Molecular insight into γ–γ tubulin lateral interactions within the γ-tubulin ring complex (γ-TuRC)

γ-tubulin is essential for the nucleation and organization of mitotic microtubules in dividing cells. It is localized at the microtubule organizing centers and mitotic spindle fibres. The most well accepted hypothesis for the initiation of microtubule polymerization is that α/β-tubulin dimers add onto a γ-tubulin ring complex (γTuRC), in which adjacent γ-tubulin subunits bind to the underlying non-tubulin components of the γTuRC. This template thus determines the resulting microtubule lattice. In this study we use molecular modelling and molecular dynamics simulations, combined with computational MM-PBSA/MM-GBSA methods, to determine the extent of the lateral atomic interaction between two adjacent γ-tubulins within the γTuRC. To do this we simulated a γ–γ homodimer for 10 ns and calculated the ensemble average of binding free energies of ?107.76 kcal/mol by the MM-PBSA method and of ?87.12 kcal/mol by the MM-GBSA method. These highly favourable binding free energy values imply robust lateral interactions between adjacent γ-tubulin subunits in addition to their end-interactions longitudinally with other proteins of γTuRC. Although the functional reconstitution of γ-TuRC subunits and their stepwise in vitro assembly from purified components is not yet feasible, we nevertheless wanted to recognize hotspot amino acids responsible for key γ–γ interactions. Our free energy decomposition data from converting a compendium of amino acid residues identified an array of hotspot amino acids. A subset of such mutants can be expressed in vivo in living yeast. Because γTuRC is important for the growth of yeast, we could test whether this subset of the hotspot mutations support growth of yeast. Consistent with our model, γ-tubulin mutants that fall into our identified hotspot do not support yeast growth.     

A Facile Conversion of Halides. Alcohols and Olefins to Esters Usihg Iron(III) Perchlorate

A facile method has been developed for the ester ification of halides/alcohols/olefins with carboxylic acids using iron(III) perchlorate.     

Anthracene-based hetero bisamide chemosensor in fluorescence sensing of monocarboxylates over monocarboxylic acids

A fluorescent chemosensor 1 with different amide moieties as recognition elements has been designed and synthesised. The recognition behaviour of the chemosensor towards various monocarboxylates and their conjugate acids has been evaluated. Although the sensor 1 shows significant quenching of emission of anthracene in CH₃CN, it shows an increase in emission in CHCl₃ containing 2% CH₃CN upon complexation of aliphatic monocarboxylates. Receptor 1 shows selectivity for acetate, propanoate and dihydrogen phosphate over the other anions studied under different conditions. The binding features have been established by ¹H NMR, UV–vis and fluorescence spectroscopic methods.     

Coumarin-based symmetrical bisamide as fluorescent and colorimetric probes for copper ions

Coumarin-based new symmetrical bisamide 1 has been designed and synthesised. The bisamide 1 fluorometrically recognises Cu²⁺ in CH₃CN containing 0.06% DMSO by exhibiting an increase in emission upon complexation. In comparison, the isomeric structure 2 also reports the selectivity for Cu²⁺ under identical condition by showing an opposite mode of emission. In addition, Cu²⁺ gives rise to a change in colour of the solution of 1, which is clearly visible to the naked eye.     

Cu(II)‐Metallacryptands Self‐Assembled to Vesicular Aggregates Capable of Encapsulating and Transporting an Anticancer Drug Inside Cancer Cells

Crystallographically characterized M₂L₄ type cationic Cu(II)‐metallacryptands [MC(X)] derived from a series of bis‐pyridyl‐bis‐urea ligands (L_X; X = O, S, C) are self‐assembled to single‐layered vesicular aggregates in DMSO, DMSO/water, and DMSO/DMEM (biological media). One such vesicle is MC(O)‐vesicle that is demonstrated to be able to load and release (pH responsive) an anticancer drug, namely doxorubicin hydrochloride (DOX). DOX‐loaded MC(O)‐vesicle is also successfully transported within MDA‐MB‐231 cells—a highly aggressive human breast cancer cell line. Such self‐assembling behavior to form vesicular aggregates by metallacryptands (MCs) is hitherto unknown.     

