Regulating Spin Density using TEMPOL Molecules for Enhanced CO2-to-Ethylene Conversion by HKUST-1 Framework Derived Electrocatalysts.

The selectivity of multicarbon products in the CO2 reduction reaction (CO2RR) depends on the spin alignment of neighboring active sites, which requires a spin catalyst that facilitates electron transfer with antiparallel spins for enhanced C-C coupling. Here, we design a radical-contained spin catalyst (TEMPOL@HKUST-1) to enhance CO2-to-ethylene conversion, in which spin-disordered (SDO) and spin-ordered (SO) phases co-exist to construct an asymmetric spin configuration of neighboring active sites. The replacement of axially coordinated H2O molecules with TEMPOL radicals introduces spin-spin interactions among the Cu(II) centers to form localized SO phases within the original H2O-mediated SDO phases. Therefore, TEMPOL@HKUST-1 derived catalyst exhibited an approximately two-fold enhancement in ethylene selectivity during the CO2RR at -1.8 V versus Ag/AgCl compared to pristine HKUST-1. In situ ATR-SEIRAS spectra indicate that the spin configuration at asymmetric SO/SDO sites significantly reduces the kinetic barrier for *CO intermediate dimerization toward the ethylene product. The performance of the spin catalyst is further improved by spin alignment under a magnetic field, resulting in a maximum ethylene selectivity of more than 50%. The exploration of the spin-polarized kinetics of the CO2RR provides a promising path for the development of novel spin electrocatalysts with superior performance.

Chiral Bis-phosphate Macrocycles for Catalytic, Efficient, and Enantioselective Electrophilic Fluorination.

Incorporation of privileged catalytic scaffolds into a macrocyclic skeleton represents an attractive strategy to furnish supramolecular catalysis systems with enzyme-mimetic cavity and multi-site cooperation. Herein we reported the synthesis, structure, binding properties and catalytic application of a series of chiral bis-phosphate macrocycles toward the challenging asymmetric electrophilic fluorination. With a large, integrated chiral cavity and two cooperative phosphate sites, these macrocycles exhibited good inclusion toward 1,4-diazabicyclo[2.2.2]octane (DABCO) dicationic ammoniums through complementary ion-pair and C-H⋅⋅⋅O interactions, as confirmed by crystallographic and solution binding studies. In fluorocyclization of tryptamines with Selectfluor reagent which has a similar DABCO-based dicationic structure, only 2 mol% macrocycle catalyst afforded the desired pyrroloindoline products in moderate yields and up to 91 % ee. For comparison, the acyclic mono-phosphate analogue gave obviously lower reactivity and enantioselectivity (<20 % ee), suggesting a remarkable macrocyclic effect. The high catalytic efficiency and superior stereocontrol were ascribed to the tight ion-pair binding and cavity-directed noncovalent interaction cooperation.

Mimicking the Shape and Function of the ClC Chloride Channel Selective Pore by Combining a Molecular Hourglass Shape with Anion-π Interactions.

ClC is the main family of natural chloride channel proteins that transport Cl- across the cell membrane with high selectivity. The chloride transport and selectivity are determined by the hourglass-shaped pore and the filter located in the central and narrow region of the pore. Artificial unimolecular channel that mimics both the shape and function of the ClC selective pore is attractive, because it could provide simple molecular model to probe the intriguing mechanism and structure-function relevance of ClC. Here we elaborated upon the concept of molecular hourglass plus anion-π interactions for this purpose. The concept was validated by experimental results of molecular hourglasses using shape-persistent 1,3-alternate tetraoxacalix[2]arene[2]triazine as the central macrocyclic skeleton to control the conductance and selectivity, and anion-π interactions as the driving force to facilitate the chloride dehydration and movement along the channel.

Chiral Benzene Triimide (BTI) Radical Anions for Probing the Interplay of Unpaired Electron Spin and Chirality.

