Dynamics in the plastic crystalline phase of cyanocyclohexane and isocyanocyclohexane probed by 1H field cycling NMR relaxometry.

Proton Field-Cycling (FC) nuclear magnetic resonance (NMR) relaxometry is applied over a wide frequency and temperature range to get insight into the dynamic processes occurring in the plastically crystalline phase of the two isomers cyanocyclohexane (CNCH) and isocyanocyclohexane. The spin-lattice relaxation rate, R1(ω), is measured in the 0.01-30 MHz frequency range and transformed into the susceptibility representation χNMR ″ω=ωR1ω. Three relaxation processes are identified, namely, a main (α-) relaxation, a fast secondary (ß-) relaxation, and a slow relaxation; they are very similar for the two isomers. Exploiting frequency-temperature superposition, master curves of χNMR ″ωτ are constructed and analyzed for different processes. The α-relaxation displays a pronounced non-Lorentzian susceptibility with a temperature independent width parameter, and the correlation times display a non-Arrhenius temperature dependence-features indicating cooperative dynamics of the overall reorientation of the molecules. The ß-relaxation shows high similarity with secondary relaxations in structural glasses. The extracted correlation times well agree with those reported by other techniques. A direct comparison of FC NMR and dielectric master curves for CNCH yields pronounced difference regarding the non-Lorentzian spectral shape as well as the relative relaxation strength of α- and ß-relaxation. The correlation times of the slow relaxation follow an Arrhenius temperature dependence with a comparatively high activation energy. As the α-process involves liquid-like isotropic molecular reorientation, the slow process has to be attributed to vacancy diffusion, which modulates intermolecular dipole-dipole interactions, possibly accompanied by chair-chair interconversion of the cyclohexane ring. However, the low frequency relaxation features characteristic of vacancy diffusion cannot be detected due to experimental limitations.

Structural Refinement of Carbimazole by NMR Crystallography.

The characterization of the three-dimensional structure of solids is of major importance, especially in the pharmaceutical field. In the present work, NMR crystallography methods are applied with the aim to refine the crystal structure of carbimazole, an active pharmaceutical ingredient used for the treatment of hyperthyroidism and Grave's disease. Starting from previously reported X-ray diffraction data, two refined structures were obtained by geometry optimization methods. Experimental 1H and 13C isotropic chemical shift measured by the suitable 1H and 13C high-resolution solid state NMR techniques were compared with DFT-GIPAW calculated values, allowing the quality of the obtained structure to be experimentally checked. The refined structure was further validated through the analysis of 1H-1H and 1H-13C 2D NMR correlation experiments. The final structure differs from that previously obtained from X-ray diffraction data mostly for the position of hydrogen atoms.

Dynamics of Clay-Intercalated Ibuprofen Studied by Solid State Nuclear Magnetic Resonance.

In designing drug delivery systems with improved release properties and bioavailability, the dynamic features of the active pharmaceutical ingredient can be crucial for the final product properties. In this work, we aimed at obtaining the first characterization of the molecular dynamic properties of one of the most common nonsteroidal anti-inflammatory drug, ibuprofen, intercalated in hydrotalcite, an interesting inorganic carrier. By exploiting a variety of solid state NMR techniques, including 1H and 13C MAS spectra and T1 relaxation measurements, performed at variable temperature and carrying out a synergic analysis of all results, it has been possible to ascertain that the mobility of ibuprofen within the carrier is remarkably increased. In particular, strong indications have been obtained that ibuprofen molecules, in addition to internal interconformational dynamics, experience an overall molecular motion. Also considering that ibuprofen is "anchored" to the charged surface of the hydrotalcite layers through its carboxylate moiety, such motion could be a wobbling-in-a-cone. Activation energies and correlation times of all the motions of intercalated ibuprofen have been determined.

Magic-angle spinning NMR of cold samples.

