Solid-state Nuclear Magnetic Resonance Analysis Research Articles

Porous Ceramic Metal-Based Flow Battery Composite Membrane.

In metal-based flow battery, membranes significantly impact energy conversion efficiency and security. Unfortunately, damages to the membrane occur due to gradual accumulation of metal dendrites, causing short circuits and shortening cycle life. Herein, we developed a rigid hierarchical porous ceramic flow battery composite membrane with a sub-10-nm-thick polyelectrolyte coating to achieve high ion selectivity and conductivity, to restrain dendrite, and to realize long cycle life and high areal capacity. An aqueous zinc-iron flow battery prepared using this membrane achieved an outstanding energy efficiency of >80%, exhibiting excellent long-term stability (over 1000 h) and extremely high areal capacity (260 mAh cm-2). Low-field nuclear magnetic resonance (NMR) spectroscopy, small-angle X-ray scattering, in situ infrared spectroscopy, solid-state NMR analysis, and nano-computed tomography revealed that the rigid hierarchical pore structures and numerous hydrogen bonding networks in the membrane contributed to the stable operation and superior battery performance. This study contributes to the development of next-generation metal-based flow battery membranes for energy and power generation.

Synergetic impact of dual substitution on anionic–Cationic activity of P2-type sodium manganese oxide

P2-type sodium-deficient cathodes with the local Na–O–A configuration (A=Li, Mg, Zn, and vacancy) have attracted great interest due to their high capacity, stemming from the additional contribution of the oxygen-redox chemistry. However, such materials suffer from irreversible oxygen redox, oxygen release, structural distortion, and capacity fading. Herein, we introduce a dual-doping Li/Cu strategy to improve the properties of P2-NaxMnO2 cathode material. The unique sodium-storage mechanism in P2-Na0.75[Li0.15Cu0.15Mn0.7]O2 is verified using operando X-ray diffraction (o-XRD), X-ray absorption, X-ray photoelectron spectroscopy, and magnetic susceptibility methods. O-XRD and 7Li solid-state nuclear magnetic resonance analysis reveal that the P2 phase is maintained within charge and discharge; however, at high voltage, a small portion of O-type stacking faults are emerged due to the migration of Li to octahedral Na sites. Furthermore, various spectroscopy and magnetometry techniques combined with density functional theory calculation demonstrate the stable activity of cationic Cu2+/Cu3+ and Mn3+/Mn4+ and anionic O2−/(O2)n− redox processes. This work highlights the efficacy of Li and Cu doping in P2-type layered materials and the contribution of oxygen redox to additional capacity at high voltages, suggesting the potential for future development of cathode materials for Na-ion batteries with oxygen redox.

Post-fire and harvest legacy on soil carbon and microbial communities in boreal forest soils

The boreal forest is currently facing multiple disturbances, which are increasing in extent, frequency and severity. Of particular concern in the western boreal forest of Canada are wildfires and harvesting, which, in the short-term, may impact the forest floor, a storehouse of organic matter and site of highest soil microbial activity. However, how these disturbances may individually and cumulatively affect soil properties during ecosystem recovery is not well documented. Here we compared the separate and compound (salvage-logging) effects of wildfire and harvesting in the mixedwood boreal forest of northern Alberta. Ten years following disturbance, carbon chemical composition of the harvested forest floors was comparable to the control plots as was indicated by solid-state nuclear magnetic resonance analysis. We report a legacy effect of fire in recovering forest floors, with the continued presence of black carbon. Further, as determined by phospholipid fatty acid analysis (PLFA), both wildfire and salvage-logging disturbance resulted in distinct microbial composition from the control and harvest treatments. A shift in organic matter composition indicative of fresh plant inputs was determined to be a key driver of community differences. Despite the presence of black carbon, and shallower depth, the fire-disturbed forest floor harbored the greatest microbial biomass. However, this greater microbial biomass was not present following salvage-logging of the fire disturbed stands. Instead, the salvage-logged stands had the shallowest forest floor, low microbial biomass, and differed the most from the control forest floors based on PLFA results. Taken together, these results indicate that, ten years after disturbance, the compound disturbance of salvage-logging had a greater impact on the recovery of forest floor microbial communities than harvest or wildfire alone.

