Alkene Linker Research Articles

Cascade Defluorination of Perfluoroalkylated Catholytes Unlocks High Lithium Primary Battery Capacities

AbstractExceeding the energy density of lithium−carbon monofluoride (Li−CFx), today's leading Li primary battery, requires an increase in fluorine content (x) that determines the theoretical capacity available from C−F bond reduction. However, high F‐content carbon materials face challenges such as poor electronic conductivity, low reduction potentials (<1.3 V versus Li/Li+), and/or low C−F bond utilization. This study investigates molecular structural design principles for a new class of high F‐content fluoroalkyl‐aromatic catholytes that address these challenges. A polarizable conjugated system—an aromatic ring with an alkene linker—functions as electron acceptor and redox initiator, enabling a cascade defluorination of an adjacent perfluoroalkyl chain (RF = −CnF2n+1). The synthesized molecules successfully overcome premature deactivation observed in previously studied catholytes and achieve close‐to‐full defluorination (up to 15/17 available F), yielding high gravimetric capacities of 748 mAh g−1fluoroalkyl‐aromatic and energies of 1785 Wh kg−1fluoroalkyl‐aromatic. The voltage compatibility between fluoroalkyl‐aromatics and CFx enables design of hybrid cells containing C−F redox activity in both solid and liquid phases, with a projected enhancement of Li–CFx gravimetric energy by 35% based on weight of electrodes+electrolyte. With further improvement of cathode architecture, these “liquid CFx” analogues are strong candidates for exceeding the energy limitations of today's primary chemistries.

Reactive Chlorine Capture by Dichlorination of Alkene Linkers in Metal-Organic Frameworks.

Chlorine (Cl2) is a toxic and corrosive gas that is both an essential reagent in industry and a potent chemical warfare agent. Materials that can strongly bind Cl2 at low pressures are essential for industrial and civilian personal protective equipment (PPE). Herein, we report the first examples of irreversible Cl2 capture via the dichlorination of alkene linkages in Zr-based metal-organic frameworks. Frameworks constructed from fumarate (Zr-fum) and stilbene (Zr-stilbene) linkers retain long-range order and accessible porosity after alkene dichlorination. In addition, energy-dispersive X-ray spectroscopy reveals an even distribution of Cl throughout both materials after Cl2 capture. Cl2 uptake experiments reveal high irreversible uptake of Cl2 (>10 wt %) at low partial pressures (<100 mbar), particularly in Zr-fum. In contrast, traditional porous carbons mostly display reversible Cl2 capture, representing a continued risk to users after exposure. Overall, our results support that alkene dichlorination represents a new pathway for reactive Cl2 capture, opening new opportunities for binding this gas irreversibly in PPE.

Sites for Dynamic Protein-Carbohydrate Interactions of O- and C-Linked Mannosides on the E. coli FimH Adhesin.

Antagonists of the Escherichia coli type-1 fimbrial adhesin FimH are recognized as attractive alternatives for antibiotic therapies and prophylaxes against acute and recurrent bacterial infections. In this study α-d-mannopyranosides O- or C-linked with an alkyl, alkene, alkyne, thioalkyl, amide, or sulfonamide were investigated to fit a hydrophobic substituent with up to two aryl groups within the tyrosine gate emerging from the mannose-binding pocket of FimH. The results were summarized into a set of structure-activity relationships to be used in FimH-targeted inhibitor design: alkene linkers gave an improved affinity and inhibitory potential, because of their relative flexibility combined with a favourable interaction with isoleucine-52 located in the middle of the tyrosine gate. Of particular interest is a C-linked mannoside, alkene-linked to an ortho-substituted biphenyl that has an affinity similar to its O-mannosidic analog but superior to its para-substituted analog. Docking of its high-resolution NMR solution structure to the FimH adhesin indicated that its ultimate, ortho-placed phenyl ring is able to interact with isoleucine-13, located in the clamp loop that undergoes conformational changes under shear force exerted on the bacteria. Molecular dynamics simulations confirmed that a subpopulation of the C-mannoside conformers is able to interact in this secondary binding site of FimH.

Structural and functional analysis of biopolymers and their complexes: Enzymatic synthesis of high-modified DNA

Here, we describe the synthesis and purification of six deoxyuridine triphosphate derivatives that contain protein-like functional groups and alkene linkers of various lengths. Using KOD XL and Deep Vent polymerases, these derivatives have been incorporated into single-stranded DNA, achieving a high degree of DNA modification. These polymerases are able to utilize highly modified DNA strands as templates for synthesizing unmodified DNA. The synthesized deoxyuridine triphosphate derivatives are promising as substrates for producing modified aptamers to various target proteins using, e.g., the systematic evolution of ligands by exponential enrichment (SELEX) methodology.

