of the CD to the absorbance (AA/A) [122]. The g-factor is concentration independent and its measurement allows a more reliable determination of enantiomeric purity (without using a CSP) with reference to standards of known enantiomeric composition irrespective of their concentration [123]. A small number of recent literature examples have suggested the potential use of achiral HPLC with online CD detection for the determination of extreme enantiomeric ratios [121, 124-126] however, chiral separation techniques currently provide a more reliable measurement of enantiomeric purity. 

The influence of the solvent on chiroptical properties of synthetic polymers is dramatically illustrated in the case of poly (propylene oxide). Price and Osgan had already shown, in their first article, that this polymer presents optical activity of opposite sign when dissolved in CHCI3 or in benzene (78). The hypothesis of a conformational transition similar to the helix-coil transition of polypeptides was rejected because the optical activity varies linearly with the content of the two components in the mixture of solvents. Chiellini observed that the ORD curves in several solvents show a maximum around 235 nm, which should not be attributed to a Cotton effect and which was interpreted by a two-term Drude equation. He emphasized the influence of solvation on the position of the conformational equilibrium (383). In turn, Furakawa, as the result of an investigation in 35 different solvents, focused on the polarizability change of methyl and methylene groups in the polymer due to the formation of a contact complex with aromatic solvents (384). 

It is interesting to note that the CD spectrum of 11 can be tuned by changing the oxidation states of the TTF units in the side-chains of 11. Polymer 11 shows reversible interconversion between three univalent and two very broad mixed-valence redox states that have different chiroptical properties. 

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]. 

Upon irradiation at 435 nm in toluene, an extremely high stereoselectivity was observed, with a ratio of M- s-18a to P-trans-18b of 99 1. Compared to chiroptical switch 17, with a donor and acceptor moiety in the lower half, compound 18 suffers from poor reversibility, which can be attributed to the favorable donor-acceptor interaction in M-cis-18a. In view of the potential of gated response switching systems (see Section 5.4.1), it is noteworthy that the preference for the cis-form helicity can only be changed to a preference for the trans-form if the favorable donor-acceptor interaction is eliminated. This feature implies that it is possible to lock photochemi-cally written information and that it then, irrespective of the wavelengths used, cannot be unlocked except by affecting the donor-acceptor interaction. 

The conformational mobility of a chromophoric main chain polymer is often connected to its electronic structure. Therefore, changes in the UV-visible absorption spectra and/or chiroptical properties are spectroscopically observable as thermo-, solvato-, piezo-, or/and electrochromisms. It is widely reported that a-conjugating polysilanes exhibit these phenomena remarkably clearly [54], However, their structural origins were controversial until recently, since limited information was available on the correlation between the conformational prop-... 

For purposes of discussion, we divide applications of CPL spectroscopy into three categories (1) efforts to develop reliable CPL "sector rules", (2) use of comparative CD and CPL studies to probe excited state geometry changes, and (3) the specific use of the selectivity and sensitivity of CPL to probe details of molecular and electronic structure, and dynamics. Since in this book we are primarily concerned with "analytical" applications of these chiroptical methods, we will emphasize here the last of these categories. 

In spite of all the successes of this structural work, the extraordinary discriminatory potential that chiroptical methods would obviously have if applied to the rather mundane task of preliminary routine screening for drugs has never been exploited. One reason for this may be that the sensitivity to stereochemistry has not been fully explained in theoretical terms. The utter inadequacy of the aforementioned theoretical models is easier to understand and appreciate when one realizes that the spatial redirection of just one bond in a molecule, while not affecting the absorption spectra for the structural analogs, will produce changes in the CD spectra that are so dramatic that their individual distinction is elementary. Outstanding illustrations are plentiful in the CD literature of the steroids, for example testosterone and its dihydro-derivative, Figure 1. 

The methods above are based on the direct measurement of the CD curves of the test compounds at one or more wavelengths. Now several difference CD (ACD) methods are described that are based upon the changes brought about in the CD curves by either physical or chemical effects. Difference chiroptical methods are generally introduced for the purpose of increasing analytical selectivity [25]. 

---