MRC special issue on NMR of small molecules in anisotropic media

Abstract

It was a great pleasure to edit and even a greater one to present this special issue to the readers of Magnetic Resonance in Chemistry. The relatively recent developments of weak alignment media compatible with organic solvents have opened new avenues on the structural analysis of complex natural and synthetic small organic molecules by NMR spectroscopy.1 The first NMR experiment of a small molecule in anisotropic media was performed by Saupe and Englert in 1963, in which benzene was partially aligned in the nematic phase of p-azoxyanisole.2 This experiment led to the later development of the theory of alignment3 and also permitted the empirical determination of the chemical shielding anisotropy of the benzene ring. The strong degree of alignment induced by nematic liquid crystal prevented their practical application to the structural analysis of complex small organic molecules. However, NMR spectroscopy of liquid crystals developed itself into a strong field of research and applications. This topic is outside the scope of this special issue. Weak alignment was first introduced by Tjandra and Bax in 1997 as a new and powerful tool for the study of the structure and dynamics of proteins.4 Its application quickly extended to the analysis of nucleic acids, and several alignment media compatible with water were developed since then. However, small organic molecules had to wait nearly 40 years to be analyzed by NMR in weak alignment media compatible with organic solvents. The deuterium quadrupolar coupling and the dipolar coupling are anisotropic NMR parameters not observable in conventional liquid state NMR experiments, but save for relaxation effects, they can be revealed when molecules are exposed to orienting media. Residual dipolar couplings (RDCs) have proven to be very powerful for the constitutional, configurational, and conformational analysis of small molecules,1 as a complementary tool to existing NMR parameters used for the same purpose, e.g. NOE and the J-based analysis. For certain compounds, the use of only these two existing NMR parameters leads to more than one solution structure, and this ambiguity can be lifted if RDCs are added to the analysis. The residual deuterium quadrupolar coupling has been extensively used as a tool for enantio-discrimination when small molecules are aligned in chiral non-racemic lyotropic liquid crystalline phases, e.g. different types of helical polymers dissolved in organic solvents.5 On the other side, a third anisotropic NMR parameter, the residual chemical shift anisotropy, has been explored as a complementary tool to the application of RDCs to the structural analysis of small molecules.6 This special issue is focused on new NMR methodologies for the analysis of small organic molecules oriented in weak alignment media. This is an emerging field with plenty of room for new discoveries and development of necessary tools such as software and methodologies for data analysis, pulse sequences, and alignment media. However, its application is not yet widespread in the small molecules community. In this special issue, the readers will have the opportunity to enjoy a diverse set of research articles contributed by the experts in the field. I hope that the scientific community finds this special issue particularly inspiring to bring these new methodologies into their everyday work. I want to thank the Editor In Chief, Prof. James Keeler, for the invitation to edit this special issue. I also want to thank the members of the Editorial Board, Prof. Helmut H. Duddeck, Prof. Bozhana P. Mikhova, and Prof. Angela M. Gronenborn for their encouragement and support. Finally, my thanks to all my colleagues who gave me the honor of editing their contributions.