Origin of Reactivity Trends of an Elusive Metathesis Intermediate from NMR Chemical Shift Analysis of Surrogate Analogues.

Olefin metathesis has become an efficient tool in synthetic organic chemistry to build carbon-carbon bonds, thanks to the development of Grubbs- and Schrock-type catalysts. Olefin coordination, a key and often rate-determining elementary step for d0 Schrock-type catalysts, has been rarely explored due to the lack of accessible relevant molecular analogues. Herein, we present a fully characterized surrogate of this key olefin-coordination intermediate, namely, a cationic d0 tungsten oxo-methylidene complex bearing two N-heterocyclic carbene ligands─[WO(CH2)Cl(IMes)2](OTf) (1) (IMes = 1,3-dimesitylimidazole-2-ylidene, OTf-triflate counteranion), resulting in a trigonal bipyramidal (TBP) geometry, along with its neutral octahedral analogue [WO(CH2)Cl2(IMes)2] (2)─and an isostructural oxo-methylidyne derivative [WO(CH)Cl(IMes)2] (3). The analysis of their solid-state 13C and 183W MAS NMR signatures, along with computed 17O NMR parameters, helps to correlate their electronic structures with NMR patterns and evidences the importance of the competition among the three equatorial ligands in the TBP complexes. Anchored on experimentally obtained NMR parameters for 1, computational analysis of a series of olefin coordination intermediates highlights the interplay between σ- and π-donating ligands in modulating their stability and further paralleling their reactivity. NMR spectroscopy descriptors reveal the origin for the advantage of the dissymmetry in σ-donating abilities of ancillary ligands in Schrock-type catalysts: weak σ-donors avoid the orbital-competition with the oxo ligand upon formation of a TBP olefin-coordination intermediate, while stronger σ-donors compromise M≡O triple bonding and thus render olefin coordination step energy demanding.

Solid-State 183W NMR Spectroscopy as a High-Resolution Probe of Polyoxotungstate Structures and Dynamics.

Polyoxometalates such as ammonium paratungstate (APT) constitute an important class of metal oxides with applications for catalysis, (opto)electronics, and functional materials. Structural analyses of solid polyoxometalates mostly rely on X-ray or neutron diffraction techniques, which are largely limited to compounds that can be isolated with long-range crystallographic order. While 183W NMR has been shown to probe polyoxotungstate structures and dynamics in solution, its application to solids has been extremely limited. Here, state-of-the-art methods for the detection of solid-state 183W NMR spectra are tested and compared for APT in different hydration states. The highly resolved solid-state spectra distinguish each crystallographically distinct site in the tungstate structure. Furthermore, the 183W chemical shifts are shown to be highly sensitive to the local structure, dynamics, and symmetry of APT, establishing solid-state 183W NMR spectroscopy as a potent probe for analysis of polyoxotungstates and other tungsten-derived materials to complement solution NMR and diffraction-based techniques.

Exploring the acute muscle fatigue response in resistance trained individuals during eccentric quasi-isometric elbow flexions-a cross-sectional comparison of repetition and sex.

Eccentric quasi-isometrics (EQIs) are a novel, low-velocity resistance exercise technique that incorporates a holding isometric contraction to positional fatigue, followed by voluntary resistance of the resulting eccentric muscle action. As females are typically more fatigue resistant than males during isometric and low-velocity dynamic muscle actions, this study explored sex-differences in the muscle fatigue response to an EQI protocol. Twenty-five (n = 12 female) participants completed 4 unilateral EQI elbow flexions. Absolute and relative surface electromyography (sEMG) amplitude (iEMG, LE peak), mean power frequency (MPF), angular impulse (aIMP), and elbow angle were compared across repetitions and between sexes using discrete values and statistical parametric/non-parametric mapping. There were significant and substantial sex and repetition differences in absolute iEMG, MPF, and aIMP, however, males and females had statistically similar absolute aIMP by repetition 4. When expressed relatively, there were no significant sex-differences. Additionally, there were significant between repetition changes in sEMG amplitude and elbow angle with an increasing number of repetitions, largely in the first-two thirds of repetition time. The current study suggests that there are absolute, but not relative sex-differences in EQI induced muscle fatigue, and the effects across repetitions occur predominately in the first two-thirds of repetition time.

