Dynamic Nuclear Magnetic Resonance Spectroscopy Research Articles

A focus on detection of polymorphs by dynamic nuclear polarization solid-state nuclear magnetic resonance spectroscopy.

Solid-state nuclear magnetic resonance (ssNMR) spectroscopy has found increasing application as a method for quantification and structure determination of solid forms (polymorphs) of organic solids and active pharmaceutical ingredients (APIs). However, ssNMR spectroscopy suffers from low sensitivity and resolution, making it challenging to detect dilute solid forms that may be present after recrystallization or reaction with co-formers. Cousin et al. (S. F. Cousin et al., Chem. Sci., 2023, https://doi.org/10.1039/D3SC02063K) have demonstrated that dynamic nuclear polarization (DNP) enhanced 13C cross-polarization (CP) saturation recovery experiments can be used to detect dilute polymorphic forms that are present within a mixture of solid forms. Enhancement of the NMR signal by DNP and differences in signal build-up rates for different polymorphs provide the sensitivity and contrast needed to resolve NMR signals from minor polymorphic forms. This method demonstrated by Cousin et al. should aid the discovery of solid drug forms.

Structure and properties of cerium phosphate and silicophosphate glasses

AbstractWe report on the fabrication, properties, and structure of cerium pyrophosphate glasses and partially substituted cerium silicophosphates. In those glasses, cerium occurs predominantly as Ce(III). A combination of dynamic nuclear magnetic resonance and electrical impedance spectroscopy is used to overcome the problem of assessing cerium speciation. While optical spectroscopy is unable to quantify the ratio of Ce(III)/Ce(IV) due to spectral overlap, proxy observations of the effect of silica‐for‐cerium substitution on optical extinction and the shape and width of the UV band gap corroborate vibrational spectroscopic data of the structural roles of cerium and silica. While silica bonding to phosphate units appears to stabilize Ce(IV), it also impedes the polaron transport, leading to higher polaron activation energy and lower electronic conductivity. On the other hand, Ce(III) is stabilized by coordinating to P = O.

Line Shape Analysis of Dynamic NMR Spectra for Characterizing Coordination Sphere Rearrangements at a Chiral Rhenium Polyhydride Complex.

Dynamic solution nuclear magnetic resonance (NMR) spectroscopy is the typical method of characterizing the dynamic rearrangements of atoms within the coordination sphere for transition metal polyhydride complexes. Line shape fitting of the dynamic NMR spectra can lead to estimates for the activation parameters of the dynamic rearrangement processes. A combination of dynamic 31P-{1H} NMR spectroscopy of metal-bound phosphorus atoms with dynamic 1H-{31P} NMR spectroscopy of hydride ligands may identify hydride ligand rearrangements that occur in conjunction with a phosphorus atom rearrangement. For molecules that exhibit such a coupled pair of rearrangements, dynamic NMR spectroscopy can be used to test theoretical models for the ligand rearrangements. Dynamic 1H-{31P} NMR spectroscopy and line shape fitting can also identify the presence of an exchange process that moves a specific hydride ligand beyond the metal's inner coordination sphere through a proton exchange with a solvent molecule such as adventitious water. The preparation of a new compound, ReH5(PPh3)2(sec-butyl amine), that exemplifies multiple dynamic rearrangement processes is presented along with line shape fitting of dynamic NMR spectra of the complex. Line shape fitting results can be analyzed by the Eyring equation to estimate the activation parameters for the identified dynamic processes.

Colloidal-ALD-Grown Hybrid Shells Nucleate via a Ligand-Precursor Complex.

Colloidal atomic layer deposition (c-ALD) enables the growth of hybrid organic-inorganic oxide shells with tunable thickness at the nanometer scale around ligand-functionalized inorganic nanoparticles (NPs). This recently developed method has demonstrated improved stability of NPs and of their dispersions, a key requirement for their application. Nevertheless, the mechanism by which the inorganic shells form is still unknown, as is the nature of multiple complex interfaces between the NPs, the organic ligands functionalizing the surface, and the shell. Here, we demonstrate that carboxylate ligands are the key element that enables the synthesis of these core-shell structures. Dynamic nuclear polarization surface-enhanced nuclear magnetic resonance spectroscopy (DNP SENS) in combination with density functional theory (DFT) structure calculations shows that the addition of the aluminum organometallic precursor forms a ligand-precursor complex that interacts with the NP surface. This ligand-precursor complex is the first step for the nucleation of the shell and enables its further growth.

Mechanistic Insights into the Structural Stability of Collagen-Containing Biomaterials Such as Bones and Cartilage.

