Network pharmacology analysis and experimental validation to explore the effect and mechanism of tetramethylpyrazine for spinal cord injury.

OBJECTIVE: To investigate the effect and mechanism of Tetramethylpyrazine (TMP) in treating Spinal Cord Injury (SCI) using network pharmacology analysis and animal experiments. METHODS: This study was based on public databases, including PharmMapper, BATMAN-TCM, and STRING, as well as KEGG pathway analysis and other methods of network pharmacology were used to preliminarily explore the molecular mechanism of TMP in the treatment of SCI. Using a mouse SCI compression injury model, the efficacy of TMP was evaluated, and the expression of predictive targets on the PI3K/AKT and MAPK signaling pathways was measured using Western blotting and q-PCR. RESULTS: Network pharmacology analysis showed that TMP may exert therapeutic effects through the MAPK and PI3K/AKT signaling pathways. In animal experimental validation studies, it was shown that after treatment with TMP, the hind limb motor function scores and ramp test scores of the TMP-treated mice improved significantly. HE staining showed that after treatment with TMP, cavities decreased, fewer glial cells proliferated, and fewer inflammatory cells infiltrated; Nielsen staining showed less neuronal loss. Western blot studies showed that compared with the model group, expression of RAS, ERK1/2, RAF1, PI3K, and p-AKT proteins in the spinal cord tissue of mice treated with high-dose TMP was significantly lower. Accordingly, q-PCR studies showed that compared with the model group, the expression levels of RAS, ERK1/2, RAF1, PI3K, and p-AKT genes in the spinal cords of mice in the high-dose TMP group were significantly lower. CONCLUSION: TMP exhibits a good neuroprotective effect after SCI, which may be related to inhibition of the MAPK and PI3K/AKT signaling pathways.

[Neuroprotective effect of tetramethylpyrazine on mice after spinal cord injury].

This study aims to investigate the neuroprotective effect of tetramethylpyrazine on mice after spinal cord injury and its mechanism. Seventy-five female C57BL/6 mice were randomly divided into 5 groups, namely, a sham operation group, a model group, a tetramethylpyrazine low-dose group(25 mg·kg~(-1)), a tetramethylpyrazine medium-dose group(50 mg·kg~(-1)), and a tetramethylpyrazine high-dose group(100 mg·kg~(-1)), with 15 mice in each group. Modified Rivlin method was used to establish the mouse model of acute spinal cord injury. After 14 d of tetramethylpyrazine intervention, the motor function of hind limbs of mice was evaluated by basso mouse scale(BMS) and inclined plate test. The levels of inflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) in the spinal cord homogenate were determined by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe the histology of the spinal cord, and Nissl's staining was used to observe the changes in the number of neurons. Western blot and immunofluorescence method were used to detect the expression of glial fibrillary acidic protein(GFAP) and C3 protein. Tetramethylpyrazine significantly improved the motor function of the hind limbs of mice after spinal cord injury, and the BMS score and inclined plate test score of the tetramethylpyrazine high-dose group were significantly higher than those of the model group(P<0.01). The levels of TNF-α, IL-6, and IL-1ß in spinal cord homogenate of the tetramethylpyrazine high-dose group were significantly decreased(P<0.01). After tetramethylpyrazine treatment, the spinal cord morphology recovered, the number of Nissl bodies increased obviously with regular shape, and the loss of neurons decreased. As compared with the model group, the expression of GFAP and C3 protein was significantly decreased(P<0.05,P<0.01) in tetramethylpyrazine high-dose group. In conclusion, tetramethylpyrazine can promote the improvement of motor function and play a neuroprotective role in mice after spinal cord injury, and its mechanism may be related to inhibiting inflammatory response and improving the hyperplasia of glial scar.

CO oxidation over embedded Pt nanoparticles on Al2O3 with Al coordination flexibility.

A Pt/Al2O3 catalyst is prepared on pentahedral Al-rich Al2O3 with flexible Al coordination, enabling embedment of Pt nanoparticles into the support. The embedded Pt nanoparticles show higher CO oxidation performance than the surface Pt species at appropriate GHSV, suggesting a promising way to tune the properties of the supported Pt catalysts.

Active Ensembles in Methane Dehydroaromatization over Molybdenum/ZSM-5 Zeolite Identified by 2D 1 H-95 Mo Magic Angle Spinning Nuclear Magnetic Resonance Correlation Spectroscopy.

