An Extremely Versatile Polyglutamate Alignment Medium to Measure Residual Dipolar Couplings in non-Polar and Polar Solvents

Helical structures are ubiquitous in nature and exhibit fascinating properties. They are inherently chiral, and many rely on hydrogen bonds to stabilize their conformation. Homopolypeptides of the glutamate-type form α-helical sec-ondary structures and are considered rigid-rod polymers. They form lyotropic liquid crystalline phases in helicogenic sol-vents. Over the last decade this property has been exploited in the NMR-based structure elucidation of organic compounds making anisotropic NMR observables, such as residual dipolar couplings (RDCs), accessible. However, many alignment media are limited in their compatibility, especially with polar (non-helicogenic) solvents like DMSO, and thus also in their analyte compatibility. Herein, we present poly-γ-(4-propargyloxybenzyl)-L-glutamate (PPOBLG) as an exceptionally versatile align-ment medium compatible with several organic solvents, including DMSO and acetone. The polymer not only allows extraction of RDCs in all these solvents but also provides linearly independent orientations of a model compound by simple variation of the solvent. Moreover, a remarkably high enantiodifferentiation is observed. We furthermore show that these improved prop-erties make it compatible with various natural products containing a wide variety of functional groups.