Olefinic Linkage Research Articles

Does Ortho-Substitution Enhance Cytotoxic Potencies in a Series of 3,5-Bis(benzylidene)-4-piperidones?

Background: A series of 3,5-benzylidene-4-piperidones, 1a–n, were prepared to evaluate the hypothesis that the placement of different groups in the ortho-location of the aryl rings led to compounds with greater cytotoxic potencies than structural analogs. Methods: The bioevaluation of 1a–n was undertaken using human Molt/4C8 and CEM cells as well as murine L1210 cells. Correlations were sought between the interplanar angles θA and θB and the cytotoxic potencies. A QSAR analysis was also undertaken. In order to evaluate whether these compounds demonstrated greater toxicity to neoplasms than non-malignant cells, 1a–n were evaluated against HSC-2, HSC-3, HSC-4 and HL60 neoplasms as well as non-malignant HGF, HPC and HPLF cells. Results: A positive correlation was noted between the interplanar angle θA of one of the aryl rings and the adjacent olefinic linkage with IC50 values in the Molt4/C8 screens. The QSAR analysis revealed a positive correlation between the Hansch pi (π) value of the aryl substituents and the IC50 values of the compounds towards the Molt4/C8 and CEM cells. The dienones in series 1 demonstrated higher tumor-selective toxicity towards HSC-2, HSC-3, HSC-4 and HL-60 neoplasms than HGF, HPC and HPLF cells. Conclusions: The bioevaluations revealed some support for greater cytotoxic potencies to be displayed by compounds having ortho-substituents.

An ultrastable luminescent covalent organic polymer for selective Pd2+ detection in strong acid

AbstractThe low natural abundance of palladium (10 ppb) in the Earth's crust highlights its considerable potential as a valuable resource, especially given that spent nuclear fuel contains approximately 1–2 kg of Pd per ton. However, the detection and separation of Pd2+ from high‐level liquid waste (HLLW) present significant challenges due to high acidity (2–5 M HNO3) and intense radiation conditions inherent in spent fuel reprocessing. We present a cyano‐olefin‐linked covalent organic polymer (COP‐TnPp) that exhibits remarkable stability in strong acidic environments and resilience to radiation. Thanks to its olefin linkage, which facilitates π‐electron conjugation, COP‐TnPp exhibits strong luminescence, whose intensity remains stable across a range of 1–5 M nitric acid solutions. Pd2+ ions can effectively quench the fluorescence of COP‐TnPp in 1 and 5 M HNO3 solutions with detection limits of 0.37 and 0.63 μM, respectively. Additionally, COP‐TnPp demonstrates exceptional selectivity for Pd2+ ions, even amidst 22 other interfering ions in a simulated HLLW solution (5 M HNO3), with the detection limit remaining at 0.697 μM. This work not only marks an advancement in the development of materials for detecting Pd2+ in extreme acidic conditions but also offers new insights into the detection of other radionuclides under similarly challenging environments.

Carbon dioxide capture from open air using covalent organic frameworks.

Capture of CO2 from the air offers a promising approach to addressing climate change and achieving carbon neutrality goals1,2. However, the development of a durable material with high capacity, fast kinetics and low regeneration temperature for CO2 capture, especially from the intricate and dynamic atmosphere, is still lacking. Here a porous, crystalline covalent organic framework (COF) with olefin linkages has been synthesized, structurally characterized and post-synthetically modified by the covalent attachment of amine initiators for producing polyamines within the pores. This COF (termed COF-999) can capture CO2 from open air. COF-999 has a capacity of 0.96 mmol g-1 under dry conditions and 2.05 mmol g-1 under 50% relative humidity, both from 400 ppm CO2. This COF was tested for more than 100 adsorption-desorption cycles in the open air of Berkeley, California, and found to fully retain its performance. COF-999 is an exceptional material for the capture of CO2 from open air as evidenced by its cycling stability, facile uptake of CO2 (reaches half capacity in 18.8 min) and low regeneration temperature (60 °C).

Crystalline Olefin-Linked Chiral Covalent Organic Frameworks as a Platform for Asymmetric Catalysis.

