Two-dimensional Solid-state NMR Spectroscopy Research Articles

Two-dimensional solid-state NMR spectroscopy investigations of surface precipitation of phosphate onto calcite

The interaction of phosphate with typical soil minerals is important for understanding P cycling in natural and agricultural systems. We investigated the mechanisms of kinetics of phosphate uptake onto calcite using solid-state NMR spectroscopy. At a low phosphate concentration of 0.5 mM, the 31P single-pulse solid-state NMR peak revealed the formation of amorphous calcium phosphate (ACP) within the initial 30 min, which transformed to carbonated hydroxyapatite (CHAP) after 12 d. At a high phosphate concentration (5 mM), the results showed transformation from ACP to OCP, later to brushite, and eventually to CHAP. The formation of brushite is further supported by 31P{1H} heteronuclear correlation (HETCOR) spectra via a correlation of δP–31 = 1.7 ppm and the 1H peak at δH–1 = 6.4 ppm, which denotes the structure water of brushite. Furthermore, 13C NMR directly revealed both A-type and B-type CHAP. Generally, this work provides a detailed understanding of the aging effect on the phase transition scale of phosphate surface precipitation onto calcite in soil environments.

Probing molecular interactions of amylose-morin complex and their effect on antioxidant capacity by 2D solid-state NMR spectroscopy

Interaction of polyphenols and starch significantly governed the further applications on polyphenol-starchy foods. Elucidation of inter-molecular interaction is, however, a challenge because conventional characterizations could not detect the change of micro-environment caused by weak interactions. Herein, a facile strategy for molecular detection of amylose-polyphenol interactions was reported using two-dimensional solid-state NMR spectroscopy. Amylose-morin complex was prepared and characterized using 1H NMR, FT-IR, DSC, XRD and SEM. Significantly, variation of chemical shifts, splitted peaks and peak width, monitored by 13C CP/MAS and 1H NMR spectra, identified the strong inter-molecular interaction and binding sites. Furthermore, correlated signals from 1H–13C HETCOR confirmed the binding sites of interactions. These findings confirmed the interaction was inter-molecular hydrogen bonds, which generated between hydroxy-3,5,7 of morin and hydroxy groups of amylose. Besides, DPPH radical scavenging and reducing power assay indicated inter-molecular hydrogen bonds are not strong enough to interfere antioxidant capacity of morin.

J-upscaling in two-dimensional solid-state NMR spectroscopy

The direct measurement of homonuclear scalar couplings (J) in solids, which serve as important parameters for the elucidation of molecular structure/ characterization of materials, is difficult due to the inherent broadening of spectral lines in the solid-state NMR. The earlier reported J-measurements in solid-state NMR are based on 1D/ pseudo 2D spin echo modulation techniques, which rely on computing the J-values by fitting the spin-echo modulations to appropriate mathematical functions, and may involve expertise in the area. On the other hand, the present study demonstrates two simple 2D-NMR methods: J-upscaled mechanism uniform cross-peak double quantum filtered COSY (JS-UC2QFCOSY) and its selective refocusing variant JS2-UC2QFCOSY that allow an easy quantification of scalar couplings, which have been exemplified for unambiguous measurement of JCC values in 13C3-alanine and 13C6-histidine.2HCl samples. These versatile experimental approaches are expected to be highly useful in structural characterizations of organic solids and other materials.

Mapping the oxygen structure of \u03b3-Al2O3 by high-field solid-state NMR spectroscopy

γ-Al2O3 is one of the most widely used catalysts or catalyst supports in numerous industrial catalytic processes. Understanding the structure of γ-Al2O3 is essential to tuning its physicochemical property, which still remains a great challenge. We report a strategy for the observation and determination of oxygen structure of γ-Al2O3 by using two-dimensional (2D) solid-state NMR spectroscopy at high field. 2D 17O double-quantum single-quantum homonuclear correlation NMR experiment is conducted at an ultra-high magnetic field of 35.2 T to reveal the spatial proximities between different oxygen species from the bulk to surface. Furthermore, 2D proton-detected 1H-17O heteronuclear correlation NMR experiments allow for a rapid identification and differentiation of surface hydroxyl groups and (sub-)surface oxygen species. Our experimental results demonstrate a non-random distribution of oxygen species in γ-Al2O3.

