Solid state nuclear magnetic resonance最新文献

We study the metal-organic framework (MOF) ZIF-67 with ¹H and ¹³C nuclear magnetic resonance (NMR). In addition to the usual orbital chemical shifts, we observe spinning sideband manifolds in the NMR spectrum due to hyperfine interactions of the paramagnetic cobalt with ¹H and ¹³C. Both orbital and paramagnetic chemical shifts are in good agreement with values calculated from first principles, allowing high-confidence assignment of the observed peaks to specific sites within the MOF. Our measured resonance shifts, line shapes, and spin lattice relaxation rates are also consistent with calculated values. We show that molecules in the pores of the MOF can exhibit high-resolution NMR spectra with fast spin lattice relaxation rates due to dipole-dipole couplings to the Co²⁺ nodes in the ZIF-67 lattice, showcasing NMR spectroscopy as a powerful tool for identification and characterization of “guests” that may be hosted by the MOF in electrochemical and catalytic applications.

This paper describes the experimental application of long single pulses to strongly inhomogeneously broadened NQR spectral lines, where the pulse length significantly exceeds the transverse relaxation time. A⁶³Cu NQR resonance in the mineral covellite (CuS) was used as an exemplar for study in this specific regime, which was motivated by the requirement to obtain useful signals in very large volume applications having radiofrequency power limitations. In this study, signal transients that followed the application of the long single pulses were measured over a large range of radiofrequency field strength and pulse width. The results indicate effective generation of signal amplitudes. This is in contrast to previously reported studies involving long pulses applied to relatively narrow resonances. The results are found to be well described by simulations of the modified Bloch equations.

In the past 15 years, magic angle spinning (MAS) dynamic nuclear polarization (DNP) has emerged as a method to increase the sensitivity of high-resolution solid-state NMR spectroscopy experiments. Recently, γ-irradiation has been used to generate significant concentrations of homogeneously distributed free radicals in a variety of solids, including quartz, glucose, and cellulose. Both γ-irradiated quartz and glucose previously showed significant MAS DNP enhancements. Here, γ-irradiation is applied to twelve small organic molecules to test the applicability of γ-irradiation as a general method of creating stable free radicals for MAS DNP experiments on organic solids and pharmaceuticals. Radical concentrations in the range of 0.25 ​mM–10 ​mM were observed in irradiated glucose, histidine, malic acid, and malonic acid, and significant ¹H DNP enhancements of 32, 130, 19, and 11 were obtained, respectively, as measured by ¹H→¹³C CPMAS experiments. However, concentrations of free radicals below 0.05 ​mM were generally observed in organic molecules containing aromatic rings, preventing sizeable DNP enhancements. DNP sensitivity gains for several of the irradiated compounds exceed that which can be obtained with the relayed DNP approach that uses exogeneous polarizing agent solutions and impregnation procedures. In several cases, significant ¹H DNP enhancements were realized at room temperature. This study demonstrates that in many cases γ-irradiation is a viable alternative to addition of stable exogenous radicals for DNP experiments on organic solids.

Metal-organic frameworks (MOFs) are emerging materials with many current and potential applications due to their unique properties. One critical feature is that the physical and chemical properties of MOFs are tunable. One of the methods for tuning MOF properties is to introduce defects by design for desired applications. Characterization of MOF defects is important, but very challenging due to the local nature and short-range ordering. In this work, we have introduced the ordered vacancies (the defects) in the form of the coordinatively unsaturated sites (CUSs) into the framework of MOF MIL-120(Al). The creation of ordered vacancies is achieved by replacing one quarter of the BTEC (1,2,4,5-benzenetetracarboxylate) with BDC (benzene-1,4-dicarboxylate) linkers. Both parent and defective MOFs were characterized by multinuclear solid-state NMR spectroscopy. ¹H MAS NMR is used to characterize the hydrogen bonding in these MOFs, whereas ¹³C CP MAS NMR confirms unambiguously that the BDC is incorporated into the framework. One-dimensional ²⁷Al MAS NMR provides direct evidence of the coordinatively unsaturated Al sites (the defects). Furthermore, ²⁷Al 3QMAS experiments at 21.1 ​T allow direct identification of one penta-coordinated and three chemically inequivalent octahedral Al sites in the defective MIL-120(Al). Two of the above-mentioned octahedral Al sites are in the domain which appears defect-free. The third octahedral Al site is near the defective site. This work clearly demonstrates the power of solid-state NMR spectroscopy for characterization of defective MOFs.

Solid-state dynamic nuclear polarization enhanced magic angle spinning (DNP-MAS) NMR measurements coupled with density functional theory (DFT) calculations enable the full resonance assignment of a complex pharmaceutical drug molecule without the need for isotopic enrichment. DNP dramatically enhances the NMR signals, thereby making possible previously intractable two-dimensional correlation NMR spectra at natural abundance. Using inputs from DFT calculations, herein we describe a significant improvement to the structure elucidation process for complex organic molecules. Further, we demonstrate that a series of two-dimensional correlation experiments, including ¹⁵N–¹³C TEDOR, ¹³C–¹³C INADEQUATE/SARCOSY, ¹⁹F–¹³C HETCOR, and ¹H–¹³C HETCOR, can be obtained at natural isotopic abundance within reasonable experiment times, thus enabling a complete resonance assignment of sitagliptin, a pharmaceutical used for the treatment of type 2 diabetes.