The construction of olefin-linked chiral covalent organic frameworks (COFs) with high crystallinity is highly desirable while remains great challenge due to the poor reversibility of the formation reaction for the olefin linkages during the in situ structural self-healing process. Herein, we successfully synthesized two sets of enantiomeric olefin-linked COFs. The chiral catalytic groups are uniformly distributed on the pore walls of COFs, resulting in the full exposure of catalytic sites to the reactants in asymmetric catalysis. The as-prepared (R)/(S)-CCOF8 exhibits excellent catalytic performance with exceeding 99 % enantiomeric excess in the enantioselective electrophilic amination reaction. Moreover, the heterogeneous chiral catalysts are conveniently recycled and could maintain the performance after ten catalytic cycles. Our findings expand the scope to construct stable and crystalline chiral COFs for the asymmetric catalysis.

Crystalline Olefin‐Linked Chiral Covalent Organic Frameworks as a Platform for Asymmetric Catalysis

AbstractThe construction of olefin‐linked chiral covalent organic frameworks (COFs) with high crystallinity is highly desirable while remains great challenge due to the poor reversibility of the formation reaction for the olefin linkages during the in situ structural self‐healing process. Herein, we successfully synthesized two sets of enantiomeric olefin‐linked COFs. The chiral catalytic groups are uniformly distributed on the pore walls of COFs, resulting in the full exposure of catalytic sites to the reactants in asymmetric catalysis. The as‐prepared (R)/(S)‐CCOF8 exhibits excellent catalytic performance with exceeding 99 % enantiomeric excess in the enantioselective electrophilic amination reaction. Moreover, the heterogeneous chiral catalysts are conveniently recycled and could maintain the performance after ten catalytic cycles. Our findings expand the scope to construct stable and crystalline chiral COFs for the asymmetric catalysis.

Upgrading structural conjugation in covalent organic framework with spatial dual sites enables boosting solar-to-H2O2-to-•OH for environmental remediation

Designing photocatalysts with well-defined structure-function relationships is imperative for propelling the progression of desired photocatalytic oxidation. Herein, the efficient conversion of solar energy to H2O2 and subsequently to hydroxyl radicals (•OH) is achieved through a synergistic interplay between olefin linkage (-CC-) and spatially separated benzene-triazine dual reaction sites within covalent organic frameworks (COFs). The upgraded -CC- can increase the conjugation degree of COFs, which establishes an expanded superstructure for boosting charge separation/transfer and stability. This precise modulation renders more opportunities for the hot electrons to migrate to the benzene site for solar-to-H2O2 generation, and to the triazine site for H2O2-to-•OH, separately. The optimized •OH generation pathway enables remarkable oxidation performances against recalcitrant organic pollutants, and pathogenic microorganisms under visible light irradiation. This work provides new insights for tuning the synergistic interactions of various building blocks within the COFs for the selective generation of highly reactive •OH for environmental remediation.

Efficient construction of ABC-tricyclic core of schweinfurthins and its application in amide based analog synthesis

To accelerate the medicinal chemistry efforts, an efficient and reliable synthesis of amide isosteres of Schweinfurthin G, where the central olefinic linkage between C and D rings has been replaced with amide bond, is described. The approach relied on a copper mediated coupling reaction of organo-magnesium species with allylic chloride is easily amenable to rapid analoging to generate amide based isosteres of the natural product.

A metal-free strategy to construct fluoroalkyl-olefin linkages using fluoroalkanes.

We present a metal-free strategy to access fluoroalkyl-olefin linkages from fluoroalkane precursors and vinyl-pinacol boronic ester (BPin) reagents. This reaction sequence is templated by the boron reagent, which induces C-C bond formation upon oxidation. We developed this strategy into a one-pot synthetic protocol using RCF2H precursors directly with vinyl-BPin reagents in the presence of a Brønsted base, which tolerated oxygen- and nitrogen-containing heterocycles, and aryl halogens. We also found that HCF3 (HCF-23; a byproduct of the Teflon industry) and CH2F2 (HCF-32; a low-cost refrigerant) are amenable to this protocol, representing distinct strategies to generate RCF2H and RCF3 molecules. Finally, we demonstrate that the vinyldifluoromethylene products can be readily derivatized, representing an avenue for late-stage modification after installing the fluoroalkyl unit.