NMR Signatures and Electronic Structure of Ti Sites in Titanosilicalite-1 from Solid-State 47/49Ti NMR Spectroscopy.

Although titanosilicalite-1 (TS-1) is among the most successful oxidation catalysts used in industry, its active site structure is still debated. Recent efforts have mostly focused on understanding the role of defect sites and extraframework Ti. Here, we report the 47/49Ti signature of TS-1 and molecular analogues [Ti(OTBOS)4] and [Ti(OTBOS)3(OiPr)] using novel MAS CryoProbe to enhance the sensitivity. While the dehydrated TS-1 displays chemical shifts similar to those of molecular homologues, confirming the tetrahedral environment of Ti consistent with X-ray absorption spectroscopy, it is associated with a distribution of larger quadrupolar coupling constants, indicating an asymmetric environment. Detailed computational studies on cluster models highlights the high sensitivity of the NMR signatures (chemical shift and quadrupolar coupling constant) to small local structural changes. These calculations show that, while it will be difficult to distinguish mono- vs dinuclear sites, the sensitivity of the 47/49Ti NMR signature should enable distinguishing the Ti location among specific T site positions.

Lithium Promotes Acetylide Formation on MgO During Methane Coupling Under Non-Oxidative Conditions.

A prototypical material for the oxidative coupling of methane (OCM) is Li/MgO, for which Li is known to be essential as a dopant to obtain high C2 selectivities. Herein, Li/MgO is demonstrated to be an effective catalyst for non-oxidative coupling of methane (NOCM). Moreover, the presence of Li is shown to favor the formation of magnesium acetylide (MgC2 ), while pure MgO promotes coke formation as evidenced by solid-state 13 C NMR, thus indicating that Li promotes C-C bond formation. Metadynamic simulations of the carbon mobility in MgC2 and Li2 C2 at the density functional theory (DFT) level show that carbon easily diffuses as a C2 unit at 1000 °C. These insights suggest that the enhanced C2 selectivity for Li-doped MgO is related to the formation of Li and Mg acetylides.

Tailored Lewis Acid Sites for High-Temperature Supported Single-Molecule Magnetism.

Generating or even retaining slow magnetic relaxation in surface immobilized single-molecule magnets (SMMs) from promising molecular precursors remains a great challenge. Illustrative examples are organolanthanide compounds that show promising SMM properties in molecular systems, though surface immobilization generally diminishes their magnetic performance. Here, we show how tailored Lewis acidic Al(III) sites on a silica surface enable generation of a material with SMM characteristics via chemisorption of (Cpttt)2DyCl ((Cpttt)- = 1,2,4-tri(tert-butyl)-cyclopentadienide). Detailed studies of this system and its diamagnetic Y analogue indicate that the interaction of the metal chloride with surface Al sites results in a change of the coordination sphere around the metal center inducing for the dysprosium-containing material slow magnetic relaxation up to 51 K with hysteresis up to 8 K and an effective energy barrier (Ueff) of 449 cm-1, the highest reported thus far for a supported SMM.

Promoting active site renewal in heterogeneous olefin metathesis catalysts.

As an atom-efficient strategy for the large-scale interconversion of olefins, heterogeneously catalysed olefin metathesis sees commercial applications in the petrochemical, polymer and speciality chemical industries1. Notably, the thermoneutral and highly selective cross-metathesis of ethylene and 2-butenes1 offers an appealing route for the on-purpose production of propylene to address the C3 shortfall caused by using shale gas as a feedstock in steam crackers2,3. However, key mechanistic details have remained ambiguous for decades, hindering process development and adversely affecting economic viability4 relative to other propylene production technologies2,5. Here, from rigorous kinetic measurements and spectroscopic studies of propylene metathesis over model and industrial WOx/SiO2 catalysts, we identify a hitherto unknown dynamic site renewal and decay cycle, mediated by proton transfers involving proximal Brønsted acidic OH groups, which operates concurrently with the classical Chauvin cycle. We show how this cycle can be manipulated using small quantities of promoter olefins to drastically increase steady-state propylene metathesis rates by up to 30-fold at 250 °C with negligible promoter consumption. The increase in activity and considerable reduction of operating temperature requirements were also observed on MoOx/SiO2 catalysts, showing that this strategy is possibly applicable to other reactions and can address major roadblocks associated with industrial metathesis processes.

