Transient Zwitterions Dynamics Empowered Adaptive Interface for Ultra-Stable Zn Plating/Stripping.

A highly reversible zinc anode is crucial for the commercialization of zinc-ion batteries. However, the change in the microstructure of the electric double layer originated from the dynamic change in charge density on the electrode greatly impacts anode reversibility during charge/discharge, which is rarely considered in previous research. Herein, the zwitterion additive is employed to create an adaptive interface by coupling the transient zwitterion dynamics upon the change of interfacial charge density. Ab initio molecular dynamics simulations suggest the molecular orientation and adsorption groups of zwitterions will be determined by the charging state of the electrode. ZnSO4 electrolyte with zwitterion fulfills a highly reversible Zn anode with an average Coulombic efficiency of up to 99.85%. Zn/Zn symmetric cells achieve greatly enhanced cycling stability for 700 h with extremely small voltage hysteresis of 29 mV under 5 mA cm-2 with 5 mAh cm-2 . This study validates the adaptive interface based on transient dynamics of zwitterions, which sheds new light on developing highly reversible metal anodes with a high utilization rate.

Se-p Orbitals Induced "Strong d-d Orbitals Interaction" Enable High Reversibility of Se-Rich ZnSe/MnSe@C Electrode as Excellent Host for Sodium-Ion Storage.

The heterostructure of transition-metal chalcogenides is a promising approach to boost alkali ion storage due to fast charge kinetics and reduction of activation energy. However, cycling performance is a paramount challenge that is suffering from poor reversibility. Herein, it is reported that Se-rich particles can chemically interact with local hexagonal ZnSe/MnSe@C heterostructure environment, leading to effective ions insertion/extraction, enabling high reversibility. Enlightened by theoretical understanding, Se-rich particles endow high intrinsic conductivities in term of low energy barriers (1.32 eV) compared with those without Se-rich particles (1.50 eV) toward the sodiation process. Moreover, p orbitals of Se-rich particles may actively participate and further increase the electronegativity that pushes the Mn d orbitals (dxy and dx2-y2) and donate their electrons to dxz and dyz orbitals, manifesting strong d-d orbitals interaction between ZnSe and MnSe. Such fundamental interaction will adopt a well-stable conducive electronic bridge, eventually, charges are easily transferred from ZnSe to MnSe in the heterostructure during sodiation/desodiation. Therefore, the optimized Se-rich ZnSe/MnSe@C electrode delivered high capacity of 576 mAh g-1 at 0.1 A g-1 after 100 cycles and 384 mAh g-1 at 1 A g-1 after 2500 cycles, respectively. In situ and ex situ measurements further indicate the integrity and reversibility of the electrode materials upon charging/discharging.

Ionic Hydrogen Bond-Assisted Catalytic Construction of Nitrogen Stereogenic Center via Formal Desymmetrization of Remote Diols.

The control of noncarbon stereogenic centers is of profound importance owing to their enormous interest in bioactive compounds and chiral catalyst or ligand design for enantioselective synthesis. Despite various elegant approaches have been achieved for construction of S-, P-, Si- and B-stereocenters over the past decades, the catalyst-controlled strategies to govern the formation of N-stereogenic compounds have garnered less attention. Here, we disclose the first organocatalytic approach for efficient access to a wide range of nitrogen-stereogenic compounds through a desymmetrization approach. Intriguingly, the pro-chiral remote diols, which are previously not well addressed with enantiocontrol, are well differentiated by potent chiral carbene-bound acyl azolium intermediates. Preliminary studies shed insights on the critical importance of the ionic hydrogen bond (IHB) formed between the dimer aggregate of diols to afford the chiral N-oxide products that feature a tetrahedral nitrogen as the sole stereogenic element with good yields and excellent enantioselectivities. Notably, the chiral N-oxide products could offer an attractive strategy for chiral ligand design and discovery of potential antibacterial agrochemicals.

Exploring Molecular Complexity by N-Heterocyclic Carbene Organocatalysis: New Activation and Reaction Diversity.

The development of catalytic synthetic approaches towards molecular complexity from simple materials continues to be an ultimate goal in synthetic chemistry. Over the past decades, N-heterocyclic carbene (NHC) organocatalysis has been extensively investigated to provide opportunities for a vast number of novel chemical transformations. Various activation modes and reactive intermediates enabled by NHC small-molecule catalysts, such as Breslow intermediates, (homo)enolates, acyl azoliums and their derived unsaturated azoliums exhibit great potential in the construction of complicated skeletons. This personal account will summarize our group's recent work in the exploration of new activation modes of NHC catalysis towards molecular complexity with a focus on the development and applications of NHC to achieve diversity and enantioselectivity in the preparation of functional molecules.

Organocatalytic C-H Functionalization of Simple Alkanes.