Structural stability of various collagen-containing biomaterials such as bones and cartilage is still a mystery. Despite the spectroscopic development of several decades, the detailed mechanism of collagen interaction with citrate in bones and glycosaminoglycans (GAGs) in the cartilage extracellular matrix (ECM) in its native state is unobservable. We present a significant advancement to probe the collagen interactions with citrate and GAGs in the ECM of native bones and cartilage along with specific/non-specific interactions inside the collagen assembly at the nanoscopic level through natural-abundance dynamic nuclear polarization-based solid-state nuclear magnetic resonance spectroscopy. The detected molecular-level interactions between citrate-collagen and GAG-collagen inside the native bone and cartilage matrices and other backbone and side-chain interactions in the collagen assembly are responsible for the structural stability and other biomechanical properties of these important classes of biomaterials.

Structure evolution of single-site Pt in a metal-organic framework.

Heterogeneous single-metal-site catalyst or single-atom catalyst research has grown rapidly due to the accessibility of modern characterization techniques that can provide invaluable information at the atomic-scale. Herein, we study the structural evolution of isolated single Pt sites incorporated in a metal-organic framework containing bipyridine functional groups using in situ diffuse reflectance infrared Fourier transform spectroscopy with CO as the probe molecule. The structure and electronic properties of the isolated Pt sites are further corroborated by x-ray photoelectron spectroscopy and aberration-corrected scanning transmission electron microscopy. We find the prerequisite of high temperature He treatment for Pt activation and CO insertion and inquire into the structural transformation of Pt site process by dynamic nuclear polarization-enhanced solid-state nuclear magnetic resonance spectroscopy.

The Nonlinear Designs on a Frequency-Tunable THz Gyrotron With Three Frequency Regimes at 140, 250, and 263 GHz

Gyrotron, as a most likely practical high-power terahertz (THz) radiation source, has been widely applied to THz dynamic nuclear polarization-enhanced nuclear magnetic resonance (DNP-NMR) spectroscopy. In this article, an iris cavity with high-quality factor is theoretically designed for a frequency-tunable THz gyrotron, which could be tuned at three frequency regimes: 140, 250, and 263 GHz, respectively. Based on the self-developed nonlinear code, the beam wave interactions in the designed cavity are studied in detail when the corresponding high-order axial modes (HOAMs) are ${\mathrm {TE}}_{-\mathrm {6.1.q}}$ , ${\mathrm {TE}}_{\mathrm {0.4.}\mathrm {q}^{\prime }}$ , and ${\mathrm {TE}}_{\mathrm {8.2.q}''}$ . By tuning the applied magnetic field under the condition that the beam voltage U0 is 20 kV and beam current I0 is 0.10 A, the output power and frequency tuning ranges could achieve 0.75 kW and 1.15 GHz, 0.63 kW and 3.10 GHz, and 0.59 kW and 2.54 GHz. Meanwhile the calculation results are compared with the 3-D particle software CST, which have confirmed that the frequency and power tuning ranges of ${{\mathrm {TE}}}_{-\mathrm {6.1.q}}$ , ${\mathrm {TE}}_{\mathrm {0.4.q}'}$ , and ${\mathrm {TE}}_{\mathrm {8.2.q''}}$ could reach 0.46 kW and 1.07 GHz, 0.37 kW and 2.24 GHz, and 0.34 kW and 1.96 GHz. These results could be beneficial for the development of frequency-tunable gyrotron toward some up-and-coming novel THz applications.

Elucidating the Location of Cd2+ in Post-synthetically Treated InP Quantum Dots Using Dynamic Nuclear Polarization 31P and 113Cd Solid-State NMR Spectroscopy

Indium phosphide quantum dots (InP QD) are a promising alternative to traditional QD materials that contain toxic heavy elements such as lead and cadmium. However, InP QD obtained from colloidal synthesis are often plagued by poor photoluminescence quantum yields (PL-QYs). In order to improve the PL-QY of InP QD, a number of post-synthetic treatments have been devised. Recently, it has been shown that InP post-synthetically treated with Lewis acid metal divalent cations (M-InP) exhibit enhanced PL-QY; however, the molecular structure and mechanism behind the improved PL-QY are not fully understood. To determine the surface structure of M-InP QD, dynamic nuclear polarization surface-enhanced nuclear magnetic resonance spectroscopy (DNP SENS) experiments were employed on a series of InP magic size clusters treated with Cd ions, InP QD, cadmium phosphide (Cd₃P₂) QD, and Cd-treated InP QD (Cd–InP QD). With the use of DNP SENS, we were able to obtain the 1D ³¹P and ¹¹³Cd NMR spectra, ¹¹³Cd{³¹P} rotational-echo double-resonance (REDOR) NMR spectra, and ³¹P{¹¹³Cd} dipolar heteronuclear multiple quantum correlation (D-HMQC) sequence. Changes in the phosphide ³¹P chemical shifts after Cd treatment provide indirect evidence that some Cd alloys into the sub-surface regions of the particle. DNP-enhanced ¹¹³Cd solid-state NMR spectra suggest that most Cd ions are coordinated by oxygen atoms from either carboxylate ligands or surface phosphate groups. ¹¹³Cd{³¹P} REDOR and ³¹P{¹¹³Cd} D-HMQC experiments confirm that a subset of Cd ions are located on the surface of Cd–InP QD and coordinated with phosphate groups.

