Integrated analysis identified the role of three family members of ARHGAP in pancreatic adenocarcinoma.

The Rho GTPase activating protein family (ARHGAPs) is expressed in pancreatic adenocarcinoma (PAAD) but its function is unclear. The aim of this study was to explore the role and potential clinical value of ARHGAPs in PAAD. Using TCGA and GEO databases to analyze expression of ARHGAPs in PAAD and normal tissues. Survival curve was drawn by Kaplan-Meier. ARHGAPs were integrated analyzed by GEPIA2, TIMER, UCLCAN, cBioPortal and R language. Protein level and prognostic value were evaluated via IHC staining or survival analysis. We totally identify 18 differentially expressed (DE) ARHGAPs in PAAD. Among the 18 DE genes, 8 were positively correlated with tumor grade; abnorrmal expression of 5 was positively correlated with copy number variation; expression of 4 was positively correlated with promoter hypomethylation. Multivariate Cox regression identified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors of PAAD. The function of ARHGAPs was mainly related to GTPase activity and signaling, axon guidance, proteoglycans in cancer and focal adhesion. Expression of 7 ARHGAPs was strongly correlated with immune infiltration. Immunohistochemistry showed increased protein levels of ARHGAP5, ARHGAP11A, and ARHGAP12 in PAAD tissues. Survival analysis confirmed a negative correlation between ARHGAP5, ARHGAP11A, and ARHGAP12 expression and patient prognosis. Multivariate Cox regression proved ARHGAP5, ARHGAP11A, and ARHGAP12 could serve as independent prognostic indicators for PAAD. Finally, this study verified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors in PAAD, suggesting their significance for the diagnosis and treatment of PAAD.

Transmembrane Transporter Constructed from PlatinumMetal-organic Cage.

A perylene diimide-based metal-organic cage (MOC4c) was found to be an efficient transmembrane transporter for ions and small molecules through the internal cavity of the cage. MOC4c could selectively transport different anions, as evidenced by vesicle-based fluorescenceassays and planar lipid bilayer-based current recordings.Furthermore, MOC4c appears tofacilitate calcein transport across the lipid bilayer membrane of a livingcell, suggesting that MOC4c could be used as a biologicaltool for small molecule drugstransmembrane transportation.

Dihydrophenazine-derived oligomers from industrial waste as sustainable superior cathode materials for rechargeable lithium-ion batteries.

Organic materials with the 5,10-dihydrophenazine motif are superior cathode materials for lithium-ion batteries. However, the difficult accessibility and low capacity of such cathodes materials are obstacles to their practical applications. Herein, two novel oligomers, termed poly(5-methyl-10-(2-methacryloxypropyl)-5,10-dihydrophenazine) (PMPPZ) and poly(5-methyl-10-(2-methacryloxyethyl)-5,10-dihydrophenazine) (PMEPZ), were effectively synthesized from an industrial waste phenazine. Both oligomers were exploited successfully as excellent cathode materials for sustainable lithium-ion batteries. PMPPZ and PMEPZ exhibited good electrochemical stability and high initial discharge specific capacities of 88 mA h g-1 and 152 mA h g-1, respectively. Furthermore, upon in situ composition with MWCNTs, a composite material, named PMEPZ-MWCNTs, was achieved with enhanced stability and superior specific discharge capacity with the active-site utilization rate of up to 99%. PMEPZ-MWCNTs delivers high initial discharge capacity of up to 303 mA h g-1 and even 252 mA h g-1 after 300 cycles. Both oligomers exhibit double-electron transfer mechanisms. This work affords an alternative approach to utilizing phenazine as a useful material, circumventing the emission of vast environment harmful gases.

A reversible single-molecule ligand-gating ion transportation switch of ON-OFF-ON type through a photoresponsive pillar[6]arene channel complex.

A reversible pseudo-single-ligand-gated ion transportation switch of ON-OFF-ON type was achieved through host-guest complexation with pillar[6]arene (P[6]) as the ion channel, and a photoresponsive azobenzene as the dual-role (open and close) ligand.