Hyperpolarization of Biomolecules in Eutectic Crystals at Room Temperature Using Photoexcited Electrons.

The hyperpolarization of biomolecules at room temperature could facilitate highly sensitive magnetic resonance imaging for metabolic studies and nuclear magnetic resonance (NMR)-based screenings for drug discovery. In this study, we demonstrate the hyperpolarization of biomolecules in eutectic crystals using photoexcited triplet electrons at room temperature. Eutectic crystals composed of the domains of benzoic acid doped with the polarization source and analyte domains were prepared using a melting-quenching process. Spin diffusion between the benzoic acid and analyte domain was elucidated using solid-state NMR analysis, indicating that hyperpolarization was transferred from the domain of benzoic acid to the domain of the analyte.

Assessment of heat and radiation impacts on natural organic matter composition in bentonite for used nuclear fuel disposal

Bentonite clay (Wyoming, USA) is proposed as a buffer layer for the engineered barrier system for the deep geologic repository to store Canada's used nuclear fuels in the long-term. The presence of natural organic matter (NOM) in the mined bentonite may support microbial activity which may promote the corrosion of used fuel containers. The NOM found in Wyoming-type bentonite is diagenetically altered, however, there is limited knowledge about how NOM chemistry may change with heat and radiation when exposed to the proposed deep geologic repository conditions. To investigate this further, molecular-level techniques were used to analyze NOM compositional differences in bentonite with different heat (30–105 °C for 3 days, and 90 °C for 14, 28 and 42 days) and gamma-radiation exposure (100 kGy for 3 days). Elemental analysis results indicated that all bentonite samples exhibited low total organic carbon concentrations (0.15–0.27%) and 1.6–3.3% of these were in the form of extractable dissolved organic carbon. Solution-state 1H nuclear magnetic resonance (NMR) and solid-state 13C NMR analyses revealed that chemical signatures of dissolved organic matter and overall NOM composition did not vary between samples. Slightly increased concentrations of short-chain (C9-C19) n-alkanoic acids were observed with heat (14, 28 and 42 days at 90 °C), which is likely due to the oxidation of long-chain (≥C20) n-alkanes or n-alkanols. However, the broader assessment of NOM composition via principal component analysis of forty-four targeted NOM compounds indicated no significant differences after heat or radiation exposure. Collectively, the molecular-level analyses indicate that heat and radiation only imparted nanogram-level differences in some targeted compound concentrations, but the overall NOM chemistry was not altered. These results expand the understanding of NOM chemistry in bentonite clay and suggest that under the conditions tested, NOM composition in bentonite was largely insensitive to heat and radiation exposure. Further work is warranted to investigate longer exposure durations and the overall stability of NOM in a deep geologic repository setting.

Segmental molecular dynamics boosts Li-ion conduction in metal-organic solid electrolytes for Li-metal batteries

Metal-organic frameworks have emerged as a promising class of solid electrolytes for Li batteries. However, previous efforts to enhance Li-ion conductivity exclusively rely on the incorporation of solvents/salts and modifications of the rigid frameworks. In this study, we demonstrate metal-organic solid electrolytes with superionic conductivity by grafting hemilabile anionic chains with segmental motions in the pore channels of an Al-based metal-organic framework. High room-temperature ionic conductivity of 1.4×10–5 and 1.1×10−3 S cm–1 have been achieved under solvent-free and lean-solvent conditions, respectively. Solid-state nuclear magnetic resonance analysis reveals the localized molecular rotation and vibration of the anionic chains within in the rigid framework. Such segmental molecular dynamics would build Li transport highways and facilitate the Li-ion transport even without solvent. The metal-organic solid electrolyte shows excellent stability against Li metal anode, and the as-developed Li-metal batteries exhibit remarkable rate performance up to 4 C and long lifespan over 300 cycles. This work sheds light on the design principles of advanced metal-organic solid electrolytes for solid-state Li batteries.