Methane dehydroaromatization (MDA) over Mo-modified zeolite is a potential catalytic route for converting natural gas into valuable aromatics. However, the active species in this reaction are highly complex, involving diverse Mo species, acidic sites of zeolite, and organic molecules. Herein, we apply 1D 95 Mo NMR and 2D 1 H-95 Mo heteronuclear correlation solid-state NMR spectroscopy to directly observe the active ensembles in the confined channels of Mo/ZSM-5 zeolite during the MDA reaction. We monitor the evolution of the spatial correlations of Mo species with the Brønsted acid sites and organic products (olefins and aromatics) in the zeolite channels. We identified two kinds of MoOx Cy species, with the more carbidic one (MoOx Cy -II) exhibiting higher activity for methane activation and benzene formation. The strong spatial interactions between the active Mo species and the organic species in the Mo/ZSM-5 pores are related to the MDA activity.

Methane Oxidation to Methanol.

The direct transformation of methane to methanol remains a significant challenge for operation at a larger scale. Central to this challenge is the low reactivity of methane at conditions that can facilitate product recovery. This review discusses the issue through examination of several promising routes to methanol and an evaluation of performance targets that are required to develop the process at scale. We explore the methods currently used, the emergence of active heterogeneous catalysts and their design and reaction mechanisms and provide a critical perspective on future operation. Initial experiments are discussed where identification of gas phase radical chemistry limited further development by this approach. Subsequently, a new class of catalytic materials based on natural systems such as iron or copper containing zeolites were explored at milder conditions. The key issues of these technologies are low methane conversion and often significant overoxidation of products. Despite this, interest remains high in this reaction and the wider appeal of an effective route to key products from C-H activation, particularly with the need to transition to net carbon zero with new routes from renewable methane sources is exciting.

Insight into Carbocation-Induced Noncovalent Interactions in the Methanol-to-Olefins Reaction over ZSM-5 Zeolite by Solid-State NMR Spectroscopy.

Carbocations such as cyclic carbenium ions are important intermediates in the zeolite-catalyzed methanol-to-olefins (MTO) reaction. The MTO reaction propagates through a complex hydrocarbon pool process. Understanding the carbocation-involved hydrocarbon pool reaction on a molecular level still remains challenging. Here we show that electron-deficient cyclopentenyl cations stabilized in ZSM-5 zeolite are able to capture the alkanes, methanol, and olefins produced during MTO reaction via noncovalent interactions. Intermolecular spatial proximities/interactions are identified by using two-dimensional 13 C-13 C correlation solid-state NMR spectroscopy. Combined NMR experiments and theoretical analysis suggests that in addition to the dispersion and CH/π interactions, the multiple functional groups in the cyclopentenyl cations produce strong attractive force via cation-induced dipole, cation-dipole and cation-π interactions. These carbocation-induced noncovalent interactions modulate the product selectivity of hydrocarbon pool reaction.

Unraveling Hydrocarbon Pool Boosted Propane Aromatization on Gallium/ZSM-5 Zeolite by Solid-State Nuclear Magnetic Resonance Spectroscopy.

Propane aromatization on metal-modified zeolites provides a promising route to produce valuable chemicals such as benzene, toluene and xylene via non-petroleum feedstocks. The mechanistic understanding of propane conversion to aromatics is still challenging due to the complexity of the aromatization process. Herein, by using solid-state NMR spectroscopy and GC-MS, it is shown that cyclopentenyl cations are formed as active intermediates during propane aromatization on Ga/ZSM-5 zeolite. Autocatalysis of propane to aromatics is identified in the induction period. The cyclopentenyl cations serve as key hydrocarbon pool species to co-catalyze propane conversion and promote aromatics formation, revealing a dominant hydrocarbon pool process in propane aromatization.

Solid-state NMR studies of internuclear correlations for characterizing catalytic materials.

Understanding the nature of heterogeneous catalysts is critical for the rational design of highly active catalysts, which necessitates in-depth characterization of the structure and properties of catalysts as well as reaction mechanisms. Solid-state NMR correlation spectroscopy is becoming increasingly recognized as a powerful tool in the study of catalysts and catalytic reactions because of its capability to provide atomic-level insights into the structure, interaction and dynamics of molecules by establishing connectivity and proximity between the same or distinct nuclei. This tutorial review focuses on the fundamentals and state-of-the-art applications of solid-state NMR correlation techniques to structural characterization of catalytic materials including zeolites, metal oxides, organometallic complexes and MOFs as well as relevant studies regarding synthesis, synergistic catalysis, host-guest interactions and reaction mechanisms. Various correlation NMR methods that have been employed to address the challenging issues in heterogeneous catalysis are highlighted. This review concludes with outlooks on the promising applications and potential developments of solid-state NMR correlation spectroscopy in catalytic materials.

