High Intrinsic Reactivity Research Articles

Elucidating the pivotal molecular mechanisms, therapeutic and neuroprotective effects of lithium in traumatic brain injury.

Traumatic brain injury (TBI) refers to damage to brain tissue by mechanical or blunt force via trauma. TBI is often associated with impaired cognitive abilities, like difficulties in memory, learning, attention, and other higher brain functions, that typically remain for years after the injury. Lithium is an elementary light metal that is only utilized in salt form due to its high intrinsic reactivity. This current review discusses the molecular mechanisms and therapeutic and neuroprotective effects of lithium in TBI. The "Boolean logic" was used to search for articles on the subject matter in PubMed and PubMed Central, as well as Google Scholar. Lithium's therapeutic action is extremely complex, involving multiple effects on gene secretion, neurotransmitter or receptor-mediated signaling, signal transduction processes, circadian modulation, as well as ion transport. Lithium is able to normalize multiple short- as well as long-term modifications in neuronal circuits that ultimately result in disparity in cortical excitation and inhibition activated by TBI. Also, lithium levels are more distinct in the hippocampus, thalamus, neo-cortex, olfactory bulb, amygdala as well as the gray matter of the cerebellum following treatment of TBI. Lithium attenuates neuroinflammation and neuronal toxicity as well as protects the brain from edema, hippocampal neurodegeneration, loss of hemispheric tissues, and enhanced memory as well as spatial learning after TBI.

Structural characterization and reactivity of a room-temperature-stable, antiaromatic cyclopentadienyl cation salt.

The singlet states of cyclopentadienyl (Cp) cations are considered as true prototypes of an antiaromatic system. Unfortunately, their high intrinsic reactivity inhibited their isolation in the solid state as a salt, and controlled reactions are also scarce. Here we present the synthesis and solid state structure of the room-temperature-stable Cp cation salt [Cp(C6F5)5]+[Sb3F16]-. Although the aromatic triplet state of the [Cp(C6F5)5]+ cation is energetically favoured in the gas phase according to quantum chemical calculations, coordination of the cation by either [Sb3F16]- or C6F6 in the crystal lattice stabilizes the antiaromatic singlet state, which is present in the solid state. The calculated hydride and fluoride ion affinities of the [Cp(C6F5)5]+ cation are higher than those of the perfluorinated tritylium cation [C(C6F5)3]+. Reactions of [Cp(C6F5)5]+[Sb3F16]- with CO, which probably yields the corresponding carbonyl complex, and of radical Cp(C6F5)5∙ with selected model substrates (Cp2Fe, (Ph3C∙)2 and Cp*Al) are also presented.

Facilitated Synthetic Access to Boronic Acid-Modified Nucleoside Triphosphates and Compatibility with Enzymatic DNA Synthesis

AbstractDecorating nucleic acids with boronic acids can extend the usefulness of oligonucleotide-based tools to the development of medical imaging agents, the promotion of binding of aptamers to markedly more challenging targets, or the detection of (poly)saccharides. However, due to the hygroscopic nature and high intrinsic reactivity of boronic acids, protocols for their introduction into nucleic acids are scarce. Here, we have explored various synthetic routes for the crafting of nucleoside triphosphates equipped with phenylboronic acids. Strain-promoted azide–alkyne cycloaddition appears to be the method of choice for this purpose and it enabled us to prepare a modified nucleotide. Enzymatic DNA synthesis permitted the introduction of up to thirteen boronic acid residues in oligonucleotides, which bodes well for its extension to SELEX and related methods of in vitro selection of functional nucleic acids.

Lysine-Reactive N-Acyl-N-aryl Sulfonamide Warheads: Improved Reaction Properties and Application in the Covalent Inhibition of an Ibrutinib-Resistant BTK Mutant.

