A strategy for probing the evolution of crystallization processes by low-temperature solid-state NMR and dynamic nuclear polarization

Crystallization plays an important role in many areas, and to derive a fundamental understanding of crystallization processes, it is essential to understand the sequence of solid phases produced as a function of time. Here, we introduce a new NMR strategy for studying the time evolution of crystallization processes, in which the crystallizing system is quenched rapidly to low temperature at specific time points during crystallization. The crystallized phase present within the resultant “frozen solution” may be investigated in detail using a range of sophisticated NMR techniques. The low temperatures involved allow dynamic nuclear polarization (DNP) to be exploited to enhance the signal intensity in the solid-state NMR measurements, which is advantageous for detection and structural characterization of transient forms that are present only in small quantities. This work opens up the prospect of studying the very early stages of crystallization, at which the amount of solid phase present is intrinsically low

Insights into the crystallization and structural evolution of glycine dihydrate by in situ solid-state NMR spectroscopy

In situ solid‐state NMR spectroscopy is exploited to monitor the structural evolution of a glycine/water glass phase formed on flash cooling an aqueous solution of glycine, with a range of modern solid‐state NMR methods applied to elucidate structural properties of the solid phases present. The glycine/water glass is shown to crystallize into an intermediate phase, which then transforms to the β polymorph of glycine. Our in situ NMR results fully corroborate the identity of the intermediate crystalline phase as glycine dihydrate, which was first proposed only very recently

Monitoring crystallization processes in confined porous materials by dynamic nuclear polarization solid-state nuclear magnetic resonance

Establishing mechanistic understanding of crystallization processes at the molecular level is challenging, as it requires both the detection of transient solid phases and monitoring the evolution of both liquid and solid phases as a function of time. Here, we demonstrate the application of dynamic nuclear polarization (DNP) enhanced NMR spectroscopy to study crystallization under nanoscopic confinement, revealing a viable approach to interrogate different stages of crystallization processes. We focus on crystallization of glycine within the nanometric pores (7–8 nm) of a tailored mesoporous SBA-15 silica material with wall-embedded TEMPO radicals. The results show that the early stages of crystallization, characterized by the transition from the solution phase to the first crystalline phase, are straightforwardly observed using this experimental strategy. Importantly, the NMR sensitivity enhancement provided by DNP allows the detection of intermediate phases that would not be observable using standard solid-state NMR experiments. Our results also show that the metastable β polymorph of glycine, which has only transient existence under bulk crystallization conditions, remains trapped within the pores of the mesoporous SBA-15 silica material for more than 200 days

Etude de la nucléation par résonance magnétique nucléaire et polarisation dynamique nucléaire

La cristallisation est un processus connu depuis des siècles et joue un rôle important dans de nombreux domaines, malheureusement il reste encore mal compris. L'identification des phases solides produites pendant le processus de cristallisation ainsi que la détection de la formation des premiers cristaux sont des étapes cruciales pour améliorer notre compréhension de ce processus. Cependant, l'étude de la formation des premiers cristaux nécessite à la fois la détection des phases solides transitoires, ce qui est extrêmement difficile en raison de leur petite taille et de leur courte durée de vie, mais aussi le suivi de l'évolution des phases liquides et solides en fonction du temps. Nous avons développé une méthodologie utilisant la spectroscopie RMN DNP pour identifier les phases solides produites pendant le processus de cristallisation, et dans laquelle le processus est rapidement refroidis à basse température à un moment spécifique de la cristallisation. La combinaison de cette méthodologie avec les avantages de la cristallisation en milieu confiné a ensuite été utilisée pour accéder aux premières étapes de la cristallisation. Les résultats montrent que l'amélioration de la sensibilité de la RMN fournie par la DNP permet la détection de phases transitoires qui ne seraient pas observables avec des expériences traditionnelles de RMN du solide. L'efficacité de ces stratégies a été démontré sur un composé modèle. Par la suite, la généralisation de ces stratégies présente un fort potentiel pour fournir un outil permettant de détecter les propriétés polymorphiques d'une large gamme de molécules ainsi que d'étudier les premières étapes de leur cristallisationCrystallization is a process known for centuries and plays an important role in many areas, yet it is still ill-understood. Identifying the sequence of solid phases produced during the crystallization process as well as detecting the early stages of crystallization are crucial steps to improve our understanding of the field. However, studying the formation of the first crystals required both the detection of transient solid phases, which is extremely challenging due to their small size and short lifetime, but also monitoring the evolution of liquid and solid phases as a function of time. Here we developed a methodology based on dynamic nuclear polarisation (DNP) enhanced nuclear magnetic resonance (NMR) spectroscopy to identify the sequence of solid phases produced during the crystallization process, and in which crystallizing systems are rapidly quenched to low temperature at a specific time during crystallization. The combination of this methodology with the advantages of confined crystallization was also used to access the very early stages of crystallization. The results show that the NMR sensitivity enhancement provided by DNP allows the detection of transient phase that would not be observable with standard solid-state NMR experiments. In addition, our results show that it was possible to delay the transformation of a metastable form for more than 200 days with the developed methodology. The generalization of these strategies has the potential to provide a general tool to detect the polymorphic properties of a molecule as well as study the early stages of crystallization for a large range of molecule