Active Site Descriptors from 95Mo NMR Signatures of Silica-Supported Mo-Based Olefin Metathesis Catalysts.

The olefin metathesis activity of silica-supported molybdenum oxides depends strongly on metal loading and preparation conditions, indicating that the nature and/or amounts of the active sites vary across compositionally similar catalysts. This is illustrated by comparing Mo-based (pre)catalysts prepared by impregnation (2.5-15.6 wt % Mo) and a model material (2.3 wt % Mo) synthesized via surface organometallic chemistry (SOMC). Analyses of FTIR, UV-vis, and Mo K-edge X-ray absorption spectra show that these (pre)catalysts are composed predominantly of similar isolated Mo dioxo sites. However, they exhibit different reaction properties in both liquid and gas-phase olefin metathesis with the SOMC-derived catalyst outperforming a classical catalyst of a similar Mo loading by ×1.5-2.0. Notably, solid-state 95Mo NMR analyses leveraging state-of-the-art high-field (28.2 T) measurement conditions resolve four distinct surface Mo dioxo sites with distributions that depend on the (pre)catalyst preparation methods. The intensity of a specific deshielded 95Mo NMR signal, which is most prominent in the SOMC-derived catalyst, is linked to reducibility and catalytic activity. First-principles calculations show that 95Mo NMR parameters directly manifest the local strain and coordination environment: acute (SiO-Mo(O)2-OSi) angles and low coordination numbers at Mo lead to highly deshielded 95Mo chemical shifts and small quadrupolar coupling constants, respectively. Natural chemical shift analyses relate the 95Mo NMR signature of strained species to low LUMO energies, which is consistent with their high reducibility and corresponding reactivity. The 95Mo chemical shifts of supported Mo dioxo sites are thus linked to their specific electronic structures, providing a powerful descriptor for their propensity toward reduction and formation of active sites.

Assigning 1H chemical shifts in paramagnetic mono- and bimetallic surface sites using DFT: a case study on the Union Carbide polymerization catalyst.

The Union Carbide (UC) ethylene polymerization catalyst, based on silica-supported chromocene, is one of the first industrial catalysts prepared by surface organometallic chemistry, though the structure of the surface sites remains elusive. Recently, our group reported that monomeric and dimeric Cr(ii) sites, as well as Cr(iii) hydride sites, are present and that their proportion varies as a function of the Cr loading. While 1H chemical shifts extracted from solid-state 1H NMR spectra should be diagnostic of the structure of such surface sites, unpaired electrons centered on Cr atoms induce large paramagnetic 1H shifts that complicate their NMR analysis. Here, we implement a cost-efficient DFT methodology to calculate 1H chemical shifts for antiferromagnetically coupled metal dimeric sites using a Boltzmann-averaged Fermi contact term over the population of the different spin states. This method allowed us to assign the 1H chemical shifts observed for the industrial-like UC catalyst. The presence of monomeric and dimeric Cr(ii) sites, as well as a dimeric Cr(iii)-hydride sites, was confirmed and their structure was clarified.

Ankle bracing's effects during a modified agility task: analysis of sEMG, impulse, and time to complete using a crossover, repeated measures design.

