DNP NMR of polymers

Nowadays polymers constitute a fascinating class of materials that play key roles in our daily lives. This craze is closely related to the joint development of ever more efficient polymerization techniques and ever more precise analytical techniques. Indeed, these advances make it possible to better describe the microstructure/morphology/properties in polymers, which are essential for understanding and optimizing their macroscopic properties. NMR is traditionally considered as the spectroscopic technique of choice for studying the structure and dynamics of polymers. However, it remains strongly limited by its low sensitivity, which generally results in NMR spectra characterized by a low signal-to-noise (S/N) ratio. Among the methods capable of increasing this sensitivity, Dynamic Nuclear Polarization (DNP) is probably among the most promising. Based on an electron-to-nucleus polarization transfer, this technique allows to impressively increase the NMR signal intensity (e.g. a theoretical gain of the order of 660 and 2600 can be obtained for 1H and 13C nuclei, respectively). Although the principles of DNP were known as early as the 1950s, its use in high-resolution NMR has long encountered technological and theoretical obstacles. This situation has recently changed with the commercialization of high-resolution DNP NMR devices and the development of new high-performance radicals used as DNP polarizing agents. In this context, our team has shown that the high-resolution DNP NMR technique can efficiently contribute to the structural analysis of synthetic polymers by significantly increasing the sensitivity of NMR experiments.

This project currently federates several teams within the ICR (SACS, SREP, CROPS, CMO). It has been supported by AMIDEX (Étoile Montante 2013 project, leader: S. Viel; Emergence & Innovation 2017 project, leader: S. Viel) and the Institut Universitaire de France.

Keywords

Nuclear magnetic resonance, structural elucidation, molecular mobility, dynamic nuclear polarization.

Selected publications

  • Improved structural elucidation of synthetic polymers by DNP solid-state NMR, O. Ouari, T. Phan, F. Ziarelli, G. Casano, F. Aussenac, P. Thureau, D. Gigmes, P. Tordo, S. Viel* ACS Macro Lett. 2013, 2, 715-719 https://doi.org/10.1021/mz4003003
  • Optimizing sample preparation methods for DNP solid-state NMR of synthetic polymers, D. Le, G. Casano, T. Phan, F. Ziarelli, O. Ouari, F. Aussenac, P. Thureau, G. Mollica, D. Gigmes, P. Tordo, S. Viel* Macromolecules 2014, 47, 3909-3916 https://doi.org/10.1021/ma500788n
  • Dynamic nuclear polarisation NMR of nanosized zirconium phosphate polymer fillers, F. Ziarelli, M. Casciola, M. Pica, A. Donnadio, F. Aussenac, C. Sauvée, D. Capitani, S. Viel* Chem. Commun. 2014, 50, 10137-10139 https://doi.org/10.1039/C4CC02723J

DNP NMR of polymorphic solids

Polymorphism – i.e. the ability of a chemical compound to crystallize in different forms – is ubiquitous in organic solids. It can have enormous economic and practical consequences for many industrial applications (e.g. in pharmacy) because different polymorphs of the same chemical compound have radically different physicochemical properties. Despite its importance, this phenomenon remains poorly understood today. In this context, there are two major challenges:

  • Determine structure-properties relationships. For this, the experimental challenge consists in developing new approaches to determine the structure of the different polymorphs at the angstrom scale.
  • Controlling the production of a specific solid form (targeted polymorphism). For this, it is necessary to study the process of formation of the different polymorphs of a chemical compound, i.e. its crystallization, at the atomic level.

To meet these challenges, our team develops new experimental tools based on solid-state NMR coupled or not with Dynamic Nuclear Polarization (DNP), which impressively increase the NMR sensitivity by transferring the electronic spin polarization to nuclei under the presence of microwave irradiation.

This project is supported by the ERC (STRUCTURE 2017 project, lead: Giulia Mollica), the ANR (SHARP 2013 project, lead: Pierre Thureau) and the CNRS (International Emerging Actions, lead: Pierre Thureau).

Keywords

Nuclear magnetic resonance, dynamic nuclear polarization, solid, crystal, structure, polymorph, distance, conformation, crystallization

NMR crystallography of powders

Single crystal X-ray diffraction has revolutionized our knowledge of crystalline matter by providing precise structural data (~ Å) for a very wide variety of samples, thus contributing to the emergence of spectacular scientific advances in many fields. This technique is nevertheless unsuitable in certain cases, especially when there are no single crystals of sufficient size (a few microns). Therefore, elucidating the crystal structure of a sample in powder form represents a major challenge for chemistry, biology and physics. In this context, solid state NMR appears to be an essential technique because it can provide structural details at the atomic scale without requiring long-range ordering (unlike diffraction techniques). In particular, for samples in powder form, solid state NMR can access the relative position of atoms in space by measuring internuclear distances, thus potentially determining the conformation and crystal arrangement of a molecular crystal.