Fluorescence completely separated ratiometric probe for HClO in lysosomes

Hypochlorous acid (HClO), as one of the reactive oxygen species (ROS), was reported to be involved in a number of human diseases and many efforts have therefore been made to probe its biological roles at molecular level. In this work, a ratiometric probe (BFClO) with completely separated fluorescent signals consisting of a boron-dipyrromethene (BODIPY) dye conjugated with Fisher aldehyde was designed and synthesized for the selective and sensitive detection of HOCl via oxidative cleavage of the alkene linker. The probe evinced more than 300-fold enhancement in fluorescence ratio (I511nm/I713nm) in the presence of HClO over other ROS with fast response time (within 10s) and low detection limit (10.6nM). Confocal fluorescence images demonstrated that the probe could well permeate through plasma membrane and visualize exogenous and endogenous HOCl in lysosomes of living cells.

Doxorubicin/Ce6-Loaded Nanoparticle Coated with Polymer via Singlet Oxygen-Sensitive Linker for Photodynamically Assisted Chemotherapy.

It is widely known that the therapeutic effect of nanoparticle-based chemotherapeutics could be greatly enhanced by the introduction of the photodynamic effect. Herein we report a chlorin e6-incorporated mesoporous silica nanoparticles (MSNs) covered with a polyethylene glycol shell conjugated via a singlet oxygen-sensitive labile bis(alkylthio)alkene linker (CeAP-L-PEG). In this study, single irradiation with biocompatible red light induced both intracellular doxorubicin release and photochemical internalization, and consequently enhanced anti-cancer effect was observed in vitro and in vivo. This study suggests the potential of our precisely designed nanoparticle system for photodynamically assisted chemotherapy.

Enzymatic synthesis of high-modified DNA

Here, we describe the synthesis and purification of six deoxyuridine triphosphate derivatives that contain protein-like functional groups and alkene linkers of various lengths. Using KOD XL and Deep Vent polymerases, these derivatives have been incorporated into single-stranded DNA, achieving a high degree of DNA modification. These polymerases are able to utilize highly modified DNA strands as templates for synthesizing unmodified DNA. The synthesized deoxyuridine triphosphate derivatives are promising as substrates for producing modified aptamers to various target proteins using, e.g., the systematic evolution of ligands by exponential enrichment (SELEX) methodology.

Resveratrol and Its Analogs As Antitumoral Agents For Breast Cancer Treatment.

Resveratrol (3,5,4'-tri-hydroxystilbene) (RSV), a naturally occurring phytoalexin, readily available in the diet, has gained interest as a non-toxic agent capable of displaying cancer-preventing and anti-cancer properties. Several studies, using both in vitro and in vivo models, have illustrated RSV capacity to modulate a multitude of signaling pathways associated with cellular growth and division, apoptosis, angiogenesis, invasion and metastasis. However, its clinical application is limited because of a low oral bioavailability with high adsorption but rapid metabolism and low tissue concentrations. Several chemical modifications to the backbone structure have been made for the purpose of improving pharmacokinetic parameters. One promising strategy involves the introduction of methoxylic or hydroxylic groups on the phenylic rings of RSV. Moreover, by replacing the alkene linker between the two aromatic rings with a heterocyclic system rigid analogs such as 2,3- thiazolidin-4-ones and 3-chloro-azetidin-2-ones that displayed higher cytotoxic activity and hence higher ability to inhibit in vitro breast cancer cell growth have been synthesized. In vitro studies have demonstrated, for some of these compounds, a greater bioaccessibility than RSV and more selective inhibitory effects on breast cancer cell growth. Further investigations, particularly in vivo, are required as next step to implicate these analogs as pharmacologic agents for a possible clinical anticancer application.

An ICT based ultraselective and sensitive fluorescent probe for detection of HClO in living cells

An ICT based ultraselective and sensitive probe for colorimetric and fluorescent detection of HClOviaoxidative cleavage of an alkene linker to epoxide and then to aldehydes was developed through the conjugation of pyridinium with vanilline.

A quenched binuclear ruthenium(ii) dimer activated by another photosensitizer

A binuclear ruthenium(II) dimer (BiRD) bridged by an alkene linker was synthesized that was labile to reactive oxygen species generated by another photosensitizer. Compared to the monomeric Ru(II) complex, the BiRD had attenuated fluorescence and singlet oxygen production which could be restored by a longer-wavelength photosensitizer. This two-step amplification strategy demonstrates proof-of-principal for photosensitization chain-reactions.