Magic-angle-spinning solid-state NMR provides site-resolved structural and chemical information about molecules that complements many other physical techniques. Recent technical advances have made it possible to perform magic-angle-spinning NMR experiments at low temperatures, allowing researchers to trap reaction intermediates and to perform site-resolved studies of low-temperature physical phenomena such as quantum rotations, quantum tunneling, ortho-para conversion between spin isomers, and superconductivity. In examining biological molecules, the improved sensitivity provided by cryogenic NMR facilitates the study of protein assembly or membrane proteins. The combination of low-temperatures with dynamic nuclear polarization has the potential to boost sensitivity even further. Many research groups, including ours, have addressed the technical challenges and developed hardware for magic-angle-spinning of samples cooled down to a few tens of degrees Kelvin. In this Account, we briefly describe these hardware developments and review several recent activities of our group which involve low-temperature magic-angle-spinning NMR. Low-temperature operation allows us to trap intermediates that cannot be studied under ambient conditions by NMR because of their short lifetime. We have used low-temperature NMR to study the electronic structure of bathorhodopsin, the primary photoproduct of the light-sensitive membrane protein, rhodopsin. This project used a custom-built NMR probe that allows low-temperature NMR in the presence of illumination (the image shows the illuminated spinner module). We have also used this technique to study the behavior of molecules within a restricted environment. Small-molecule endofullerenes are interesting molecular systems in which molecular rotors are confined to a well-insulated, well-defined, and highly symmetric environment. We discuss how cryogenic solid state NMR can give information on the dynamics of ortho-water confined in a fullerene cage. Molecular motions are often connected with fundamental chemical properties; therefore, an understanding of molecular dynamics can be important in fields ranging from material science to biochemistry. We present the case of ibuprofen sodium salt which exhibits different degrees of conformational freedom in different parts of the same molecule, leading to a range of line broadening and line narrowing phenomena as a function of temperature.

Nuclear spin conversion of water inside fullerene cages detected by low-temperature nuclear magnetic resonance.

The water-endofullerene H2O@C60 provides a unique chemical system in which freely rotating water molecules are confined inside homogeneous and symmetrical carbon cages. The spin conversion between the ortho and para species of the endohedral H2O was studied in the solid phase by low-temperature nuclear magnetic resonance. The experimental data are consistent with a second-order kinetics, indicating a bimolecular spin conversion process. Numerical simulations suggest the simultaneous presence of a spin diffusion process allowing neighbouring ortho and para molecules to exchange their angular momenta. Cross-polarization experiments found no evidence that the spin conversion of the endohedral H2O molecules is catalysed by (13)C nuclei present in the cages.

Solid-State Nuclear Magnetic Resonance of Triple-Cation Mixed-Halide Perovskites.

Mixed-cation lead mixed-halide perovskites are the best candidates for perovskite-based photovoltaics, thanks to their higher efficiency and stability compared to the single-cation single-halide parent compounds. TripleMix (Cs0.05MA0.14FA0.81PbI2.55Br0.45 with FA = formamidinium and MA = methylammonium) is one of the most efficient and stable mixed perovskites for single-junction solar cells. The microscopic reasons why triple-cation perovskites perform so well are still under debate. In this work, we investigated the structure and dynamics of TripleMix by exploiting multinuclear solid-state nuclear magnetic resonance (SSNMR), which can provide this information at a level of detail not accessible by other techniques. 133Cs, 13C, 1H, and 207Pb SSNMR spectra confirmed the inclusion of all ions in the perovskite, without phase segregation. Complementary measurements showed a peculiar longitudinal relaxation behavior for the 1H and 207Pb nuclei in TripleMix with respect to single-cation single-halide perovskites, suggesting slower dynamics of both organic cations and halide anions, possibly related to the high photovoltaic performances.

Influence of Sulfur-Curing Conditions on the Dynamics and Crosslinking of Rubber Networks: A Time-Domain NMR Study.