Herein a series of chiral BTI radical anions bearing different chiral substituents were efficiently prepared by chemical reduction. X-ray crystallography revealed finely-tuned packing and helix assemblies of the radicals by the size of chiral substituents in crystalline state. In accordance with the crystalline-state packing, the powder ESR spectra indicate that 4 a- ⋅CoCp2 + and 4 c- ⋅CoCp2 + π-dimers exhibit thermally excited triplet states arising from strong spin-spin interactions, while discrete 4 b- ⋅CoCp2 + shows a broad doublet-state signal reflecting weak spin-spin interactions. The interplay between the unpaired electron spin and chiral substituents was studied by UV-Vis-NIR spectra, electronic circular dichroism (ECD) and TD DFT calculations. Different NIR absorptions of the radicals attributing to isolated SOMO→LUMO+1 (~889 nm) transitions were recorded. The emergence of Cotton effects (CEs) at the NIR region for 4 c- ⋅CoCp2 + radical enantiomers suggest the interplay between chirality and unpaired electron spin. The origin of the different circularly polarized light absorptions regarding SOMO derived transitions (around 880 nm) was attributed to chiral substitutes regulated electric and magnetic transition dipole moments of the unpaired electron participated transition.

Reversing the ion transport selectivity through arm modification of an artificial molecular hourglass.

An arm modification strategy, by replacing relatively rigid, electron-deficient side arms with flexible ether chain arms and linking them onto a tetraoxacalix[2]arene[2]triazine skeleton, was utilized to design an artificial molecular hourglass. The planar bilayer experiments confirmed the unimolecular channel mechanism and suggested reversed ion selectivity from the previously reported anion selectivity to weak cation selectivity.

Changes in the skin microbiome during male maturation from 0 to 25 years of age.

BACKGROUND: Skin microorganisms co-develop with the human body and age influences the skin microenvironment and thus the skin bacterial community. OBJECTIVES: To investigate the changes in the skin microbiota during male development. METHODS: High-throughput 16S ribosomal RNA pyrosequencing was utilized to analyze the differences in bacterial composition of the skin in healthy males aged 0-25 years. RESULTS: There were significant differences in facial skin bacterial diversity (Shannon index) and richness (Chao index) among the 4 groups of subjects (p < 0.05). Streptococcus, Staphylococcus, Cutibacterium are dominant in males during growth, and regular changes occur with age after birth. Further analysis of skin bacteria between the 4 groups showed that the bacterial abundance of Cutibacterium acnes and Staphylococcus epidermidis tended to increase with age, and the bacterial abundance of Streptococcus, Rothia mucilaginosa, and Staphylococcus hominis tended to decrease with age. CONCLUSIONS: There are some changes in cheek skin bacterial diversity during male development, and there is a relationship between skin bacterial changes and skin development processes.

Intermolecular n→π* Interactions in Supramolecular Chemistry and Catalysis.

The n→π* interactions describing attractive force between lone pairs (lps) of nucleophile and carbonyl or polarized unsaturated bonds have recently attracted growing attentions in various disciplines. So far, such non-covalent driving force are mainly concentrated to intramolecular systems. Intermolecular n→π* interactions in principle could produce fascinated supramolecular systems or facilitate organic reactions, however, they remain largely underexplored due to the very weak energy of individual interaction. This review attempts to give an overview of the challenging intermolecular n→π* interactions, much efforts emphasize the supramolecular systems, catalytic processes and spectroscopic measurements.

mmu-miRNA-342-3p promotes hepatic stellate cell activation and hepatic fibrosis induced by Echinococcus multilocularis infection via targeting Zbtb7a.

Liver fibrosis is one of the histopathological characters during Echinococcus multilocularis infection. The activation of hepatic stellate cells (HSCs) is a key event in the development of liver fibrosis. However, the molecular mechanism of HSC activation in the E. multilocularis infection-induced liver fibrosis remains largely unclear. Here, we reported that mmu-miR-342-3p was most dominantly expressed in HSCs and was upregulated in the HSCs in response to E. multilocularis infection. We further showed that mmu-miR-342-3p was able to bind to the 3' UTR of the Zbtb7a gene and regulated its expression. Moreover, mmu-miR-342-3p expression was negatively correlated with its target gene Zbtb7a in HSCs during E. multilocularis infection. Knockdown of mmu-miR-342-3p promoted the expression of Gfap in the activated HSCs in vitro. In the E. multilocularis-infected mice, knockdown of mmu-miR-342-3p suppressed the expression of α-Sma, Col1α1, and TGF-ß but promoted the expression of Gfap. Therefore, mmu-miR-342-3p is a key regulator for activation of HSCs, and inhibiting mmu-miR-342-3p to suppressed Zbtb7a-mediated TGF-ß signaling in activated HSCs could be a novel strategy to treat liver fibrosis induced by E. multilocularis.

