Solution structure of the Legionella pneumophila Mip-rapamycin complex

<p>Abstract</p> <p>Background</p> <p><it>Legionella pneumphila </it>is the causative agent of Legionnaires' disease. A major virulence factor of the pathogen is the homodimeric surface protein Mip. It shows peptidyl-prolyl cis/trans isomerase activty and is a receptor of FK506 and rapamycin, which both inhibit its enzymatic function. Insight into the binding process may be used for the design of novel Mip inhibitors as potential drugs against Legionnaires' disease.</p> <p>Results</p> <p>We have solved the solution structure of free Mip^77–213and the Mip^77–213-rapamycin complex by NMR spectroscopy. Mip^77–213showed the typical FKBP-fold and only minor rearrangements upon binding of rapamycin. Apart from the configuration of a flexible hairpin loop, which is partly stabilized upon binding, the solution structure confirms the crystal structure. Comparisons to the structures of free FKBP12 and the FKBP12-rapamycin complex suggested an identical binding mode for both proteins.</p> <p>Conclusion</p> <p>The structural similarity of the Mip-rapamycin and FKBP12-rapamycin complexes suggests that FKBP12 ligands may be promising starting points for the design of novel Mip inhibitors. The search for a novel drug against Legionnaires' disease may therefore benefit from the large variety of known FKBP12 inhibitors.</p

Decoupling Charge Transport and Electroluminescence in a High Mobility Polymer Semiconductor.

Fluorescence enhancement of a high-mobility polymer semiconductor is achieved via energy transfer to a higher fluorescence quantum yield squaraine dye molecule on 50 ps timescales. In organic light-emitting diodes, an order of magnitude enhancement of the external quantum efficiency is observed without reduction in the charge-carrier mobility resulting in radiances of up to 5 W str(-1) m(-2) at 800 nm.We gratefully acknowledge funding from the Engineering and Physical Sciences Research Council (EPSRC) through a programme grant EP/M005143/1. We would like to thank the Doctoral Training Centre in Plastic Electronics EP/G037515/1. K. B. acknowledges financial support by the Deutsche Forschungsgemeinschaft (BR-4869/1-1). The group at Würzburg would like to acknowledge support from the Deutsche Forschungsgemeinschaft (DFG Research Unit FOR 1809) and from the SolTech Initiative of the Bavarian State Ministry of Science, Research and the Arts. D. H. and K.B. would like to thank Dr. Jiři Novak and Jakub Rozbořil (Central European Institute of Technology, Masaryk University, Czech Republic) and Dr. Tom Arnold (Diamond Light Source, Didcot, UK) for assistance during the synchrotron experiment and Diamond Light Source, Didcot, UK for financial support

Synthese und Optisch Spektroskopische Eigenschaften von Squarain Superchromophoren