Photo-initiated Thiol-ene Click Reactions as a Potential Strategy for Incorporation of [MI(CO)3]+(M = Re,99mTc) Complexes

Click reactions offer a rapid technique to covalently assemble two molecules. In radiopharmaceutical construction, these reactions can be utilized to combine a radioactive metal complex with a biological targeting molecule to yield a potent tool for imaging or therapy applications. The photo-initiated radical thiol-ene click reaction between a thiol and an alkene was examined for the incorporation of [M(I)(CO)3](+) (M = Re, (99m)Tc) systems for conjugating biologically active targeting molecules containing a thiol. In this strategy, a potent chelate system, 2,2'-dipicolylamine (DPA), for [M(I)(CO)3](+) was functionalized at the central amine with a terminal alkene linker that was explored with two synthetic approaches, click then chelate and chelate then click, to determine the flexibility and applicability of the thiol-ene click reaction to specifically incorporate ligand systems and metal complexes with a thiol containing molecule. In the click then chelate approach, the thiol-ene click reaction was carried out with the DPA chelate followed by complexation with [M(I)(CO)3](+). In the chelate then click approach, the alkene functionalized DPA chelate was first complexed with [M(I)(CO)3](+) followed by the conduction of the thiol-ene click reaction. Initial studies utilized benzyl mercaptan as a model thiol for both strategies to generate the identical product from either route to provide information on reactivity and product formation. DPA ligands functionalized with two unique linker systems (allyl and propyl allyl ether) were prepared to examine the effect of the proximity of the chelate or complex on the thiol-ene click reaction. Both the thiol-ene click and coordination reactions with Re, (99m)Tc were performed in moderate to high yields demonstrating the potential of the thiol-ene click reaction for [M(I)(CO)3](+) incorporation into thiol containing biomolecules.

Effect of oligoethylene glycol moieties in porous silicon surface functionalisation on protein adsorption and cell attachment

We report on the synthesis of two carboxy-functional alkene compounds as modifiers of porous silicon (pSi) surface chemistry by means of thermal hydrosilylation. Both alkene compounds have hydrophobic, aliphatic carbon segments, with terminal carboxylic acid functionality appended through a thioether linkage. In one of the alkene linkers, we incorporated a short oligoethylene glycol (OEG) moiety to explore its low-fouling properties when attached to porous silicon. We examined surface stability of the surface-modified porous silicon in aqueous milieu. Albumin and fibronectin were adsorbed and, using carbodiimide chemistry, covalently immobilised to linker-modified porous silicon, and the propensity for mammalian cells to attach to these surfaces investigated. Surface chemistry was characterised by infrared spectroscopy and the stability of porous silicon in an aqueous milieu was investigated by interferometric reflectance spectroscopy (IRS). Surfaces functionalised with the alkene linker containing OEG displayed greater resistance to the adsorption of albumin. This linker also facilitated higher levels of covalent protein immobilisation to the functionalised pSi surface. Higher levels of cell attachment were observed on pSi surfaces with fibronectin covalently immobilised onto the OEG linker, than for fibronectin covalently immobilised on the non-OEG linker.

From Serendipity to Rational Antituberculosis Drug Discovery of Mefloquine-Isoxazole Carboxylic Acid Esters

Both in vitro and in vivo metabolism studies suggested that 5-(2,8-bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester (compound 3) with previously reported antituberculosis activity is rapidly converted to two metabolites 3a and 3b. In order to improve the metabolic stability of this series, chemistry efforts were focused on the modification of the oxymethylene linker of compound 3 in the present study. Compound 9d with an alkene linker was found to be both more metabolically stable and more potent than compound 3, with a minimum inhibitory concentration (MIC) of 0.2 microM and 2.6 microM against replicating and nonreplicating Mycobaterium tuberculosis, respectively. These attributes make 9d an interesting lead compound. A number of modifications were made to the structure of 9d, and a series of active compounds were discovered. Although some neurotoxicity was observed at a high dosage, this new series was endowed with both improved in vitro anti-TB activity and metabolic stability in comparison to compound 3.

Suzuki Coupling of Aryl Organics on Diamond

We demonstrate a facile method for the Suzuki coupling of aryl molecules on the diamond surface. This is a more versatile alternative compared to previous coupling methods based on alkene linkers because it opens up possibilities for the application of diamond in molecular electronics and photovoltaics. The diamond surface is premodified with aryldiazonium salt in order to functionalize it with aryl halide or aryl boronic acid, and these are then used as synthons in the subsequent Suzuki coupling to aryl molecules. This method is highly specific and can be used for the uninterrupted molecular conjugation of diamond to a large class of organic molecules. As a proof of concept, we also demonstrate a diamond−fullerene photocurrent converter by using Suzuki coupled oligothiophene as the conjugated linker between diamond (electron donor) and fullerene (electron acceptor).

