Solid‐state nuclear magnetic resonance investigation of neurosteroid compounds and magnesium interactions

The neurosteroid trans‐dehydroandrosterone (DHEA) and its analogs with slightly different modifications in the side chain attached to C17, that is, (3S)‐acetoxypregn‐5‐en‐20‐one ( 1 ) and (3S,20R)‐acetoxypregn‐5‐en‐20‐ol ( 2 ), have been synthesized to investigate DHEA–cation interactions. In this study, we applied solid‐state ¹H/¹³C cross‐polarization/magic‐angle spinning (CP/MAS) nuclear magnetic resonance (NMR) spectroscopy to a series of DHEA analog/Mg²⁺ mixtures at different Mg²⁺ concentrations. The high‐resolution ¹³C NMR spectra of 1 /Mg²⁺ mixtures exhibit two distinct ¹³C spectral patterns, one attributable to 1 free from Mg²⁺, and the other attributable to 1 with bound Mg²⁺. For 2 , the ¹³C NMR spectra exhibit three distinct spectral patterns; besides that of the free form, the other two can be assigned to Mg²⁺‐bound forms. Based on the analysis of the chemical shift deviations (CSDs), we conclude that both 1 and 2 might be subject to a cation–π interaction via the C5–C6 double bond, in contrast to that observed previously for DHEA. As demonstrated, DHEA possesses two Mg²⁺ binding sites, that is, C17–O and C5–C6 double bond, in which the binding affinity of the former is at least three times stronger than that of the latter. The solid‐state ¹³C NMR investigation allows better understanding of the underlying cation binding effects of neurosteroid molecules in vitro.     

Advanced solid‐state nuclear magnetic resonance for polymer science

Today, solid‐state nuclear magnetic resonance (NMR) is one of the most powerful and versatile tools for elucidating the structures and dynamics of molecular, macromolecular, and supramolecular systems. It provides information on molecular and collective phenomena over large length scales and timescales and is particularly suited to handle noncrystalline materials. This report describes how developments in solid‐state NMR were triggered by the possibilities that became available about 30 years ago by neutron scattering and synchrotron radiation. Close analogies between NMR spectroscopy and scattering are pointed out to emphasize that the two approaches nicely complement each other. Specific examples applying the new NMR techniques to amorphous polymers and supramolecular systems are described. The findings are related to the mechanical properties of polymers as well as specific functions such as photoconductivity and proton conductivity. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5031–5044, 2004     

Saturation-dependent nuclear magnetic resonance relaxation of fluids confined inside porous media with micrometer-sized pores

In the present study, we investigate the relationship between the relaxation rate and the filling factor in partially saturated porous media. The filling fluids are polar (water, acetone) and nonpolar (cyclohexane, hexane). The porous sample is a silica glass (Vitrapor#5) with the nominal mean pore size of d = 1 μm ( ± 0.6 μm). All nuclear magnetic resonance relaxation experiments are performed at 20 °C using a NMR instrument operable at 20 MHz proton resonance frequency. The experimental results are compared with a two-phase exchange model providing us information on the strength of surface relaxation and fluid distribution inside pores. These results will affect the NMR estimations about fluid content of porous media.     

Solid‐state NMR studies of cis‐1,4‐polyisoprene crosslinked with dicumyl peroxide in the presence of triallyl cyanurate

The network of dicumyl peroxide (DCP)/triallyl cyanurate (TAC) crosslinked cis‐1,4‐polyisoprene was studied by solid‐state NMR techniques such as direct‐polarization (DP), cross‐polarization (CP), and proton T₂ experiments. Line broadening and cis/trans isomerization of mobile carbons were observed in the DP experiments. The information on rigid carbons of network structures was observed with the CP technique. Motional heterogeneity was examined by proton T₂ relaxation experiments. Decreases in long T₂ (T_2L) values from the mobile non‐network structures and short T₂ (T_2S) values from the rigid network structures were observed with an increase in peroxide or coagent concentration. The percentage of T_2S in T₂ relaxation, which is related to network density, was observed to increase with peroxide and coagent addition. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 1417–1423, 2000     

Frequency‐dependent NMR relaxation of liquids confined inside porous media containing an increased amount of magnetic impurities

