Diversity Oriented Preparation of Pillararene-Containing Rotaxanes by a Stopper Exchange Strategy.
ABSTRACT: Rotaxane building blocks bearing 3,5-bis(trifluoromethyl) benzenesulfonate (BTBS) stoppers have been efficiently prepared from a pillararene derivative, 3,5-bis(trifluoromethyl) benzenesulfonyl chloride (BTBSCl) and different diols, namely 1,10-decanediol and 1,12-dodecanediol. The BTBS moieties of these compounds are good leaving groups and stopper exchange reactions could be achieved by treatment with different nucleophiles thus affording rotaxanes with ester, thioether or ether stoppers.
Project description:The data in this paper are related to the research article entitled "Assessing the percentage of cork that a stopper should have from a mechanical perspective" (González and Terrazas, 2018). This data article contains data on the mechanical properties of different types of wine stoppers: 18 types of micro-agglomerated stoppers, three types of natural stoppers, and one type of co-extruded synthetic closure. Mechanical properties were evaluated with different analysis: Compression test for the maximum radial compression force, the young's moduli and the diameter recovery, relaxation test for the relaxation force and the extraction test for the displacement force.
Project description:The simple and reversible control of the degree of polymerization, and thereby the bulk material properties, of a supramolecular polymer is reported. Noncovalent capping agents (chain stoppers) modulate the length of supramolecular polymers by stacking on the surfaces of the polymer's ends. Methylene blue (MB) is a positively charged, planar polycyclic dye that acts as a chain stopper. It can be reversibly switched between its colored, planar, cationic state and a colorless, nonplanar, neutral state (leucomethylene blue, LMB) by reduction with ascorbic acid and then reoxidized to MB by O2. LMB does not act as a chain stopper. This behavior was utilized to reversibly trigger the gel to sol transformation of supramolecular polymers formed by the self-assembly of hexameric rosettes comprising 2,4,6-triaminopyrimidine and a hexanoic acid-substituted cyanuric acid (CyCo6) in aqueous media. The results of our experiments highlight the ability of this approach to reversibly switch between the gel and solution states of materials formed from supramolecular polymers and thereby control their bulk properties.
Project description:Rotaxanes, pseudorotaxanes, and catenanes are supramolecular complexes with potential use in nanomachinery, molecular computing, and single-molecule studies. Here we constructed a protein rotaxane in which a polypeptide thread is encircled by a Cytolysin A (ClyA) nanopore and capped by two protein stoppers. The rotaxane could be switched between two states. At low negative applied potentials (<-50 mV) one of the protein stoppers resided inside the nanopore indefinitely. Under this configuration the rotaxane prevents the diffusion of protein molecules across the lipid bilayer and provides a useful platform for single-molecule analysis. High negative applied potentials (-100 mV) dismantled the interlocked rotaxane system by the forceful translocation of the protein stopper, allowing new proteins to be trapped inside or transported across the nanopore. The observed voltage threshold for the translocation of the protein stopper through the nanopore related well to the biphasic voltage dependence of the residence time measured for the freely diffusing protein stopper. We propose a model in which molecules translocate through a nanopore when the average dwell time decreases with the applied potential.
Project description:Carbon-oxygen single bonds are ubiquitous in natural products whereas efficient methods for their reductive defunctionalization are rare. In this work an environmentally benign protocol for the activation of carbon-oxygen single bonds of alcohols towards a reductive bond cleavage under visible light photocatalysis was developed. Alcohols were activated as 3,5-bis(trifluoromethyl)-substituted benzoates and irradiation with blue light in the presence of [Ir(ppy)2(dtb-bpy)](PF6) as visible light photocatalyst and Hünig's base as sacrificial electron donor in an acetonitrile/water mixture generally gave good to excellent yields of the desired defunctionalized compounds. Functional group tolerance is high but the protocol developed is limited to benzylic, ?-carbonyl, and ?-cyanoalcohols; with other alcohols a slow partial C-F bond reduction in the 3,5-bis(trifluoromethyl)benzoate moiety occurs.
Project description:BACKGROUND:(R)-[3,5-bis(trifluoromethyl)phenyl] ethanol [(R)-3,5-BTPE] is a valuable chiral intermediate for Aprepitant (Emend) and Fosaprepitant (Ivemend). Biocatalyzed asymmetric reduction is a preferred approach to synthesize highly optically active (R)-3,5-BTPE. However, the product concentration and productivity of reported (R)-3,5-BTPE synthetic processes remain unsatisfied. RESULTS:A NADPH-dependent carbonyl reductase from Lactobacillus kefir (LkCR) was discovered by genome mining for reduction of 3,5-bis(trifluoromethyl) acetophenone (3,5-BTAP) into (R)-3,5-BTPE with excellent enantioselectivity. In order to synthesize (R)-3,5-BTPE efficiently, LkCR was coexpressed with glucose dehydrogenase from Bacillus subtilis (BsGDH) for NADPH regeneration in Escherichia coli BL21 (DE3) cells, and the optimal recombinant strain produced 250.3 g/L (R)-3,5-BTPE with 99.9% ee but an unsatisfied productivity of 5.21 g/(L h). Then, four different linker peptides were used for the fusion expression of LkCR and BsGDH in E. coli to regulate catalytic efficiency of the enzymes and improved NADPH-recycling efficiency. Using the best strain (E. coli/pET-BsGDH-ER/K(10 nm)-LkCR), up to 297.3 g/L (R)-3,5-BTPE with enantiopurity >99.9% ee was produced via reduction of as much as 1.2 M of substrate with a 96.7% yield and productivity of 29.7 g/(L h). CONCLUSIONS:Recombinant E. coli/pET-BsGDH-ER/K(10 nm)-LkCR was developed for the bioreduction of 3,5-BTAP to (R)-3,5-BTPE, offered the best results in terms of high product concentration and productivity, demonstrating its great potential in industrial manufacturing of (R)-3,5-BTPE.