Design, synthesis, and properties of olefin‐linked covalent organic frameworks modified by heck coupling reaction

AbstractThe covalent organic frameworks (COFs) with olefin linkages are attractive materials for nonlinear optics due to their small energy band gap and large π‐electron separation domain. In this paper, a post‐synthetic modification (PSM) by applying a heck coupling reaction on olefin‐linked COFs was applied for the first time to obtain five functionalized triazine‐based covalent organic framework materials. The synthesized materials were tested for their relevant photophysical and electrochemical properties, and their third‐order nonlinear optical properties were tested using the Z‐scan technique. The experimental results indicate that the post‐modified COF (W4‐2) exhibits third‐order nonlinear polarizability χ3 that is 1.51 times higher than the unmodified COF (W4).

Cyano Substituent on the Olefin Linkage: Promoting Rather than Inhibiting the Performance of Covalent Organic Frameworks

It is generally believed that the electron-withdrawing cyano group in the olefin linkage would inhibit the stability and π-conjugation of covalent organic frameworks (COFs), which raises concerns about their optoelectronic properties. However, the structure–activity relationship between the structure of olefin linkages and properties of COFs is still inconclusive. In this work, imine-, vinylene-, and acrylonitrile-linked COFs with identical triphenyltriazine building blocks were designed and synthesized. Our work demonstrated that construction of acrylonitrile linkages not only enhanced the chemical stability and photostability but also led to remarkable optoelectronic properties with a record fluorescence quantum yield of 35.37% in the solid state. Further, the acrylonitrile linkage endows TTAN-COF/Pt NPs with superior and durable photocatalytic activity in both the hydrogen evolution reaction (11.94 mmol g–1 h–1; BET surface area, 739.28 m2 g–1) and aerobic oxidation reaction. This work demonstrates that the acrylonitrile linkage can significantly enhance the optoelectronic properties and photocatalytic activities of COFs compared with the highly π-conjugated vinylene linkage, providing a valuable reference for the design of optoelectronic functional materials.

Olefin-linked covalent organic frameworks with twisted tertiary amine knots for enhanced ultraviolet detection

Though Olefin-linked covalent organic frameworks (oCOFs) possess excellent π-electron delocalization, the barely reversible olefin linkage brings challenges for oCOFs’ synthesis and functionalization. Here, we synthesize new oCOFs with tertiary amine knots which have twisted configuration and electron-donating nature. Investigation into the structural variation and photoelectric performance shows that the twisted configuration of oCOF-TFPA could favor to the intramolecular charge transfer process and reduce the possibility of aggregation-caused quenching. Photoelectrical measurements and electric band structure calculation both verify the superiority of this oCOFs’ structure in photoelectric sensing.

A general design approach toward covalent organic frameworks for highly efficient electrochemiluminescence

Electrochemiluminescence (ECL) plays a key role in analysis and sensing because of its high sensitivity and low background. Its wide applications are however limited by a lack of highly tunable ECL luminophores. Here we develop a scalable method to design ECL emitters of covalent organic frameworks (COFs) in aqueous medium by simultaneously restricting the donor and acceptor to the COFs’ tight electron configurations and constructing high-speed charge transport networks through olefin linkages. This design allows efficient intramolecular charge transfer for strong ECL, and no exogenous poisonous co-reactants are needed. Olefin-linked donor-acceptor conjugated COFs, systematically synthesized by combining non-ECL active monomers with C2v or C3v symmetry, exhibit strong ECL signals, which can be boosted by increasing the chain length and conjugation of monomers. The present concept demonstrates that the highly efficient COF-based ECL luminophores can be precisely designed, providing a promising direction toward COF-based ECL phosphors.

A metal-free approach to bipyridinium salt-based conjugated porous polymers with olefin linkages

A metal-free bipyridinium salt-activated Knoevenagel condensation strategy was developed to synthesize olefin-linked conjugated porous polymers with π-extended networks, positively charged skeletons, high stability and antibacterial activity.

Crystalline C-C and C═C Bond-Linked Chiral Covalent Organic Frameworks.