The covalent inhibition of a target protein has gained widespread attention in the field of drug discovery. Most of the current covalent drugs utilize the high reactivity of cysteines toward modest electrophiles. However, there is a growing need for warheads that can target lysine residues to expand the range of covalently druggable proteins and to deal with emerging proteins with mutations resistant to cysteine-targeted covalent drugs. We have recently developed an N-acyl-N-alkyl sulfonamide (NASA) as a lysine-targeted electrophile. Despite its successful application, this NASA warhead suffered from instability in physiological environments, such as serum-containing medium, because of its high intrinsic reactivity. In this study, we sought to modify the structure of the NASA warhead and found that N-acyl-N-aryl sulfonamides (ArNASAs) are promising electrophiles for use in a lysine-targeted covalent inhibition strategy. We prepared a focused library of ArNASA derivatives with diverse structures and reactivity and identified several warhead candidates with suppressed hydrolysis-mediated inactivation and reduced nonspecific reactions with off-target proteins, without sacrificing the reactivity toward the target. These reaction properties enabled the improved covalent inhibition of intracellular heat shock protein 90 (HSP90) in the presence of serum and the development of the first irreversible inhibitor for ibrutinib-resistant Bruton's tyrosine kinase (BTK) bearing the C481S mutation. This study clearly demonstrated the use of a set of ArNASA warheads to create highly potent covalent drugs and highlighted the importance of enriching the current arsenal of lysine-reactive warheads.

Enhanced nonenzymatic RNA copying with in-situ activation of short oligonucleotides.

The nonenzymatic copying of RNA is thought to have been necessary for the transition between prebiotic chemistry and ribozyme-catalyzed RNA replication in the RNA World. We have previously shown that a potentially prebiotic nucleotide activation pathway based on phospho-Passerini chemistry can lead to the efficient synthesis of 2-aminoimidazole activated mononucleotides when carried out under freeze-thaw cycling conditions. Such activated nucleotides react with each other to form 5'-5' 2-aminoimidazolium bridged dinucleotides, enabling template-directed primer extension to occur within the same reaction mixture. However, mononucleotides linked to oligonucleotides by a 5'-5' 2-aminoimidazolium bridge are superior substrates for nonenzymatic primer extension; their higher intrinsic reactivity and their higher template affinity enable faster template copying at lower substrate concentrations. Here we show that eutectic phase phospho-Passerini chemistry efficiently activates short oligonucleotides and promotes the formation of monomer-bridged-oligonucleotide species during freeze-thaw cycles. We then demonstrate that in-situ generated monomer-bridged-oligonucleotides lead to efficient nonenzymatic template copying in the same reaction mixture. Our demonstration that multiple steps in the pathway from activation chemistry to RNA copying can occur together in a single complex environment simplifies this aspect of the origin of life.

Core–shell structured Fe–N–C wrapped by an ultrathin porous carbon shell as a robust electrocatalyst for the oxygen reduction reaction

Porous carbon supported FeNx catalysts have become one of the candidates to replace platinum group metal (PGM) catalysts for the oxygen reduction reaction (ORR) due to their high intrinsic reactivity and substantial accessible active sites.

Rapid hydrogen detection with low temperature realized by regulating chemisorbed oxygen species of mesoporous indium tin oxide microsphere

With the quick development of hydrogen energy, it is necessary to fabricate hydrogen sensor with high sensitivity, fast response/recovery and low detection limit to monitor the leakage of hydrogen. In this work, a series of indium tin oxide (ITOs) microspheres were successfully synthesized by alkoxide precursors method. Among them, 10.7% In-doped SnO2 (named ITO-II) based sensor exhibits high sensitivity, excellent selectivity, great stability and ultra-fast dynamic process (response time and recovery time<3 s), at a low working temperature of 200 °C. The excellent hydrogen sensing performance of ITO-II should be attributed to the increased chemisorbed oxygen and the high intrinsic reactivity of SnO2 toward hydrogen. This work provides inspiration for the design of novel hydrogen sensing material.