Organophotoredox‐Catalyzed Cascade Radical Annulation of 2‐(Allyloxy)arylaldehydes with N‐(acyloxy)phthalimides: Towards Alkylated Chroman‐4‐one Derivatives

An organophotoredox catalyzed efficient and robust approach for the synthesis of highly important 3‐alkyl substituted chroman‐4‐one scaffold is developed using visible light induced radical cascade cyclization strategy. The reaction is initiated through the generation of alkyl radicals from N‐(acyloxy)phthalimides under photoredox conditions, which subsequently undergo intermolecular cascade radical cyclization on 2‐(allyloxy)arylaldehydes to afford chroman‐4‐one scaffolds. The presented strategy is attractive with regard to mild reaction conditions, operational simplicity, high functional group tolerance and broad substrate scope.     

CAAC‐Based Thiele and Schlenk Hydrocarbons

Diradicals have been of tremendous interest for over a century ever since the first reports of p‐ and m‐phenylene‐bridged diphenylmethylradicals in 1904 by Thiele and 1915 by Schlenk. Reported here are the first examples of cyclic(alkyl)(amino)carbene (CAAC) analogues of Thiele's hydrocarbon, a Kekulé diradical, and Schlenk's hydrocarbon, a non‐Kekulé diradical, without using CAAC as a precursor. The CAAC analogue of Thiele's hydrocarbon has a singlet ground state, whereas the CAAC analogue of Schlenk's hydrocarbon contains two unpaired electrons. The latter forms a dimer, by an intermolecular double head‐to‐tail dimerization. This straightforward synthetic methodology is modular and can be extended for the generation of redox‐active organic compounds.     

Study of energy transfer from 7-amino coumarin donors to the rhodamine 6G acceptor in lecithin vesicles and sodium taurocholate-lecithin mixed aggregates

The energy transfer using 7-amino coumarin dyes as the donor and rhodamine 590 (Rh6G) as the acceptor was investigated in lecithin vesicles and sodium taurocholate (NaTC)-lecithin mixed aggregates using steady-state and time-resolved fluorescence spectroscopy. All energy transfer parameters were calculated. The coumarin 153-Rh6G pair is the most efficient donor-acceptor pair as reflected by the value of k(ET). With addition of NaTC in lecithin, in the case of the coumarin 153-Rh6G pair, the energy transfer rate or efficiency does not change very much, whereas in the case of the coumarin 151-Rh6G pair, the energy transfer rate decreases 2-fold upon going from lecithin vesicles to NaTC-lecithin mixed aggregates where the molar ratio is 2.5. It is mainly due to the deeper location of coumarin 153 in the lipid bilayer or in mixed aggregates. Rotational relaxation data also support this idea.     

Reactions of indoles with mercury (II) salts

A number of mercurated indoles were prepared. Their spectroscopic data (UV,ir,^1H-NMR and13C-nmr) are reported. Our results contradict certain data appearing in previous reports on similar compounds. When heated in acetic acid mercurated compounds decomposed, although the products formed were not identical with those obtained earlier from the same substrates by the action of thallium(III) acetate in acetic acid. Reaction of l-methylindole-3-mercuriacetate with styrene in the presence of lithium tetrachloropalladate furnished a product which was tentatively assigned the structure 9-methyl-1,3-diphenyl-1, 2, 3, 4-tetrahydrocarbazole.     

Visualization of the tip vortices in a wind turbine wake

Abstract  

In the present study, an experimental study was conducted to characterize the formation and the evolution of the helical tip vortices and turbulent flow structures in the wake of a horizontal axis wind turbine model placed in an atmospheric boundary layer wind. A high-resolution particle image velocimetry system was used to make detailed flow field measurements to quantify the time evolution of the helical tip vortices in relation to the position of the rotating turbine blades in order to elucidate the underlying physics associated with turbine power generation and fatigue loads acting on the wind turbines.