Solid-State NMR Spectra of Protons and Quadrupolar Nuclei at 28.2 T: Resolving Signatures of Surface Sites with Fast Magic Angle Spinning

Advances in solid-state nuclear magnetic resonance (NMR) methods and hardware offer expanding opportunities for analysis of materials, interfaces, and surfaces. Here, we demonstrate the application of a very high magnetic field strength of 28.2 T and fast magic-angle-spinning rates (MAS, >40 kHz) to surface species relevant to catalysis. Specifically, we present as case studies the 1D and 2D solid-state NMR spectra of important catalyst and support materials, ranging from a well-defined silica-supported organometallic catalyst to dehydroxylated γ-alumina and zeolite solid acids. The high field and fast-MAS measurement conditions substantially improve spectral resolution and narrow NMR signals, which is particularly beneficial for solid-state 1D and 2D NMR analysis of 1H and quadrupolar nuclei such as 27Al at surfaces.

Evolution of mechanical properties of kerogen with thermal maturity

Kerogen is the most abundant form of naturally occurring organic matter in organic-rich shale, and it can affect the macro-mechanical characteristics of shale reservoirs during the whole shale thermal evolution process. However, the magnitude and mechanism of this effect are not clear. Here, a relatively low-maturity kerogen isolated from an organic-rich shale was used to prepare a series of kerogen samples of different maturities in an artificial pyrolysis experiment. Raman spectroscopy and solid-state 13C nuclear magnetic resonance (NMR) spectroscopy were used to determine changes in the chemical structures of the kerogen samples, and in situ nanoindentation analysis was employed to characterize the evolution of their mechanical properties. Raman spectral analyses indicate that Raman band separation (RBS) is very sensitive to thermal maturity, increasing with maturity and displaying a strong linear correlation with mechanical properties of kerogen such as hardness and Young's modulus. Based on the solid-state 13C NMR and nanoindentation analysis, the evolution of kerogen mechanical properties with maturity can be divided into two stages: oil-generation wet-gas stage (corresponding to 0.7%–2.5% EasyRo), and dry-gas stage (2.5%–4.5% EasyRo). In the former, kerogen exhibits a soft nature with relatively low hardness and Young's modulus, possibly attributable to its relatively large proportion of aliphatic carbon and long-chain alkanes. When maturity reaches the gas stage, kerogen becomes increasingly stiff due to the markedly increased proportion of aromatic and bridgehead carbon. Considering the strong positive correlation between mechanical parameters and chemical-structure parameters (RBS, and aromatic and bridgehead carbon ratios) of kerogen during the overall thermal evolution process, we suggest that the stiffening of kerogen may result from the decreasing content of aliphatic chains and increasing aromatic carbon. This study will be beneficial to the development of rock mechanical models that are critical for accurately evaluating borehole stability and optimizing hydraulic fracture design.

Phase Transformations and Phase Segregation during Potassiation of Sn x P y Anodes.

K-ion batteries (KIBs) have the potential to offer a cheaper alternative to Li-ion batteries (LIBs) using widely abundant materials. Conversion/alloying anodes have high theoretical capacities in KIBs, but it is believed that electrode damage from volume expansion and phase segregation by the accommodation of large K-ions leads to capacity loss during electrochemical cycling. To date, the exact phase transformations that occur during potassiation and depotassiation of conversion/alloying anodes are relatively unexplored. In this work, we synthesize two distinct compositions of tin phosphides, Sn4P3 and SnP3, and compare their conversion/alloying mechanisms with solid-state nuclear magnetic resonance (SSNMR) spectroscopy, powder X-ray diffraction (XRD), and density functional theory (DFT) calculations. Ex situ31P and 119Sn SSNMR analyses reveal that while both Sn4P3 and SnP3 exhibit phase separation of elemental P and the formation of KSnP-type environments (which are predicted to be stable based on DFT calculations) during potassiation, only Sn4P3 produces metallic Sn as a byproduct. In both anode materials, K reacts with elemental P to form K-rich compounds containing isolated P sites that resemble K3P but K does not alloy with Sn during potassiation of Sn4P3. During charge, K is only fully removed from the K3P-type structures, suggesting that the formation of ternary regions in the anode and phase separation contribute to capacity loss upon reaction of K with tin phosphides.