This study explored the effects of no braces, softshell (AE), and semi-rigid (T1) ankle braces on time to complete a modified agility task, as well as lower extremity muscle activity and impulse during the change of direction component of the task. Thirty-nine healthy, active individuals completed a modified agility task under the three brace conditions. Time to complete the modified agility task, along with mean surface electromyographic activity (sEMG) and impulse during the deceleration and propulsive phases of the task were measured. There were no significant differences across conditions with respect to sEMG or impulse measures during the deceleration or propulsive phases. There was a significant change in time to complete the modified agility task, F(2,76) = 17.242, p< 0.001, ηp2 = 0.312. Post-hoc analysis revealed a significant increase in time to complete the modified agility task when wearing the AE (0.16 (95% CI, 0.062 to 0.265) seconds, p< 0.001) and T1 (0.20 (95% CI, 0.113 to 0.286) seconds, p< 0.001) ankle braces compared to no braces. It appears that performance on a modified agility task may be diminished when wearing ankle braces, although sEMG activity and impulse are unaffected.

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.

Classifying and Understanding the Reactivities of Mo-Based Alkyne Metathesis Catalysts from 95Mo NMR Chemical Shift Descriptors.

The most active alkyne metathesis catalysts rely on well-defined Mo alkylidynes, X3Mo≡CR (X = OR), in particular the recently developed canopy catalyst family bearing silanolate ligand sets. Recent efforts to understand catalyst reactivity patterns have shown that NMR chemical shifts are powerful descriptors, though previous studies have mostly focused on ligand-based NMR descriptors. Here, we show in the context of alkyne metathesis that 95Mo chemical shift tensors encode detailed information on the electronic structure of these catalysts. Analysis by first-principles calculations of 95Mo chemical shift tensors extracted from solid-state 95Mo NMR spectra shows a direct link of chemical shift values with the energies of the HOMO and LUMO, two molecular orbitals involved in the key [2 + 2]-cycloaddition step, thus linking 95Mo chemical shifts to reactivity. In particular, the 95Mo chemical shifts are driven by ligand electronegativity (σ-donation) and electron delocalization through Mo-O π interactions, thus explaining the reactivity patterns of the silanolate canopy catalysts. These results further motivate exploration of transition metal NMR signatures and their relationships to electronic structure and reactivity.

Olefin-Surface Interactions: A Key Activity Parameter in Silica-Supported Olefin Metathesis Catalysts.

Molecularly defined and classical heterogeneous Mo-based metathesis catalysts are shown to display distinct and unexpected reactivity patterns for the metathesis of long-chain α-olefins at low temperatures (<100 °C). Catalysts based on supported Mo oxo species, whether prepared via wet impregnation or surface organometallic chemistry (SOMC), exhibit strong activity dependencies on the α-olefin chain length, with slower reaction rates for longer substrate chain lengths. In contrast, molecular and supported Mo alkylidenes are highly active and do not display such dramatic dependence on the chain length. State-of-the-art two-dimensional (2D) solid-state nuclear magnetic resonance (NMR) spectroscopy analyses of postmetathesis catalysts, complemented by Fourier transform infrared (FT-IR) spectroscopy and molecular dynamics calculations, evidence that the activity decrease observed for supported Mo oxo catalysts relates to the strong adsorption of internal olefin metathesis products because of interactions with surface Si-OH groups. Overall, this study shows that in addition to the nature and the number of active sites, the metathesis rates and the overall catalytic performance depend on product desorption, even in the liquid phase with nonpolar substrates. This study further highlights the role of the support and active site composition and dynamics on activity as well as the need for considering adsorption in catalyst design.

Closed-loop sacral neuromodulation for bladder function using dorsal root ganglia sensory feedback in an anesthetized feline model.