While crystalline covalent organic frameworks (COFs) linked by C-C bonds are highly desired in synthetic chemistry, it remains a formidable challenge to synthesize. Efforts to generate C-C single bonds in COFs via de novo synthesis usually afford amorphous structures rather than crystalline phases. We demonstrate here that C-C single bond-based COFs can be prepared by direct reduction of C═C bond-linked frameworks via crystal-to-crystal transformation. By Knoevenagel polycondensation of chiral tetrabenzaldehyde of dibinaphthyl-22-crown-6 with 1,4-phenylenediacetonitrile or 4,4'-biphenyldiacetonitrile, two olefin-linked chiral COFs with 2D layered tetragonal structure are prepared. Reduction of olefin linkages of the as-prepared CCOFs produces two C-C single bond linked frameworks, which retains high crystallinity and porosity as well as high chemical stability in both strong acids and bases. The quantitative reduction is confirmed by Fourier transform infrared and cross-polarization magic angle spinning 13C NMR spectroscopy. Compared to the pristine structures, the reduced CCOFs display blue-shifted emission with enhanced quantum yields and fluorescence lifetimes, while the parent CCOFs exhibit higher enantioselectivity than the reduced analogs when be used as fluorescent sensors to detect chiral amino alcohols via supramolecular interactions with the built-in crown ether moieties. This work provides an attractive strategy for making chemically stable functionalized COFs with new linkages that are otherwise hard to produce.

Semiconducting 2D Triazine-Cored Covalent Organic Frameworks with Unsubstituted Olefin Linkages

Establishing an sp2-carbon-bonding pattern is one of the efficient accesses to various organic semiconducting materials. However, the less-reversible carbon-carbon bond formation makes it still challenging to spatially construct a well-defined organic framework with π-extended two-dimensional (2D) structure through solution process. Here, a Knoevenagel condensation approach to synthesize two new 2D covalent organic frameworks (COFs) connected by unsubstituted carbon-carbon double bond linkages through activating the methyl carbons of a 2,4,6-trimethyl-1,3,5-triazine monomer is presented. The resulting sp2-carbon-linked triazine-cored 2D sheets are vertically stacked into high-crystalline honeycomb-like structures, endowing this kind of COF with extended π-delocalization, tunable energy levels, as well as high surface areas, regular open channels, and chemical stabilities. On the other hand, their microfibrillar morphologies allow for the facile manipulation of thin films as photoelectrodes without additive. Accordingly, such kinds of COF-based photoelectrodes exhibit photocurrents up to ∼45 μA cm-2 at 0.2 V vs RHE as well as rapid charge transfer rates, in comparison with imine-linked COF-based photoelectrodes. In addition, both COFs are applicable for conducting photocatalytic hydrogen generation from water splitting by visible-light irradiation.

Porous Crystalline Olefin-Linked Covalent Organic Frameworks.

The first unsubstituted olefin-linked covalent organic framework, termed COF-701, was made by linking 2,4,6-trimethyl-1,3,5-triazine (TMT) and 4,4'-biphenyldicarbaldehyde (BPDA) through Aldol condensation. Formation of the unsubstituted olefin (-CH═CH-) linkage upon reticulation is confirmed by Fourier transform infrared (FT-IR) spectroscopy and solid-state 13C cross-polarization magic angle spinning (CP-MAS) NMR spectroscopy of the framework and of its 13C-isotope-labeled analogue. COF-701 is found to be porous (1715 m2 g-1) and to retain its composition and crystallinity under both strongly acidic and basic conditions. The high chemical robustness is attributed to the unsubstituted olefin linkages. Immobilization of the strong Lewis acid BF3·OEt2 in the pores of the structure yields BF3⊂COF-701. In the material, the catalytic activity of the guest is retained, as evidenced in a benchmark Diels-Alder reaction.