In this work the successful synthesis, the linear and nonlinear spectroscopic properties as well as the electrochemical behaviour of some linear and star-shaped squaraine superchromophores that are based on indolenine derivatives were presented. The attempt to synthesise similar chromophores which contained only benzothiazole squaraines failed unfortunately. However, one trimer that contained mixed benzothiazole indolenine squaraines could be synthesised and investigated as well. The linear spectroscopic properties, like red-shift and broadening of the absorption, of all superchromophores could be explained by exciton coupling theory. The heterochromophores (SQA)2(SQB)-N, (SQA)(SQB)2-N and (SQA)(SQB)-NH displayed additional to the typical squaraine fluorescence from the lowest excited state some properties that could be assigned to localised states. While the chromophores with N-core showed very small emission quantum yields, the chromophores with the other cores and the linear oligomers display an enhancement compared to the monomers. Transient absorption spectroscopy experiments of the star-shaped superchromophores showed, that their formally degenerated S1 states are split due to a deviation of the ideal C3 symmetry. This is also the reason for the observation of an absorption band for the highest exciton state, which is derived from the S1-state of the monomers, as its transition-dipole moment would be zero in the symmetrical case. The linear oligomers and the star-shaped superchromophores with a benzene or triarylamine core showed at least additive, sometimes even weak cooperative, behaviour in the two-photon absorption experiments. Additional to higher two-photon absorption cross sections the chromophores showed a pronounced broadening of the nonlinear absorption, due to symmetry breaking and a higher density of states. Unfortunately it was not possible to solve the problem of the equilibrium of the cisoid and the transoid structure of donor substituted azulene squaraines, due to either instability of the squaraines or steric hindrance.Diese Arbeit beschreibt die Synthese von einigen linearen und stern-förmigen Squarain Superchromophoren die auf Indol Derivaten basieren. Außerdem werden sowohl deren lineare und nicht lineare spektroskopische Eigenschaften als auch ihr elektrochemisches Verhalten präsentiert. Der Versuch ähnliche Farbstoffe mit Benzothiazol Derivaten zu synthetisieren schlug leider fehl. Allerdings konnte ein stern-förmiges Trimer hergestellt und untersucht werden, dessen Äste aus einem gemischten Indol-Benzothiazol Squarain bestehen. Die linearen spektroskopischen Eigenschaften, wie Rotverschiebung und die Verbreiterung der Absorption, aller Superchromophore konnten mit Hilfe der Exzitonen-Kopplungs Theorie erklärt werden. Die Heterochromophore (SQA)2(SQB)-N, (SQA)(SQB)2-N und (SQA)(SQB)-NH zeigten zusätzlich zu der typischen Squarain Fluoreszenz aus dem niedrigsten angeregten Zustand einige Besonderheiten die lokalisierten Zuständen zugeordnet werden konnten. Während die Farbstoffe mit einem Stickstoffkern lediglich geringe Fluoreszenzquantenausbeuten zeigen, zeigen die anderen Superchromophore im Vergleich mit den monomeren Squarainen teilweise erheblich größere Fluoreszenzquantenausbeuten. Transiente Absorptionsspektroskopie Messungen der stern-förmigen Farbstoffe legen nahe, dass deren formell degenerierte S1 Zustände wegen einer Abweichung von der C3-Symmetrie aufspalten. Durch diese Abweichung bekommt auch der Übergang vom Grundzustand zum höchsten exzitonischen Zustand, der sich aus den S1-Zuständen der Monomere ableiten lässt, ein merkliches Übergangsdipolmoment und kann daher in den linearen Absorptionsspektren beobachtet werden. Die linearen Oligomere und die stern-förmigen Superchromophore die einen Benzol oder Triarylamin Kern haben zeigten mindestens additives, manchmal auch verstärkendes Verhalten in der Zweiphotonenabsorption. Zusätzlich zu den größeren molekularen Zweiphotonenabsorptions-Querschnitten sind auf Grund von Symmetriebrüchen und einer hohen Dichte von Zuständen die nicht linearen Absorptionsbanden merklich verbreitert. Im Falle der Donor substituierten Azulen-Squaraine, war es nicht möglich wegen sterischen Gründen oder unstabilen Zwischenprodukten in der Synthese, das Gleichgewicht der cisoiden und der transoiden Struktur so zu verschieben das in Lösung nur noch eine der beiden Strukturen beobachtet wird

Ultrafast bi-excitonic dynamics and annihilation in molecular and mesoscopic systems

We present 5th and 3rd order 2D spectra of a squarine trimer. Slowly decaying (τ = 0.8 ps) and intensity dependent features unique to the 5th order signal are attributed to exciton-exciton annihilation

Cooperative enhancement versus additivity of two-photon-absorption cross sections in linear and branched squaraine superchromophores

The linear and nonlinear optical properties of a series of oligomeric squaraine dyes were investigated by one-photon absorption spectroscopy (1PA) and two-photon absorption (2PA) induced fluorescence spectroscopy. The superchromophores are based on two indolenine squaraine dyes with transoid (SQA) and cisoid configuration (SQB). Using these monomers, linear dimers and trimers as well as star-shaped trimers and hexamers with benzene or triphenylamine cores were synthesised and investigated. The red-shifted and intensified 1PA spectra of all superchromophores could well be explained by exciton coupling theory. In the linear chromophore arrangements we also found superradiance of fluorescence but not in the branched systems. Furthermore, the 2PA showed enhanced cross sections for the linear oligomers but only additivity for the branched systems. This emphasizes that the enhancement of the 2PA cross section in the linear arrangements is probably caused by orbital interactions of higher excited configurations