Overactive bladder patients suffer from a frequent, uncontrollable urge to urinate, which can lead to a poor quality of life. We aim to improve open-loop sacral neuromodulation therapy by developing a conditional stimulation paradigm using neural recordings from dorsal root ganglia (DRG) as sensory feedback. Experiments were performed in 5 anesthetized felines. We implemented a Kalman filter-based algorithm to estimate the bladder pressure in real-time using sacral-level DRG neural recordings and initiated sacral root electrical stimulation when the algorithm detected an increase in bladder pressure. Closed-loop neuromodulation was performed during continuous cystometry and compared to bladder fills with continuous and no stimulation. Overall, closed-loop stimulation increased bladder capacity by 13.8% over no stimulation (p < 0.001) and reduced stimulation time versus continuous stimulation by 57.7%. High-confidence bladder single units had a reduced sensitivity during stimulation, with lower linear trendline fits and higher pressure thresholds for firing observed during stimulation trials. This study demonstrates the utility of decoding bladder pressure from neural activity for closed-loop control of sacral neuromodulation. An underlying mechanism for sacral neuromodulation may be a reduction in bladder sensory neuron activity during stimulation. Real-time validation during behavioral studies is necessary prior to clinical translation of closed-loop sacral neuromodulation.

A Structure-based Design Approach for Generating High Affinity BRD4 D1-Selective Chemical Probes.

Chemical probes for epigenetic proteins are essential tools for dissecting the molecular mechanisms for gene regulation and therapeutic development. The bromodomain and extra-terminal (BET) proteins are master transcriptional regulators. Despite promising therapeutic targets, selective small molecule inhibitors for a single bromodomain remain an unmet goal due to their high sequence similarity. Here, we address this challenge via a structure-activity relationship study using 1,4,5-trisubstituted imidazoles against the BRD4 N-terminal bromodomain (D1). Leading compounds 26 and 30 have 15 and 18 nM affinity against BRD4 D1 and over 500-fold selectivity against BRD2 D1 and BRD4 D2 via ITC. Broader BET selectivity was confirmed by fluorescence anisotropy, thermal shift, and CETSA. Despite BRD4 engagement, BRD4 D1 inhibition was unable to reduce c-Myc expression at low concentration in multiple myeloma cells. Conversely, for inflammation, IL-8 and chemokine downregulation were observed. These results provide new design rules for selective inhibitors of an individual BET bromodomain.

Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration.

Traumatic spinal cord injury (SCI) is a devastating neurological condition that results in a loss of motor and sensory function. Although extensive research to develop treatments for SCI has been performed, to date, none of these treatments have produced a meaningful amount of functional recovery after injury. The primary injury is caused by the initial trauma to the spinal cord and results in ischemia, oxidative damage, edema, and glutamate excitotoxicity. This process initiates a secondary injury cascade, which starts just a few hours post-injury and may continue for more than 6 months, leading to additional cell death and spinal cord damage. Inflammation after SCI is complex and driven by a diverse set of cells and signaling molecules. In this review, we utilize an extensive literature survey to develop the timeline of local immune cell and cytokine behavior after SCI in rodent models. We discuss the precise functional roles of several key cytokines and their effects on a variety of cell types involved in the secondary injury cascade. Furthermore, variations in the inflammatory response between rats and mice are highlighted. Since current SCI treatment options do not successfully initiate functional recovery or axonal regeneration, identifying the specific mechanisms attributed to secondary injury is critical. With a more thorough understanding of the complex SCI pathophysiology, effective therapeutic targets with realistic timelines for intervention may be established to successfully attenuate secondary damage.

Through the Looking Glass: Insights Into Visualization Pedagogy Through Sentiment Analysis of Peer Review Text.

Peer review is a widely utilized feedback mechanism for engaging students. As a pedagogical method, it has been shown to improve educational outcomes, but we have found limited empirical measurement of peer review in visualization courses. In addition to increasing engagement, peer review provides diverse feedback and reinforces recently learned course concepts through critical evaluation of others' work. We discuss the construction and application of peer review in two visualization courses from different colleges at the University of South Florida. We then analyze student projects and peer review text via sentiment analysis to infer insights for visualization educators, including the focus of course content, engagement across student groups, student mastery of concepts, course trends over time, and expert intervention effectiveness. Finally, we provide suggestions for adapting peer review to other visualization courses to engage students and increase instructor understanding of the peer review process.

Acute effect of inhibitory kinesio-tape of the upper trapezius on lower trapezius muscle excitation in healthy shoulders.