Frequency‐dependent NMR relaxation studies have been carried out on water (polar) and cyclohexane (nonpolar) molecules confined inside porous ceramics containing variable amounts of iron oxide (III). The porous ceramics were prepared by compression of powders mixed with iron oxide followed by thermal treatment. The pore size distribution was estimated using a technique based on diffusion in internal fields that exposed a narrow distribution of macropore sizes with an average pore dimension independent of iron oxide content. The relaxation dispersion curves were obtained at room temperature using a fast field cycling NMR instrument. They display an increase of the relaxation rate proportional to the iron oxide concentration. This behavior is more prominent at low Larmor frequencies and is independent of the polar character of the confined molecules. The results reported here can be fitted well with a relaxation model considering exchange between molecules in the close vicinity of the paramagnetic centers located in the surface and bulk‐like molecules inside the pores. This model allows the extraction of the transverse diffusional correlation time that can be related to the polar character of the confined molecules. Copyright © 2013 John Wiley & Sons, Ltd.     

Broadband excitation pulses for high‐field solid‐state nuclear magnetic resonance spectroscopy

In nuclear magnetic resonance spectroscopy, experimental limits due to the radiofrequency transmitter and/or coil means that conventional radiofrequency pulses (“hard pulses”) are sometimes not sufficiently powerful to excite magnetization uniformly over a desired range of frequencies. Effects due to nonuniform excitation are most frequently encountered at high magnetic fields for nuclei with a large range of chemical shifts. Using optimal control theory, we have designed broadband excitation pulses that are suitable for solid‐state samples under magic‐angle‐spinning conditions. These pulses are easy to implement, robust to spinning frequency variations, and radiofrequency inhomogeneities, and only four times as long as a corresponding hard pulse. The utility of these pulses for uniformly exciting ¹³C nuclei is demonstrated on a 900 MHz (21.1 T) spectrometer. Copyright © 2012 John Wiley & Sons, Ltd.     

Evaluation of alumina slurry dispersion by nuclear magnetic resonance relaxation as a comparison to conventional dispersion evaluation methods

In this paper, we evaluated the particle dispersion degree of alumina slurry containing a dispersant by solvent nuclear magnetic resonance (NMR) relaxation and compared it with conventional dispersion evaluation methods such as viscosity, particle size, and sedimentation height measurements. The dispersion of slurry was evaluated via numerical analysis of the transverse relaxation time (T₂). The effect of the changes in different parameters of the experiment in terms of milling time, solid loading, and dispersant amount was investigated by NMR relaxation as well as conventional methods. The results of NMR relaxation measurements revealed that T₂ correlates well with other dispersion evaluation methods; thus, it is an efficient technique to evaluate the dispersion of alumina slurry, specifically, when studying the effect of the change in milling time and dispersion amount.     

Nuclear magnetic resonance relaxation of methane protons in aqueous solutions

Proton nuclear magnetic resonance longitudinal relaxation rates are reported at 100MHz for CH₄ and CHD₃ in deuterium oxide solutions. The results demonstrate that methane reorients with a correlation time on the order of 0.1 psec, considerably faster than molecule correlation times in aqueous solutions.     

Quantitative nuclear magnetic resonance imaging of liquids in swelling polymers

The variation of nuclear magnetic resonance (NMR) relaxation parameters (T₁, T₂) within a polymer during swelling, limits the absolute accuracy with which liquid concentration profiles can be obtained using NMR imaging. In this article a study of the diffusion of decalin into ultra-high molecular weight polyethylene (UHMWPE) is reported. The study illustrates the use of a method of analysis whereby quantitative solvent profiles can be obtained from data influenced by both T₁ and T₂ contrast effects. A T₁ and T₂ map are obtained at a point in the uptake of liquid where the greatest range in liquid concentration is obtained at a point in the uptake of liquid where the greatest range in liquid concentration is observed. The intensity of signal corresponding to liquid in the polymer is compared to that of pure liquid in a reference sample, and correlations for T₁ and T₂ values versus signal intensity are used to deconvolve relaxation contrast, to yield the true liquid concentration. The technique was used to study the effect of degree of crosslinking of UHMWPE on the swelling kinetics and decalin transport within the polymer. A spin-echo imaging technique was used with a recycle delay approximately equal to the average spin-lattice relaxation time of the liquid, and an echo time approximately half the average spin-spin relaxation time. Under these conditions the relaxation contrast was significant, yet the mass uptake data derived from the concentration profiles obtained, using the method of analysis described, agreed well with gravimetric data. © 1995 John Wiley & Sons, Inc.     