General Synthesis of Ordered Mesoporous Carbonaceous Hybrid Nanostructures with Molecularly Dispersed Polyoxometallates.

Hybrid nanomaterials with controlled dimensions, intriguing components and ordered structures have attracted significant attention in nanoscience and technology. Herein, we report a facile and green polyoxometallate (POM)-assisted hydrothermal carbonization strategy for synthesis of carbonaceous hybrid nanomaterials with molecularly dispersed POMs and ordered mesopores. By using various polyoxometallates such as ammonium phosphomolybdate, silicotungstic acid, and phosphotungstic acid, our approach can be generalized to synthesize ordered mesoporous hybrid nanostructures with diverse compositions and morphologies (nanosheet-assembled hierarchical architectures, nanospheres, and nanorods). Moreover, the ordered mesoporous nanosheet-assembled hierarchical hybrids with molecularly dispersed POMs exhibit remarkable catalytic activity toward the dehydration of tert-butanol with the high isobutene selectivity (100 %) and long-term catalytic durability (80 h).

Through-space 11 B-27 Al correlation: Influence of the recoupling channel.

Through-space heteronuclear correlation (D-HETCOR) experiments based on heteronuclear multiple-quantum correlation (D-HMQC) and refocused insensitive nuclei enhanced by polarization transfer (D-RINEPT) sequences have been proven to be useful approaches for the detection of the spatial proximity between half-integer quadrupolar nuclei in solids under magic-angle spinning (MAS) conditions. The corresponding pulse sequences employ coherence transfers mediated by heteronuclear dipolar interactions, which are reintroduced under MAS by radiofrequency irradiation of only one of the two correlated nuclei. We investigate herein using numerical simulations of spin dynamics and solid-state NMR experiments on magnesium aluminoborate glass how the choice of the channel to which the heteronuclear dipolar recoupling is applied affects the transfer efficiency of D-HMQC and D-RINEPT sequences between 11 B and 27 Al nuclei. Experimental results show that maximum transfer efficiency is achieved when the recoupling scheme is applied to the channel, for which the spin magnetization is parallel to the B0 axis in average.

Dual Active Sites on Molybdenum/ZSM-5 Catalyst for Methane Dehydroaromatization: Insights from Solid-State NMR Spectroscopy.

Methane dehydroaromatization (MDA) on Mo/ZSM-5 zeolite catalyst is promising for direct transformation of natural gas. Understanding the nature of active sites on Mo/ZSM-5 is a challenge for applications. Herein, using 1 H{95 Mo} double-resonance solid-state NMR spectroscopy, we identify proximate dual active sites on Mo/ZSM-5 catalyst by direct observation of internuclear spatial interaction between Brønsted acid site and Mo species in zeolite channels. The acidic proton-Mo spatial interaction is correlated with methane conversion and aromatics formation in the MDA process, an important factor in determining the catalyst activity and lifetime. The evolution of olefins and aromatics in Mo/ZSM-5 channels is monitored by detecting their host-guest interactions with both active Mo sites and Brønsted acid sites via 1 H{95 Mo} double-resonance and two-dimensional 1 H-1 H correlation NMR spectroscopy, revealing the intermediate role of olefins in hydrocarbon pool process during the MDA reaction.

Probing the active sites for methane activation on Ga/ZSM-5 zeolites with solid-state NMR spectroscopy.

Ga-modified zeolites represent the most effective catalyst for catalytic transformation of light alkanes to aromatics. GaO+ ions and GaOx clusters on Ga/ZSM-5 zeolites are probed by solid-state NMR. These two types of Ga species show strong Lewis acidity and are quantitatively correlated with the catalytic activity of Ga/ZSM-5 for methane C-H bond activation. The interaction between the surface Ga species and zeolite is characterized by using double-resonance solid-state NMR spectroscopy, which provides direct spectroscopic evidence for the location and distribution of active Ga species. These results provide new insight into the understanding of the nature and role of Ga species in Ga-modified zeolites for the conversion of light alkanes.

Hydrogen Spillover to Oxygen Vacancy of TiO2-xHy/Fe: Breaking the Scaling Relationship of Ammonia Synthesis.

