In this article, approaches towards the paramagnetic tagging of diamagnetic proteins are reviewed. Alignment can be achieved by adding paramagnetic fusion proteins or peptides to the C- or the N-terminus or by attaching paramagnetic tags to Cystein residues. Applications for the study of homodimer structures and protein/ligand interactions, as well as protein domain dynamics, are reviewed.

Organic molecules of different complexity are aligned by a DMSO‐compatible gel in such a way that C–H dipolar couplings up to 29 Hz are observed. This paves the way to the simultaneous determination of conformation and configuration of organic compounds by NMR spectroscopy and thus enables the determination of the stereochemistry of natural products (e.g. hormaomycin, see picture) that cannot be crystallized.

[structure: see text] A short synthesis of EDTA-based metal chelates that can be attached to the cysteine residue of a protein via a disulfide bond is described. The complexes were used after coordination of lanthanides to align trigger factor and apo-calmodulin in solution to yield residual dipolar couplings and pseudocontact shifts. Alignment tensors for the new tags are linearly independent compared to those of previously published tags.

The elucidation of the relative stereochemistry of asymmetric centers of organic molecules is an important challenge in chemistry since it requires the simultaneous determination of conformation and configuration. Whereas conventional NMR spectroscopy parameters such as NOE and 3 J coupling constants, which provide internuclear distances and dihedral angles, yield the configuration of stereocenters in rigid compounds, this approach is difficult or impossible in cases in which the molecule is flexible or the stereocenters are remote in the bonding network. Residual dipolar couplings (RDCs) provide additional structural restraints, as has been abundantly shown in structural biology, [1] and might enhance the power of NMR spectroscopy in the determination of the conformation and configuration of small organic molecules at the same time. They rely on the weak alignment of molecules in solution and provide angular as well as distance information that are not contained in the NOE or J coupling values. RDCs have proven to be very efficient in the stereochemical assignment of moieties and hold promise as parameters for the determination of the stereochemistry, even in nonrigid molecules.