Alignmentmedia

Helical Polymers: Enantiodifferentiating alignment media

Nuclear Magnetic Resonance Spectroscopy (NMR) is the most important analytical tool to elucidate structures of dissolved molecules at atomic resolution. This is true not only for the determination of the constitution, but even more so for the analysis of the spatial arrangement of the atoms within molecules. This latter stereochemical problem is associated with the simultaneous determination of the relative (and maybe some day the absolute) configuration of molecules with more than one stereogenic element including their respective conformations.

NOE-derived distances, dihedral angles from J-couplings and projection angle restraints from cross-correlated relaxation experiments have dominated configurational assignments and conformational analyses for decades. Since the second half of the 1990is anisotropic parameters, especially residual dipolar couplings (RDCs), attracted notice to the NMR-community. These dipolar couplings contain angular and distance information with respect to the magnetic field vector which means that they do not rely on parametrization and are global in nature. A precondition for their measurement is to restrict the isotropic tumbling of the analyte molecule to such an extent that the dipolar coupling is scaled down to approximately 1/1000th of its maximum value (weak alignment).

The two most prominent ways to achieve this is to place the compound into a stretchable polymer gel (SAG: strain induced alignment in a gel) or the dissolve it in a lyotropic liquid crystalline (LLC) phase. If this alignment medium is chiral and of uniform configuration a differential order effect can be expected which leads to enantiomer-differentiating alignment which in turn may be the basis for the determination of absolute configurations of dissolved molecules by NMR.

Left: Polyarylacetylenes with characteristic structural features used for the preparation of chiral alignmen media. Right: The corresponding Polyarylisonitrile
Left: Polyarylacetylenes with characteristic structural features used for the preparation of chiral alignmen media. Right: The corresponding Polyarylisonitrile

We develop both chiral gels as well as chiral LLC-phases for the above mentioned purposes. For both types of media we focus on the application of helically-chiral polyacetylenes and polyisonitriles with lateral amino acid based side chains. Especially the polyacetylenes haven proven to be versatile alignment media with exceptional enantiomer-differentiating capabilities (Angew. Chem. Int. Ed. 2012, 51, 8334 – 8338; Magn. Reson. Chem. 2012, 50, 545 – 552).

In a recent publication, we describe the development and application of a new computer program (ConArch+) for the determination of relative configurations based on RDC-driven floating chirality distance geometry calculations.

How to prepare a lyotropic liquid crystalline phase of PPA-L-Val