Study of triacylglycerol polymorphs by nuclear magnetic resonance: effects of temperature and chain length on relaxation parameters

It is very important to monitor the characteristics of triacylglycerol crystal network in fats, as these crystals have an impact on many food properties such as texture, sensory taste, and extended shelf life. Although time-domain NMR (TD-NMR) is now the reference technique to determine the solid fat index in food, the entire possibilities of this technique are not used. Some NMR studies have been performed to determine its power for the discrimination of polymorphism. In this study, extended investigations proved that TD-NMR could evaluate triacylglycerol (TA) polymorphism, independently from temperature and chain length. Study of the dipolar interactions through second moment M(2), which is characteristic of proton mobility in solid-state samples, provided a new understanding of the structural organization of crystal molecules. Proton spin-lattice relaxation, which has been proved to be a true probe of polymorphism, has provided information on crystal networks. Combination of the two techniques revealed two very interesting kinds of results, i.e. the presence of a minimum spin-lattice relaxation time T(1) for tristearin alpha, which is a characteristic of a dynamic molecular process, and differences in behavior between long and short chain lengths, both at a molecular and a crystal level.     

1H nuclear magnetic resonance relaxation investigation of huperzine E binding to acetylcholinesterase

In order to search for better acetylcholinesterase (AchE) inhibitors, the binding properties of AchE with huperizine E, which is a derivative of huperzine A, were investigated with ¹H nuclear magnetic resonance (¹H NMR) method. The nonselective, selective and double-selective spin-lattice relaxation rates of some protons in huperzine E were acquired in the absence and presence of AchE at a concentration ratio of [ligand]/[protein] = 1: 0.005. The enhancements of selective relaxation rates of these protons were obvious after adding AchE. The molecular motional correlation times of two pairs of protons, H-1a/H-1b and H-2/H-3, in the bound state at T = 298 K were 11.7 and 9.46 ns respectively, while they were 27.7 and 35.2 ps in the free state. All of these show that huperzine E has high binding affinity with AchE. __________ Translated from Acta Chimica Sinica, 2007, 65(5): 415–420 [译自: 化学学报]     

Molecular dynamics and composition of crude oil by low‐field nuclear magnetic resonance

Nuclear magnetic resonance (NMR) techniques are widely used to identify pure substances and probe protein dynamics. Oil is a complex mixture composed of hydrocarbons, which have a wide range of molecular size distribution. Previous work show that empirical correlations of relaxation times and diffusion coefficients were found for simple alkane mixtures, and also the shape of the relaxation and diffusion distribution functions are related to the composition of the fluids. The 2D NMR is a promising qualitative evaluation method for oil composition. But uncertainty in the interpretation of crude oil indicated further study was required. In this research, the effect of each composition on relaxation distribution functions is analyzed in detail. We also suggest a new method for prediction of the rotational correlation time distribution of crude oil molecules using low field NMR (LF‐NMR) relaxation time distributions. A set of down‐hole NMR fluid analysis system is independently designed and developed for fluid measurement. We illustrate this with relaxation–relaxation correlation experiments and rotational correlation time distributions on a series of hydrocarbon mixtures that employ our laboratory‐designed downhole NMR fluid analyzer. The LF‐NMR is a useful tool for detecting oil composition and monitoring oil property changes. Copyright © 2016 John Wiley & Sons, Ltd.     

Layered metal(IV) phosphonate materials: Solid‐state 1H, 13C, 31P NMR spectra and NMR relaxation

Multinuclear solid‐state NMR and powder X‐ray diffraction data collected for phosphonate materials Zr(O₃PC₆H₄PO₃) · 3.6H₂O and Sn(O₃PC₆H₄PO₃)_0.85(O₃POH)_0.30 · 3.09H₂O have resulted in the layered structure, where the phosphonic acids cross‐link the layers. The main structural motif (the 111 connectivity in the PO₃ group) has been established by determination of chemical shift anisotropy parameters for phosphorus nuclei in the phosphonate groups. An analysis of the variable‐temperature ³¹P T₁ measurements and the shapes of the phosphorus resonances in the ³¹P static NMR spectra have resulted in the dipolar mechanism of the phosphorus spin‐lattice relaxation, where the rotating phenylene rings reorient dipolar vectors P^…H as a driving force of the relaxation process. It has been found that water protons do not affect the ³¹P T₁ times. The activation energy of the phenylene rotation in both compounds has been determined as low as 12.5 kJ/mol. The interpretation of the phosphorus relaxation data has been independently confirmed by the measurements of ¹H T₁ times for protons of the phenylene rings.     