Recent progress in nuclear magnetic resonance strategies for time-resolved atomic-level investigation of crystallization from solution

International audienceCrystallization underpins essential processes in our everyday life, creating exceptional materials. Yet, fundamental understanding of the mechanisms underlying crystallization processes is still lacking because of the scarcity of experimental approaches allowing atomic-level investigation of thesequence of intermediate phases formed during crystallization as a function of time. We review recent progress of Nuclear Magnetic Resonance(NMR) in tackling this challenge across the last four years. New in-situ and ex-situ strategies are discussed, in which cryogenic conditions are combined with dynamic nuclear polarization (DNP) NMR to monitor crystallization. Under these conditions, both the temporal and structural resolution of theanalysis increase, enabling the detection of – previously elusive – transient forms. We conclude with suggestions of future directions that could extend the capabilities of NMR even further, bringing key mechanistic details of crystallization process that could expand our fundamental understanding ofcrystallization and improve control over crystallization outcome

Recent temperature and wave propagation results between 30 and 100 km obtained by Lidar techniques

International audienceLidar sounding obtained from two stations using two different scattering process have led to results on photochemisty, structure and dynamics in the altitude range from 30 to 100 km. Information about temperature and wave propagation which can be obtained from this type of measurement is emphasized. It is concluded that if both scattering processes are used, a continuous survey of temperature and motion can be provided

Brute-force solvent suppression for DNP studies of powders at natural isotopic abundance

International audienceA method based on highly concentrated radical solutions is investigated for the suppression of the NMR signals arising from solvents that are usually used for dynamic nuclear polarization experiments. The presented method is suitable in the case of powders, which are impregnated with a radical-containing solution. It is also demonstrated that the intensity and the resolution of the signals due to the sample of interest is not affected by the high concentration of radicals. The method proposed here is therefore valuable when sensitivity is of the utmost importance, namely samples at natural isotopic abundance

Monitoring the influence of additives on the crystallization processes of glycine with dynamic nuclear polarization solid-state NMR

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Polarization Amplification in Dynamic Nuclear Polarization Magic-Angle Spinning Solid-State Nuclear Magnetic Resonance by Solubilizing Traditional Ionic Salts

International audienceDynamic nuclear polarization can improve the sensitivity of magic-angle spinning solid-state NMR experiments by 1–2 orders of magnitude. In aqueous media, experiments are usually performed using the so-called DNP juice, a glycerol-d8/D2O/H2O mixture (60/30/10, v/v/v) that can form a homogeneous glass at cryogenic temperatures. This acts as a cryoprotectant and prevents phase separation of the paramagnetic polarizing agents (PAs) that are added to the mixture to provide the source of electron spin polarization required for DNP. Here, we show that relatively high 1H DNP enhancements (∼60) can also be obtained in water without glycerol (or other glass forming agents) simply by dissolving high concentrations of electrolytes (such as NaCl or LiCl), which perturb the otherwise unavoidable ice crystallization observed upon cooling, thereby reducing PA phase separation and restoring DNP efficiency

A Strategy for Probing the Evolution of Crystallization Processes by Low-temperature Solid-state NMR and Dynamic Nuclear Polarization

International audienceCrystallization plays an important role in many areas, and to derive a fundamental understanding of crystallization processes, it is essential to understand the sequence of solid phases produced as a function of time. Here, we introduce a new NMR strategy for studying the time-evolution of crystallization processes, in which the crystallizing system is quenched rapidly to low temperature at specific time points during crystallization. The crystallized phase present within the resultant "frozen solution" may be investigated in detail using a range of sophisticated NMR techniques. The low temperatures involved allow dynamic nuclear polarization (DNP) to be exploited to enhance the signal intensity in the solid-state NMR measurements, which is advantageous for detection and structural characterization of transient forms that are present only in small quantities. This work opens up the prospect of studying the very early stages of crystallization, at which the amount of solid phase present is intrinsically low