Interaction of silane with 10-MDP on affecting surface chemistry and resin bonding of zirconia

ObjectiveTo investigate the effect of silane contents on their chemical interaction with 10-methacryloyloxydecyl-dihydrogen phosphate (MDP), and affecting the bonding of MDP to zirconia by time-of-flight secondary ion mass spectrometry (TOF-SIMS) and solid-state nuclear magnetic resonance (SSNMR) spectroscopy. MethodsZirconia (Cercon ht, Dentsply) slabs were prepared and fully sintered. Experimental primers SE-5 and SE-10 were formulated by adding 5 wt% and 10 wt% γ-methacryloxypropyltrimethoxysilane to an MDP-based primer SE BOND (SE), respectively. SE, SE-5, and SE-10 were applied on the assigned zirconia slabs. The chemical compositions on the surface and adhesive interfaces were examined by TOF-SIMS in a depth-profiling mode. Hydrophilicity and resin affinity of treated zirconia were analyzed. The bond strengths to resin cylinder were examined either after 24-h storage or thermocycles. In addition, zirconia powders treated with three primers were assessed by SSNMR spectrometry for the adsorption of MDP. ResultsTOF-SIMS analysis showed that SE treatment generated the greatest amount of P-O-Zr related ions, which reduced in SE-5 and SE-10 groups. The 3D ion-images illustrated the generation of ZrO2(OH)- ions with silane contents. The SSNMR analysis revealed that the chemical bonding was mainly P-O-Zr ionic bonds in SE but shifted to P-OH-Zr hydrogen bonds in SE-5 and SE-10. SE-5 and SE-10 treated zirconia presented higher hydrophilicity and affinity to resin compared to Zr did. SE showed the highest initial bond strength which significantly decreased after thermocycling. SignificanceMDP adsorption onto zirconia via P-O-Zr ionic bond promotes bonding with resin. The silane enhances the hydroxylation of zirconia and impairs the adsorption of MDP, but does not adversely affect the bond durability.

Improvement of Flame Retardancy and Antidripping Properties of Intumescent Polybutylene Succinate Combining Piperazine Pyrophosphate and Zinc Borate

Developing flame-retarded polybutylene succinate (PBS) is a challenging task owing to its high flammability, noncharring, and melt-dripping during burning. In this work, based on the synergistic combination between piperazine pyrophosphate (PAPP) and zinc borate (ZnB), a promising intumescent PBS system was developed as an efficient strategy to impart PBS with improved flame retardancy and antidripping properties. The results showed that PBS/PAPP15%/ZnB5% passed V-0 rating in the UL-94 vertical burning test (3 mm), while only a V-2 rating was achieved for PBS/PAPP20%. Compared to PBS/PAPP20%, the combination of PAPP and zinc borate (ratio of 15:5) led to significant reductions in the peak heat release rate (pHRR, −55%), fire growth rate index (FIGRA, −40%), and maximum average rate of heat emission (MARHE, −47%) evaluated by mass loss cone calorimetry. Meanwhile, the flame retardancy index of PBS/PAPP15%/ZnB5% reached up to 5.18 and the flameout time significantly increased to 1049 s. Fourier transform infrared and solid-state nuclear magnetic resonance analyses were employed to gain insight into the reaction-to-fire mechanism in the condensed phase. The results confirmed the fact that the formation of a crack-free protective intumescent char layer, reinforced by thermally stable inorganic species (boron–zinc phosphates), effectively restricted the heat and fuel transfer between condensed and gas phases, hence resulting in the excellent enhancement in flame retardancy.

Variable-Temperature NMR Analysis of the Thermodynamics of Polymer Partitioning between Aqueous and Drug-Rich Phases and Its Significance for Amorphous Formulations.