YfeX - A New Platform for Carbene Transferase Development with High Intrinsic Reactivity.

Carbene transfer biocatalysis has evolved from basic science to an area with vast potential for the development of new industrial processes. In this study, we show that YfeX, naturally a peroxidase, has great potential for the development of new carbene transferases, due to its high intrinsic reactivity, especially for the N-H insertion reaction of aromatic and aliphatic primary and secondary amines. YfeX shows high stability against organic solvents (methanol and DMSO), greatly improving turnover of hydrophobic substrates. Interestingly, in styrene cyclopropanation, WT YfeX naturally shows high enantioselectivity, generating the trans product with 87 % selectivity for the (R,R) enantiomer. WT YfeX also catalyzes the Si-H insertion efficiently. Steric effects in the active site were further explored using the R232A variant. Quantum Mechanics/Molecular Mechanics (QM/MM) calculations reveal details on the mechanism of Si-H insertion. YfeX, and potentially other peroxidases, are exciting new targets for the development of improved carbene transferases.

Identification of Interface Structure for a Topological CoS2 Single Crystal in Oxygen Evolution Reaction with High Intrinsic Reactivity.

Transition metal chalcogenides such as CoS2 have been reported as competitive catalysts for oxygen evolution reaction. It has been well confirmed that surface modification is inevitable in such a process, with the formation of different re-constructed oxide layers. However, which oxide species should be responsible for the optimized catalytic efficiencies and the detailed interface structure between the modified layer and precatalyst remain controversial. Here, a topological CoS2 single crystal with a well-defined exposed surface is used as a model catalyst, which makes the direct investigation of the interface structure possible. Cross-sectional transmission electron microscopy of the sample reveals the formation of a 2 nm thickness Co3O4 layer that grows epitaxially on the CoS2 surface. Thick CoO pieces are also observed and are loosely attached to the bulk crystal. The compact Co3O4 interface structure can result in the fast electron transfer from adsorbed O species to the bulk crystal compared with CoO pieces as evidenced by the electrochemical impedance measurements. This leads to the competitive apparent and intrinsic reactivity of the crystal despite the low surface geometric area. These findings are helpful for the understanding of catalytic origins of transition metal chalcogenides and the designing of high-performance catalysts with interface-phase engineering.

Synergistic Experimental and Computational Investigation of the Bioorthogonal Reactivity of Substituted Aryltetrazines.

Tetrazines (Tz) have been applied as bioorthogonal agents for various biomedical applications, including pretargeted imaging approaches. In radioimmunoimaging, pretargeting increases the target-to-background ratio while simultaneously reducing the radiation burden. We have recently reported a strategy to directly 18F-label highly reactive tetrazines based on a 3-(3-fluorophenyl)-Tz core structure. Herein, we report a kinetic study on this versatile scaffold. A library of 40 different tetrazines was prepared, fully characterized, and investigated with an emphasis on second-order rate constants for the reaction with trans-cyclooctene (TCO). Our results reveal the effects of various substitution patterns and moreover demonstrate the importance of measuring reactivities in the solvent of interest, as click rates in different solvents do not necessarily correlate well. In particular, we report that tetrazines modified in the 2-position of the phenyl substituent show high intrinsic reactivity toward TCO, which is diminished in aqueous systems by unfavorable solvent effects. The obtained results enable the prediction of the bioorthogonal reactivity and thereby facilitate the development of the next generation of substituted aryltetrazines for in vivo applications.

