Exploring the crystallisation of aspirin in a confined porous material using solid-state nuclear magnetic resonance.

In this study, nuclear magnetic resonance (NMR) is used to investigate the crystallisation behaviour of aspirin within a mesoporous SBA-15 silica material. The potential of dynamic nuclear polarisation (DNP) experiments is also investigated using specifically designed porous materials that incorporate polarising agents within their walls. The formation of the metastable crystalline form II is observed when crystallisation occurs within the pores of the mesoporous structure.

A facile approach for estimating radio-frequency field strength of low-receptivity nuclei.

Radio-frequency (RF) field calibration is essential in NMR spectroscopy. A common practice is to collect a nutation curve by varying the pulse length in a direct single-pulse excitation experiment or in a cross-polarization magic-angle spinning with a flip-back pulse experiment. From the null points on this curve, one can calculate the RF field strength.

Internal Dynamics and Modular Peripheral Binding in Stimuli-Responsive 3 : 2 Host:Guest Complexes.

Now that the chemistry of 1 : 1 host:guest complexes is well-established, it is surprising to note that higher stoichiometry (oligomeric) complexes, especially those with excess host, remain largely unexplored. Yet, proteins tend to oligomerize, affording new functions for cell machinery. Here, we show that cucurbit[n]uril (CB[n]) macrocycles combined with symmetric, linear di-viologens form unusual 3 : 2 host:guest complexes exhibiting remarkable dynamic properties, host self-sorting, and external ring-translocation.

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

Dynamic 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-/DO/HO 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.

Exploiting solid-state dynamic nuclear polarization NMR spectroscopy to establish the spatial distribution of polymorphic phases in a solid material.

Solid-state DNP NMR can enhance the ability to detect minor amounts of solid phases within heterogenous materials. Here we demonstrate that NMR contrast based on the transport of DNP-enhanced polarization can be exploited in the challenging case of early detection of a small amount of a minor polymorphic phase within a major polymorph, and we show that this approach can yield quantitative information on the spatial distribution of the two polymorphs. We focus on the detection of a minor amount (<4%) of polymorph III of -aminobenzoic acid within a powder sample of polymorph I at natural isotopic abundance.

Polyacrylate-Cholesterol Amphiphilic Derivative: Formulation Development and Scale-up for Health Care Applications.

The novel amphiphilic polyacrylate grafted with cholesterol moieties, PAAbCH, previously synthesized, was deeply characterized and investigated in the lab and on a pre-industrial scale. Solid-state NMR analysis confirmed the polymer structure, and several water-based pharmaceutical and cosmetic products were developed. In particular, stable oil/water emulsions with vegetable oils, squalene, and ceramides were prepared, as well as hydrophilic medicated films loaded with diclofenac, providing a prolonged drug release.

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

Crystallization is fundamental in many domains, and the investigation of the sequence of solid phases produced as a function of crystallization time is thus key to understand and control crystallization processes. Here, we used a solid-state nuclear magnetic resonance strategy to monitor the crystallization process of glycine, which is a model compound in polymorphism, under the influence of crystallizing additives, such as methanol or sodium chloride. More specifically, our strategy is based on a combination of low-temperatures and dynamic nuclear polarization (DNP) to trap and detect transient crystallizing forms, which may be present only in low quantities.

Investigating the efficiency of silica materials with wall-embedded nitroxide radicals for dynamic nuclear polarisation NMR.

Dynamic nuclear polarisation (DNP) can significantly enhance the sensitivity of solid-state nuclear magnetic resonance (SSNMR) experiments by transferring the electron spin polarisation of paramagnetic species to nuclei through microwave irradiation of the sample at cryogenic temperatures. Paramagnetic species required for DNP can be provided in the form of mesoporous silica materials containing nitroxide radicals either located on the porous surface or embedded in the pore walls. The present study focuses specifically on porous materials with wall-embedded radicals that were synthesised using conventional molecular imprinting protocols.

Supercritical CO impregnation process applied to polymer samples preparation for dynamic nuclear polarization solid-state NMR.

In this study, supercritical CO (scCO ) was used to impregnate polymers with paramagnetic polarizing agents to prepare samples for dynamic nuclear polarization (DNP) solid-state NMR (ssNMR) experiments. As a proof of concept, we impregnated polystyrene samples with bTbK, which stands for bis-TEMPO-bisketal where TEMPO is 2,2,6,6-tetra-methylpiperindin-1-oxyl. Substantial DNP signal enhancements could be measured on DNP-enhanced H →  C cross-polarization (CP) magic-angle spinning (MAS) spectra recorded at 9.

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.

Aqueous aging of a silica coated TiO UV filter used in sunscreens: investigations at the molecular scale with dynamic nuclear polarization NMR.

Short-term, aqueous aging of a commercial nanocomposite TiO UV filter with a protective SiO shell was examined in abiotic simulated fresh- and seawater. Under these conditions, the SiO layer was quantitatively removed (∼88-98%) within 96 hours, as determined using inductively coupled plasma-atomic emission spectroscopy (ICP-AES). While these bulk ICP-AES analyses suggested almost identical SiO shell degradation after aging in fresh- and seawater, surface sensitive Si dynamic nuclear polarization (DNP) solid-state nuclear magnetic resonance (SSNMR), with signal enhancements of 5-10× compared to standard SSNMR, was able to distinguish differences in the aged nanocomposites at the molecular level.

Solvent suppression in solid-state DNP NMR using Electronic Mixing-Mediated Annihilation (EMMA).