The direct functionalization of inert C(sp3 )-H bonds to form carbon-carbon and carbon-heteroatom bonds offers vast potential for chemical synthesis and therefore receives increasing attention. At present, most successes come from strategies using metal catalysts/reagents or photo/electrochemical processes. The use of organocatalysis for this purpose remains scarce, especially when dealing with challenging C-H bonds such as those from simple alkanes. Here we disclose the first organocatalytic direct functionalization/acylation of inert C(sp3 )-H bonds of completely unfunctionalized alkanes. Our approach involves N-heterocyclic carbene catalyst-mediated carbonyl radical intermediate generation and coupling with simple alkanes (through the corresponding alkyl radical intermediates generated via a hydrogen atom transfer process). Unreactive C-H bonds are widely present in fossil fuel feedstocks, commercially important organic polymers, and complex molecules such as natural products. Our present study shall inspire a new avenue for quick functionalization of these molecules under the light- and metal-free catalytic conditions.

Carbene-Catalyzed Intermolecular Dehydrogenative Coupling of Aldehydes with C(sp3 )-H Bonds.

The development of catalyst-controlled methods for direct functionalization of two distinct C-H bonds represents an appealing approach for C-C formations in synthetic chemistry. Herein, we describe an organocatalytic approach for straightforward acylation of C(sp3 )-H bonds employing readily available aldehyde as "acyl source" involving dehydrogenative coupling of aldehydes with ether, amine, or benzylic C(sp3 )-H bonds. The developed method affords a broad range of ketones under mild conditions. Mechanistically, simple ortho-cyanoiodobenzene is essential in the oxidative radical N-heterocyclic carbene catalysis to give a ketyl radical and C(sp3 ) radical through a rarely explored intermolecular hydrogen atom transfer pathway, rendering the acylative C-C formations in high efficiency under a metal- and light-free catalytic conditions. Moreover, the prepared products show promising anti-bacterial activities that shall encourage further investigations on novel agrochemical development.

Stereoselective Synthesis of Atropisomeric Acridinium Salts by the Catalyst-Controlled Cyclization of ortho-Quinone Methide Iminiums.

Quinone methides are fundamental intermediates for a wide range of reactions in which catalyst stereocontrol is often achieved by hydrogen bonding. Herein, we describe the feasibility of an intramolecular Friedel-Crafts 6π electrocyclization through ortho-quinone methide iminiums stereocontrolled by a contact ion pair. A disulfonimide catalyst activates racemic trichloroacetimidate substrates and imparts stereocontrol in the cyclization step, providing a new avenue for selective ortho-quinone methide iminium functionalization. A highly stereospecific oxidation readily transforms the enantioenriched acridanes into rotationally restricted acridiniums. Upon ion exchange, the method selectively affords atropisomeric acridinium tetrafluoroborate salts in high yields and an enantioenrichment of up to 93 : 7 e.r. We envision that ion-pairing catalysis over ortho-quinone methide iminiums enables the selective synthesis of a diversity of heterocycles and aniline derivatives with distinct stereogenic units.

Gold and Carbene Relay Catalytic Enantioselective Cycloisomerization/Cyclization Reactions of Ynamides and Enals.

The combined use of gold as transition metal catalyst and N-heterocyclic carbene (NHC) as organic catalyst in the same solution for relay catalytic reactions was disclosed. The ynamide substrate was activated by gold catalyst to form unsaturated ketimine intermediate that subsequently reacted with the enals (via azolium enolate intermediate generated with NHC) effectively to form bicyclic lactam products with excellent diastereo- and enantio-selectivities. The gold and NHC coordination and dissociation can be dynamic and tunable events, and thus allow the co-existence of both active metal and carbene organic catalysts in appreciable concentrations, for the dual catalytic reaction to proceed.

A-44G transition in SMN2 intron 6 protects patients with spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by reduced expression of survival of motor neuron (SMN), a protein expressed in humans by two paralogous genes, SMN1 and SMN2. These genes are nearly identical, except for 10 single-nucleotide differences and a 5-nucleotide insertion in SMN2. SMA is subdivided into four main types, with type I being the most severe. SMN2 copy number is a key positive modifier of the disease, but it is not always inversely correlated with clinical severity. We previously reported the c.859G > C variant in SMN2 exon 7 as a positive modifier in several patients. We have now identified A-44G as an additional positive disease modifier, present in a group of patients carrying 3 SMN2 copies but displaying milder clinical phenotypes than other patients with the same SMN2 copy number. One of the three SMN2 copies appears to have been converted from SMN1, but except for the C6T transition, no other changes were detected. Analyzed with minigenes, SMN1C6T displayed a ∼20% increase in exon 7 inclusion, compared to SMN2. Through systematic mutagenesis, we found that the improvement in exon 7 splicing is mainly attributable to the A-44G transition in intron 6. Using RNA-affinity chromatography and mass spectrometry, we further uncovered binding of the RNA-binding protein HuR to the -44 region, where it acts as a splicing repressor. The A-44G change markedly decreases the binding affinity of HuR, resulting in a moderate increase in exon 7 inclusion.