Optimizing kinetic barriers of ammonia synthesis to reduce the energy intensity has recently attracted significant research interest. The motivation for the research is to discover means by which activation barriers of N2 dissociation and NHz (z = 1-2, surface intermediates) destabilization can be reduced simultaneously, that is, breaking the "scaling relationship". However, by far only a single success has been reported in 2016 based on the discovery of a strong-weak N-bonding pair: transition metals (nitrides)-LiH. Described herein is a second example that is counterintuitively founded upon a strong-strong N-bonding pair unveiled in a bifunctional nanoscale catalyst TiO2-xHy/Fe (where 0.02 ≤ x ≤ 0.03 and 0 < y < 0.03), in which hydrogen spillover (H) from Fe to cascade oxygen vacancies (OV-OV) results in the trapped form of OV-H on the TiO2-xHy component. The Fe component thus enables facile activation of N2, while the OV-H in TiO2-xHy hydrogenates the N or NHz to NH3 easily.

Mapping the oxygen structure of γ-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.

gem-Diol-Type Intermediate in the Activation of a Ketone on Sn-ß Zeolite as Studied by Solid-State NMR Spectroscopy.

Lewis acid zeolites have found increasing application in the field of biomass conversion, in which the selective transformation of carbonyl-containing molecules is of particular importance due to their relevance in organic synthesis. Mechanistic insight into the activation of carbonyl groups on Lewis acid sites is challenging and critical for the understanding of the catalytic process, which requires the identification of reaction intermediates. Here we report the observation of a stable surface gem-diol-type species in the activation of acetone on Sn-ß zeolite. 13 C, 119 Sn, and 13 C-119 Sn double-resonance NMR spectroscopic studies demonstrate that only the open Sn site ((SiO)3 Sn-OH) on Sn-ß is responsible for the formation of the surface species. 13 C MAS NMR experiments together with density functional theory calculations suggest that the gem-diol-type species exhibits high reactivity and can serve as an active intermediate in the Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reaction of acetone with cyclohexanol. The gem-diol-type species offers an energy-preferable pathway for the direct carbon-to-carbon hydrogen transfer between ketone and alcohol. The results provide new insights into the transformation of carbonyl-containing molecules catalyzed by Lewis acid zeolites.

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.

Observation of an oxonium ion intermediate in ethanol dehydration to ethene on zeolite.

Zeolite-catalyzed dehydration of ethanol offers promising perspectives for the sustainable production of ethene. Complex parallel-consecutive pathways are proposed to be involved in the reaction network of ethanol dehydration on zeolites, where the initial step of ethanol dehydration is still unclear particularly for the favorable production of ethene at lower temperature. Here we report the observation of a triethyloxonium ion (TEO) in the dehydration of ethanol on zeolite H-ZSM-5 by using ex situ and in situ solid-state NMR spectroscopy. TEO is identified as a stable surface species on the working catalyst, which shows high reactivity during reaction. Ethylation of the zeolite by TEO occurs at lower temperature, leading to the formation of surface ethoxy species and then ethene. The TEO-ethoxide pathway is found to be energetically preferable for the dehydration of ethanol to ethene in the initial stage, which is also supported by theoretical calculations.

The acidic nature of "NMR-invisible" tri-coordinated framework aluminum species in zeolites.

The unambiguous characterization of different acid sites in zeolites is of great importance for understanding their catalytic performance and the rational design of highly efficient zeolite catalysts. In addition to various well-characterized extra-framework Al species, a tri-coordinated framework aluminum species can also serve as a Lewis acid site in zeolites, which is "NMR-invisible" owing to its extremely distorted local environment. Here we provide a feasible and reliable approach to elucidate the acidic nature of the tri-coordinated framework Al in dehydrated H-ZSM-5 zeolites via sensitivity-enhanced two-dimensional (2D) multiple nuclear correlation NMR experiments coupled with trimethylphosphine oxide (TMPO) probe molecules. Two types of tri-coordinated framework Al sites have been unambiguously identified, which amount to 11.6% of the total Brønsted and Lewis acid sites. Furthermore, it was found that synergistic effects arising from the close spatial proximity between the tri-coordinated framework Al site and the Brønsted acid site lead to the generation of superacidity (with an acid strength stronger than 100% H2SO4) in the zeolite.

Extra-Framework Aluminum-Assisted Initial C-C Bond Formation in Methanol-to-Olefins Conversion on Zeolite H-ZSM-5.

Surface methoxy species bound to an extra-framework Al (SMS-EFAL) was unambiguously identified by advanced 13 C-{27 Al} double-resonance solid-state NMR technique in the methanol-to-olefins reaction on H-ZSM-5 zeolite. The high reactivity of the SMS-EFAL leads to the formation of surface ethoxy species and ethanol as the key intermediates for ethene generation in the early reaction stage. A direct route for the initial C-C bond formation in ethene was proposed and corroborated by density functional theory calculations.