Hypercrosslinked phenothiazine-based polymers as high redox potential organic cathode materials for lithium-ion batteries.

Organic cathode materials have been demonstrated to be highly promising sustainable cathode materials for rechargeable lithium-ion batteries. However, the low redox potentials, low electrical conductivity, and the undesirable dissolution in organic electrolytes greatly limit their applications. Herein, two insoluble hypercrosslinked porous conductive polymers with phenothiazine motifs, HPEPT and HPPT, were successfully accomplished with high and stable discharge potentials at 3.65 and 3.48 V versus Li/Li+. HPEPT and HPPT with good electrical conductivity exhibited outstanding rate capabilities (up to 800 mA g-1) even at a high mass loading up to 70 wt%. This study shows that excellent organic cathode materials could be achieved readily through this prudent design.

A reversible ion transportation switch of ON-OFF-ON type by a ligand-gated calix[6]arene channel.

Calix[6]arene (CX6) was found to be an efficient ion transmembrane channel, which could be blocked by methylene blue (MB) through host-guest interactions. The blocked CX6 channel could be reopened by 4-sulfonated calix[6]arene owing to its stronger affinity with MB, thereby achieving a reversible ON-OFF-ON type switch.

Solvent Effects on the Intramolecular Charge Transfer Character of N,N-Diaryl Dihydrophenazine Catalysts for Organocatalyzed Atom Transfer Radical Polymerization.

The nature of intramolecular charge transfer of N,N-diaryl dihydrophenazine photocatalysts (PCs) in different solvents is explored in context of their performance in organocatalyzed atom transfer radical polymerization (O-ATRP). PCs having a computationally predicted lowest energy excited state exhibiting charge transfer (CT) character can operate a highly controlled O-ATRP in a wide range of solvent polarities, from non-polar hexanes to highly polar N,N-dimethylacetamide. For PCs having a computationally predicted lowest energy excited state not possessing CT character, their ability to operate a controlled O-ATRP is decreased. This study confirms the importance of CT character in the excited state for N,N-diaryl dihydrophenazine PCs, and a deeper understanding of the activity of CT PCs has enabled the synthesis of polymers of low dispersity ( < 1.10) in a controlled fashion.

Strongly Reducing, Visible-Light Organic Photoredox Catalysts as Sustainable Alternatives to Precious Metals.

Photoredox catalysis is a versatile approach for the construction of challenging covalent bonds under mild reaction conditions, commonly using photoredox catalysts (PCs) derived from precious metals. As such, there is need to develop organic analogues as sustainable replacements. Although several organic PCs have been introduced, there remains a lack of strongly reducing, visible-light organic PCs. Herein, we establish the critical photophysical and electrochemical characteristics of both a dihydrophenazine and a phenoxazine system that enables their success as strongly reducing, visible-light PCs for trifluoromethylation reactions and dual photoredox/nickel-catalyzed C-N and C-S cross-coupling reactions, both of which have been historically exclusive to precious metal PCs.

Photochemical Synthesis of Oligomeric Amphiphiles from Alkyl Oxoacids in Aqueous Environments.

The aqueous phase photochemistry of a series of amphiphilic α-keto acids with differing linear alkyl chain lengths was investigated, demonstrating the ability of sunlight-initiated reactions to build molecular complexity under environmentally relevant conditions. We show that the photochemical reaction mechanisms for α-keto acids in aqueous solution are robust and generalizable across alkyl chain lengths. The organic radicals generated during photolysis are indiscriminate, leading to a large mixture of photoproducts that are observed using high-resolution electrospray ionization mass spectrometry, but these products are identifiable following literature photochemical mechanisms. The alkyl oxoacids under study here can undergo a Norrish Type II reaction to generate pyruvic acid, increasing the diversity of observed photoproducts. The major products of this photochemistry are covalently bonded dimers and trimers of the starting oxoacids, many of which are multi-tailed lipids. The properties of these oligomers are discussed, including their spontaneous self-assembly into aggregates.