The Hsp90 Chaperone: 1H and 19F Dynamic Nuclear Magnetic Resonance Spectroscopy Reveals a Perfect Enzyme.

Hsp90 is a crucial chaperone whose ATPase activity is fundamental for stabilizing and activating a diverse array of client proteins. Binding and hydrolysis of ATP by dimeric Hsp90 drive a conformational cycle characterized by fluctuations between a compact, N- and C-terminally dimerized catalytically competent closed state and a less compact open state that is largely C-terminally dimerized. We used 19F and 1H dynamic nuclear magnetic resonance (NMR) spectroscopy to study the opening and closing kinetics of Hsp90 and to determine the kcat for ATP hydrolysis. We derived a set of coupled ordinary differential equations describing the rate laws for the Hsp90 kinetic cycle and used these to analyze the NMR data. We found that the kinetics of closing and opening for the chaperone are slow and that the lower limit for kcat of ATP hydrolysis is ∼1 s-1. Our results show that the chemical step is optimized and that Hsp90 is indeed a "perfect" enzyme.

Illuminating the dark metabolome to advance the molecular characterisation of biological systems.

The latest version of the Human Metabolome Database (v4.0) lists 114,100 individual entries. Typically, however, metabolomics studies identify only around 100 compounds and many features identified in mass spectra are listed only as 'unknown compounds'. The lack of ability to detect all metabolitespresent,andfully identify all metabolites detected (the dark metabolome) means that, despite the great contribution of metabolomics to a range of areas in the last decade, a significant amount of useful information from publically funded studies is being lost or unused each year. This loss of data limits our potential gain in knowledge and understanding of important research areas such as cell biology, environmental pollution, plant science, food chemistry and health and biomedical research. Metabolomics therefore needs to develop new tools and methods for metabolite identification to advance as a field. In this critical review, some potential issues with metabolite identification are identified and discussed. New and novel emerging technologies and tools which may contribute to expanding the number of compounds identified in metabolomics studies (thus illuminating the dark metabolome) are reviewed. The aim is to stimulate debate and research in the molecular characterisation of biological systems to drive forward metabolomic research. The work specifically discusses dynamic nuclear polarisation nuclear magnetic resonance spectroscopy (DNP-NMR), non-proton NMR active nuclei, two-dimensional liquid chromatography (2DLC) and Raman spectroscopy (RS). It is suggested that developing new methods for metabolomics with these techniques could lead to advances in the field and better characterisation of biological systems.

Disruption of collagen triple helix hydrogen bonding in ochronotic human cartilage in alkaptonuria observed by dynamic nuclear polarisation-enhanced solid-state nuclear magnetic resonance spectroscopy

Disruption of collagen triple helix hydrogen bonding in ochronotic human cartilage in alkaptonuria observed by dynamic nuclear polarisation-enhanced solid-state nuclear magnetic resonance spectroscopy

Synthesis of Supported Pd0 Nanoparticles from a Single-Site Pd2+ Surface Complex by Alkene Reduction

A surface metal–organic complex, (-AlOx)Pd(acac) (acac = acetylacetonate), is prepared by chemically grafting the precursor Pd(acac)2 onto γ-Al2O3 in toluene at 25 °C. The resulting surface complex is characterized by inductively coupled plasma atomic emission spectroscopy (ICP-AES), X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), and dynamic nuclear polarization surface-enhanced solid-state nuclear magnetic resonance spectroscopy (DNP SENS). This surface complex is a precursor in the direct synthesis of size-controlled Pd nanoparticles under mild reductive conditions and in the absence of additional stabilizers or pretreatments. Indeed, upon exposure to gaseous ethylene or liquid 1-octene at 25 °C, the Pd2+ species is reduced to form Pd0 nanoparticles with a mean diameter of 4.3 ± 0.6 nm, as determined by scanning transmission electron microscopy (STEM). These nanoparticles are catalytically relevant using the aerobic 1-phenylethanol oxidation as a probe reaction, with rates ...