Weak hydrogen bonds are important structure-directing elements in supramolecular chemistry and biochemistry. We consider here weak CH⋯O hydrogen bonds in a series of cocrystals of theophylline and caffeine and assess to what extent the CH⋯O distance and angle govern the observed ¹³C and ¹H isotropic chemical shifts. Gauge-including projector-augmented wave density functional theory (GIPAW DFT) calculations consistently predict a decrease in the ¹³C and ¹H magnetic shielding constants upon hydrogen bond formation on the order of 2–5 ppm (¹³C) and 1–2 ppm (¹H). These trends are reproduced using the machine-learning approach implemented in ShiftML. Experimental ¹³C and ¹H chemical shifts obtained for powdered samples using one-dimensional NMR spectroscopy as well as heteronuclear correlation (HETCOR) spectroscopy correlate well with the GIPAW DFT results. However, the experimental ¹³C NMR response only correlates moderately well with the hydrogen bond length and angle, while the experimental ¹H chemical shifts only show very weak correlations to these local structural elements. DFT computations on isolated imidazole-formaldehyde models show that the ¹³C and ¹H chemical shifts generally decrease with the C⋯O distance but show no clear dependence on the CH⋯O angle. These results demonstrate that the ¹³C and ¹H response to weak CH⋯O hydrogen bonding is influenced significantly by additional weak contacts within cocrystal heterodimeric units.

UiO-66 (Zr) is a metal-organic framework (MOF) known for its thermal and chemical stability and wide range of adsorption-based applications. This MOF exhibits high separation selectivity for butane isomers. It has been earlier inferred that the separation performance of the material depends on the hydroxylation state of the zirconia cluster. In this contribution, we apply ²H solid-state NMR to characterize the dynamics of both the MOF organic framework itself and butane isomers in hydroxylated and dehydroxylated forms of UiO-66. It is established that the rate of π-flipping and the amplitude of the phenylene ring plane librations in the framework are higher for the dehydroxylated form. Self-diffusion coefficients of butane isomers have been estimated for both forms of UiO-66. The diffusivity is higher for n-butane in the dehydroxylated form, whereas the diffusion of isobutane is not affected by the presence of OH groups in the zirconia cluster of the MOF. Higher diffusivity of n-butane in dehydroxylated form is accounted for by the larger effective diameter of the window between the adjacent cages in this form, which arises from faster rotation and larger amplitude of framework linker libration. This rationalizes the higher efficiency of the dehydroxylated form of UiO-66(Zr) material for butane isomers separation.

Irbesartan (IRB) is an antihypertensive drug which exhibits the rare phenomenon of desmotropy; its 1H- and 2H- tetrazole tautomers can be isolated as distinct crystalline forms. The crystalline forms of IRB are poorly soluble, hence the amorphous form is potentially of interest for its faster dissolution rate. The tautomeric form and the nature of hydrogen bonding in amorphous IRB are unknown. In this study, crystalline form A and amorphous form of irbesartan were studied using ¹³C, ¹⁵N and ¹H solid-state NMR. Variable-temperature ¹³C SSMNR studies showed alkyl chain disorder in the crystalline form of IRB, which may explain the conflicting literature crystal structures of form A (the marketed form). ¹⁵N NMR indicates that the amorphous material contains an approximately 2:1 ratio of 1H- and 2H-tetrazole tautomers. Static ¹H SSNMR and relaxation time measurements confirmed different molecular mobilities of the samples and provided molecular-level insight into the nature of the glass transition. SSNMR is shown to be a powerful technique to investigate the solid state of disordered active pharmaceutical ingredients.

Fast magic-angle spinning (≥60 ​kHz) technique has enabled the acquisition of high-resolution ¹H NMR spectra of solid materials. However, the spectral interpretation is still difficult because the ¹H peaks are overlapped due to the narrow chemical shift range and broad linewidths. An additional ¹³C or ¹⁴N or ¹H dimension possibly addresses the issues of overlapped proton resonances, but it leads to the elongated experimental time. Herein, we introduce a single-channel ¹H experiment to separate the overlapped ¹H peak and identify its spatially proximal ¹H–¹H correlations. This sequence combines selective excitation, selective ¹H–¹H polarization transfer by selective recoupling of protons (SERP), and broadband ¹H recoupling by back-to-back (BABA) recoupling sequences. The concept for ¹H separation is based on (i) the selective excitation of a well-resolved ¹H peak and (ii) the selective dipolar polarization transfer from this isolated ¹H peak to one of the ¹H peaks in the overlapped/poor resolution region by SERP and (iii) the detection of ¹H–¹H correlations from these two ¹H peaks to other neighboring ¹Hs by BABA. We demonstrated the applicability of this approach to identify overlapped peaks on two molecules, β-L-aspartyl-l-alanine and Pioglitazone.HCl. The sequence allows the clear observation of ¹H–¹H correlations from an overlapped ¹H peak without an additional heteronuclear dimension and ensures efficient polarization transfers that leads to twelve fold reduction in experimental time compared to ¹⁴N edited experiments. The limitation and the conditions of applicability for this approach are discussed in detail.