No abstract

In recent years, four different chiroptical spectroscopic methods, namely vibrational circular dichroism, vibrational Raman optical activity, electronic circular dichroism, and optical rotatory dispersion, have become popular for establishing the absolute configuration and predominant conformations of chiral molecules in solution state. Many individual laboratories normally utilize only one of these methods to derive the molecular structural information. Although that approach may be satisfactory for most of the molecules studied, it is to be noted that in some instances a single method can give ambiguous conclusions or may not give complete structural information. This article summarizes the situations where simultaneous use of more than one chiroptical spectroscopic method is required to obtain molecular structural information and recommends the routine application of more than one chiroptical spectroscopic method for any given molecule.

To quantitatively determine the agreement between experimental and calculated vibrational circular dichroism (VCD) spectra, a new approach, based on the similarity of dissymmetry factor spectra has been developed and implemented. This method, which places emphasis on robust regions both in the experimental and in the calculated spectra, has been tested with six chiral compounds of known absolute configurations, namely, (R)-(+)-3-chloro-1-butyne, (3R)-(+)-methylcyclopentanone, (3R)-(+)-methylcyclohexanone, (1S)-(-)-α-pinene, (1R)-(+)-camphor, and (S)-(+)-epichlorohydrin. The criterion of maximum overlap among experimental and calculated dissymmetry factor spectra is shown to have definite advantages over those using maximum overlap among VCD or absorption spectra individually. The new method provides a better assessment of the comparison between experimental observations and quantum chemical VCD predictions and improves the confidence in the assignment of absolute configurations.

The field of optical rotations is currently undergoing a renaissance, which is a direct result of the advances in quantum mechanics and the availability of faster desktop computers. In the last few years, the field of optical rotations has taken an important role for determining the three-dimensional molecular structure (absolute configuration and conformations) with confidence. The purpose of this review is to present the latest advances in this area so that practicing chemists can utilize them in their respective areas of research and development.

For three different chiroptical spectroscopic methods, namely, vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and Raman optical activity (ROA), the measures of similarity of the experimental spectra to the corresponding spectra predicted using quantum chemical theories are summarized. In determining the absolute configuration and/or predominant conformations of chiral molecules, these similarity measures provide numerical estimates of agreement between experimental observations and theoretical predictions. Selected applications illustrating the similarity measures for absorption, circular dichroism, and corresponding dissymmetry factor (DF) spectra, in the case of VCD and ECD, and for Raman, ROA, and circular intensity differential (CID) spectra in the case of ROA, are presented. The analysis of similarity in DF or CID spectra is considered to be much more discerning and accurate than that in absorption (or Raman) and circular dichroism (or ROA) spectra, undertaken individually.

Two of the chiroptical spectroscopic methods, namely optical rotatory dispersion (ORD) and electronic circular dichroism (ECD), have been around for several decades. But their use in determining the absolute configuration and predominant conformation is gaining renewed interest with the availability of quantum mechanical methods for predicting ORD and ECD. Two other methods, namely vibrational circular dichroism (VCD) and vibrational Raman optical activity (VROA), are relatively new and offer convenient approaches for deducing the structural information in chiral molecules. With the availability of quantum mechanical programs for predicting VCD and VROA, these methods have attracted numerous new researchers to this area. This review summarizes the latest developments in these four areas and provides examples where more than one method has been used to confirm the information obtained from individual methods.

COMMUNICATIONSaccording to the Nernst equation (3) (E, = -323 mV at pH 7.0 and -366 mV at pH 8.1 for DDTE7]). Because of the relatively Facile reduction of the mixed Se-S bridge in the [Sec",Cy~'~]octapeptide with DTT and thus possibly nonideal conditions of equilibrium, reduction of this peptide was also performed with [hdfanylethanol (Eo = -207 mV at p H 7.0L7]). The redox potentials of the [Sec",Cy~'~]-octapeptide extracted from the two experiments ( E = -326 mV against DDT and -332 mV against [I-sulfanylethanol at pH 7.0) compare well within the limits of error of the measurements. The differences of the redox Figure 2. The redox potentials of [Cys' '.Cys"]-. [Sec' I .Cysi4.Lysih]-and [Seci1.Sec'4.Ly9'h]-grx-(10-17) at pH 7.0 and 20 C referred to that of glutathione (GSSG). The redox potential of [Cys". Cy~'~]-grx-(lO 17) of -180 mV was calculated from the K,,, v;iIue determined previously with glutathione as redox buffer [XI with the value of E,, = -205 mV for glutathione determined by Szajewski and Whitesides [7]potentials of the Sec-and Cys-peptides referred to glutathione (as the main redox system of the living cells['31) are reported in Figure 2.The redox potential ( E = -381 mV a t pH 7.0 and -389 mV at pH 8.5 and 20°C) of the selenocystine peptide [Sec", Se~'~,Lys'~]-grx-(lO-17)proved to be remarkably lower than that of DTT ( E = -3 23mV) in contrast to previous speculations,[*] but in good agreement with that of selenocystamine ( E = 349 mV; calculated from the KO, value of 7 . 1 4~-' determined with DTT as reductantr3]). Conversely, the redox properties of the mixed Sec,Cys-peptide are very similar to those of DTT ( E = -326 mV vs -323 mV for DTT) and thus significantly more reducing than glutathione (-205 mVr71). Since the KO, of the Sec,Sec-peptide is remarkably higher than that of the mixed Sec,Cys-peptide (Table l ) , formation of mixed Se-S bridges is apparently very disfavored relative to the formation of an Se-Se bridge. This observation could open an interesting new approach for the design of productive intermediates in the oxidative folding pathway of synthetic peptides and recombinant proteins, since Se-Se bridging should occur independently of the presence of additional cysteine residues. Moreover, alkaneselenols are known to enhance the rates of thiol/disulfide interchange reactions;[3. I4l thus, such a built-in chemical device in protein sequences could facilitate the oxidative refolding process by mimicking the action of protein disulfide isomerase.Bromochlorofluoromethane 1 is one of the simplest examples of the Le Be1 and van't Hoff asymmetric carbon atom, and since its first synthesis by Swarts a century ago"] a number of attempts have been made to separate its enantiomers and measure their optical rotation. These efforts culminated in 1985 with the first analytical resolution['] of a weakly enantiomerically enriched sample obtained by Wilen et al.,[31 which enabled a maximum specific rotation (i.e., the rotation for the pure enantiomer) of [a];' = k1.6 (neat, p = 1.91 kgdm-) to be e...

Ab initio computations indicate the existence of several stable and some unstable conformers in isolated Q and p glucose molecules. All of the lower-energy conformers exhibit a strikingly regular pattern of internal hydrogen bonding. Five such stable structures have been identified for each of the Q and p anomers, differing primarily in the orientation of the CHzOH group. In each conformer, the a anomer is predicted to be lower in energy than the corresponding conformers of p anomer. The difference is about 2 kcal/mol in the 4-31G basis but only 0.4 kcal/mol in the 6-31G* basis. It is found that the electronic contributions to the free energy difference stabilize the Q anomer while the nuclear motion contributions stabilize the / 3 anomer. The implications of these predictions and the future investigations required to understand the relative stabilities of the two anomers are pointed out. 0 1992 by John Wiley & Sons. Inc.