Project description:Symmetrical N,N'-diarylureas: 1,3-bis(3,4-dichlorophenyl)-, 1,3-bis[4-chloro-3-(trifluoromethyl)phenyl]- and 1,3-bis[3,5-bis(trifluoromethyl)phenyl]urea, were identified as potent activators of the eIF2? kinase heme regulated inhibitor. They reduce the abundance of the eIF2·GTP·tRNA(i)(Met) ternary complex and inhibit cancer cell proliferation. An optimization process was undertaken to improve their solubility while preserving their biological activity. Non-symmetrical hybrid ureas were generated by combining one of the hydrophobic phenyl moieties present in the symmetrical ureas with the polar 3-hydroxy-tolyl moiety. O-alkylation of the later added potentially solubilizing charge bearing groups. The new non-symmetrical N,N'-diarylureas were characterized by ternary complex reporter gene and cell proliferation assays, demonstrating good bioactivities. A representative sample of these compounds potently induced phosphorylation of eIF2? and expression of CHOP at the protein and mRNA levels. These inhibitors of translation initiation may become leads for the development of potent, non-toxic, and target specific anti-cancer agents.
Project description:The synthesis of chiral tetrahydrofurans and pyrrolidines starting from 1,2-diols or ?-amino alcohols, respectively, by visible-light-mediated deoxygenation is described. Easily accessible monoallylated/propargylated substrates were activated either as inexpensive ethyl oxalates or as recyclable 3,5-bis(trifluoromethyl)benzoates to generate alkyl radicals suitable for 5-exo-trig/5-exo-dig cyclizations under visible-light irradiation.
Project description:Phenylacetylene-based rotaxanes were synthesized by a covalent-template approach by aminolysis of the corresponding prerotaxanes. The wheel and the bulky stoppers are made of phenylene-ethynylene-butadiynylene macrocycles of the same size. The stoppers are large enough to enable the synthesis and purification of the rotaxane. However, the wheel unthreads from the axle at elevated temperatures. The deslipping kinetics and the activation parameters were determined. We described theoretically the unthreading by state-of-the-art DFT-based molecular-mechanics models and a string method for the simulation of rare events. This approach enabled us to characterize in detail the unthreading mechanism, which involves the folding of the stopper during its passage through the wheel opening, a process that defies intuitive geometrical considerations. The conformational and energetic features of the transition allowed us to infer the molecular residues controlling the disassembly timescale.
Project description:Ankaferd blood stopper is a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica and has been used as a topical hemostatic agent and with its clinical application established in randomized controlled trials and case reports. Ankaferd has been successfully used in gastrointestinal endobronchial mucosal and cutaneous bleedings and also in abdominal, thoracic, dental and oropharyngeal, and pelvic surgeries. Ankaferd's hemostatic action is thought to form a protein complex with coagulation factors that facilitate adhesion of blood components. Besides its hemostatic action, Ankaferd has demonstrated pleiotropic effects, including anti-neoplastic and anti-microbial activities and tissue-healing properties; the underlying mechanisms for these have not been well studied. Ankaferd's individual components were determined by proteomic and chemical analyses. Ankaferd also augments transcription of some transcription factors which is shown with transcriptomic analysis. The independent effects of these ingredients and augmented transcription factors are not known precisely. Here, we review what is known of Ankaferd blood stopper components from chemical, proteomic, and transcriptomic analyses and propose that individual components can explain some pleiotropic effects of Ankaferd. Certainly more research is needed focusing on individual ingredients of Ankaferd to elucidate their precise and effects.
Project description:Amyloids characterized by unbounded growth of fibrillar structures cause many pathological processes. Such unbounded propagation is due to the presence of a propagating hydrophobicity field around the fibril's main axis, preventing its closure (unlike in globular proteins). Interestingly, similar fragments, commonly referred to as solenoids, are present in many naturally occurring proteins, where their propagation is arrested by suitably located "stopper" fragments. In this work, we analyze the distribution of hydrophobicity in solenoids and in their corresponding "stoppers" from the point of view of the fuzzy oil drop model (called FOD in this paper). This model characterizes the unique linear propagation of local hydrophobicity in the solenoid fragment and allows us to pinpoint "stopper" sequences, where local hydrophobicity quite closely resembles conditions encountered in globular proteins. Consequently, such fragments perform their function by mediating entropically advantageous contact with the water environment. We discuss examples of amyloid-like structures in solenoids, with particular attention to "stop" segments present in properly folded proteins found in living organisms.