π‐Interactions between Cyclic Carbocations and Aromatics Cause Zeolite Deactivation in Methanol‐to‐Hydrocarbon Conversion

The understanding of catalyst deactivation represents one of the major challenges for the methanol-to-hydrocarbon (MTH) reaction over acidic zeolites. Here we report the critical role of intermolecular π-interactions in catalyst deactivation in the MTH reaction on zeolites H-SSZ-13 and H-ZSM-5. π-interaction-induced spatial proximities between cyclopentenyl cations and aromatics in the confined channels and/or cages of zeolites are revealed by two-dimensional solid-state NMR spectroscopy. The formation of naphtalene as a precursor to coke species is favored due to the reaction of aromatics with the nearby cyclopentenyl cations and correlates with both acid density and zeolite topology.

Supramolecular Modulation of Hybrid Perovskite Solar Cells via Bifunctional Halogen Bonding Revealed by Two-Dimensional 19F Solid-State NMR Spectroscopy.

There has been an ongoing effort to overcome the limitations associated with the stability of hybrid organic-inorganic perovskite solar cells by using different organic agents as additives to the perovskite formulations. The functionality of organic additives has been predominantly limited to exploiting hydrogen-bonding interactions, while the relevant atomic-level binding modes remain elusive. Herein, we introduce a bifunctional supramolecular modulator, 1,2,4,5-tetrafluoro-3,6-diiodobenzene, which interacts with the surface of the triple-cation double-halide perovskite material via halogen bonding. We elucidate its binding mode using two-dimensional solid-state 19F NMR spectroscopy in conjunction with density functional theory calculations. As a result, we demonstrate a stability enhancement of the perovskite solar cells upon supramolecular modulation, without compromising the photovoltaic performances.

Molecular Interactions in Posaconazole Amorphous Solid Dispersions from Two-Dimensional Solid-State NMR Spectroscopy.

Molecular interactions between the active pharmaceutical ingredient and polymer have potentially substantial impacts on the physical stability of amorphous solid dispersions (ASDs), presumably by manipulating molecular mobility and miscibility. However, structural details for understanding the nature of the molecular contacts and mechanistic roles in various physicochemical and thermodynamic events often remain unclear. This study provides a spectroscopic characterization of posaconazole (POSA) formulations, a second-generation triazole antifungal drug (Noxafil, Merck & Co., Inc., Kenilworth, NJ, USA), at molecular resolution. One- and two-dimensional (2D) solid-state NMR (ssNMR) techniques including spectral editing, heteronuclear 1H-13C, 19F-13C, 15N-13C, and 19F-1H polarization transfer, and spin correlation and ultrafast magic angle spinning, together with the isotopic labeling strategy, were utilized to uncover molecular details in POSA ASDs in a site-specific manner. Active groups in triazole and difluorophenyl rings exhibited rich but distinct categories of interactions with two polymers, hypromellose acetate succinate and hypromellose phthalate, including intermolecular O-H···O═C and O-H···F-C hydrogen bonding, π-π aromatic packing, and electrostatic interaction. Interestingly, the chlorine-to-fluorine substituent in POSA, one of the major structural differences from itraconazole that could facilitate binding to the biological target, offers an additional contact with the polymer. These findings exhibit 2D ssNMR as a sensitive technique for probing sub-nanometer structures of pharmaceutical materials and provide a structural basis for optimizing the type and strength of drug-polymer interactions in the design of amorphous formulations.

Novel insights from NMR spectroscopy into seasonal changes in the composition of dissolved organic matter exported to the Bering Sea by the Yukon River