The characterization of the structural and dynamic properties of rubber networks is of fundamental importance in rubber science and technology to design materials with optimized mechanical properties. In this work, natural and isoprene rubber networks obtained by curing at three different temperatures (140, 150, and 170 °C) and three different sulfur contents (1, 2, and 3 phr) in the presence of a 3 phr accelerator were studied using a combination of low-field time-domain NMR (TD-NMR) techniques, including 1H multiple-quantum experiments for the measurement of residual dipolar couplings (Dres), the application of the Carr-Purcell-Meiboom-Gill pulse sequence for the measurement of the transverse magnetization decay and the extraction of 1H T2 relaxation times, and the use of field cycling NMR relaxometry for the determination of T1 relaxation times. The microscopic properties determined by TD-NMR experiments were discussed in comparison with the macroscopic properties obtained using equilibrium swelling, moving die rheometer, and calorimetric techniques. The obtained correlations between NMR observables, crosslink density values, maximum torque values, and glass transition temperatures provided insights into the effects of the vulcanization temperature and accelerator/sulfur ratio on the structure of the polymer networks, as well as on the effects of crosslinking on the segmental dynamics of elastomers. Dres and T2 were found to show linear correlations with the crosslink density determined by equilibrium swelling, while T1 depends on the local dynamics of polymer segments related to the glass transition, which is also affected by chemical modifications of the polymer chains occurring during vulcanization.

Detailed characterization of the dynamics of ibuprofen in the solid state by a multi-technique NMR approach.

The internal rotations and interconformational jumps of ibuprofen in the solid state are fully characterized by the simultaneous analysis of a variety of low- and high-resolution NMR experiments for the measurement of several (13)C and (1)H spectral and relaxation properties, performed at different temperatures and, in some cases, frequencies. The results are first qualitatively analyzed to identify the motions of the different molecular fragments and to assign them to specific frequency ranges (slow, <10(3) Hz; intermediate, 10(3)-10(6) Hz; and fast, >10(6) Hz). In a second step, a simultaneous fit of the experimental data sets most sensitive to each frequency range is performed by means of suitable motional models to obtain, for each motion, values of correlation times and activation energies. The rotations of the three methyl groups around their ternary symmetry axes, which occur in the fast regime, are characterized by slightly different activation energies. Thanks to the simultaneous analysis of (1)H and (13)C data, the π-flip of the dimeric structure made by the acidic groups is also identified and seen to occur in the fast regime. On the contrary, the π-flip of the phenyl ring is found to occur in the slow motional regime, while the rotations of the isobutyl and propionic groups are frozen. The approach used appears to be of general applicability for studying the dynamics of small organic molecules.

Dynamics by solid-state NMR: detailed study of ibuprofen Na salt and comparison with ibuprofen.

The various internal rotations and interconformational jumps of the Na-salt form of ibuprofen in the solid state were characterized in detail by means of the simultaneous analysis of a variety of low- and high-resolution NMR experiments aimed at measuring several (13)C and (1)H spectral and relaxation properties at different temperatures and frequencies. The results were first qualitatively analyzed to identify the motions of the different molecular fragments and to assign them to specific frequency regimes (slow, <10(3) Hz; intermediate, 10(3)-10(6) Hz; and fast, >10(6) Hz). Subsequently, a simultaneous fit of the experimental data sets most sensitive to each frequency range was performed by using suitable motional models, thus obtaining, for each motion, correlation times and activation energies. The motions so characterized were: the rotations of the three methyl groups and of the isobutyl group, occurring in the fast regime, and the π-flip of the phenyl ring, belonging to the intermediate motional regime. The results obtained for the Na-salt form were compared with those of the acidic form of ibuprofen, previously obtained from a similar solid-state NMR approach: despite the very similar chemical structure of the two compounds, their dynamic properties in the solid state are noticeably different.

Glassy and Polymer Dynamics of Elastomers by 1H-Field-Cycling NMR Relaxometry: Effects of Fillers.