Characterization of the sodium binding state in several food products by 23Na nuclear magnetic resonance spectroscopy

In food, salt has several key roles including conservative and food perception. For this latter, it is well-known that the interaction of sodium with the food matrix modifies the consumer perception. It is then critical to characterize these interactions in various real foods. For this purpose, we exploited the information obtained on both single and double quantum ²³Na nuclear magnetic resonance (NMR) spectroscopies. All salted food samples studied showed strong interactions with the food matrix leading to quadrupolar interactions. However, for some of them, the single quantum analysis did not match the theoretical prediction. This was explained by the presence of another type of sodium population, which did not produce quadrupolar interactions. This finding is of critical importance to perform quantitative magnetic resonance imaging (MRI) and to understand the consumer salty taste perception.     

Solid‐state NMR study of dopant effects on the chemical properties of Mg‐, In‐, and Al‐doped SnP2O7

The effects of doped low‐valence cations on the properties of the SnP₂O₇ proton conductor at ambient temperature are investigated from changes in solid‐state NMR spectra and nuclear magnetic relaxation times. Although the T₁H values increased with decreasing acidity as a result of cation exchange, the ¹H chemical shifts moved to lower field in Al‐ and In‐doped materials compared with undoped ones. Furthermore, the shifts changed to higher field in Mg‐doped materials, suggesting the existence of different protonic species in those materials. The bulk phosphate chemical shifts in the ³¹P dipolar‐decoupling MAS NMR spectra were very similar, regardless of the nature and amount of the doping species. On the other hand, by ¹H/³¹P cross‐polarization MAS NMR, P₂O₇ signals interacting with an interstitial proton [Q¹(proton)] were observed in all the undoped and doped SnP₂O₇, while acidic P–OH‐type phosphate signals [Q¹(acid)] were additionally observed in the Mg‐doped conductor. The different affinity of the proton with the dopants and phosphates caused lower conductivity and larger activation energy in the Mg‐doped materials, compared with those in the In‐ and Al‐doped materials. Copyright © 2014 John Wiley & Sons, Ltd.     

Solid state nuclear magnetic resonance studies of hydroxypropylmethylcellulose acetyl succinate polymer,a useful carrier in pharmaceutical solid dispersions

Hydroxypropylmethylcellulose (HPMC) acetyl succinate (HPMC-AS) is a key polymer used for the enablement of amorphous solid dispersions (ASDs) in oral solid dosage forms. Choice of the appropriate grade within the material is often made empirically by the manufacturer of small-scale formulations, followed by extensive real time stability. A key factor in understanding and predicting the performance of an ASD is related to the presence of hydrogen (or other) bonds between the polymer and active pharmaceutical ingredient (API), which will increase stability over the parameters captured by miscibility and predicted by the Gordon–Taylor equation. Solid state nuclear magnetic resonance (NMR) is particularly well equipped to probe spatial proximities, for example, between polymer and API; however, in the case of HPMC-AS, these interactions have been sometimes difficult to identity as the carbon-13 NMR spectra assignment is yet to be firmly established. Using feedstock, selectively substituted HPMC polymers, and NMR editing experiments, we propose here a comprehensive understanding of the chemical structure of HPMC-AS and a definitive spectral assignment of the ¹³C NMR spectra of this polymer. The NMR data also capture the molar ratios of the acetate and succinate moieties present in HPMC-AS of various grades without the need for post treatment required by chromatography methods commonly use in pharmacopoeia. This knowledge will allow the prediction and measurement of interactions between polymers and APIs and therefore a rational choice of polymer grade to enhance the solid state stability of ASDs.     