Design and Fabrication of High Performance Photoanode of Fe2(MoO4)3/RGO Hybrid Composites for Triiodide Reduction in Dye-Sensitized Solar Cells

Here in, synthesis of Fe2(MoO4)3/reduced graphene oxide (RGO) nanocomposite was prepared by simple hydrothermal approach and used as high efficient dye sensitized solar cells (DSSCs). The decoration of RGO into the Fe2(MoO4)3 was proved by various physic-chemical studies such as XRD, SEM, TEM, Raman, UV, PL and BET analysis. The individual spherical shaped nanoparticles of Fe2(MoO4)3 with sizes in the range of 25–35 nm was uniformly decorated on the surface of RGO nanosheets. Due to the synergic effect between the Fe2(MoO4)3 and RGO the light absorption property is significantly improved as well the high surface area (112.5 m2/g) and pore size (38.7 nm) was achieved than compared with bare Fe2(MoO4)3 (88.5 m2/g and 17.8 nm). The Fe2(MoO4)3/RGO hybrid photoanode establish to display an outstanding catalytic activity toward the reduction of triiodide to iodide in a dye-sensitized solar cell (DSSC) and can provide a solar cell efficiency of 9.6 ± 0.001%, which is superior to a Pt-based DSSC (6.1 ± 0.002%). The better electro-catalytic ability of Fe2(MoO4)3/RGO electrode is obtained by a synergistic effect that resulted in the high specific surface area and intrinsic reactivity of the materials.

Catalytic centers with multiple oxidation states: a strategy for breaking the overpotential ceiling from the linear scaling relation in oxygen evolution

The multiple-oxidation-state catalyst enhanced the oxygen evolution kinetics and energetics by facilitating the charge transfer and breaking the scaling relation, leading to an excellent oxygen evolution activity.

Scalable CNTs/NiCoSe2 Hybrid Films for Flexible All-Solid-State Asymmetric Supercapacitors.

The rapidly developing wearable flexible electronics makes the development of high-performance flexible energy storage devices, such as all-solid-state supercapacitors (SCs), particularly important. Herein, we report the fabrication of CNTs/NiCoSe2 hybrid films on carbon cloth (CC) through a facile co-electrodeposition method based on flexible electrodes for all-solid-state SCs. The NiCoSe2 sheets grown on CNTs uniformly with a diameter of 50-100 nm act as the active materials. The CNTs in the hybrid films act as the scaffold to offer more deposition sites for NiCoSe2 and provide a conductive network to facilitate the transfer of electrons. Moreover, the one-step electrodeposition process avoids the usage of any organic binders. Benefiting from the high intrinsic reactivity and unique 3D architecture, the obtained CNTs/NiCoSe2 electrode delivers high specific capacity (218.1 mA h g-1) and satisfactory durability (over 5000 cycles). Remarkably, the CNTs/NiCoSe2//AC flexible all-solid-state (FASS) ASC provides remarkable energy density (112.2 W h kg-1) within 0-1.7 V and maintains 98.1% of its initial capacity after 10,000 cycles. In addition, this flexible ASC device could be fabricated at a large scale (5 × 6 cm2), and the LED arrays (>3.7 V) can be easily lighted up by three ASCs in series, showing its potential practical application.

Binder-free CuS@PEDOT and Co–V–Se electrodes for flexible quasi-solid-state asymmetric supercapacitor

For the development of high‐performance modern electronics, fabrication of high-energy density flexible supercapacitors (SCs) composed of advanced functional electrodes with tailored nanoarchitectures is of great significance. Faradaic copper sulphide (CuS) with high theoretical capacity promises great potential as a negative electrode in SCs and to further boost its electrochemical performance, an effective strategy of rational surface engineering by electronically conducting poly(3,4-ethylenedioxythiophene) (PEDOT) is hereby proposed. Herein, construction of novel nanostructured CuS@PEDOT hybrid negative electrode on mechanically flexible conducting carbon cloth (CC) substrate (CC/CuS@PEDOT) via a combined solvothermal and potentiostatic electrodeposition route is successfully demonstrated. Benefiting from high intrinsic reactivity and microstructural characteristics, the CC/CuS@PEDOT hybrid exhibits a marked improvement in areal capacity and ultralong electrochemical cycling stability. As the positive electrodes, nanoarchitectured CC/Co–V–Se (CC/CVS) arrays are prepared and investigated. A novel alkaline polymer gel electrolyte-based quasi-solid-state asymmetric supercapacitor (ASC) assembled with optimized CC/CuS@PEDOT hybrid negative electrode and CC/CVS positive electrode delivers a maximum volumetric energy density of 2.21 mWh cm−3 and superior cycling life (96.7% capacity retention after 10,000 cycles). Additionally, for the ASC device, no obvious performance loss upon bending or twisting is observed, ensuring its adaptability for modern portable and wearable energy storage devices.

