Solid state nuclear magnetic resonance最新文献

Many solids crystallize as microcrystalline powders, thus precluding the application of single crystal X-Ray diffraction in structural elucidation. In such cases, a joint use of high-resolution solid-state NMR and crystal structure prediction (CSP) calculations can be successful. However, for molecules showing significant conformational freedom, the CSP-NMR protocol can meet serious obstacles, including ambiguities in NMR signal assignment and too wide conformational search space to be covered by computational methods in reasonable time. Here, we demonstrate a possible way of avoiding these obstacles and making as much use of the two methods as possible in difficult circumstances. In a simple case, our experiments led to crystal structure elucidation of a cocrystal of linezolid (LIN), a wide-range antibiotic, with 2,3-dihydroxybenzoic acid, while a significantly more challenging case of a cocrystal of LIN with 2,4-dihydroxybenzoic acid led to the identification of the most probable conformations of LIN inside the crystal. Having four rotatable bonds, some of which can assume many discreet values, LIN molecule poses a challenge in establishing its conformation in a solid phase. In our work, a set of 27 conformations were used in CSP calculations to yield model crystal structures to be examined against experimental solid-state NMR data, leading to a reliable identification of the most probable molecular arrangements.

Within the present contribution, we describe solid-state NMR spectroscopic studies of the paddle wheel unit in the prototypic flexible MOF compound DUT-8(M) (M = Ni, Co, Zn). The ¹³C NMR chemical shift of these carboxylates shows a remarkable behavior. The pure 2,6-H₂ndc linker carboxylates as well as DUT-8(Zn) exhibit a¹³C chemical shift of only about 170 ppm. In contrast, much higher values are observed for DUT-8(Ni) and especially DUT-8(Co). In the open pore state, the shift strongly depends on the solvent polarity in these two latter cases. The present contribution elucidates the reason for this solvent influence. It is concluded that the solvent mainly modifies the isotropic Fermi contact coupling constant for the excited high-spin states in DUT-8(Ni) and DUT-8(Co).

Analysis of short-to-intermediate range intermolecular interactions offers a great way of characterizing the solid-state organization of small molecules and materials. This can be achieved by two-dimensional (2D) homo- and heteronuclear correlation NMR spectroscopy, for example, by carrying out experiments at high magnetic fields in conjunction with fast magic-angle spinning (MAS) techniques. But, detecting 2D peaks for heteronuclear dipolar coupled spin pairs separated by greater than 3 Å is not always straightforward, particularly when low-gamma quadrupolar nuclei are involved. Here, we present a 2D correlation NMR experiment that combines the advantages of heteronuclear-multiple quantum coherence (HMQC) and proton-based spin-diffusion (SD) pulse sequences using radio-frequency-driven-recouping (RFDR) to probe inter and intramolecular ¹H-X (X = ¹⁴N, ³⁵Cl) interactions. This experiment can be used to acquire 2D ¹H{X}-HMQC filtered ¹H–¹H correlation as well as 2D ¹H-X HMQC spectra. Powder forms of dopamine·HCl and l-histidine·HCl·H₂O are characterized at high fields (21.1 T and 18.8 T) with fast MAS (60 kHz) using the 2D HMQC-SD-RFDR approach. Solid-state NMR results are complemented with NMR crystallography analyses using the gauge-including projector augmented wave (GIPAW) approach. For histidine·HCl·H₂O, 2D peaks associated with ¹⁴N–¹H–¹H and ³⁵Cl–¹H–¹H distances of up to 4.4 and 3.9 Å have been detected. This is further corroborated by the observation of 2D peaks corresponding to ¹⁴N–¹H–¹H and ³⁵Cl–¹H–¹H distances of up to 4.2 and 3.7 Å in dopamine·HCl, indicating the suitability of the HMQC-SD-RFDR experiments for detecting medium-range proximities in molecular solids.

Solid-state NMR has been increasingly recognized as a high-resolution and versatile spectroscopic tool to characterize drug substances and products. However, the analysis of pharmaceutical materials is often carried out at natural isotopic abundance and a relatively low drug loading in multi-component systems and therefore suffers from challenges of low sensitivity. The fact that fluorinated therapeutics are well represented in pipeline drugs and commercial products offers an excellent opportunity to utilize fluorine as a molecular probe for pharmaceutical analysis. We aim to review recent advancements of ¹⁹F magic angle spinning NMR methods in modern drug research and development. Applications to polymorph screening at the micromolar level, structural elucidation, and investigation of molecular interactions at the Ångström to submicron resolution in drug delivery, stability, and quality will be discussed.

Due to their high gyromagnetic ratio, there is considerable interest in measuring distances and correlations involving protons, but such measurements are compounded by the simultaneous recoupling of chemical shift anisotropy (CSA). This secondary recoupling adds additional modulations to the signal intensities that ultimately lead to t₁-noise and signal decay. Recently, Venkatesh et al. demonstrated that the addition of CSA refocusing periods during ¹H-X dipolar recoupling led to sequences with far higher stability and performance. Herein, we describe a related effort and develop a symmetry-based recoupling sequence that continually refocuses the ¹H CSA. This sequence shows superior performance to the regular and t₁-noise eliminated D-HMQC sequences in the case of spin-1/2 nuclei and comparable performance to the later for half-integer quadrupoles.

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.