An Artificial Single Molecular Channel Showing High Chloride Transport Selectivity and pH-Responsive Conductance.

Inspired by the unique structure and function of the natural chloride channel (ClC) selectivity filter, we present herein the design of a ClC-type single channel molecule. This channel displays high ion transport activity with half-maximal effective concentration, EC50 , of 0.10 µM, or 0.075 mol % (channel molecule to lipid ratio), as determined by fluorescent analysis using lucigenin-encapsulated vesicles. Planar bilayer lipid membrane conductance measurements indicated an excellent Cl- /K+ selectivity with a permeability ratio P Cl - ${{_{{\rm Cl}{^{- }}}}}$ /P K + ${{_{{\rm K}{^{+}}}}}$ up to 12.31, which is comparable with the chloride selectivity of natural ClC proteins. Moreover, high anion/anion selectivity (P Cl - ${{_{{\rm Cl}{^{- }}}}}$ /P Br - ${{_{{\rm Br}{^{- }}}}}$ =66.21) and pH-dependent conductance and ion selectivity of the channel molecule were revealed. The ClC-like transport behavior is contributed by the cooperation of hydrogen bonding and anion-π interactions in the central macrocyclic skeleton, and by the existence of pH-responsive terminal phenylalanine residues.

Intermolecular n→π* Interactions Based on a Tailored Multicarbonyl-Containing Macrocycle.

Towards unexplored intermolecular n→π* interactions, presented herein are the synthesis, structure, self-assembly and function of a multicarbonyl-containing macrocycle calix[2]arene[2]barbiturate 1. X-ray single crystal diffraction reveals the presence of Cl⋅⋅⋅C=O interactions in CH2 Cl2 ⊂1 host-guest complex and multiple intermolecular C=O⋅⋅⋅C=O interactions between molecules 1 in crystalline state. The intermolecular C=O⋅⋅⋅C=O interactions as attractive driving force led to unprecedented self-assembly of nanotube with diameter around 1.4 nm and inner surface engineered by aromatic rings. SEM and TEM images of the self-assembly of 1 demonstrated temperature-dependent morphologies which allows the observation of spheres at 25 °C and rods at 0 °C, respectively. XRD analysis indicated consistent hexagonal patterns in the self-assembly and single crystal lattice, indicating the nanotubes driven by C=O⋅⋅⋅C=O interactions constitute the basic structural architectures of both aggregates. The nanoscopic tubes (pores) formed in the rodlike single crystal engendering the separation of moving dyes were preliminarily investigated by a single-crystal chromatography and crystal-packed column chromatography.

Xenon Induces Its Own Preferred Heterochiral Host from Exclusive Homochiral Assembly.

Xenon binding represents a formidable challenge, and efficient hosts remain rare. Here we report our findings that while enantiomeric bis(urea)-bis(thiourea) macrocycles form exclusive homochiral dimeric assemblies, xenon is able to overcome the narcissism and induces an otherwise-nonobservable heterochiral assembly as its preferred host. An experimental approach and fitting model were developed to obtain binding constants associated with the invisible assembly species. The determined xenon binding affinity with the heterochiral capsule reaches 1600 M-1, which is 15 times higher than that with the homochiral capsule and represents the highest record for an assembled host. The origin of the large difference in xenon affinity between the two subtle diastereotopic assemblies was revealed by single-crystal analysis. In the heterochiral capsule with S4 symmetry, the xenon atom is more tightly enclosed by van der Waals surroundings of the four thiourea groups arranged in a spherical cross-array, superior to the antiparallel array in the homochiral capsule with D2 symmetry.

Inherently Chiral Cages via Hierarchical Desymmetrization.