Photo‐ and electrochemical bonding of DNA to single crystalline CVD diamond

AbstractAlkene and nitrophenyl molecules have been covalently bonded to single crystal diamond using photochemical and electrochemical techniques. The surface density of electrochemically grafted nitrophenyl groups is about 5% of a monolayer (8 × 1013 molecules/cm2) on initially H‐terminated diamond. Covalently‐bonded nitrophenyl groups on single‐crystalline diamond are characterized to have two successive reversible one‐electron transfer reactions due to a regularly‐oriented arrangement. On oxidized surface of boron doped electrodes, a slightly (10%) smaller density is detected. Photochemical attachment of alkene molecules results also in a well arranged films as detected by angle resolved X‐ray photoelectron spectroscopy (XPS). The density of 10‐amino‐dec‐1‐ene molecules protected with trifluoroacetic acid (“TFAAD”) is calculated to be in the range 2 × 1014 molecules/cm2. The bonding mechanism of Alkene molecules to high quality hydrogen terminated single crystalline CVD diamond has been characterized using a variety of experiments which show that photo‐excited electrons of 5 eV energy trigger the photochemical attachment. The minimum time required to achieve a monolayer attachment of TFAAD molecules on (100)(2 × 1):H diamond is discussed and compared with experimental data from XPS. The benzene and alkene linker molecules are then reacted with the heterobifunctional cross linker sulphosuccinimidyl‐4‐(N‐maleimidomethyl)cyclohexane‐1‐carboxylate and finally with thiol‐modified ss‐DNA to produce a DNA‐modified diamond surface. The interaction with complementary and partially mismatched DNA is characterized by fluorescence microscopy. Microscopic properties of DNA layers on diamond have been characterized by contact‐ and oscillatory‐mode atomic force microscopy (AFM). A comparison of bonding forces, detected by contact mode AFM, reveals significant bonding strength differences. For both, electro‐ and photochemically bonded DNA, tilted molecule arrangements are detected, with angles in the range 30 ° to 46° with respect to the diamond surface. The DNA films are dense with a surface roughness of about 5 Å. (© 2006 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)

Synthesis of achiral and racemic catenanes based on terpyridine and a directionalized terpyridine mimic, pyridyl-phenanthroline

Concatenated macrocycles containing manisyl-substituted tridentate ligands 2,2':6',2''-terpyridine and 2-pyridin-2-yl-1,10-phenanthroline (simply referred to as terpyridine and pyridyl-phenanthroline herein) have been prepared via dual cyclization procedures. The manisyl derivative (manisyl = 4-methoxy-2,6-dimethylphenyl) was chosen for its ability to improve solubility while simultaneously incorporating functionality. Deprotection of the methoxy groups provided a soluble ligand that was re-alkylated with an array of terminal alkyne and alkene linkers. The tridentate coordinating ability of these ligands enabled complexation with Ru(ii) and Fe(ii), generating achiral and racemic octahedral complexes for terpyridine and pyridyl-phenanthroline, respectively. Subsequent macrocyclization via olefin metathesis or copper-mediated alkyne coupling afforded the corresponding catenanes, and in some cases a figure-eight macrocycle. The difference in symmetry and the presence of the manisyl group allowed the distinction between the catenane and the undesired figure-eight to be made directly by (1)H NMR. Metal-free achiral and racemic catenanes were obtained by liberating Fe(ii) from the octahedral bound title ligands by treatment with hydrogen peroxide.

Polymer-supported tin carbohydrate chemistry.

It was anticipated that stannylation of carbohydrates could be achieved using tin on a polymer-support. Such immobilization simplifies the purification of the carbohydrate because the toxic tin reagent can be removed by filtration. In this case an alkene linker (3-buten-1-ol) was added to chloromethylated 2% cross-linked polystyrene by etherification. Photochemical hydrostannylation with dibutyltinchlorohydride gave a polymer bound trialkyl tin chloride. The Sn-Cl could be hydrolysed with NaOH to yield a resin with terminal Sn-O bonds. Highly regioselective acylation of methyl alpha-D-mannopyranoside (alphaMeMan) to its 3-O-benzoyl derivative was achieved. Traces of the mono 6-O-benzoate and the 3,6-di-O-benzoate were also obtained. Methyl alpha-D-glucopyranoside was also selectively acylated to its 2-O-benzoate but this reaction gave a more complex mixture. The isolated yields (10-30% based on sugar) were disappointingly low. The yields were improved to about 60% with 5% cross-linked resin.