Localization/Delocalization of Charges in Bay-Linked Perylene Bisimides

The copper-mediated Ullmann coupling of 1,7-dibromoperylene bisimides afforded structurally perfect singly-linked perylene bisimide (PBI) arrays, whilst the homo-coupling of 1,12-dibromoperylene bisimides gave doubly-linked and triply-linked diperylene bisimides. The interactions of three bay-linked diperylene bisimides that differed in their linkage (singly, doubly, and triply) were investigated in their neutral and reduced forms (mono-anion to tetra-anion). UV/Vis absorption and fluorescence spectroscopy revealed different degrees of interaction, which was explained by exciton coupling and conjugation effects. The electrochemical properties and spectroelectrochemistry also showed quite-different degrees of PBI interactions in the reduced mixed-valence species, which was apparent by the observation of CT bands. The interpretation of the experimental findings was supported by spin-restricted and -unrestricted DFT and time-dependent TDDFT calculations with the long-rangecorrected CAM-B3LYP functional. Accordingly, the degree of interaction in both the neutral and reduced forms of the bay-linked PBIs was qualitatively in the order doubly linke

Coupled Oscillators for Tuning Fluorescence Properties of Squaraine Dyes

Combining a squaraine (S) and a BODIPY (B) chromophore in a heterodimer (SB) and two heterotrimers (BSB and SBS) by alkyne bridges leads to the formation of coupled oscillators whose fluorescence properties are superior compared to the parent squaraine chromophore. The lowest energy absorption and emission properties of these superchromophores are mainly governed by the squaraine part and are shifted by more than 1000 cm^–1 to the red by excitonic interaction between the squaraine and the BODIPY dye. Employing polarization-dependent transient absorption and fluorescence upconversion measurements, we could prove that the lowest energy absorption in SB and BSB is caused by a single excitonic state but by two for SBS. Despite the spectral red-shift of their lowest absorption band, the fluorescence quantum yields increase for SB and BSB compared to the parent squaraine chromophore SQA. This is caused by intensity borrowing from the BODIPY states, which increases the squared transition moments of the lowest energy band dramatically by 29% for SB and 63% for BSB compared to SQA. Thereby, exciton coupling leads to a substantial enhancement of fluorescence quantum yield by 26% for SB and by 46% for BSB and shifts the emission from the red into the near-infrared. In this way, the BODIPY-squaraine conjugates combine the best properties of each class of dye. Thus, exciton coupling in heterodimers and -trimers is a valuable alternative to tuning fluorescence properties by, e.g., attaching substituents to chromophores

Diversity of polyphenols in the peel of apple ( Malus

This study investigated ten polyphenolic compounds in the peel of 145 apple cultivars grown in the same location while originated from different countries over two successive years. Despite significant year effect of individual and total polyphenol concentrations on each cultivar, both concentrations showed similar distributions in the 2 years, and genotypic correlations among them were relatively stable. Genotypic variations were considerable, with total polyphenol concentration ranging from 363.9 to 2516.9 mu g g(-1) FW. Cyanidin-3-galactoside was found only in red apple peels, at levels of 67.8-371.6 mu g g(-1) FW. Flavanols (epicatechin and catechin) and dihydrochalcones (mainly phloridzin) accounted for 8.8-66.1% and 8.58-61.2% of total polyphenols, respectively. Six flavonols (quercetin-3-galactoside, quercetin-3-glucoside, quercetin-3-rhamnoside, quercetin-3-xyloside, quercetin-3-arabinoside, and quercetin-3-rhamnoglucoside) were identified. The proportion of flavonols was 9.3-70.6% of total polyphenols. This wide variation could help in selecting cultivars with different polyphenol patterns in the peel. Principal component analysis showed that cultivars originated from different countries could not be distinguished in terms of polyphenol profiles

Exciton Dynamics from Strong to Weak Coupling Limit Illustrated on a Series of Squaraine Dimers

We present a joint theoretical and experimental study on the light-induced exciton relaxation dynamics in a series of three squaraine dimers spanning the range from weak to intermediate to strong excitonic coupling strength regime. As revealed by transient-absorption spectroscopy and mixed quantum-classical dynamics simulations that explicitly take into account excitation by the laser pulse, three different types of exciton dynamics could be observed, although the investigated systems exhibit very similar spectral features. While in the strongly coupled system (Frenkel limit), the exciton remains delocalized over both dye monomers, in the system with intermediate coupling, transient localization–delocalization on a femtosecond time scale can be observed. Finally, in the weakly coupled heterodimer (Förster limit), efficient exciton transfer, mediated by transient delocalization that correlates with a strong nonadiabatic coupling, takes place. By delivering the first systematic microscopic study on different regimes of exciton transfer, our findings shed new light on the possible mechanisms of energy transport in organic molecular excitonic materials