Preparation of reduced graphite oxide loaded with cobalt(II) and nitrogen co-doped carbon polyhedrons from a metal-organic framework (type ZIF-67), and its application to electrochemical determination of metronidazole.

The integration of derivatives of granular metal-organic frameworks (MOFs) and an electrically conductive carbon substrate is an effective way to circumvent the deficiency of powdered pristine MOFs or MOF-derived carbon in practical application. The authors describe the use of graphite oxide (GO) as a substrate for in-situ assembly with the zeolitic imidazole framework ZIF-67. The GO and ZIF-67 composites were converted, via pyrolysis, into reduced graphite oxide loaded with Co/N-co-doped carbon polyhedrons (ZIF-67C@rGO). By using various amounts of GO, a series of ZIF-67C@rGO-x with different fractions of GO were synthesized and utilized as electrode modifiers for the detection of the antibiotic metronidazole (MNZ). The results revealed that the ZIF-67C@rGO-0.06 display best sensing performance. This is likely to be due to its hierarchically open pores, abundant active sites and good electrical conductivity. The sensor, best operated near a working potential around -0.6 V (vs. SCE), has a linear response in the 0.5 to 1000 µM MNZ concentration range and a 0.05 µM detection limit. The sensor was applied to the analysis of pharmaceutical samples where it showed excellent selectivity, good repeatability and satisfying recoveries. Graphical abstract Schematic representation of preparation and application of ZIF-67C@rGO-x.

Sulfinate and Carbene Co-catalyzed Rauhut-Currier Reaction for Enantioselective Access to Azepino[1,2-a]indoles.

A carbene and sulfinate co-catalyzed intermolecular Rauhut-Currier reaction between enals and nitrovinyl indoles is disclosed. The carbene catalyst activates the enal and the sulfinate co-catalyst activates the nitrovinyl indole. Both activation processes are realized via the formation of covalent bonds between the catalysts and substrates to generate catalyst-bound intermediates. The dual catalytic reaction affords azepino[1,2-a]indole products with excellent stereoselectivity. Our study demonstrates the unique involvement of sulfinate as an effective nucleophilic catalyst in activating electron-deficient alkenes for asymmetric reactions. This dual catalytic approach should also encourage future explorations of both sulfinate and carbene catalysts for new reactions.

Highly Selective and Sensitive Colorimetric and Fluorescent Chemosensor for Rapid Detection of Ag+, Cu2+ and Hg2+ Based on a Simple Schiff Base.

A new reversible colorimetric and fluorescent chemosensor MMIP based on a simple Schiff base has been successfully synthesized. MMIP exhibited high selectivity and sensitivity towards Ag+, Cu2+ and Hg2+ ions with a short response time in DMSO/H2O (1/1, v/v) solution among various metal ions, and the results could be monitored directly by naked eyes. The binding stoichiometry between MMIP and Ag+/Hg2+/Cu2+ has been determined to be 1:2 by Job's plot and FT-IR analysis. MMIP could effectively detect Ag+, Cu2+ and Hg2+ over a wide pH range of 3-10. The good linear correlations were obtained in the concentration ranges of 0-20 µM for Ag+, Cu2+ and Hg2+. Thus sensor MMIP could be potentially used for the quantification of Ag+, Cu2+ and Hg2+ in aqueous solution.

Construction of Fused Pyrrolidines and ß-Lactones by Carbene-Catalyzed C-N, C-C, and C-O Bond Formations.

A carbene-catalyzed intermolecular C-N bond formation, which initiates a highly selective cascade reaction for the synthesis of pyrrolidine fused ß-lactones, is disclosed. The nitrogen-containing bicyclic ß-lactone products are obtained with good yields and excellent stereoselectivities. Synthetic transformations of the reaction products into useful functional molecules, such as amino catalysts, can be efficiently realized under mild reaction conditions. Mechanistically, this study provides insights into modulating the reactivities of heteroatoms, such as nitrogen atoms, in challenging carbene-catalyzed asymmetric carbon-heteroatom bond-forming reactions.

Polyhalides as Efficient and Mild Oxidants for Oxidative Carbene Organocatalysis by Radical Processes.

Simple and inexpensive polyhalides (CCl4 and C2 Cl6 ) have been found to be effective and versatile oxidants in removing electrons from Breslow intermediates under N-heterocyclic carbene (NHC) catalysis. This oxidative reaction involves multiple single-electron-transfer (SET) processes and several radical intermediates. The α, ß, and γ-carbon atoms of aldehydes and enals could be readily functionalized. Given the low cost of the oxidants and the broad applicability of the reactions, this study is expected to greatly enhance the feasibility of oxidative NHC catalysis for large-scale applications. Also this new SET radical process with polyhalides as single-electron oxidants will open a new avenue in the development of NHC-catalyzed radical reactions.

