Hydrogen-Mediated Noncovalent Interactions in Solids: What Can NMR Crystallography Tell About?

Ioana Georgeta Grosu,Maria O Miclăuș,Xenia Filip,Claudiu Filip

doi:10.3390/molecules25163757

Abstract

Hydrogen atoms play a crucial role in the aggregation of organic (bio)molecules through diverse number of noncovalent interactions that they mediate, such as electrostatic in proton transfer systems, hydrogen bonding, and CH–π interactions, to mention only the most prominent. To identify and adequately describe such low-energy interactions, increasingly sensitive methods have been developed over time, among which quantum chemical computations have witnessed impressive advances in recent years. For reaching the present state-of-the-art, computations had to rely on a pool of relevant experimental data, needed at least for validation, if not also for other purposes. In the case of molecular crystals, the best illustration for the synergy between computations and experiment is given by the so-called NMR crystallography approach. Originally designed to increase the confidence level in crystal structure determination of organic compounds from powders, NMR crystallography is able now to offer also a wealth of information regarding the noncovalent interactions that drive molecules to pack in a given crystalline pattern or another. This is particularly true for the noncovalent interactions which depend on the exact location of labile hydrogen atoms in the system: in such cases, NMR crystallography represents a valuable characterization tool, in some cases complementing even the standard single-crystal X-ray diffraction technique. A concise introduction in the field is made in this mini-review, which is aimed at providing a comprehensive picture with respect to the current accuracy level reached by NMR crystallography in the characterization of hydrogen-mediated noncovalent interactions in organic solids. Different types of practical applications are illustrated with the example of molecular crystals studied by our research group, but references to other representative developments reported in the literature are also made. By summarizing the major concepts and methodological progresses, the present work is also intended to be a guide to the practical potential of this relatively recent analytical tool for the scientists working in areas where crystal engineering represents the main approach for rational design of novel materials.

Highlights

The interest of chemists and scientists has been focused in the past century on the access to robust compounds with strong covalent bonds between atoms that exhibit high stability in environmental and harsh chemical conditions
We show that the same general considerations apply when characterizing any hydrogen bond that may form in organic solids, whether it implies proton transfer or not
The present work reviews recent achievements of NMR crystallography in the characterization of crystalline organic solids, with the main emphasis being put on the specific tools developed with the purpose of locating the labile hydrogen atoms with increasing precision in between donor and acceptor sites

Summary

Introduction

The interest of chemists and scientists has been focused in the past century on the access to robust compounds with strong covalent bonds between atoms that exhibit high stability in environmental and harsh chemical conditions. The progresses witnessed by NMR crystallography over the last two decades offer the possibility of extending structural determination from powders to virtually any kind of crystalline organic solids, with accuracy levels approaching in some cases that of single-crystal X-Ray diffraction This covers the problem of better locating labile hydrogen atoms, with real benefits for crystal engineering approaches aimed at developing materials with tailored functionalities based on the directional and reversible character of hydrogen bonding. As most of these studies reveal, the power of this technique comes from the fact that potential ambiguities of the PXRD structural models, or limitations in the DFT geometry optimization, can be identified and corrected in practice via the analysis of the numerous ss-NMR experimental parameters that are sensitive to the interactions experienced by 1 H nuclei

To Transfer or Not to Transfer

Intermolecular

Conclusions and Outlook

H-1 H Magnetization Exchange