Isolation and reactivity of an elusive diazoalkene.

Most functional groups, especially those consisting of the abundant elements of organic matter-carbon, nitrogen and oxygen-have been extensively studied and only very few remain speculative due to their high intrinsic reactivity. In contrast to the well-explored chemistry of diazoalkanes (R2C=N2), diazoalkenes (R2C=C=N2) have been postulated in several organic transformations, but remain elusive long-sought intermediates. Here, we present a room-temperature stable diazoalkene, utilizing a dinitrogen transfer from nitrous oxide. This functional group shows dual-site nucleophilicity (C and N atoms) and features a bent C-C-N entity (124°) and a long N-N bond together with a remarkable low infrared absorption (1,944 cm-1). Substitution of N2 by an isocyanide leads to a vinylidene ketenimine. Furthermore, photochemically triggered loss of dinitrogen might proceed through a transient triplet vinylidene. We anticipate the existence of a stable diazoalkene functional group to pave an exciting avenue into the chemistry of low-valent carbon and unsaturated carbenes.

Coupling PEDOT on Mesoporous Vanadium Nitride Arrays for Advanced Flexible All-Solid-State Supercapacitors.

Tailored construction of advanced flexible supercapacitors (SCs) is of great importance to the development of high-performance wearable modern electronics. Herein, a facile combined wet chemical method to fabricate novel mesoporous vanadium nitride (VN) composite arrays coupled with poly(3,4-ethylenedioxythiophene) (PEDOT) as flexible electrodes for all-solid-state SCs is reported. The mesoporous VN nanosheets arrays prepared by the hydrothermal-nitridation method are composed of cross-linked nanoparticles of 10-50nm. To enhance electrochemical stability, the VN is further coupled with electrodeposited PEDOT shell to form high-quality VN/PEDOT flexible arrays. Benefiting from high intrinsic reactivity and enhanced structural stability, the designed VN/PEDOT flexible arrays exhibit a high specific capacitance of 226.2 F g-1 at 1 A g-1 and an excellent cycle stability with 91.5% capacity retention after 5000 cycles at 10 A g-1 . In addition, high energy/power density (48.36Wh kg-1 at 2 A g-1 and 4kW kg-1 at 5 A g-1 ) and notable cycling life (91.6% retention over 10 000 cycles) are also achieved in the assembled asymmetric flexible supercapacitor cell with commercial nickel-cobalt-aluminum ternary oxides cathode and VN/PEDOT anode. This research opens up a way for construction of advanced hybrid organic-inorganic electrodes for flexible energy storage.

Construction of mesoporous Li4Ti5O12 hollow spheres for high rate lithium ion batteries

In this study, a simple targeted etching approach was developed for the controlled fabrication of mesoporous Li4Ti5O12 (LTO) hollow spheres, which can be used as an advanced anode material in lithium-ion batteries. We investigated the controllable synthesis of mesoporous LTO hollow spheres with various hollow structures based on different compositions, such as yolk-shelled and hollow structures with porous shells. The as-prepared mesoporous LTO hollow spheres had several main structural advantages, including high intrinsic interfacial reactivity with the electrolyte due to a high specific surface area, extra space for the storage of lithium ions, and reduced transport path lengths for both e– and Li+, thereby leading to excellent rate performance. Moreover, the high reversible capacity of the mesoporous LTO hollow spheres was 229.2 mA h g−1 after 1000 cycles at 0.5C and the highest rate discharge capacity was 114.2 mA h g−1 at 10 C, thereby indicating the outstanding cycle stability and rate performance of LTO as an anode in lithium-ion batteries.