1H spin-lattice relaxation rate (R1) dispersions were acquired by field-cycling (FC) NMR relaxometry between 0.01 and 35 MHz over a wide temperature range on polyisoprene rubber (IR), either unfilled or filled with different amounts of carbon black, silica, or a combination of both, and sulfur cured. By exploiting the frequency-temperature superposition principle and constructing master curves for the total FC NMR susceptibility, χ″(ω) = ωR1(ω), the correlation times for glassy dynamics, τs, were determined. Moreover, the contribution of polymer dynamics, χpol″(ω), to χ″(ω) was singled out by subtracting the contribution of glassy dynamics, χglass″(ω), well represented by the Cole-Davidson spectral density. Glassy dynamics resulted moderately modified by the presence of fillers, τs values determined for the filled rubbers being slightly different from those of the unfilled one. Polymer dynamics was affected by the presence of fillers in the Rouse regime. A change in the frequency dependence of χpol″(ω) at low frequencies was observed for all filled rubbers, more pronounced for those reinforced with silica, which suggests that the presence of the filler particles can affect chain conformations, resulting in a different Rouse mode distribution, and/or interchain interactions modulated by translational motions.

Glassy and Polymer Dynamics of Elastomers by 1H Field-Cycling NMR Relaxometry: Effects of Cross-Linking.

1H spin lattice relaxation rate (R 1) dispersions were acquired by field-cycling (FC) NMR relaxometry between 0.01 and 35 MHz over a wide temperature range on polyisoprene (IR), polybutadiene (BR), and poly(styrene-co-butadiene) (SBR) rubbers, obtained by vulcanization under different conditions, and on the corresponding uncured elastomers. By exploiting the frequency-temperature superposition principle, χ″(ωτs) master curves were constructed by shifting the total FC NMR susceptibility, χ″(ω) = ωR 1(ω), curves along the frequency axis by the correlation times for glassy dynamics, τs. Longer τs values and, correspondingly, higher glass transition temperatures were determined for the sulfur-cured elastomers with respect to the uncured ones, which increased by increasing the cross-link density, whereas no significant changes were found for fragility. The contribution of polymer dynamics, χ pol ″(ω), to χ″(ω) was singled out by subtracting the contribution of glassy dynamics, χ glass ″(ω), well represented using a Cole-Davidson spectral density. For all elastomers, χ pol ″(ω) was found to represent a small fraction, on the order of 0.05-0.14, of the total χ″(ω), which did not show a significant dependence on cross-link density. In the investigated temperature and frequency ranges, polymer dynamics was found to encompass regimes I (Rouse dynamics) and II (constrained Rouse dynamics) of the tube reptation model for the uncured elastomers and only regime I for the vulcanized ones. This is clear evidence that chemical cross-links impose constraints on chain dynamics on a larger space and time scale than free Rouse modes.

Rubber-Filler Interactions in Polyisoprene Filled with In Situ Generated Silica: A Solid State NMR Study.

In this paper we used high- and low-resolution solid state Nuclear Magnetic Resonance (NMR) techniques to investigate a series of polyisoprene samples filled with silica generated in situ from tetraethoxysilane by sol-gel process. In particular, ¹H spin-lattice and spin-spin relaxation times allowed us to get insights into the dynamic properties of both the polymer bulk and the bound rubber, and to obtain a comparative estimate of the amount of bound rubber in samples prepared with different compositions and sol-gel reaction times. In all samples, three fractions with different mobility could be distinguished by ¹H T2 and ascribed to loosely bound rubber, polymer bulk, and free chain ends. The amount of bound rubber was found to be dependent on sample preparation, and it resulted maximum in the sample showing the best dispersion of silica domains in the rubber matrix. The interpretation of the loosely bound rubber in terms of "glassy" behaviour was discussed, also on the basis of ¹H T1 and T1ρ data.

Dynamics of Dimethylbutanols in Plastic Crystalline Phases by Field Cycling 1H NMR Relaxometry.