A Phenylamine-Oligothiophene-Based Fluorescent Chemosensor for Selective Detection of Hg(II).

A phenylamine-oligothiophene-based fluorescent chemosensor I3TEA was reported. This sensor exhibited highly selective and fast detection of Hg(2+) ion in MeCN/H2O (8/2, v/v) solution through fluorescence quenching. The detection was unaffected by the other competitive metal cations. The low detection limit was found to be 5.92 × 10(-7) M. In addition, the recognition process is reversible and confirmed by EDTA experiment.

Sinomenine hydrochloride-loaded dissolving microneedles enhanced its absorption in rabbits.

Sinomenine hydrochloride-loaded dissolving microneedles (SH-DM) were fabricated by maltose and poly-lactic-co-glycolic acid using a casting method. The mechanical strength of SH-DM was investigated by an insertion test. In vivo transdermal absorption experiment was performed to evaluate the percutaneous absorption of SH-DM, sinomenine hydrochloride gel (SH-G) was used as a control. The results demonstrated that prepared SH-DM was morphologically intact with sufficient mechanical strength after inserting into aluminum foil and rat skin. The value of area under curve obtained after administration of SH-DM through transdermal in rabbits showed a significantly rise and was 1.99 times higher than that of SH-G, and the relative bioavailability value was 199.21%. These results showed that SH-DM enhanced bioavailability and permeability of SH.

Enantioselective Nucleophilic ß-Carbon-Atom Amination of Enals: Carbene-Catalyzed Formal [3+2] Reactions.

An enantioselective ß-carbon amination for enals is disclosed. The nitrogen atom from a protected hydrazine with suitable electronic properties readily behaves as a nucleophile. Addition of the nitrogen nucleophile to a catalytically generated N-heterocyclic-carbene-bound α,ß-unsaturated acyl azolium intermediate constructs a new carbon-nitrogen bond asymmetrically. The pyrazolidinone products from our catalytic reactions are common scaffolds in bioactive molecules, and can be easily transformed into useful compounds such as ß(3) -amino-acid derivatives.

N-heterocyclic carbene-catalyzed radical reactions for highly enantioselective ß-hydroxylation of enals.

An N-heterocyclic carbene-catalyzed ß-hydroxylation of enals is developed. The reaction goes through a pathway involving multiple radical intermediates, as supported by experimental observations. This oxidative single-electron-transfer reaction allows for highly enantioselective access to ß-hydroxyl esters that are widely found in natural products and bioactive molecules.

A Fast-Responsive Fluorescent Sensor for Hg(2+) with High Selectivity and Sensitivity in Aqueous Media.

A fast-responsive fluorescent phenylamine-oligothiophene sensor 2TBDA was reported. This sensor exhibited highly selective and sensitive detection of Hg(2+) ion in THF/H2O (7/3, v/v) solution through fluorescence quenching. The detection was not affected by the coexistence of other competitive metal ions. In addition, the detection limit was found to be as low as 3.841 × 10(-7) M.

Phytantriol-based in situ liquid crystals with long-term release for intra-articular administration.

The purpose of this study was to develop an injectable in situ liquid crystal formulation for intra-articular (IA) administration, and in situ forming a viscous liquid crystalline gel with long-term release of sinomenine hydrochloride (SMH) upon water absorption. The pseudo-ternary phase diagram of phytantriol (PT)-ethanol (ET)-water was constructed, and isotropic solutions were chosen for further optimization. The physicochemical properties of isotropic solutions were evaluated, and the phase structures of liquid crystalline gels formed by isotropic solutions in excess water were confirmed by crossed polarized light microscopy (CPLM) and small-angle X-ray scattering (SAXS). In vitro drug release studies were conducted by using a dialysis membrane diffusion method. The optimal in situ cubic liquid crystal (ISV2) (PT/ET/water, 64:16:20, w/w/w) loaded with 6 mg/g of SMH showed a suitable pH, showed to be injectable, and formed a cubic liquid crystalline gel in situ with minimum water absorption within the shortest time. The optimal ISV2 was able to sustain the drug release for 6 days. An in situ hexagonal liquid crystal (ISH2) system was prepared by addition of 5% vitamin E acetate (VitEA) into PT in the optimal ISV2 system to improve the sustained release of SMH. This ISH2 (PT/VitEA/ET/water, 60.8:3.2:16:20, w/w/w/w) was an injectable isotropic solution with a suitable pH range. The developed ISH2 was found to be able to sustain the drug release for more than 10 days and was suitable for IA injection for the treatment of rheumatoid arthritis (RA).