Ethacrynic acid decreases expression of proinflammatory intestinal wall cytokines and ameliorates gastrointestinal stasis in murine postoperative ileus

OBJECTIVES:Several compounds characterized by an olefin linkage conjugated to a carbonyl group have anti-inflammatory properties. The diuretic ethacrynic acid (EA) is a compound of this type. Herein, we tested the hypothesis that ethacrynic acid can modulate the development of ileus after bowel manipulation.METHODS:Groups (n=9) of male C57Bl/6 mice underwent surgical manipulation of the small intestine using a pair of cotton-tipped applicators (MAN). Control animals (CONT) did not undergo any surgical intervention or receive treatment. MAN mice were pre- and post-treated with four intraperitoneal doses of phosphate buffered saline (PBS), EA1 (1mg/kg per dose), or EA10 (10mg/kg per dose). Gastrointestinal transit of non-absorbable FITC-labeled dextran was assessed by gavaging the mice with the tracer 24h after operation and assessing FD70 concentration 120 min later in the bowel contents from the stomach, 10 equally long segments of small intestine, cecum, and two equally long segments of colon. The geometric center for the tracer was calculated for each animal. Expression of interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) transcripts in the ileal muscularis propria was assessed using semiquantitative reverse transcriptase-polymerase chain reaction.RESULTS:In control animals, the mean (±SE) geometric center for the transit marker was 9.89±0.47, whereas it was 4.59±0.59 for PBS-treated animals (p<0.05 vs CONT). The geometric center for pre- post treatment with low (1mg/kg) and high (10mg/kg) doses of ethacrynic acid were 7.23±0.97 and 5.15±0.57, respectively. Compared to PBS, treatment with ethacrynic acid (1mg/kg) significantly decreased manipulation-induced IL-6 and iNOS mRNA expression in the wall of the small bowel.CONCLUSIONS:Pre- and post-treatment with ethacrynic acid ameliorates ileus and modulates inflammation in the gut wall induced by bowel manipulation.

Ethacrynic Acid Decreases Expression of Proinflammatory Cytokines in Intestinal Wall and Ameliorates Gastrointestinal Motility after Small Bowel Manipulation

Background: Gastrointestinal dysmotility is frequently observed after visceral transplantation. The development of postoperative GI dysmotility is multifactorial with an intricate interaction between inflammatory, hormonal, neurogenic, and humoral components. Several studies have shown an increased expression of proinflammatory cytokines in the gut wall as well as infiltration by polymorphonuclear leukocytes into the muscularis propria after SB manipulation. A number of compounds characterized by an olefin linkage conjugated to a carbonyl group have anti-inflammatory properties. The diuretic, ethacrynic acid (EA), is a compound of this type. Herein, we tested the hypothesis that EA can modulate the development of GI dysmotility after bowel manipulation. Methods: Groups (n=9) of male C57Bl/6 mice underwent surgical manipulation of the small intestine using a pair of cotton-tipped applicators (MAN). Control animals (CONT) did not undergo any surgery or receive treatment. MAN mice were pre- and post-treated with four i.p. doses of PBS (phosphate buffered saline), EA1 (1mg/kg per dose) or EA10 (10mg/kg per dose). Gastrointestinal transit of non-absorbable FITC-labeled dextran (MW 70 kDA; FD70) was assessed by gavaging the mice with the tracer 24 h after operation and assessing FD70 concentration 120 min later in bowel contents from the stomach, 10 equally long segments of small intestine, cecum, and two equally long segments of colon. The geometric center (GC) for the tracer was calculated for each animal. Expression of interleukin-6 and inducible nitric oxide synthase transcripts in ileal muscularis propria was assessed using the semiquantitative reverse transcriptase-polymerase chain reaction. Results: In control animals, the mean (±SE) geometric center for the transit marker was 9.89±0.47, whereas for PBS treated animals was 4.59±0.59 (p<0.05 vs CONT). The GC for pre- post treatment with low (1mg/kg) and high (10mg/kg) doses of ethacrynic acid were 7.23±0.97 and 5.15±0.57, respectively. Compared to PBS, treatment with EA (1mg/kg) significantly decreased manipulation-induced IL-6 and iNOS mRNA expression in the wall of the small bowel. Conclusions: Pre- and post-treatment with EA ameliorates ileus and modulate inflammation in the gut wall induced by bowel manipulation.

Synthesis and properties of the derivatives of triphenylamine and 1,8-naphthalimide with the olefinic linkages between chromophores

Two donor–acceptor type molecules consisting of triphenylamine and 1,8-naphthalimide moieties with the olefinic linkages between chromophores were synthesized by Heck reaction.

A two-dimensional conjugated polymer framework with fully sp2-bonded carbon skeleton

2D conjugated COF based on olefin (CC) linkages has been readily synthesized using the Knoevenagel condensation reaction.