We show here that the Electronic Mixing-Mediated Annihilation (EMMA) method, previously reported for the suppression of background signals in solid-state nuclear magnetic resonance spectra, can be successfully applied to remove the solvent signals observed in the case of nuclear magnetic resonance spectra obtained with dynamic nuclear polarization. The methodology presented here is applied to two standard sample preparation methods for dynamic nuclear polarization, namely, glass forming and incipient wetness impregnation. It is demonstrated that the Electronic Mixing-Mediated Annihilation method is complementary to the different methods for solvent suppression based on relaxation filters and that it can be used to preserve the quantitative information that might be present in the pristine spectra.

A Karplus Equation for the Conformational Analysis of Organic Molecular Crystals.

Vicinal scalar couplings ( J) are extensively used for the conformational analysis of organic compounds in the liquid state through empirical Karplus equations. In contrast, there are no examples of such use for the structural investigation of solids. With the support of first principles calculations, we demonstrate here that C- C J coupling constants ( J ) measured on a series of isotopically enriched solid amino acids and sugars can be related to dihedral angles by a simple Karplus-like relationship, and we provide a parameterized Karplus function for the conformational analysis of organic molecular crystals.

A Cucurbit[8]uril 2:2 Complex with a Negative pK Shift.

A viologen derivative carrying a benzimidazole group (V-P-I  ; viologen-phenylene-imidazole V-P-I) can be dimerized in water using cucurbit[8]uril (CB[8]) in the form of a 2:2 complex resulting in a negative shift of the guest pK , by more than 1 pH unit, contrasting with the positive pK shift usually observed for CB-based complexes. Whereas 2:2 complex protonation is unclear by NMR, silver cations have been used for probing the accessibility of the imidazole groups of the 2:2 complexes. The protonation capacity of the buried imidazole groups is reduced, suggesting that CB[8] could trigger proton release upon 2:2 complex formation.

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.

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

A 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.

Triangular Regulation of Cucurbit[8]uril 1:1 Complexes.

Triangular shapes have inspired scientists over time and are common in nature, such as the flower petals of oxalis triangularis, the triangular faces of tetrahedrite crystals, and the icosahedron faces of virus capsids. Supramolecular chemistry has enabled the construction of triangular assemblies, many of which possess functional features. Among these structures, cucurbiturils have been used to build supramolecular triangles, and we recently reported paramagnetic cucurbit[8]uril (CB[8]) triangles, but the reasons for their formation remain unclear.

Reducing the computational cost of NMR crystallography of organic powders at natural isotopic abundance with the help of C- C dipolar couplings.

Structure determination of functional organic compounds remains a formidable challenge when the sample exists as a powder. Nuclear magnetic resonance crystallography approaches based on the comparison of experimental and Density Functional Theory (DFT)-computed H chemical shifts have already demonstrated great potential for structure determination of organic powders, but limitations still persist. In this study, we discuss the possibility of using C- C dipolar couplings quantified on powdered theophylline at natural isotopic abundance with the help of dynamic nuclear polarization, to realize a DFT-free, rapid screening of a pool of structures predicted by ab initio random structure search.

The synthesis and characterization of giant Calixarenes.

Calixarenes are cyclic oligomers obtained by condensation of suitable p-functionalised phenols with formaldehyde, usually allowing for the synthesis of the well known small calixarenes (including up to eight phenolic subunits). We report here the discovery of much larger members of this family, exhibiting sizes up to 90 phenolic subunits: the giant calixarenes. These macrocycles are obtained according to simple, easily scalable processes, in yields up to 65%.

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.

Synthesis and properties of a series of β-cyclodextrin/nitrone spin traps for improved superoxide detection.

Three new DEPMPO-based spin traps have been designed and synthesized for improved superoxide detection, each carrying a cyclodextrin (CD) moiety but with a different alkyl chain on the phosphorus atom or with a long spacer arm. EPR spectroscopy allowed us to estimate the half-life of the superoxide spin adducts which is close to the value previously reported for CD-DEPMPO (t ≈ 50-55 min under the conditions investigated). The spectra are typical of superoxide adducts (almost no features of the HO˙ adduct that usually forms with time for other nitrone spin traps such as DMPO) and we show that at 250 μM, the new spin trap enables the reliable detection of superoxide by 1 scan at the position opposite to the corresponding spin trap without the CD moiety.

Dynamic Nuclear Polarization NMR as a new tool to investigate the nature of organic compounds occluded in plant silica particles.

The determination of the chemical nature of the organic matter associated with phytoliths remains a challenge. This difficulty mainly stems from amounts of organic carbon (C) that are often well below the detection limit of traditional spectroscopic tools. Conventional solid-state C Nuclear Magnetic Resonance (NMR) is widely used to examine the nature and structure of organic molecules, but its inherent low sensitivity prohibits the observation of diluted samples.

Intramolecular Hydrogen Bond Reverting the Solvent Effect on Phosphorus Hyperfine Coupling Constants of β-Phosphorylated Nitroxides.

Recently, we reported a dramatic solvent effect on the phosphorus hyperfine coupling constant a of β-phosphorylated six-membered ring nitroxides, that is, approximately 25 G of difference in a from n-hexane to water (Org. Biomol. Chem.

Determining carbon-carbon connectivities in natural abundance organic powders using dipolar couplings.

We present a solid-state NMR methodology capable of investigating the carbon skeleton of natural abundance organic powders. The methodology is based on the (13)C-(13)C dipolar coupling interaction and allows carbon-carbon connectivities to be unambiguously established for a wide range of organic solids. This methodology is particularly suitable for disordered solids, such as natural or synthetic macromolecules, which cannot be studied using conventional diffraction or NMR techniques.