We previously reported that the polymers used in amorphous solid dispersion (ASD) formulations, such as polyvinylpyrrolidone (PVP), polyvinylpyrrolidone/vinyl acetate (PVP-VA), and hypromellose (HPMC), distribute into the drug-rich phase of ibuprofen (IBP) formed by liquid-liquid phase separation, resulting in a reduction in the maximum drug supersaturation in the aqueous phase. Herein, the mechanism underlying the partitioning of the polymer into the drug-rich phase was investigated from a thermodynamic perspective. The dissolved IBP concentration in the aqueous phase and the amount of polymer distributed into the IBP-rich phase were quantitatively analyzed in IBP-supersaturated solutions containing different polymers using variable-temperature solution-state nuclear magnetic resonance (NMR) spectroscopy. The polymer weight ratio in the IBP-rich phase increased at higher temperatures, leading to a more notable reduction of IBP amorphous solubility. Among the polymers, the amorphous solubility reduction was the greatest for the PVP-VA solution at lower temperatures, while HPMC reduced the amorphous solubility to the greatest extent at higher temperatures. The change in the order of polymer impact on the amorphous solubility resulted from the differences in the temperature dependency of polymer partitioning. The van't Hoff plot of the polymer partition coefficient revealed that both enthalpy and entropy changes for polymer transfer into the IBP-rich phase from the aqueous phase (ΔHaqueous→IBP-rich and ΔSaqueous→IBP-rich) gave positive values for most of the measured temperature range, indicating that polymer partitioning into the IBP-rich phase was an endothermic but entropically favorable process. The polymer transfer into the IBP-rich phase was more endothermic for HPMC than for PVP and PVP-VA. The solid-state NMR analysis of the IBP/polymer ASD implied that the newly formed IBP/polymer interactions in the IBP-rich phase upon polymer incorporation were weaker for HPMC, providing a rationale for the larger positive transfer enthalpy for HPMC. The change in Gibbs free energy for polymer transfer (ΔGaqueous→IBP-rich) showed negative values across the experimental temperature range, decreasing with an increase in temperature, indicating that the distribution of the polymer into the IBP-rich phase is favored at higher temperatures. Moreover, ΔGaqueous→IBP-rich for HPMC showed the greatest decrease with the temperature, likely reflecting the temperature-induced dehydration of HPMC in the aqueous phase. This study contributes fundamental insights into the phenomenon of polymer partitioning into drug-rich phases, furthering the understanding of achievable supersaturation levels and ultimately providing information on polymer selection for ASD formulations.

Solid-State NMR Analysis of Interface Flexibility in Pleomorphic Protein Assemblies

The structural proteins of the human immunodeficiency virus are characterized by their capacity to self-assemble and restructure themselves during the infectivity cycle. To understand the structural mechanisms that drive these protein assemblies, novel methods have been developed for the elucidation of molecular structure and dynamics. In this presentation, I will describe solid-state nuclear magnetic resonance (NMR) spectroscopy experiments for the analysis of the mature and the immature protein lattices of HIV-1 at the atomic level, with emphasis on the interactions that stabilize self-assembly and the mechanisms that facilitate structural reorganization in the critical maturation step of the virus infectivity cycle. I will also describe the application of solution NMR spectroscopy to guide batch-crystallization of proteins for solid-state NMR analysis of conformation and flexibility, with emphasis in the interfaces that give rise to variable curvature in asymmetric protein lattices.

Thermal Evolution of Natural Layered Double Hydroxides: Insight from Quintinite, Hydrotalcite, Stichtite, and Iowaite as Reference Samples for CO3- and Cl-Members of the Hydrotalcite Supergroup

In Situ high-temperature powder X-ray diffraction experiments were undertaken for the coarse crystalline natural layered double hydroxides (LDHs) quintinite, hydrotalcite, stichtite, and iowaite in the temperature range 25–1000 °C, with thermal analyses of these minerals and their annealed forms carried out in parallel. In the temperature range from 25 °C to 170–210 °C quintinite, hydrotalcite, and stichtite (carbonate members of the LDH family) demonstrated contraction of the basal d00n-value of 0.1–0.3 Å, followed by a sharp contraction of 1.0–1.1 Å at T > 170–210 °C. The high-temperature modified states were stable up to 380–420 °C, before decomposing to an amorphous phase. Iowaite (chloride member of the family) was stable up to 320 °C and transformed to an amorphous phase at higher temperature. Iowaite experiences continuous contraction of the d00n-value of up to 0.5 Å in the temperature range 25–200 °C, reaching a plateau at a temperature range of 200–320 °C. Assessing the reversibility of thermal transformation shows complete reconstruction of the crystal structure of the hydrotalcite and iowaite heated to 300 °C. Solid-state nuclear magnetic resonance analysis shows that some Al changes coordination from 6- to 4-fold, synchronously with quintinite transformation to the amorphous phase. All phases transform to periclase and a spinel-type compound upon further heating. Thermal analysis of samples annealed at 125 °C shows that carbonate members do not have a tendency to form dehydrated phases, whereas for iowaite, a dehydrated phase having 0.9 apfu lesser water content as in the initial sample has been obtained. Thermal evolution of LDHs is found to depend on the nature of the interaction of interlayer species and water molecules to H atoms of the metal-hydroxide layer.