Highly Active Multidentate Ligand-Based Alkyne Metathesis Catalysts.

Alkyne metathesis catalysts composed of molybdenum(VI) propylidyne and multidentate tris(2-hydroxylbenzyl)methane ligands have been developed, which exhibit excellent stability (remains active in solution for months at room temperature), high activity, and broad functional-group tolerance. The homodimerization and cyclooligomerization of monopropynyl or dipropynyl substrates, including challenging heterocycle substrates (e.g., pyridine), proceed efficiently at 40-55 °C in a closed system. The ligand structure and catalytic activity relationship has been investigated, which shows that the ortho groups of the multidentate phenol ligands are critical to the stability and activity of such a catalyst system.

Organocatalyzed atom transfer radical polymerization driven by visible light.

Atom transfer radical polymerization (ATRP) has become one of the most implemented methods for polymer synthesis, owing to impressive control over polymer composition and associated properties. However, contamination of the polymer by the metal catalyst remains a major limitation. Organic ATRP photoredox catalysts have been sought to address this difficult challenge but have not achieved the precision performance of metal catalysts. Here, we introduce diaryl dihydrophenazines, identified through computationally directed discovery, as a class of strongly reducing photoredox catalysts. These catalysts achieve high initiator efficiencies through activation by visible light to synthesize polymers with tunable molecular weights and low dispersities.

Ionic Covalent Organic Frameworks with Spiroborate Linkage.

A novel type of ionic covalent organic framework (ICOF), which contains sp(3)  hybridized boron anionic centers and tunable countercations, was constructed by formation of spiroborate linkages. These ICOFs exhibit high BET surface areas up to 1259 m(2) g(-1) and adsorb a significant amount of H2 (up to 3.11 wt %, 77 K, 1 bar) and CH4 (up to 4.62 wt %, 273 K, 1 bar). Importantly, the materials show good thermal stabilities and excellent resistance to hydrolysis, remaining nearly intact when immersed in water or basic solution for two days. The presence of permanently immobilized ion centers in ICOFs enables the transportation of lithium ions with room-temperature lithium-ion conductivity of 3.05×10(-5)  S cm(-1) and an average Li(+) transference number value of 0.80±0.02. Our approach thus provides a convenient route to highly stable COFs with ionic linkages, which can potentially serve as absorbents for alternative energy sources such as H2, CH4, and also as solid lithium electrolytes/separators for the next-generation lithium batteries.

Mesoporous 2D covalent organic frameworks based on shape-persistent arylene-ethynylene macrocycles.

Macrocycle-to-framework strategy was explored to prepare covalent organic frameworks (COFs) using shape-persistent macrocycles as multitopic building blocks. We demonstrate well-ordered mesoporous 2D COFs (AEM-COF-1 and AEM-COF-2) can be constructed from tritopic arylene-ethynylene macrocycles, which determine the topology and modulate the porosity of the materials. According to PXRD analysis and computer modelling study, these COFs adopt the fully eclipsed AA stacking mode with large accessible pore sizes of 34 or 39 Å, which are in good agreement with the values calculated by NLDFT modelling of gas adsorption isotherms. The pore size of COFs can be effectively expanded by using larger size of the macrocycles. Provided a plethora of polygonal shape-persistent macrocycles with various size, shape and internal cavity, macrocycle-to-framework strategy opens up a promising approach to expand the structural diversity of COFs and build hierarchical pore structures within the framework.

Mechanistic study of glycosylation using a prop-1-enyl donor.

Studies have been conducted to elucidate the mechanism of glycosylation reactions using a prop-1-enyl donor isomerized directly from an allyl glycoside. The reactions promoted by NIS/TfOH can take place in high yields in acetonitrile at room temperature. Activation of the anomeric prop-1-enyl group often leads to both the desired glycoside (e.g., 9) and the addition-reaction product (e.g., the anomeric mixed acetal 10). TfOH perhaps has a dual role in the reaction: i.e., (a) producing IOTf in situ to activate the prop-1-enyl group and (b) catalyzing the transformation from the addition-reaction product to the desired glycoside (e.g., from 10 to 9). The latter process involves multiple competing pathways.