Seasonal (spring freshet, summer–autumn, and winter) variability in the chemical composition of dissolved organic matter (DOM) from the Yukon River was determined using advanced one- and two-dimensional (2D) solid-state NMR spectroscopy, coupled with isotopic measurements and UV–visible spectroscopy. Analyses were performed on two major DOM fractions, the hydrophobic organic acid (HPOA) and transphilic organic acid (TPIA) fractions obtained using XAD resins. Together these two fractions comprised 64–74% of the total DOM. Carboxyl-rich alicyclic molecules (CRAM) accounted for the majority of carbon atoms in the HPOA (63–77%) and TPIA (54–78%) samples, and more so in winter and summer than in spring samples. 2D and selective NMR data revealed association of abundant nonprotonated O-alkyl and quaternary alkyl C (OCnp, OCnpO and Cq, 13–17% of HPOA and 15–20% of TPIA) and isolated O–CH structures with CRAM, which were not recognized in previous studies. Spectral editing and 2D NMR allowed for the discrimination of carbohydrate-like O-alkyl C from non-carbohydrate O-alkyl C. Whereas two spring freshet TPIA samples contained carbohydrate clusters such as carboxylated carbohydrates (16% and 26%), TPIA samples from other seasons or HPOA samples mostly had small amounts (<8%) of sugar rings dispersed in a nonpolar alkyl environment. Though nonprotonated aromatic C represented the largest fraction of aromatic C in all HPOA/TPIA isolates, only a small fraction (∼5% in HPOA and 3% in TPIA) was possibly associated with dissolved black carbon. Our results imply a relatively stable portion of DOM exported by the Yukon River across different seasons, due to the predominance of CRAM and their associated nonprotonated C–O and O–C–O structures, and elevated reactivity (bio- and photo-lability) of spring DOM due to the presence of terrestrial inputs enriched in carbohydrates and aromatic structures.

Hydrophobization of Silica Aerogels: Insights from Quantitative Solid-State NMR Spectroscopy

Silica aerogels have exceptional physical and chemical properties related to their nanoporous structure and high specific surface area. The hydrophobization of the silica surfaces, for example by modification with trimethylsilyl groups (TMS), is of central importance for silica aerogel production by ambient drying methods, particularly on an industrial scale. This study monitored the chemical modification of silica aerogels by quantitative and two-dimensional solid-state NMR spectroscopy. A series of two-step, acid/base-catalyzed silica alcogels were hydrophobized for different times in hexamethyldisiloxane (HMDSO) and subsequently dried at ambient pressure. Two-dimensional 1H–29Si heteronuclear correlation NMR spectroscopy confirms that both ethoxy and TMS groups are chemically bonded to the silica surfaces. For the single-pulse spectra, a procedure to calibrate the absolute 1H, 13C, and 29Si NMR signal intensities with external references was developed. The quantification procedure is validated by the internal consistency between the 1H, 13C, and 29Si results and the agreement between the measured sample mass and that predicted from the NMR data. The quantitative speciation data on the aerogel samples show that the silica surface is covered by a monolayer of ethoxy, TMS, and silanol groups. Silanol groups are progressively replaced by TMS groups with increasing modification time, and the TMS content has a strong effect on the density of the final aerogel.

Disentangling Crystallographic Inequivalence and Crystallographic Forms of l-Arginine by One- and Two-Dimensional Solid-State NMR Spectroscopy

Overlapping (13)C or (15)N solid-state NMR spectra from crystallographically different forms of L-arginine hydrochloride can be separated by exploiting differential proton T(1) relaxation in conjunction with cross-polarization. Dipolar (13)C-(13)C and (15)N-(15)N two-dimensional correlation experiments reveal resonances belonging to crystallographically and magnetically inequivalent molecules.

Evidence from Solid-State NMR for Nonhelical Conformations in the Transmembrane Domain of the Amyloid Precursor Protein

The amyloid precursor protein (APP) is subject to proteolytic processing by γ-secretase within neuronal membranes, leading to Alzheimer's disease-associated β-amyloid peptide production by cleavage near the midpoint of the single transmembrane (TM) segment of APP. Conformational properties of the TM segment may affect its susceptibility to γ-secretase cleavage, but these properties have not been established definitively, especially in bilayer membranes with physiologically relevant lipid compositions. In this article, we report an investigation of the APP-TM conformation, using 13C chemical shifts obtained with two-dimensional solid-state NMR spectroscopy as site-specific conformational probes. We find that the APP-TM conformation is not a simple α-helix, particularly at 37°C in multilamellar vesicles with compositions that mimic the composition of neuronal cell membranes. Instead, we observe a mixture of helical and nonhelical conformations at the N- and C-termini and in the vicinity of the γ-cleavage site. Conformational plasticity of the TM segment of APP may be an important factor in the γ-secretase cleavage mechanism.

Extra-framework aluminium species in hydrated faujasite zeolite as investigated by two-dimensional solid-state NMR spectroscopy and theoretical calculations

Extra-framework aluminium (EFAL) species in hydrated dealuminated HY zeolite were thoroughly investigated by various two-dimensional solid-state NMR techniques as well as density functional theoretical calculations. (27)Al MQ MAS NMR experiments demonstrated that five-coordinated and four-coordinated extra-framework aluminium subsequently disappeared with the increase of water loading, and the quadrupole interaction of each aluminium species decreased gradually during the hydration process. (1)H double quantum MAS NMR revealed that the EFAL species in the hydrated zeolite consisted of three components: a hydroxyl AlOH group, and two types of water molecule (rigid and mobile water). (1)H-(27)Al LG-CP HETCOR experiments indicated that both the extra-framework and the framework Al atoms were in close proximity to the rigid water in the fully rehydrated zeolite. The experimental results were further confirmed by DFT theoretical calculations. Moreover, theoretical calculation results further demonstrated that the EFAL species in the hydrated zeolite consisted of the three components and the calculated (1)H NMR chemical shift for each component agreed well with our NMR observations. It is the rigid water that connects the extra-framework aluminium with the four-coordinated framework aluminium through strong hydrogen bonds.

Protein dynamics detected in a membrane-embedded potassium channel using two-dimensional solid-state NMR spectroscopy

We report longitudinal 15N relaxation rates derived from two-dimensional ( 15N, 13C) chemical shift correlation experiments obtained under magic angle spinning for the potassium channel KcsA-Kv1.3 reconstituted in multilamellar vesicles. Thus, we demonstrate that solid-state NMR can be used to probe residue-specific backbone dynamics in a membrane-embedded protein. Enhanced backbone mobility was detected for two glycine residues within the selectivity filter that are highly conserved in potassium channels and that are of core relevance to the filter structure and ion selectivity.

Location of the Retinal Chromophore in the Activated State of Rhodopsin

Rhodopsin is a highly specialized G protein-coupled receptor (GPCR) that is activated by the rapid photochemical isomerization of its covalently bound 11-cis-retinal chromophore. Using two-dimensional solid-state NMR spectroscopy, we defined the position of the retinal in the active metarhodopsin II intermediate. Distance constraints were obtained between amino acids in the retinal binding site and specific (13)C-labeled sites located on the beta-ionone ring, polyene chain, and Schiff base end of the retinal. We show that the retinal C20 methyl group rotates toward the second extracellular loop (EL2), which forms a cap on the retinal binding site in the inactive receptor. Despite the trajectory of the methyl group, we observed an increase in the C20-Gly(188) (EL2) distance consistent with an increase in separation between the retinal and EL2 upon activation. NMR distance constraints showed that the beta-ionone ring moves to a position between Met(207) and Phe(208) on transmembrane helix H5. Movement of the ring toward H5 was also reflected in increased separation between the Cepsilon carbons of Lys(296) (H7) and Met(44) (H1) and between Gly(121) (H3) and the retinal C18 methyl group. Helix-helix interactions involving the H3-H5 and H4-H5 interfaces were also found to change in the formation of metarhodopsin II reflecting increased retinal-protein interactions in the region of Glu(122) (H3) and His(211) (H5). We discuss the location of the retinal in metarhodopsin II and its interaction with sequence motifs, which are highly conserved across the pharmaceutically important class A GPCR family, with respect to the mechanism of receptor activation.

Molecular Mechanism of Rhodopsin Photoactivation

Rhodopsin is a highly specialized GPCR that is activated by the rapid photochemical isomerization of its covalently bound 11-cis retinal chromophore. Using two-dimensional solid-state NMR spectroscopy, we define the position of the retinal in the active metarhodopsin II intermediate and the protein conformational changes that couple retinal isomerization to breaking of the “ionic lock” between transmembrane (TM) helices H3 and H6. Retinal isomerization leads to steric strain within the retinal binding site between the β-ionone ring and helix H5, and between the C19/C20 methyl groups and EL2. These interactions trigger the displacement of EL2, deprotonation of the Schiff base nitrogen and protonation of Glu113. Motion of the β-ionone ring leads to rearrangement of the hydrogen bonding network centered on H5, while interactions of the C19 and C20 methyl groups are involved in rearrangement of the EL2. Motion of the β-ionone ring is also coupled to the motion of Trp265, which triggers the shift of helices H6 and H7 into active conformations and the rearrangement of the hydrogen bonding network centered on the conserved NPxxY sequence. Motion of helices H5, H6 and H7, in turn, is coupled to the rearrangement of electrostatic interactions involving the conserved ERY sequence at the cytoplasmic end of H3, exposing the G protein binding site on the cytoplasmic surface of the protein. The location of the retinal and reorganization of the protein upon receptor activation provides a structural basis for understanding the action of agonists and antagonists in the large family of class A GPCRs.

Molecular Disorder and Structure of Spider Dragline Silk Investigated by Two-Dimensional Solid-State NMR Spectroscopy

We have studied the molecular disorder in (13C)Ala- and (13C)Gly-labeled dragline silk from Nephila edulis through the distributions of isotropic chemical shifts in one- and two-dimensional 13C−13C NMR spectra obtained under MAS. The alanine residues were found to be present in two distinct major structural environments, in agreement with previous studies, where β-sheets and 31-helices were found. The distributions in chemical shift within each residue were found to be uncorrelated, even between spins in the same amino acid residue, and were of similar widths for both the crystalline and noncrystalline parts. Upon long-term mechanical stretching of the silk, the NMR spectra showed no significant changes in conformation nor changes in the degree of disorder but did show increasing structural damage to the silk threads.

Distance measurements in disodium ATP hydrates by means of 31P double quantum two-dimensional solid-state NMR spectroscopy

POST-C7 measurements provide constraints allowing distinguishing crystal lattice organization and establishing intra and/or intermolecular distances between phosphorus atoms of triphosphate chains for different hydrates of disodium ATP salts. Double-quantum efficiency in function of excitation time obtained from series of two-dimensional spectra for POST-C7 experiments was used to set up of buildup curves and semi-quantitative measure of 31P– 31P length.

What High‐Resolution Solid‐State NMR Spectroscopy Can Offer to Organic Chemists

AbstractFor Abstract see ChemInform Abstract in Full Text.

Constraints on supramolecular structure in amyloid fibrils from two-dimensional solid-state NMR spectroscopy with uniform isotopic labeling.

We show that strong constraints on supramolecular structure in amyloid fibrils can be obtained from solid-state nuclear magnetic resonance measurements on samples with uniformly 13C-labeled segments. The measurements exploit two-dimensional (2D) 13C-13C exchange spectroscopy in conjunction with high-speed magic angle spinning, with proton-mediated exchange of 13C nuclear spin magnetization as recently demonstrated by Baldus and co-workers (J. Am. Chem. Soc. 2002, 124, 9704-9705). Proton-mediated 2D exchange spectra of fibrils formed by residues 16-22 of the 40-residue Alzheimer's beta-amyloid peptide show strong nonsequential, intermolecular cross-peaks between alpha-carbons that dictate an antiparallel beta-sheet structure in which residue 16+k aligns with residue 22-k. The strong alpha/alpha cross-peaks are absent from conventional, direct 2D exchange spectra. Proton-mediated 2D exchange spectra of fibrils formed by residues 11-25 indicate an antiparallel beta-sheet structure with a pH-dependent intermolecular alignment. In contrast, proton-mediated 2D exchange spectra of fibrils formed by the full-length beta-amyloid peptide are consistent with a parallel beta-sheet structure. These data show that the supramolecular structure of amyloid fibrils is not determined by the amino acid sequence at the level of 7-residue or 15-residue segments. The proton-mediated 2D exchange spectra additionally demonstrate that the intermolecular alignment in the beta-sheets of these amyloid fibrils is highly ordered, with no detectable evidence for "misalignment" defects.

Observation of a H-agostic bond in a highly active rhenium-alkylidene olefin metathesis heterogeneous catalyst by two-dimensional solid-state NMR spectroscopy.

Keywords: agostic interactions ; heterogeneous catalysis ; NMR spectroscopy ; rhenium Reference EPFL-ARTICLE-204447doi:10.1002/1521-3773(20021202)41:23 3.0.CO;2-OView record in Web of Science Record created on 2015-01-08, modified on 2017-12-03