Fast detection and structural identification of carbocations on zeolites by dynamic nuclear polarization enhanced solid-state NMR.

Acidic zeolites are porous aluminosilicates used in a wide range of industrial processes such as adsorption and catalysis. The formation of carbocation intermediates plays a key role in reactivity, selectivity and deactivation in heterogeneous catalytic processes. However, the observation and determination of carbocations remain a significant challenge in heterogeneous catalysis due to the lack of selective techniques of sufficient sensitivity to detect their low concentrations. Here, we combine 13C isotopic enrichment and efficient dynamic nuclear polarization magic angle spinning nuclear magnetic resonance spectroscopy to detect carbocations in zeolites. We use two dimensional 13C-13C through-bond correlations to establish their structures and 29Si-13C through-space experiments to quantitatively probe the interaction between multiple surface sites of the zeolites and the confined hydrocarbon pool species. We show that a range of various membered ring carbocations are intermediates in the methanol to hydrocarbons reaction catalysed by different microstructural β-zeolites and highlight that different reaction routes for the formation of both targeted hydrocarbon products and coke exist. These species have strong van der Waals interaction with the zeolite framework demonstrating that their accumulation in the channels of the zeolites leads to deactivation. These results enable understanding of deactivation pathways and open up opportunities for the design of catalysts with improved performances.

A novel THz-band double-beam gyrotron for high-field DNP-NMR spectroscopy.

We present the first experimental results of the study on a novel second harmonic THz-band double-beam gyrotron. The tube has demonstrated a stable single-mode operation with output parameters that are appropriate for the next-generation 1.2 GHz dynamic nuclear polarization-nuclear magnetic resonance spectroscopy. Besides the design mode (TE8,5), a series of other fundamental and second harmonic modes have been excited. This makes the new gyrotron a versatile radiation source, which can be used also in other applications of the high-power science and technologies.

Stable Alkali-Metal Complexes of Hybrid Disila-Crown Ethers.

The complexation ability of hybrid disilane and ethylene containing crown ether ring systems was analyzed using 1,2-disila[12]crown-4 (1), 1,2-disila[15]crown-5 (2), 1,2-disila[18]crown-6 (3), and 1,2,7,8-tetrasila[12]crown-4 (7). Alkali-metal complexes (Li(+), Na(+), K(+)) were obtained and analyzed via X-ray diffraction. The complex stability of [Li(1,2-disila[12]crown-4)](+) and [Li(1,2,7,8-tetrasila[12]crown-4)](+) was determined, in relation to the lithium complex of [12]crown-4, by density functional theory (DFT) calculations employing the BP86/def2-TZVP level of theory. In solution, the exchange of lithium cations between pure [12]crown-4 and hybrid [12]crown-4 is on even terms, as has been shown from the relative binding affinity of compounds 1 and 7 by means of dynamic proton nuclear magnetic resonance (NMR) spectroscopy.

Using Structural and Dynamic NMR Analyses to Dissect the Pathologic Function of a Novel Chemokine

Chemokines are small, secreted proteins that bind G protein-coupled receptors (GPCRs) to orchestrate cellular chemotaxis in the immune system and beyond. While the ∼50 members of the chemokine family share a remarkably conserved tertiary structure, they still manage to coordinate diverse, non-redundant physiologic and pathologic functions in the human body. It is therefore assumed that more subtle nuances in the structure and dynamics of each chemokine-receptor pair are the key determinants of their biologic function. Here we present the molecular structure of CCL28, an especially intriguing chemokine recently identified to play a major role in asthma pathogenesis, solved by solution-state nuclear magnetic resonance spectroscopy (NMR). The structure reveals that while CCL28 adopts the conserved chemokine tertiary fold, it has a particularly curious structural feature not seen in other chemokines. An intrinsically disordered C-terminal domain of ∼30 residues extends from the globular core of the chemokine, part of which is tethered by a non-conserved disulfide bond. Dynamic NMR experiments including backbone 1H-15N heteronuclear NOE measurements, heteronuclear single quantum coherence (HSQC) titrations, and pulsed field gradient (PFG) diffusion measurements collectively indicate the disordered, dynamic nature of the C-terminal extension. Combined with mutational and in vitro functional studies, our findings suggest that the unique structural and dynamic features of CCL28 may be key determinants of its pathologic function.

Conformations and Conformational Processes of Hexahydrobenzazocines by NMR and DFT Studies.