Temperature-dependent Crystallization and Phase Transition of Poly(L-lactic acid)/CO2 Complex Crystals

Semicrystalline polymers can crystallize in the unique crystalline polymorph and show different phase behaviors under the high-pressure CO2 treatment. Understanding such unique crystallization and phase transition behavior is of fundamental importance for the CO2-assisited processing of semicrystalline polymers. Herein, we investigated the polymorphic crystalline structure, phase transition, and structure-property relationships of poly(L-lactic acid) (PLLA) treated by CO2 at different pressures (1–13 MPa) and crystallization temperatures (Tc’s, 10–110 °C). PLLA crystallized in the PLLA/CO2 complex crystals under 7–13 MPa CO2 at Tc ≤ 50 °C but the common a crystals under the high-pressure CO2 at Tc ≥ 70 °C. Solid-state nuclear magnetic resonance analysis indicated that the PLLA/CO2 complex crystals possessed weaker interactions between the PLLA chains than the common a crystals. The PLLA/CO2 complex crystals were metastable and transformed into the thermally stable a crystals via the solid-to-solid route during heating or annealing at the temperature above 50 °C. The complex crystals of PLLA produced at low Tc was more ductile than the a crystals due to the lower crystallinity and the plasticizing effect of CO2.

Solid-state 17O NMR analysis of synthetically 17O-enriched d-glucosamine

The hydroxyl groups of carbohydrates are critical determinants of their conformational dynamics and intermolecular interactions but are difficult to characterize by conventional 1H nuclear magnetic resonance (NMR) approaches in solution. Here, we report a solid-state 17O NMR analysis of synthetic glucosamine with 17O enrichment at position 6. Based on magic-angle spinning and stationary spectral data obtained at varying magnetic fields in conjunction with quantum chemical calculations, we successfully estimated 17O chemical shift and electric field gradient tensors, providing benchmark for 17O NMR analyses of oligosaccharide structures.

Phosphorus complexation of sewage sludge during thermal hydrolysis with different reaction temperature and reaction time by P K-edge XANES and 31P NMR

Thermal hydrolysis pretreatment (THP) can improve sludge disintegration and biogas production. Phosphorus (P) is immobilized on hydrochars of sewage sludge (SS). It is critical to understand changes in P speciation in SS hydrochars under different reaction temperatures and reaction times during THP for reclamation and (re)cycling of P. This study combined sequential extraction, 31P liquid and solid-state nuclear magnetic resonance (NMR), and P K-edge X-ray absorption near edge structure (XANES) spectroscopy to systematically analyze variation in P speciation and related metals in hydrochars. The temperature of the THP has more influence on P extraction content than reaction time; the bioavailability of P from hydrochars declined with increasing temperature. A 31P liquid and solid-state NMR analysis demonstrated that orthophosphate was the most abundant phosphate present small deviations in the chemical shift were observed in different samples under different conditions. The results of XANES demonstrated that CaP was more stable than FeP and AlP. LCF results suggested OcataCa proportion raised under stable CaP ratio in samples when the temperature was above 155 °C and duration was 60 min. This study provides a theoretical basis that can meet the practical application of THP for sludge disposal and P reclamation on subsequent anaerobic digestion.

Choline chloride functionalized zeolites for the conversion of biomass derivatives to 5-hydroxymethylfurfural

Choline chloride (ChCl) functionalized zeolites (HMOR, HZSM5, HBeta, NaY, and HY) have been synthesized and tested for the conversion of biomass derivatives (cellulose, glucose, and fructose) to 5-Hydroxymethylfurfural (5-HMF). The solid-state nuclear magnetic resonance (SS-NMR) spectroscopy data reveal the existence of ionic and Lewis interactions between the ChCl and the zeolite. Ionic interactions appear to be stronger in ChCl/HZSM5 as compared to interactions in other catalysts. The thermogravimetric analyses indicate that the interaction strength decreases with silica-to-alumina ratio and varies with the type of zeolite framework and the extra-framework cation (Na+ or H+). The activity of the zeolites with moderate silica-to-alumina ratios (SAR) is found to be enhanced by the functionalization with ChCl. SS-NMR analysis attributes this enhancement in activity to better interaction of ChCl with the zeolite. However, the effect is negligible for the zeolites with either low or high SAR. The ChCl functionalized HZSM5 shows a synergistic effect in enhancing the 5-HMF yield and is stable for five cycles.

