Two-channel dansyl/tryptophan emitters with a cholic acid bridge as reporters for local hydrophobicity within supramolecular systems based on bile salts

The aim of the present work is to develop two-channel emitters to probe local hydrophobicity by means of fluorescence quenching within different biomimetic supramolecular environments. To achieve this goal, the dansyl (Dns) and tryptophan (Trp) fluorophores have been covalently attached to cholic acid (CA) in order to ensure simultaneous incorporation of the two emitting units into the same compartment. In principle, the two fluorophores of the synthesized Dns-CA-Trp probes could either exhibit an orthogonal behavior or display excited state interactions. The fluorescence spectra of 3 beta-Dns-CA-Trp showed a residual Trp emission band at ca. 350 nm and an enhanced Dns maximum in the 500-550 nm region. This reveals a partial intramolecular energy transfer, which is consistent with the Dns and Trp singlet energies. Thus, the two photoactive units are not orthogonal; nevertheless, 3 beta-Dns-CA-Trp seems appropriate as a two-channel reporter for the supramolecular systems of interest. Fluorescence quenching of 3 beta-Dns-CA-Trp by iodide (which remains essentially in bulk water) was examined within sodium cholate, sodium taurocholate, sodium deoxycholate and mixed micelles. Interestingly, a decrease in the emission intensity of the two bands was observed with increasing iodide concentrations. The most remarkable effect was observed for mixed micelles, where the quenching rate constants were one order of magnitude lower than in solution. As anticipated, the quenching efficiency by iodide decreased with increasing hydrophobicity of the microenvironment, a trend that can be correlated with the relative accessibility of the probe to the ionic quencher.Financial support from the Spanish Government (CTQ2012-38754-C03-03), Predoctoral FPU fellowship (AP2008-03295), and the Generalitat Valenciana (Prometeo Program) is gratefully acknowledged.Gómez Mendoza, M.; Marín García, ML.; Miranda Alonso, MÁ. (2014). Two-channel dansyl/tryptophan emitters with a cholic acid bridge as reporters for local hydrophobicity within supramolecular systems based on bile salts. Organic and Biomolecular Chemistry. 12(42):8499-8504. https://doi.org/10.1039/c4ob01394hS849985041242Vayá, I., Lhiaubet-Vallet, V., Jiménez, M. C., & Miranda, M. A. (2014). Photoactive assemblies of organic compounds and biomolecules: drug–protein supramolecular systems. Chem. Soc. Rev., 43(12), 4102-4122. doi:10.1039/c3cs60413fGomez-Mendoza, M., Marin, M. L., & Miranda, M. A. (2011). Dansyl Derivatives of Cholic Acid as Tools to Build Speciation Diagrams for Sodium Cholate Aggregation. The Journal of Physical Chemistry Letters, 2(7), 782-785. doi:10.1021/jz200178rGomez-Mendoza, M., Marin, M. L., & Miranda, M. A. (2012). Dansyl-Labeled Cholic Acid as a Tool To Build Speciation Diagrams for the Aggregation of Bile Acids. The Journal of Physical Chemistry B, 116(51), 14776-14780. doi:10.1021/jp308624hWaissbluth, O. L., Morales, M. C., & Bohne, C. (2006). Influence of Planarity and Size on Guest Binding with Sodium Cholate Aggregates. Photochemistry and Photobiology, 82(4), 1030. doi:10.1562/2006-02-14-ra-803Rinco, O., Kleinman, M. H., & Bohne, C. (2001). Reactivity of Benzophones in the Different Binding Sites of Sodium Cholate Aggregates. Langmuir, 17(19), 5781-5790. doi:10.1021/la010526cHofmann, A. F. (1999). The Continuing Importance of Bile Acids in Liver and Intestinal Disease. Archives of Internal Medicine, 159(22), 2647. doi:10.1001/archinte.159.22.2647Nuin, E., Gómez-Mendoza, M., Andreu, I., Marin, M. L., & Miranda, M. A. (2012). New Photoactive Compounds To Probe Cholic Acid and Cholesterol inside Mixed Micelles. Organic Letters, 15(2), 298-301. doi:10.1021/ol303201yHammad, M. ., & Müller, B. . (1998). Increasing drug solubility by means of bile salt–phosphatidylcholine-based mixed micelles. European Journal of Pharmaceutics and Biopharmaceutics, 46(3), 361-367. doi:10.1016/s0939-6411(98)00037-xHammad, M. ., & Müller, B. . (1998). Solubility and stability of tetrazepam in mixed micelles. European Journal of Pharmaceutical Sciences, 7(1), 49-55. doi:10.1016/s0928-0987(98)00006-2Hammad, M. (1998). Solubility and stability of clonazepam in mixed micelles. International Journal of Pharmaceutics, 169(1), 55-64. doi:10.1016/s0378-5173(98)00117-3Hendradi, E., Obata, Y., Isowa, K., Nagai, T., & Takayama, K. (2003). Effect of Mixed Micelle Formulations Including Terpenes on the Transdermal Delivery of Diclofenac. Biological & Pharmaceutical Bulletin, 26(12), 1739-1743. doi:10.1248/bpb.26.1739Parsaee, S., Sarbolouki, M. N., & Parnianpour, M. (2002). In-vitro release of diclofenac diethylammonium from lipid-based formulations. International Journal of Pharmaceutics, 241(1), 185-190. doi:10.1016/s0378-5173(02)00238-7Yu, J., Zhu, Y., Wang, L., Peng, M., Tong, S., Cao, X., … Xu, X. (2010). Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate/phospholipid-mixed micelles. Acta Pharmacologica Sinica, 31(6), 759-764. doi:10.1038/aps.2010.55Sznitowska, M., Klunder, M., & Placzek, M. (2008). Paclitaxel Solubility in Aqueous Dispersions and Mixed Micellar Solutions of Lecithin. CHEMICAL & PHARMACEUTICAL BULLETIN, 56(1), 70-74. doi:10.1248/cpb.56.70Nuin, E., Gomez-Mendoza, M., Marin, M. L., Andreu, I., & Miranda, M. A. (2013). Influence of Drug Encapsulation within Mixed Micelles on the Excited State Dynamics and Accessibility to Ionic Quenchers. The Journal of Physical Chemistry B, 117(32), 9327-9332. doi:10.1021/jp404353uCuquerella, M. C., Rohacova, J., Marin, M. L., & Miranda, M. A. (2010). Stereodifferentiation in fluorescence quenching within cholic acid aggregates. Chemical Communications, 46(27), 4965. doi:10.1039/c0cc00176gWu, J., Liu, W., Ge, J., Zhang, H., & Wang, P. (2011). New sensing mechanisms for design of fluorescent chemosensors emerging in recent years. Chemical Society Reviews, 40(7), 3483. doi:10.1039/c0cs00224kBronshtein, I., Afri, M., Weitman, H., Frimer, A. A., Smith, K. M., & Ehrenberg, B. (2004). Porphyrin Depth in Lipid Bilayers as Determined by Iodide and Parallax Fluorescence Quenching Methods and Its Effect on Photosensitizing Efficiency. Biophysical Journal, 87(2), 1155-1164. doi:10.1529/biophysj.104.041434Rohacova, J., Marin, M. L., Martínez-Romero, A., O’Connor, J.-E., Gomez-Lechon, M. J., Donato, M. T., … Miranda, M. A. (2009). Synthesis of new, UV-photoactive dansyl derivatives for flow cytometric studies on bile acid uptake. Organic & Biomolecular Chemistry, 7(23), 4973. doi:10.1039/b912134jFőrster, T. (1959). 10th Spiers Memorial Lecture. Transfer mechanisms of electronic excitation. Discuss. Faraday Soc., 27(0), 7-17. doi:10.1039/df9592700007Eaton, D. F. (1988). Reference materials for fluorescence measurement. Pure and Applied Chemistry, 60(7), 1107-1114. doi:10.1351/pac198860071107T. Förster , Modern Quantum Chemistry , Academic Press , New York , 196