Conformational processes that occur in hexahydrobenzazocines have been studied with the (1)H and (13)C dynamic nuclear magnetic resonance (DNMR) spectroscopy. The coalescence effects are assigned to two different conformational processes: the ring-inversion of the ground-state conformations and the interconversion between two different conformers. The barriers for these processes are in the range of 42-52 and 42-43 kJ mol(-1), respectively. Molecular modeling on the density functional theory (DFT) level and the gauge invariant atomic orbitals (GIAO)-DFT calculations of isotropic shieldings and coupling constants for the set of low-energy conformations were compared with the experimental NMR data. The ground-state of all compounds in solution is the boat-chair (BC) conformation. The BC form adopts two different conformations because the nitrogen atom can be in the boat or chair parts of the BC structure. These two conformers are engaged in the interconversion process.

Probing a cell-embedded megadalton protein complex by DNP-supported solid-state NMR.

Studying biomolecules at atomic resolution in their native environment is the ultimate aim of structural biology. We investigated the bacterial type IV secretion system core complex (T4SScc) by cellular dynamic nuclear polarization-based solid-state nuclear magnetic resonance spectroscopy to validate a structural model previously generated by combining in vitro and in silico data. Our results indicate that T4SScc is well folded in the cellular setting, revealing protein regions that had been elusive when studied in vitro.

4:15 PM, Abstract No. 151 - Real-time metabolic imaging of tae-induced alterations in tumor metabolism using dynamic nuclear polarization carbon-13 magnetic resonance spectroscopy in vivo

an N1-S1 hepatocellular carcinoma in a rat model. Materials and Methods: 24 rats with implanted liver N1S1 tumors were divided into 4 groups: control group (n1⁄45, 1 mL normal saline, NS), bland embolization group (TAE, n1⁄44, 10 mg 50-150 micron PVA in 1 mL NS), TAE and caffeic acid group (TAEþCA, n1⁄45, 10mg PVA and 30 mg of caffeic acid in 1 mL NS), and TAE and ferulic acid group (TAEþFA, n1⁄45, 10 mg PVA and 30 mg ferulic acid in 1 mL NS). Embolization was through retrograde catheterization of the gastroduodenal artery and verified through contrast-enhanced ultrasound (CE-US). Tumor volume was measured by US before and twice a week until 4 weeks post-treatment. The repeated measures ANOVA was used to compare differences in pre-treatment tumor volume by group and over time. At 4 weeks, the rats were sacrificed and histopathologic evaluation performed. Results: There was no significant difference in the initial tumor sizes between each group. The control group showed rapid growth with a volume that was 3,000% larger compared with baseline. In the TAE group, tumor volume increased when compared to pre-treatment volume by 6.7 þ/-11.2%. Both TAEþCA and TAEþFA demonstrated a statistically significant decrease in tumor size when compared to TAE with a decrease in tumor volume by 86.8þ/-10.2% and 71.8þ/10.5%, respectively (po0.0001). Histopathogic evaluation showed marked decreases in amounts of residual tumor and inflammatory changes in the caffeic acid and ferulic acid groups when compared to the TAE group. Conclusion: Embolization with PVA and caffeic acid or ferulic acid provides a statistically significant improved tumor response compared to PVA alone in a rat N1S1 tumor model. Combination treatment through inhibition of both aerobic metabolism through embolization and inhibtion of anaerobic metabolism through lactate transport inhibition is a viable and effective treatment approach that shows great promise.

Experimental study from linear to chaotic regimes on a terahertz-frequency gyrotron oscillator

Basic wave-particle interaction dynamics from linear to chaotic regimes is experimentally studied on a frequency tunable gyrotron generating THz radiation in continuous mode (200 W) at 263 GHz which will be used for dynamic nuclear polarization nuclear magnetic resonance spectroscopy applications. In the studied system, the nonlinear dynamics associated to the wave-particle interaction is dominated by longitudinal mode competition of a given transverse TEm,p cavity-mode. This study covers a wide range of control parameter from gyro-traveling wave tube (gyro-TWT) to gyro-backward wave oscillator (gyro-BWO) like interactions for which extensive theoretical studies have been performed in the past on a simplified system. Besides the common route to chaos characterized by period doubling, other routes have been identified among which some are characterized by line-width frequency-broadening on the side-bands. The complex nonlinear dynamics is in good agreement with the theory and the experimental results are discussed on the basis of the prediction obtained with the nonlinear time-dependent self-consistent codes TWANG and EURIDICE both based on a slow-time scale formulation of the self-consistent equations governing the wave-particle dynamics.