2,2-Dimethylbutan-1-ol (2,2-DM-1-B), 3,3-dimethylbutan-1-ol (3,3-DM-1-B), and 3,3-dimethylbutan-2-ol (3,3-DM-2-B) show a rich solid-state polymorphism, which includes one or more plastic crystalline phases (also referred to as orientationally disordered crystalline (ODIC) phases) and glass of the liquid or ODIC phases. In this work, the dynamics of the three isomeric alcohols was investigated in the liquid and plastic crystalline phases by fast field cycling 1H NMR relaxometry in the temperature range between 213 and 303 K. The analysis of the nuclear magnetic relaxation dispersion curves (i.e., longitudinal relaxation rate R1 vs 1H Larmor frequency) acquired for the different alcohols at different temperatures gave quantitative information on internal motions, overall molecular reorientations, and molecular self-diffusion. Self-diffusion coefficients were also determined in the liquid phase and in some ODIC phases of the samples from the trends of 1H R1 as a function of the frequency square root at low frequencies. Remarkable changes in the temperature trends of correlation times and self-diffusion coefficients were found at the transition between the liquid and the ODIC phase for 2,2-DM-1-B and 3,3-DM-1-B, and between ODIC phases for 3,3-DM-2-B, the latter sample showing a markedly different dynamic and phase behavior.

Dynamics of the Chiral Liquid Crystal 4'-Butyl-4-(S)-(2-methylbutoxy)azoxybenzene in the Isotropic, Cholesteric, and Solid Phases: A Fast Field-Cycling NMR Relaxometry Study.

(1)H NMR relaxometry was applied to investigate dynamic processes in the isotropic liquid, cholesteric, and crystalline phases of the chiral mesogen 4'-butyl-4-(S)-(2-methylbutoxy)azoxybenzene (4ABO5*). To this aim, (1)H longitudinal relaxation rates were measured as a function of temperature (between 257 and 319 K) and Larmor frequency (from 10 kHz to 35 MHz by a fast field-cycling relaxometer and at 400 MHz by an NMR spectrometer). The NMR relaxation dispersion (NMRD) curves so obtained were analyzed in terms of models suitable for the description of dynamic processes in the different phases, thus quantitatively determining values of characteristic motional parameters. In particular, internal and overall rotations/reorientations, molecular translational diffusion, and collective motions contribute to relaxation in the isotropic and cholesteric phases, whereas, in the crystalline phase, relaxation is mainly determined by internal motions and molecular reorientations. The results were discussed and compared with those previously obtained on the same compound by dielectric relaxation spectroscopy.

Orientational order of two fluoro- and isothiocyanate-substituted nematogens by combination of 13C NMR spectroscopy and DFT calculations.

Orientational order properties of two nematogens containing a fluoro- and isothiocyanate-substituted biphenyl moiety have been investigated by means of (13)C NMR spectroscopy. (13)C NMR spectra acquired on static samples under high-power (1)H-decoupling allowed both (13)C chemical shift anisotropies and (13)C-(19)F couplings to be measured. These data were used to determine the local principal order parameter and biaxiality for the different rigid fragments of the molecules. To this aim, advanced DFT methods for the calculation of geometrical parameters and chemical shift tensors were used. The orientational order parameters obtained by NMR have been critically compared with those obtained by dielectric spectroscopy. Trends of order parameters with temperature have been analyzed in terms of both mean field theory and the empirical Haller equation.

Freezing of Molecular Motions Probed by Cryogenic Magic Angle Spinning NMR.

Cryogenic magic angle spinning makes it possible to obtain the NMR spectra of solids at temperatures low enough to freeze out most molecular motions. We have applied cryogenic magic angle spinning NMR to a crystalline small-molecule solid (ibuprofen sodium salt), which displays a variety of molecular dynamics. Magic angle (13)C NMR spectra are shown for a wide range of temperatures, including in the cryogenic regime down to 20 K. The hydrophobic and hydrophilic regions of the molecular structure display different behavior in the cryogenic regime, with the hydrophilic region remaining well-structured, while the hydrophobic region exhibits a broad frozen conformational distribution.