Separation of cannabinoids on three different mixed‐mode columns containing carbon/nanodiamond/amine‐polymer superficially porous particles

Three mixed‐mode high‐performance liquid chromatography columns packed with superficially porous carbon/nanodiamond/amine‐polymer particles were used to separate mixtures of cannabinoids. Columns evaluated included: (i) reversed phase (C₁₈), weak anion exchange, 4.6 × 33 mm, 3.6 μm, and 4.6 × 100 mm, 3.6 μm, (ii) reversed phase, strong anion exchange (quaternary amine), 4.6×33 mm, 3.6 μm, and (iii) hydrophilic interaction liquid chromatography, 4.6 × 150 mm, 3.6 μm. Different selectivities were achieved under various mobile phase and stationary phase conditions. Efficiencies and peak capacities were as high as 54 000 N/m and 56, respectively. The reversed phase mixed‐mode column (C₁₈) retained tetrahydrocannabinolic acid strongly under acidic conditions and weakly under basic conditions. Tetrahydrocannabinolic acid was retained strongly on the reversed phase, strong anion exchange mixed‐mode column under basic polar organic mobile phase conditions. The hydrophilic interaction liquid chromatography column retained polar cannabinoids better than the (more) neutral ones under basic conditions. A longer reversed phase (C₁₈) mixed‐mode column (4.6 × 100 mm) showed better resolution for analytes (and a contaminant) than a shorter column. Fast separations were achieved in less than 5 min and sometimes 2 min. A real world sample (bubble hash extract) was also analyzed by gradient elution.     

Slow ester side‐group flips in glassy poly(alkyl methacrylate)s characterized by centerband‐only detection of exchange nuclear magnetic resonance

Slow side‐group dynamics in a series of five poly(alkyl methacrylate)s with various side‐group sizes [poly(methacrylic acid) (PMAA), poly(methyl methacrylate) (PMMA), poly(ethyl methacrylate) (PEMA), poly(isobutyl methacrylate) (PiBMA), and poly(cyclohexyl methacrylate), with ? H, ? CH₃, ? CH₂CH₃, ? CH₂CH(CH₃)₂, and ? cyclohexyl alkyl substituents (CODEX), respectively] were studied quantitatively by centerband‐only detection of exchange nuclear magnetic resonance (NMR). Flips and small‐angle motions of the ester groups associated with the β relaxation were observed distinctly in the CODEX NMR data, and the fraction of slowly flipping groups was measured with a precision of 3%. In PMMA, 34% of the side groups flipped on a 1‐s timescale, whereas the fraction was 31% in PEMA at 25 °C. Even the large isobutylether and cyclohexylester side groups flipped in the glassy state, although the flipping fraction was reduced to 22 and about 10%, respectively. In PMAA, no slow side‐group flips were detected on the 1‐s timescale. A striking difference in the temperature dependence of the flipping fraction in PMMA versus PEMA and PiBMA was observed. In PMMA, the flipping fraction was temperature‐independent between 25 and 80 °C, whereas in PEMA, it increased continuously from 31 to 60% between 25 and 60 °C. A similar doubling was also observed in PiBMA. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 2444–2453, 2001     

Friedel–crafts reactions of pendant vinyl groups in macroporous monosized poly(meta‐divinylbenzene) and poly(para‐divinylbenzene) particles

Residual vinyl groups in macroporous monosized polymer particles of poly(meta‐DVB) and poly(para‐DVB) prepared with toluene and 2‐EHA as porogens have been reacted with aluminum chloride as Friedel–Crafts catalyst with and without the presence of lauroyl chloride. In the reaction between aluminum chloride and pendant vinyl groups a post‐crosslinking by cationic polymerization takes place. A reaction occurring simultaneously is the addition of HCl to the double bonds. The progress of these reactions was studied by characterization of vinyl group conversion, pore size distribution, specific surface area, morphology, and swelling behavior. In the reaction with aluminum chloride the poly(para‐DVB) particles showed a substantially higher conversion of pendant vinyl groups than the particles made of poly(meta‐DVB) independent of porogen type. The reaction with aluminum chloride led to a reduced swelling in organic solvents and an increased rigidity of the particles prepared with toluene as porogen. This is confirmed by an increase in the total pore volume in the dry state and a change in the pore size distribution of these particles. Also in the reaction with lauroyl chloride poly(para‐DVB) particles have shown a higher conversion of pendant vinyl groups than poly(meta‐DVB) particles and the acylation was almost complete at the early stage of the reaction. The swelling in organic solvents is reduced as a result of the incorporation of acyl groups into the particles prepared with toluene as porogen. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1366–1378, 2000