INTRODUCTION: Shoulder pain increases excitation of the upper trapezius (UT) and reduces excitation in the lower trapezius (LT). Despite inconclusive evidence, kinesio-tape (KT) is often used to modify muscular excitation within the UT and/or LT to help correct alterations in scapular position and motion associated with shoulder pain/injury. The objective of the current study was to determine if inhibitory KT to the UT acutely increases LT excitation and if load alters the magnitude of change in the excitation observed. METHODS: Twenty-two (N = 22, 11 female) individuals with healthy shoulders (24 ± 3 years) completed 10 repetitions of an arm elevation task during 3 taping conditions (no-tape, experimental KT, sham KT) and 2 loading conditions (no load and loaded). Whole-muscle (mean grid) and spatial distribution (grid row) of LT excitation (root mean squared; RMS) was measured using a single high-density surface electromyography 32-electrode grid. RESULTS: There was a main effect for loading condition on whole-muscle LT RMS, F (1, 19) = 38.038, p < .001, partial η2 = 0.667. Whole-muscle LT RMS was significantly higher in the loaded condition (0.055 V ±0 .005) compared to the no-load condition (0.038 V ±0 .004). No effect of tape condition was observed on whole-muscle or spatial distribution of RMS. CONCLUSION: Our findings suggest that inhibitory KT to the UT does not alter whole-muscle excitation or shift the distribution of excitation within the LT during a repeated arm elevation task in healthy shoulders.

Olefin metathesis: what have we learned about homogeneous and heterogeneous catalysts from surface organometallic chemistry?

Since its early days, olefin metathesis has been in the focus of scientific discussions and technology development. While heterogeneous olefin metathesis catalysts based on supported group 6 metal oxides have been used for decades in the petrochemical industry, detailed mechanistic studies and the development of molecular organometallic chemistry have led to the development of robust and widely used homogeneous catalysts based on well-defined alkylidenes that have found applications for the synthesis of fine and bulk chemicals and are also used in the polymer industry. The development of the chemistry of high-oxidation group 5-7 alkylidenes and the use of surface organometallic chemistry (SOMC) principles unlocked the preparation of so-called well-defined supported olefin metathesis catalysts. The high activity and stability (often superior to their molecular analogues) and molecular-level characterisation of these systems, that were first reported in 2001, opened the possibility for the first direct structure-activity relationships for supported metathesis catalysts. This review describes first the history of SOMC in the field of olefin metathesis, and then focuses on what has happened since 2007, the date of our last comprehensive reviews in this field.

A modified diet to support conservation of the Atala hairstreak butterfly (Eumaeus atala Poey).

Raising insects in a laboratory for release into the wild is a common conservation practice, but maintaining breeding colonies year-round can be limited by seasonal food availability. Food availability is particularly challenging for insects which depend on specific host plants. For example, our early efforts to rear the imperiled Atala hairstreak butterfly (Eumaeus atala Poey) resulted in colony failure during winter due to lack of food. To overcome this barrier, we developed a modified freeze-dried host plant diet to support the colony. The diet consisted of reconstituted freeze-dried leaves and stems from fresh-growth coontie (Zamia integrifolia), the host plant for the Atala butterflies. We fed larvae less than 9 mm on this freeze-dried diet and transferred them to live coontie plants after they were more than 9 mm. We reared a colony of Atala butterflies using these methods for 859 days, resulting in more than 3400 animals released into the wild. Comparing colony counts during that time period to the 548 days we reared them without modified freeze-dried diet showed a clear benefit in using freeze-dried diet. A growth trial (N = 40) of larvae fed on only freeze-dried diet compared to larvae fed on fresh coontie cuttings found no significant difference in larval or pupal development between groups (p = 0.71 and p = 0.47, respectively). We, therefore, conclude that the freeze-dried diet provided an appropriate alternative for Atala colonies when fresh growth from the host plant is unavailable, and we recommend use of this technique for raising other host plant-dependent insect species of conservation concern.