Residual dipolar couplings (RDCs) have recently become increasingly important in organic structure determination due to their unique information content. One main limitation for the use of RDCs in organic compounds is the orientation that needs to be induced to be able to measure RDCs. So far, there are very few possibilities to modulate the orientational properties of organic solutes and even less when chiral media are considered. Based on our recent findings that the critical concentration of the liquid-crystalline phase of homopolypeptides depends on their molecular weight, we sought for further ways to modulate the orienting properties. We were especially interested in seeing whether we could not only influence the induced degree of orientation, but whether we could also change the solute′s preferred orientation and even enhance enantiodifferentiation. We thus tried different aprotic and protic additives and were successful in all of the above-mentioned aspects by using CCl₄ as the additive. Furthermore, we consider DMSO to be a very useful additive. The LC phase of low MW poly(γ-benzyl-L-glutamate) (PBLG) is usually unstable when DMSO is added. The high MW PBLG used in this study, however, remained stable up to a DMSO/CDCl₃ ratio of 1:2. By using this combination of solvents, the alignment of the two enantiomers of a compound, which is insoluble in CDCl₃, namely, the HCl salt of a tryptophane ester, was possible leading to high-quality spectra. The two enantiomers of the tryptophane ester showed different couplings, thus indicating that enantiodifferentiation is taking place. Thus we were able to modulate the orienting properties (degree of orientation, preferred orientation and enantiodifferentiation) of PBLG by using additives and to increase the accessible solvent and solute range significantly.

The orientational properties of the two enantiomers of an example compound, namely isopinocampheol [(+)- and (−)-IPC] in the two enantiomers of a liquid crystalline phase, namely Poly-γ-benzyl-L/D-glutamate (PBLG/PBDG) with the organic cosolvent CDCl₃, were investigated. The interactions can be either enantiomorphous, leading to equal orientations and residual dipolar couplings (RDCs), or diastereomorphous, leading to different orientations and RDCs. The difference between the two diastereomorphous orientations was determined to be rather small (5° in the Euler angle β). Furthermore, we investigated whether one of the two diastereomorphous interactions is favored. Copyright © 2009 John Wiley & Sons, Ltd.

After the huge impact that residual dipolar couplings (RDCs) have had on the structure determination of biological macromolecules by NMR spectroscopy, their utility in the structure determination of small/medium-sized organic compounds is more and more recognised. This microreview will provide a short overview on how to introduce the anisotropic environment necessary to measure RDCs, the corresponding measurement methods and the applications for the determination of the relative configurations and the assignment of diastereotopic moieties. Their application to rigid compounds will be described, as will their very promising application to more flexible compounds, which is an area in which RDCs are expected to yield information that is not accessible by any other NMR spectroscopic means. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

The cover picture shows all organic compounds to which residual dipolar couplings (RDCs) were applied in the NMR spectroscopic determination of their relative configuration or in the assignment of diastereotopic moieties. The details on how RDCs can be applied for structure determination, as well as the necessary prerequisites and the current developments in the area of flexible compounds, are presented in the Microreview by C. Thiele on p. 5673 ff.

Residual dipolar couplings (RDCs) have recently become increasingly important in organic structure determination due to their unique information content. One main limitation for the use of RDCs in organic compounds, however, is that the compound in question needs to be oriented with respect to the magnetic field in order to measure RDCs. So far, there are very few possibilities for modulating the induced degree of orientation. The situation is even worse when chiral orienting media are considered, which could allow absolute configuration determination in the future. We have conducted a systematic investigation into modulating the orientation induced by one chiral orienting medium, namely organic solutions of PBLG (poly-γ-benzyl-L-glutamate), as a function of its molecular weight and the organic co-solvent used, and have obtained significant insights into factors that influence the order induced. With increasing molecular weight of the polypeptide the orientation of the solutes decreases, leading to well-resolved spectra with improved line shapes. This can be attributed exclusively to the fact that the critical concentration of the liquid-crystalline phase decreases with increasing molecular weight (pure dilution effect). Any influence of increasing flexibility on the orientation can be ruled out.

The electron-donating properties of eighteen N-heterocyclic carbenes (N,N′-bis(2,6-dimethylphenyl)imidazol)-2-ylidene and the respective dihydro ligands) with 4,4′-R substituted aryl rings (4,4′-R = NEt₂, OMe, Me, H, SMe, F, Cl, Br, I) in the respective Grubbs II complexes were studied using electrochemical techniques. The nature of the 4-R substituent has a strong influence on the Ru^II/III redox potentials ranging between ΔE_1/2=+0.196 and +0.532 V. Three unsymmetrical Grubbs II complexes with 4-R ≠ 4-R′ were also synthesized. Dynamic NMR spectroscopy revealed the restricted rotation around the (NHC)CRu bond (ΔG = 89 kJ mol⁻¹ at 333 K) resulting in two atropisomers, respectively, with an isomer ratio close to unity. Each of the isomers, that is the two orientations of the 4-R/4-R′ substituted mesityl ring with respect to the RCHPh unit, gives rise to different redox potentials (4-R = NEt₂, 4-R′ = Br: ΔE_1/2=+0.232 and +0.451 V). In the oxidized Grubbs II complex (4-R = NEt₂, H) and in the cathodic isomer the electron rich aryl ring is located above the RuCHPh unit. This orientational effect provides clear evidence for strong π–π through-space interactions in the Ru^III complexes, assuming that the alternative through-bond transfer of electron density is equally efficient in both isomers.