Development of hydrophilic photolabile hydroxyl protecting groups.

Hydrophilic photolabile protecting groups (PPGs) for hydroxyl protection have been developed. The new PPGs are derived from 3-(dimethylamino)trityl (DMATr) by replacing the two methyl groups with two hydrophilic butyryl groups. The new PPG reagents can be readily prepared and installed. They are stable in the dark but can be removed cleanly and efficiently in aqueous environments upon irradiation with a UV lamp or sunlight.

Oxidation with a photolabile carbonyl protecting group.

A novel oxidation approach utilizing a robust photolabile carbonyl protecting group reagent (1) as the oxidizing reagent has been developed. Different from existing methods, this approach oxidizes primary alcohols to the photosensitive acetals (e.g., 3), providing another unique approach to the protected aldehydes. Thus, for the first time, oxidation and protection are achieved in one reaction. Secondary alcohols are oxidized to the corresponding ketones. Moreover, the photolabile protecting group (PPG) also oxidizes ethers and esters. The oxidation is presumably via hydride abstraction by the tritylium ion generated from 1 under acidic conditions. However, the mechanisms for primary alcohols and secondary alcohols are slightly different.

Concise total synthesis of (-)-8-epigrosheimin.

A highly efficient route was developed to synthesize (-)-8-epigrosheimin in four steps from aldehyde 2 based on a substrate-controlled method. The key steps of the synthesis included (1) a stereo- and regioselective allylation addition, (2) an intramolecular translactonization, and (3) an aldehyde-ene cyclization.

Development of trityl-based photolabile hydroxyl protecting groups.

A series of trityl-based photolabile hydroxyl protecting groups have been examined. These PPGs evolve from the traditional acid-labile trityl protecting group with proper electron-donating substituents. Structure-reactivity relationships have been explored. A m-dimethylamino group is crucial to achieve high photochemical deprotection efficiency. The o-hydroxyl group in 8 greatly improves the yield of the photochemical deprotection reaction, compared with the corresponding o-methoxyl-substituted counterpart 7. However, comparison between the photoreactions of 9 and 11 does not show similar structural relevance. The PPG in ether 1 (i.e., DMATr group) is structurally simple and easy to prepare and install. Its deprotection can be successfully carried out with irradiation of sunlight without requirement of photochemical devices.

Development of a photolabile carbonyl-protecting group toolbox.

New salicyl alcohol derived photolabile carbonyl protecting groups have been developed, and the effect of substituents on the photochemical properties of photolabile protecting groups (PPGs) has been studied. The 3-(dimethylamino)phenyl groups at the α position prove to be important to the efficiency of the deprotection reactions, as shown in the photo reactions of the acetal 9. On the other hand, expansion of the salicyl alcohol's benzene skeleton to naphthalene does not improve the photochemical properties of PPGs. A neutral protecting protocol has been generalized to new PPGs with α,α-diaryl salicyl alcohol backbone. Thus, installation of PPGs onto aldehydes is readily achieved at 140 °C without using any other chemical reagents. These PPGs are stable under acidic conditions typical for hydrolyzing acetals and constitute orthogonal protecting groups with traditional 1,3-dioxane/1,3-dioxolane for carbonyl compounds. Highly efficient release of carbohydrate molecules is demonstrated, which can be potentially useful in site-specific release and immobilization of carbohydrates for preparation of high-density microarrays. With the enriched PPG toolbox, PPGs are divided into three subgroups based on their UV absorption profiles. PPGs from different subgroups can be sequentially removed by using different UV irradiation wavelengths. For PPGs absorbing UVA (λ >315 nm), photochemical deprotection can be carried out with sunlight in high yields.