Metabolite Profile of Alzheimer's Disease in the Frontal Cortex as Analyzed by HRMAS 1H NMR.

Background: Investigation on neurochemical changes in the frontal cortex in individuals with Alzheimer’s disease (AD) and different Apolipoprotein E (APOE) genotypes, using ex vivo solid-state high-resolution NMR analysis, may lead to a better understanding of the neurochemistry associated with AD as well as new AD-specific metabolite biomarkers that might potentially improve the clinical diagnosis of AD.Methods: Intact tissue samples of the frontal cortex were obtained from 11 patients and 11 age-matched non-demented controls. Metabolite profiles in all samples were analyzed ex vivo, using solid-state high-resolution magic angle spinning (HRMAS) 600 MHz 1H nuclear magnetic resonance (NMR). A logistic regression analysis was used to rank metabolites based on their level of contribution in differentiating the AD patient tissues and the controls, and different AD-associated APOE genotypes (APOE ε4 vs. APOE ε3).Results: Tissue samples from the AD patients showed significantly lower NAA/Cr (p = 0.011), Ace/Cr (p = 0.027), GABA/Cr (p = 0.005), Asp/Cr (p < 0.0001), mI/Cr (p < 0.0001), and Tau/Cr (p = 0.021), and higher PCho/Cr (p < 0.0001), GPCho/Cr (p < 0.0001), and α&β-Glc/Cr (p < 0.0001) than the controls did. Specifically, a newly observed resonance at 3.71 ppm, referred to as α&β-Glc, was observed in 90.9% of the AD samples (10/11). Samples with APOE ε4 also exhibited higher PCho/Cr (p = 0.0002), GPCho/Cr (p = 0.0001), α&β-Glc/Cr (p < 0.0001), and lower Asp/Cr (p = 0.004) and GABA/Cr (p = 0.04) than the samples with APOE ε3 did. In the logistic regression analysis, PCho, GPCho, ASP, and α&β-Glc were found to be the most relevant metabolites for differentiating the AD patient tissues and the controls, and different APOE genotypes.Conclusion: HRMAS 1H NMR with high spectral resolution and sensitivity offers a powerful tool to gain quantitative information on AD associated neurochemical changes. There are important neurochemical differences in the frontal cortex between the AD patient tissues and the controls, and between those with different APOE genotypes. The resonance (α&β-Glc) found at 3.71 ppm in the AD patient tissues may be further investigated for its potential in the diagnosis and monitoring of AD.

Amyloid-β fibrils assembled on ganglioside-enriched membranes contain both parallel β-sheets and turns

Some protein and peptide aggregates, such as those of amyloid-β protein (Aβ), are neurotoxic and have been implicated in several neurodegenerative diseases. Aβ accumulates at nanoclusters enriched in neuronal lipids called gangliosides in the presynaptic neuronal membrane, and the resulting oligomeric and/or fibrous forms accelerate the development of Alzheimer's disease. Although the presence of Aβ deposits at such nanoclusters is known, the mechanism of their assembly and the relationship between Aβ secondary structure and topography are still unclear. Here, we first confirmed by atomic force microscopy that Aβ40 fibrils can be obtained by incubating seed-free Aβ40 monomers with a membrane composed of sphingomyelin, cholesterol, and the ganglioside GM1. Using Fourier transform infrared (FTIR) reflection-absorption spectroscopy, we then found that these lipid-associated fibrils contained parallel β-sheets, whereas self-assembled Aβ40 molecules formed antiparallel β-sheets. We also found that the fibrils obtained at GM1-rich nanoclusters were generated from turn Aβ40 Our findings indicate that Aβ generally self-assembles into antiparallel β-structures but can also form protofibrils with parallel β-sheets by interacting with ganglioside-bound Aβ. We concluded that by promoting the formation of parallel β-sheets, highly ganglioside-enriched nanoclusters help accelerate the elongation of Aβ fibrils. These results advance our understanding of ganglioside-induced Aβ fibril formation in neuronal membranes and may help inform the development of additional therapies for Alzheimer's disease.