In-situ constructing of mesoporous Li4Ti5O12@rGO hybrid spheres as anode materials for lithium-ion batteries

The Li4Ti5O12@rGO (LTO@rGO) mesoporous hybrid spheres have been successfully synthesized by an in-situ conversion route in aqueous LiOH solution using TiO2 spheres as precursor, which was followed by annealing process in Ar atmosphere. The LTO@rGO composites possess a uniform mesoporous spherical structure with diameter of approximately 800 nm, which are assembled by many interconnected nanoparticles with a thin rGO conductive coating. Benefiting from the synergistic effects of the unique nanostructure hybrids, it is proved that the porous can offer large surface area which has high intrinsic interfacial reactivity with the electrolyte, extra space for the storage of Li+, and short transport distances for both e− and Li+. Meanwhile, the rGO coating could enhance effectively the interfacial contact between particles and create a three-dimensional conductive network to greatly facilitate fast transport of e− and Li+, which can improve the rate capacity. Compared with pure LTO, the as-prepared LTO@rGO mesoporous hybrid spheres deliver a higher reversible capacity of 260.1 mAh g−1 at 0.5 C after 500 cycles with highly stable capacity retention of even more than 100%, and the high rate discharge capacity reach 125.9 mAh g−1 at 10 C. Therefore, the LTO@rGO composites display superior high-rate property and ultralong cycling stability, which can provide a potential anode material for LIBs.

Streptozotocin-Induced Diabetes Mellitus – a Paradox of High Intrinsic Platelet Reactivity and Low In Vitro Platelet Aggregation

Studies of platelet function in diabetics are inconsistent, some studies reporting higher platelet reactivity, while others showed no change. We aimed to evaluate platelet indices and in vitro platelet aggregation in rats with long-lasting (28 weeks) diabetes mellitus. Twelve controls and 14 diabetic rats were investigated. Diabetes was induced in 11-week-old rats using streptozotocin (60 mg/kg,i.p.). Platelet indices and in vitro adenosine diphosphate (ADP)-, protease-activated receptor 4 (PAR4) agonist-, and arachidonic acid (AA)-induced platelet aggregation were assessed at the age of 38 weeks. Compared to controls, diabetic rats presented lower platelet count and plateletcrit (both p≤0.001), and higher mean platelet volume (p<0.01). ADP- (p=0.04) and AA-induced (p<0.01) platelet aggregation were lower in diabetic compared with control rats, whereas PAR4 agonist-induced platelet aggregation was similar between the two groups (p=1.00). This study demonstrates a paradox of high intrinsic platelet reactivity and low in vitro ADP- and AA-induced platelet aggregation in diabetic rats compared with non-diabetic controls. The relevance of in vitro platelet aggregation to the contribution of platelets to in vivo thromboembolic events in diabetic rats remains questionable.

Water Dissociation and Hydroxyl Ordering on Anatase TiO_{2}(001)-(1×4).

We studied the interaction of water with the anatase TiO_{2}(001) surface by means of scanning tunneling microscopy, x-ray photoelectron spectroscopy, and density functional theory calculations. Water adsorbs dissociatively on the ridges of a (1×4) reconstructed surface, resulting in a (3×4) periodic structure of hydroxyl pairs. We observed this process at 120K, and the created hydroxyls desorb from the surface by recombination to water, which occurs below 300K. Our calculations reveal the water dissociation mechanism and uncover a very pronounced dependence on the coverage. This strong coverage dependence is explained through water-induced reconstruction on anatase TiO_{2}(001)-(1×4). The high intrinsic reactivity of the anatase TiO_{2}(001) surface towards water observed here is fundamentally different from that seen on other surfaces of titania and may explain its high catalytic activity in heterogeneous catalysis and photocatalysis.