A new type of cage inherent chirality was accessed by hierarchical desymmetrization of a D3h-symmetric prismlike cage motif. The dissymmetric C3v cage precursor C1 bearing two different phloroglucinol caps was first synthesized. The subsequent progressive substitutions on the three triazine arms by different nucleophiles furnished the desired C1-symmetric inherently chiral cages C3 and C4 with rich structural diversity. Resolution of the racemic cages was achieved by chiral chromatography, and the enantiopure cages were readily obtained on the gram scale. Convenient post-synthetic transformations of the chiral cages with retention of enantiomeric purity were also realized. The absolute configuration was determined by X-ray crystallography, and a chirality descriptor was provided to define the cage chirality. With the inherently chiral array of the electron-deficient triazine surfaces constituting three individual chiral V-shaped π cavities, regio- and enantioselective anion-π binding was probed for the first time with minimum interference of other interactions. As exemplified with chiral phosphate anions (CPAs), it was found that cage (-)-C3a preferably binds (S)-CPA- in the most electron-deficient cavity through synergistic anion-π interactions with considerable chiral selectivity.

Thiazole Boron Difluoride Dyes with Large Stokes Shift, Solid State Emission and Room-Temperature Phosphorescence.

The small Stokes shift and weak emission in the solid state are two main shortcomings associated with the boron-dipyrromethene (BODIPY) family of dyes. This study presents the design, synthesis and luminescent properties of boron difluoro complexes of 2-aryl-5-alkylamino-4-alkylaminocarbonylthiazoles. These dyes display Stokes shifts (Δλ, 77-101 nm) with quantum yields (ϕFL ) up to 64.9 and 34.7 % in toluene solution and in solid state, respectively. Some of these compounds exhibit dual fluorescence and room-temperature phosphorescence (RTP) emission properties with modulable phosphorescence quantum yields (ϕPL ) and lifetime (τp up to 251 µs). The presence of intramolecular H-bonds and negligible π-π stacking revealed by X-ray crystal structure might account for the observed large Stokes shift and significant solid-state emission of these fluorophores, while the enhanced spin-orbit coupling (SOC) of iodine and the self-assembly driven by halogen bonding, π-π and C-H… π interactions could be responsible for the observed RTP of iodine containing phosphors.

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions.

A series of tetraamino-bisthiourea chiral macrocycles containing two diarylthiourea and two chiral diamine units were synthesized by a fragment-coupling approach in high yields. Different chiral diamine units, including cyclohexanediamines and diphenylethanediamines were readily incorporated by both homo and hetero [1 + 1] macrocyclic condensation of bisamine and bisisothiocyanate fragments. With the easy synthesis, gram-scale of macrocycle products can be readily obtained. These chiral macrocycles were applied in catalyzing bioinspired decarboxylative Mannich reactions. Only 5 mol % of the optimal macrocycle catalyst efficiently catalyzed the decarboxylative addition of a broad scope of malonic acid half thioesters to isatin-derived ketimines with excellent yields and good enantioselectivity. The rigid macrocyclic framework and the cooperation between the thiourea and tertiary amine sites were found to be crucial for achieving efficient activation and stereocontrol. As shown in control experiments, catalysis with the acyclic analogues having the same structural motifs were non-selective.

Chirality Gearing in an Achiral Cage through Adaptive Binding.

Herein we report an adaptive, achiral trithiourea molecular cage and its conformational and stereodynamics toward tricarboxylate anion binding. The cage was readily synthesized in four steps with a 44% yield for the irreversible cage-forming reaction. It possesses a flexible conformation and strongly binds 1,3,5-benzene tricarboxylate by forming a sandwich-like inclusion complex, with an affinity up to 106 M-1 in acetonitrile. Upon binding, the cage is locked in a twisted helical conformation. By incorporation of three chiral arms on the guest, a gear-like complex dominant in one given helical sense was produced. Due to the steric crowding in the helical grooves, a small change of methyl to ethyl on guest caused a striking difference on binding and chiral induction. The system thus represents a rare example of chiral induction on a flexible, achiral host and provides a decoupled model that the generation of a racemate and following chiral discrimination can be individually probed.

Triazine- and Binaphthol-Based Chiral Macrocycles and Cages: Synthesis, Structure, and Solid-State Assembly.