A novel synthetic approach to tyrosine dimers based on pterin photosensitization

Oxidative damage to proteins leads to a variety of modifications that are markers of pathogenesis. One of the most important modifications is the dityrosine (Tyr₂ ) cross-link, resulting from an oxidative covalent bond between two tyrosines (Tyr). An optimized methodology for preparation of pure Tyr₂ is important to investigate in detail its physicochemical properties and reactivity. Pterin (Ptr), the parent and unsubstituted compound of oxidized pterins, is able to photosensitize the cross-linking of free tyrosine (Tyr) and tyrosine residues of peptides and proteins through a photoinduced electron transfer mechanism. We have optimized a simple, one-step photocatalyzed formation of Tyr₂ , using Ptr as photocatalyst. Our procedure is carried out in aqueous solutions under UV-A radiation for few minutes. The purification of Tyr₂ is performed by reverse-phase chromatography. The obtained highly pure solution is used to fully characterize the Tyr₂ (exact mass and ¹H, ¹H- ¹H COSY; DEPT; HSQC and HMBC NMR experiments) and to deeper study its fluorescence properties.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Measurement of the top quark pair cross section with ATLAS in pp collisions at √s=7 TeV using final states with an electron or a muon and a hadronically decaying τ lepton

A measurement of the cross section of top quark pair production in proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 7 TeV is reported. The data sample used corresponds to an integrated luminosity of 2.05 fb -1. Events with an isolated electron or muon and a τ lepton decaying hadronically are used. In addition, a large missing transverse momentum and two or more energetic jets are required. At least one of the jets must be identified as originating from a b quark. The measured cross section, σtt-=186±13(stat.)±20(syst.)±7(lumi.) pb, is in good agreement with the Standard Model prediction

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde

Hunt for new phenomena using large jet multiplicities and missing transverse momentum with ATLAS in 4.7 fb−1 of √s=7 TeV proton-proton collisions

Results are presented of a search for new particles decaying to large numbers of jets in association with missing transverse momentum, using 4.7 fb−1 of pp collision data at s√=7TeV collected by the ATLAS experiment at the Large Hadron Collider in 2011. The event selection requires missing transverse momentum, no isolated electrons or muons, and from ≥6 to ≥9 jets. No evidence is found for physics beyond the Standard Model. The results are interpreted in the context of a MSUGRA/CMSSM supersymmetric model, where, for large universal scalar mass m 0, gluino masses smaller than 840 GeV are excluded at the 95% confidence level, extending previously published limits. Within a simplified model containing only a gluino octet and a neutralino, gluino masses smaller than 870 GeV are similarly excluded for neutralino masses below 100 GeV

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio