313 research outputs found
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Stimulus-Mediated Ultrastable Radical Formation
Organic radicals are reactive, often short-lived species typically formed through either the addition of a chemical agent or photochemical means. On account of their open-shell electronic structure they have attracted attention based upon their magnetic properties and desirable spectroscopic behaviour. Redox sensitive molecules such as viologen (V) undergo one-electron reductions to form radical species. These species hold significant potential in myriad applications but are limited as they are rapidly quenched by oxygen in air. Using methyl viologen as an example, we show that the MV radical (MV+·) can be formed through electrochemical, chemical, photochemical and a novel thermal stimulus in various Deep Eu- tectic Solvents (DES) and was found to be exceptionally stable. The conductive properties of DES allowed for fabrication of an aerobic electrochromic device through a straightforward, economical approach. Our report represents a unique approach to extend reactive radical lifetimes in air without alteration of the parent structure.J.A.M. would like to acknowledge the EPSRC for a PhD studentship (EP/K503009/1). O.A.S. acknowledges ERC Consolidator grant CAM-RIG (No.726470) and UK Engineering and Physical Sciences Research Council grant EP/L027151/1. M.F.K. and E.R. acknowledge Christian Doppler Research Association (Austrian Federal Ministry of Science, Research and Economy and the National Foundation for Research, Technology and Development), the OMV Group and the EPSRC (IAA Follow-on Fund)
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Oligopeptide-CB[8] complexation with switchable binding pathways.
Host-guest complexes exhibiting a 1 : 1 binding stoichiometry need not consist of a single host and guest. A series of oligopeptides, which were previously reported to have abnormally high binding enthalpies were investigated to deduce whether they exist as a 2 : 2 quaternary or a 1 : 1 binary complex with cucurbit[8]uril (CB[8]). Through a systematic study of the sequence-specific binding pathways of peptide-CB[8] association, a phenylalanine-leucine dipeptide was found to be capable of switching from a 1 : 1 stoichiometric complex to a 2 : 1 complex. By studying the differences in size-based diffusion properties of these two binding modes, the presence of a 1 : 1 pairwise inclusion complex was verified for the regime where CB[8] is in excess. Findings in this study can be utilised to 'customise' the precise CB[8]-oligopeptide self-assembly pathway, acting as a useful toolbox in the design of supramolecular systems.The Leverhulme Trust
Marie Curie FP7
ERC
EPSR
Careful adjustment of Epo non-viral gene therapy for β-thalassemic anaemia treatment
BACKGROUND: In situ production of a secreted therapeutic protein is one of the major gene therapy applications. Nevertheless, the plasmatic secretion peak of transgenic protein may be deleterious in many gene therapy applications including Epo gene therapy. Epo gene transfer appears to be a promising alternative to recombinant Epo therapy for severe anaemia treatment despite polycythemia was reached in many previous studies. Therefore, an accurate level of transgene expression is required for Epo application safety. The aim of this study was to adapt posology and administration schedule of a chosen therapeutic gene to avoid this potentially toxic plasmatic peak and maintain treatment efficiency. The therapeutic potential of repeated muscular electrotransfer of light Epo-plasmid doses was evaluated for anaemia treatment in β-thalassemic mice. METHODS: Muscular electrotransfer of 1 μg, 1.5 μg, 2 μg 4 μg or 6 μg of Epo-plasmid was performed in β-thalassemic mice. Electrotransfer was repeated first after 3.5 or 5 weeks first as a initiating dose and then according to hematocrit evolution. RESULTS: Muscular electrotransfer of the 1.5 μg Epo-plasmid dose repeated first after 5 weeks and then every 3 months was sufficient to restore a subnormal hematrocrit in β-thalassemic mice for more than 9 months. CONCLUSION: This strategy led to efficient, long-lasting and non-toxic treatment of β-thalassemic mouse anaemia avoiding the deleterious initial hematocrit peak and maintaining a normal hematocrit with small fluctuation amplitude. This repeat delivery protocol of light doses of therapeutic gene could be applied to a wide variety of candidate genes as it leads to therapeutic effect reiterations and increases safety by allowing careful therapeutic adjustments
Optical imaging of luminescence for in vivo quantification of gene electrotransfer in mouse muscle and knee
BACKGROUND: Optical imaging is an attractive non-invasive way to evaluate the expression of a transferred DNA, mainly thanks to its lower cost and ease of realization. In this study optical imaging was evaluated for monitoring and quantification of the mouse knee joint and tibial cranial muscle electrotransfer of a luciferase encoding plasmid. Optical imaging was applied to study the kinetics of luciferase expression in both tissues. RESULTS: The substrate of luciferase (luciferin) was injected either intraperitonealy (i.p.) or in situ into the muscle or the knee joint. Luminescence resulting from the luciferase-luciferin reaction was measured in vivo with a cooled CCD camera and/or in vitro on tissue lysate. Maximal luminescence of the knee joint and muscle after i.p. (2.5 mg) or local injection of luciferin (50 μg in the knee joint, 100 μg in the muscle) were highly correlated. With the local injection procedure adopted, in vivo and in vitro luminescences measured on the same muscles significantly correlated. Luminescence measurements were reproducible and the signal level was proportional to the amount of plasmid injected. In vivo luciferase activity in the electrotransfered knee joint was detected for two weeks. Intramuscular electrotransfer of 0.3 or 3 μg of plasmid led to stable luciferase expression for 62 days, whereas injecting 30 μg of plasmid resulted in a drop of luminescence three weeks after electrotransfer. These decreases were partially associated with the development of an immune response. CONCLUSION: A particular advantage of the i.p. injection of substrate is a widespread distribution at luciferase production sites. We have also highlighted advantages of local injection as a more sensitive detection method with reduced substrate consumption. Besides, this route of injection is relatively free of uncontrolled parameters, such as diffusion to the target organ, crossing of biological barriers and evidencing variations in local enzymatic kinetics, probably related to the reaction medium in the targeted organ. Optical imaging was shown to be a sensitive and relevant technique to quantify variations of luciferase activity in vivo. Further evaluation of the effective amount of luciferase in a given tissue by in vivo optical imaging relies on conditions of the enzymatic reaction and light absorption and presently requires in vitro calibration for each targeted organ
A novel thiazolidine compound induces caspase-9 dependent apoptosis in cancer cells
Cataloged from PDF version of article.The forward chemogenomics strategy allowed us to identify a potent cytotoxic thiazolidine compound as an apoptosis-inducing agent. Chemical structures were designed around a thiazolidine ring, a structure already noted for its anticancer properties. Initially, we evaluated these novel compounds on liver, breast, colon and endometrial cancer cell lines. The compound 3 (ALC67) showed the strongest cytotoxic activity (IC50 ∼5 μM). Cell cycle analysis with ALC67 on liver cells revealed SubG1/G1 arrest bearing apoptosis. Furthermore we demonstrated that cytotoxicity of this compound was due to the activation of caspase-9 involved apoptotic pathway, which is death receptor independent. © 2012 Elsevier Ltd. All rights reserve
Electromagnetically induced transparency in inhomogeneously broadened Lambda-transition with multiple excited levels
Electromagnetically induced transparency (EIT) has mainly been modelled for
three-level systems. In particular, a considerable interest has been dedicated
to the Lambda-configuration, with two ground states and one excited state.
However, in the alkali-metal atoms, which are commonly used, hyperfine
interaction in the excited state introduces several levels which simultaneously
participate in the scattering process. When the Doppler broadening is
comparable with the hyperfine splitting in the upper state, the three-level
Lambda model does not reproduce the experimental results. Here we theoretically
investigate the EIT in a hot vapor of alkali-metal atoms and demonstrate that
it can be strongly reduced due to the presence of multiple excited levels.
Given this model, we also show that a well-designed optical pumping enables to
significantly recover the transparency
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Surface-Bound Cucurbit[8]uril Catenanes on Magnetic Nanoparticles Exhibiting Molecular Recognition.
We demonstrate the preparation of surface-bound cucurbit[8]uril (CB[8]) catenanes on silica nanoparticles (NPs), where CB[8] was employed as a tethered supramolecular "handcuff" to selectively capture target guest molecules. In this catenane, CB[8] was threaded onto a methyl viologen (MV(2+) ) axle and immobilized onto silica NPs. The formation of CB[8] catenanes on NPs were confirmed by UV/Vis titration experiments and lithographic characterization, demonstrating a high density of CB[8] on the silica NPs surface, 0.56 nm(-2) . This CB[8] catenane system exhibits specific molecular recognition towards certain aromatic molecules such as perylene bis(diimide), naphthol and aromatic amino acids, and thus it can act as a nanoscale molecular receptor for target guests. Furthermore, we also demonstrate its use as an efficient and recyclable nano-platform for peptide separation. By embedding magnetic NPs inside silica NPs, separation could be achieved by simply applying an external magnetic field. Moreover, the peptides captured by the catenanes could be released by reversible single-electron reduction of MV(2+) . The entire process demonstrated high recoverability.X. Ren thanks the CSC Cambridge Scholarship for financial support and
Dr. Ziyi Yu for template preparation. Y. Wu is financially supported
by the EP/L504920/1, J. Liu by the Marie Curie FP7 SASSYPOL ITN
(607602) programme, and G. Wu by the Leverhulme Trust.This is the author accepted manuscript. The final version is available from Wiley at http://dx.doi.org/10.1002/asia.201600875
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Aryl-viologen pentapeptide self-assembled conductive nanofibers.
A pentapeptide sequence was functionalized with an asymmetric arylated methyl-viologen (AVI3D2) and through controllable β-sheet self-assembly, conductive nanofibers were formed. Using a combination of spectroscopic techniques and conductive atomic force microscopy, we investigated the molecular conformation of the resultant AVI3D2 fibers and how their conductivity is affected by β-sheet self-assembly. These conductive nanofibers have potential for future exploration as molecular wires in optoelectronic applications.ERC (‘ASPiRe’, 240629)
Marie Curie (FP7 ‘SASSYPOL’ ITN, 607602
Transparent Films Made of Highly Scattering Particles
Today, colloids are widely employed in various products from creams and coatings to electronics. The ability to control their chemical, optical, or electronic features by controlling their size and shape explains why these materials are so widely preferred. Nevertheless, altering some of these properties may also lead to some undesired side effects, one of which is an increase in optical scattering upon concentration. Here, we address this strong scattering issue in films made of binary colloidal suspensions. In particular, we focus on raspberry-type polymeric particles made of a spherical polystyrene core decorated by small hemispherical domains of acrylate with an overall positive charge, which display an unusual stability against aggregation in aqueous solutions. Their solid films display a brilliant red color due to Bragg scattering but appear completely white on account of strong scattering otherwise. To suppress the scattering and induce transparency, we prepared films by hybridizing them with oppositely charged PS particles with a size similar to that of the bumps on the raspberries. We report that the smaller PS particles prevent raspberry particle aggregation in solid films and suppress scattering by decreasing the spatial variation of the refractive index inside the film. We believe that the results presented here provide a simple strategy to suppress strong scattering of larger particles to be used in optical coatings
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