A series of triazine- and binaphthol-based homochiral and heterochiral macrocycles and cages were easily synthesized. Either fragment coupling or a one-pot approach afforded the desired products in 52-91% yields on a multigram scale as enantiopure forms. As disclosed by the crystal structures, these macrocycles and cages possess intriguing chiral cavities and assembly properties. In particular, (S,S,S)-Cage features a D3-symmetric double-faced propeller-like structure with three chiral pockets at the side. It forms a highly ordered hexagonal column-like assembly and multiple distinct helical channels in its crystal.

Putting Anion-π Interactions at Work for Catalysis.

Since its discovery two decades ago, anion-π interaction has been increasingly recognized as an important driving force. Extensive theoretical and experimental efforts on the ground-state anion-π binding and recognition have laid the bases for exploring its relevance in catalysis. Accordingly, the concept of "anion-π catalysis" that employing an electron-deficient π surface (π-acidic surface) for anionic reaction intermediate and transition state stabilization has emerged. This article shortly reviews the emergence and development of this concept, aiming to provide an emphasis on the general concept and key progress in this exciting area. To highlight the essential contribution of anion-π interactions, the contents are organized according to their role engaged in catalytic process, for example from both ground-state and transition-state stabilization to solely transition-state stabilization, mainly by a single π-face, and to cooperative π-face activation. A concluding remark and outlook on future development of this field is also given.

Cation-chloride cotransport mediated by an ion pair transporter.

Ion transport mediated by an ion pair receptor 1 bearing both cation and anion binding sites is presented. The ion pair binding property was revealed by means of 1H NMR titrations in organic solutions and X-ray analysis in the solid state. Single crystal structures demonstrated that 1 and CaI2 formed a solvent-separated ion-pair complex with two iodides each interacting with a triazine ring through anion-π interactions, whereas the calcium ion is bound by a pentaethylene glycol moiety. The ion transport activity was studied by monitoring the efflux of ions from salt-loaded EYPC large unilamellar vesicles (EYPC-LUVs) using ion selective electrodes. Chloride transport across the membrane mediated by the ion pair receptor through K+/Cl- or Na+/Cl- cotransport with a selectivity towards the K+/Cl- symport was realized.

π-Face Promoted Catalysis in Water: From Electron-deficient Molecular Cages to Single Aromatic Slides.

Exploiting noncovalent π-interactions particularly emerging anion-π interactions to drive efficient catalysis is fascinating. Even with exciting progresses, can anion-π activation operate in water remains elusive. Here we report the design, synthesis and catalytic studies of a class of water-soluble electron-deficient molecular cages and relevant aromatic slide compounds. The prism-like cages contain three divided, long, cationic aromatic walls which constitute three highly electron-deficient V-shape cavities. They were efficiently synthesized in two steps from a parent triformyl cage in gram-scale. Crystal structure showed the π-walls bind to the counter bromide through strong anion-π interactions. Just 5 mol% of cages were effective in catalyzing decarboxylative Aldol reactions of aldehydes and malonic acid half thioesters in water but not in organic solvents, showing a pronounced hydrophobic amplification effect. Meantime, a series of single π-slides resembling the π-wall of the cage performed equally well, while those lacking an extended π-surface were ineffective, highlighting the essential role of electron-deficient π-face on promoting the conversion.

Exploiting Anion-π Interactions for Efficient and Selective Catalysis with Chiral Molecular Cages.

Exploiting anion-π interactions in catalyst design is a fascinating direction to develop new and fundamental catalysis. For the appealing yet flexible π-face activation, can two or more π-acidic surfaces be manipulated for cooperative activation to achieve efficient transformation and particularly selectivity control is highly desirable. Here, we demonstrate a supramolecular π-catalysis strategy by establishing cooperative π-face activation in a confined electron-deficient cage cavity. The catalysts have a triazine based prism-like cage core and pendant chiral base sites. Only 2 mol % of cage catalyst efficiently catalyzed the decarboxylate Mannich reactions of sulfamate-headed cyclic aldimines and a series of malonic acid half thioesters in nearly quantitative yields and up to 97 % ee, enabling an unprecedent organocatalytic approach. The supramolecular π-cavity is essential in harnessing cooperative anion-π interactions for the efficient activation and excellent selectivity control.