Unfortunately, the lack of appropriate methodologies prevents quantitative structural data to be obtained by solid-state NMR. This is especially true in the case of organic molecules with no prior isotopic enrichment. In fact, the intrinsically-low sensitivity of NMR limits the possibility of observing the interactions between the isotopes of the active nuclei in NMR present in these molecules, such as for example carbon, nitrogen or even oxygen (13C, 15N, 17O), which have a natural abundance of only 1.1%, 0.4% and 0.038%, respectively.

To overcome this limitation, our team develops i) new NMR approaches for the analysis of uniformly enriched solids or ii) DNP NMR methods to investigate natural isotopic abundance solids.

Selected publications

  • A Karplus equation for the conformational analysis of organic molecular crystals, Thureau, P.; Carvin, I.; Ziarelli, F.; Viel, S.; Mollica, G.* Angew. Chem. Int. Ed. 2019, 58, 16047-16051 https://doi.org/10.1002/anie.201911629
  • Determining carbon-carbon connectivities in natural abundance organic powders using dipolar couplings, Dekhil, M.; Mollica, G.; Ziarelli, F.; Thureau, P.*; Viel, S. Chem. Commun. 2016, 52, 8565-8568. DOI: 10.1039/C6CC04202C
  • Quantitative structural constraints for organic powders at natural isotopic abundance via dynamic nuclear polarization solid-state NMR, Mollica, G.; Dekhil, M.; Ziarelli, F.; Thureau, P.; Viel*, S. Angew. Chem. Int. Ed. 2015, 54, 6028-6031. DOI: 10.1002/anie.201501172

Collaborations

Pr. Jonathan R. Yates, University of Oxford

NMR investigation of crystallization and nucleation

Crystallization plays an important role in many fields of biology, chemistry, and materials science, but the underlying mechanisms that govern crystallization are still poorly understood due to experimental limitations in analyzing these complex and constantly evolving systems. To gain a fundamental understanding of crystallization processes, it is essential to access the sequence of solid phases produced as a function of time, with atomic-level resolution. The rationalization of crystallization processes is particularly relevant for polymorphic materials. Indeed, polymorphism can have enormous economic and practical consequences for industrial applications in pharmaceuticals and energy because different polymorphs have different physicochemical properties. While, on the one hand, this offers great opportunities to modulate the performance of the material according to the desired application, on the other hand, unexpected polymorphic transitions induced by manufacturing or storage can compromise the end use of the solid product. Interestingly, these transformations often involve the formation of metastable forms, which are the subject of increasing attention because they may offer new crystal forms with improved properties.

Today, the detection and precise structural analysis of these – usually transient – forms remain difficult, mainly due to the current limitations of the temporal and spatial resolution of the analysis, which prevents rationalization (and therefore control) of crystallization processes. Several in situ techniques, including diffusion, spectroscopy and microscopy, have been applied to a large number of materials to try to observe the structural changes that take place in the crystallization medium, but limitations persist, both in terms of structural and time-resolution of the analysis. In this complex context, the nucleation of a solid remains one of the most interesting and difficult aspects to understand. Indeed, the supercritical species formed at the early stages of solid growth are generally nanometric, their concentration is very low and they move very fast. Therefore, it is very difficult to identify them and then follow their evolution in the crystallization medium.

In our laboratory, we develop solid-state NMR approaches combined with DNP to overcome these limitations.

We recently demonstrated that the use of DNP NMR allows i) to increase the temporal resolution of the analysis to a few seconds, and ii) to obtain structural information at the atomic scale of the different phases present in the crystallization medium by exploiting the effects of hyperpolarization. In particular, in 2019 we showed for the first time that it is possible to detect, via NMR, the presence of pre-nucleation clusters in a supersaturated solution.

Selected publications

  • Monitoring Crystallization Processes in Confined Porous Materials by Dynamic Nuclear Polarization Solid-state Nuclear Magnetic Resonance M. Juramy, R. Chèvre, P. Cerreia Vioglio, F. Ziarelli, E. Besson, S. Gastaldi, S. Viel, P. Thureau, K. D. M. Harris and G. Mollica, J. Am. Chem. Soc. 2021  https://doi.org/10.1021/jacs.0c12982
  • A Strategy for Probing the Evolution of Crystallization Processes by Low-Temperature Solid-State NMR and Dynamic Nuclear Polarization. Cerreia-Vioglio, P.; Thureau, P.; Juramy, M.; Ziarelli, F. ; Viel. S; Williams, P.A.; Hughes, C. E.; Harris, K.D.M*; Mollica, G.* J. Phys. Chem. Lett. 2019, 10, 1505-1510 https://doi.org/10.1021/acs.jpclett.9b00306
  • Insights into the Crystallization and Structural Evolution of Glycine Dihydrate by In Situ Solid-State NMR Spectroscopy, Cerreia-Vioglio, P.; Mollica, G.; Juramy, M.; Hughes, C. E. ; Williams, P.A.; Ziarelli, F. ; Viel. S; Thureau, P.*; Harris, K.D.M*. Angew. Chem. Int. Ed., 2018, 57, 6619-6623 DOI: 10.1002/anie.201801114