Synthetic Tigliane Intermediates Engage Thiols to Induce Potent Cell Line Selective Anti-Cancer Activity

The tigliane ring system, which encompasses iconic members such as phorbol and TPA, is widely renowned due to numerous observations of displaying potent biological activity, and subsequent use as mainstream biochemical tools. Traditionally, naturally occurring phorboids are regarded as tumor promotors through PKC activation, although in recent times more highly oxidized natural derivatives have been identified as anti-tumor agents. In the view that only limited synthetic investigations toward skeletal stereochemical modification have been undertaken, non-natural systems could be useful for a better understanding of the tigliane pharmacophore via interrogation of cellular sensitivity. In this context the concise construction of a number of highly functionalized non-natural D-ring inverted phorbol esters were synthesized, via a rhodium-catalyzed [4+3] cycloaddition, and biologically evaluated using a range of cancer cell lines. The biological results highlight the notion that subtle changes in structure have dramatic effects on potency. Furthermore, although the non-natural derivatives did not outcompete the natural systems in the PKC-activation sensitive MCF7 cancer cell line, they outperformed in other cancer cell lines (MM96L and CAL27). This observation strongly suggested an alternate mode of action not involving activation of PKC, but instead involves thiol addition as indicated by glutathione addition and NF-κB reporter activity.     

Scholl-Type Cycloheptatriene Ring Closure of 1,4,9,12-Tetraarylfenestrindanes: Reactivity and Selectivity in the Construction of Fenestrane-Based Polyaromatic Saddles

The Scholl-type cyclodehydrogenation, generating up to four cycloheptatriene rings around a fenestrindane core, leads to novel, saddle-shaped polyaromatic hydrocarbon derivatives. In this article, we present the results of in-depth experimental and computational work on the oxidative cyclization of various 1,4,9,12-tetraarylfenestrindanes. In particular, the kinetic control of the four-step cyclization of the electronically activated tetrakis(3,4-dimethoxyphenyl) derivative is elucidated. The reasons for the exclusive emergence of one single among the three possible doubly cyclized intermediates and for the nonappearance of the singly and triply cyclized intermediates are clarified. In addition, the origin of the concomitant bridgehead hydroxylation is studied. The reactivity of a set of fifteen symmetrically and unsymmetrically substituted 1,4,9,12-tetraarylfenestrindanes towards Scholl-type cyclodehydrogenation is presented, pinpointing the structural factors that underlie this reaction and demonstrating the potential and limitations of this synthetic approach. A particularly surprising finding of this study is that the electronically nonactivated 1,4,9,12-tetraphenylfenestrindane can also undergo the fourfold Scholl-type cyclization process and can be transformed into the parent saddle hydrocarbon.     

Large-eddy simulation of decaying isotropic turbulence across a grid refinement interface using explicit filtering and reconstruction

This paper explores numerical errors that arise when large-eddy simulation (LES) is used with adaptive mesh refinement (AMR). LES and AMR combined can reduce the computational cost of turbulence simulations compared to direct numerical simulations, but are rarely used together due to complications that arise with the application of the turbulence closure model at different grid resolutions. Errors appear at grid refinement interfaces due to dependence of computed quantities on the LES filter width and insufficient smoothness of the solution at the grid scale. Here, explicit filtering and approximate reconstruction of the unfiltered velocity field are used to mitigate the effects of these errors in a simulation of decaying isotropic turbulence advected past a grid refinement interface. In particular, different explicit filter types and levels of reconstruction are tested. Explicit filtering with zero-level reconstruction is found to produce the best long-term convergence to a uniform grid solution with minimum perturbation at the interface. Higher levels of reconstruction yield better near-interface convergence. When explicit filtering is used, the explicit filter width transition is more important than the grid spacing transition in terms of solution convergence and interface perturbation. These results inform the use of LES on more complicated AMR grids.     

Short pulse Z -scan investigations of optical nonlinearities of a novel organometallic complex: [(C2H5)4N]2[Cu(dmit)2] at 532 and 1064?nm

A novel dmit organometallic complex: [(C₂H₅)₄N]₂[Cu(dmit)₂] (dmit^2-=1,3-dithiole-2-thione-4,5-dithiolate), abbreviated as EtCu, was synthesized. Afterwards its optical nonlinearities in acetone solution at 532 nm and 1064 nm were studied by the Z-scan technique with laser pulses of picosecond duration. The two-photon absorption at 1064 nm and the saturable absorption at 532 nm were observed. The Z-scan curves also revealed that EtCu sample solutions exhibited self-defocusing effects at both wavelengths. The origins were analyzed for the differences between the results. All the outcomes suggest that this material is potential for nonlinear optical device applications. PACS 42.65.An; 42.65.Hw; 42.65.Jx; 81.20.Ka; 78.30.Jw     

Optical packet labeling based on simultaneous polarization shift keying and amplitude shift keying

We propose and demonstrate label encoding-swapping and transmission for an orthogonally labeled packet by use of a 10-Gbit/s amplitude shift keying payload and a 2.5-Gbit/s polarization shift keying (PolSK) label. A simple scheme for demodulating and demultiplexing the PolSK label based on an injection-locked Fabry-Perot laser diode is described. The extinction ratio of the newly added PolSK label can be precisely controlled and maintained after the intermediate node.     

Novel cuticular hydrocarbons from the cane beetle Antitrogus parvulus--4,6,8,10,16-penta- and 4,6,8,10,16,18-hexamethyldocosanes-unprecedented anti-anti-anti-stereochemistry in the 4,6,8,10-methyltetrad

The major cuticular hydrocarbons from the cane beetle species Antitrogus parvulus are 4,6,8,10,16-penta- and 4,6,8,10,16,18-hexamethyldocosanes, 1 and 2, respectively. Stereoisomers of 2,4,6,8-tetramethylundecanal of established relative stereochemistry were derived from 2,4,6-trimethylphenol and were then coupled with appropriate methyl-substituted phosphoranes 62 and 25 to furnish alkenes, which on reduction provided diastereomers of 1 and 2, respectively. Capillary gas chromatography, mass spectrometry, and high resolution 13C NMR spectroscopy confirmed 1 as either 84a or 84b and 2 as either 15a or 15b. The novelty of these structures and their relative stereochemistry is briefly related to polyketide assembly.     

The zwitterion effect in proton exchange membranes as synthesised by polymerisation of bicontinuous microemulsions

The bicontinuous microemulsions consisting of a polymerisable zwitterionic surfactant 3-((11-acryloyloxyundecyl)imidazolyl) propyl sulfonate (AIPS) and other monomers can be cross-polymerised to form good proton conductive membranes.     

Low-loss, wide-angle Y splitter at approximately ~1.6- mum wavelengths built with a two-dimensional photonic crystal

We report a successful experimental realization of a photonic-crystal Y splitter operating at lambda~1.6 mum . Our device has a large splitting angle of 120 degrees and a miniature size of ~3 mumx3 mum . Furthermore, the Y-splitter loss is measured to be 0.5-1 dB at lambda=1640-1680 nm, making the Y splitter promising for integrated photonic-circuit applications. These unique properties are attributed to the new guiding principle made possible by the photonic bandgap.     

A heuristic for sea-freight container selection,cargo allocation and cargo orientation

A model is proposed to generate solutions for container selection, for the allocation of cargo to containers, and for cargo orientation within a container. The model is in the form of a mixed integer program with the objective of minimizing the total shipping cost. The practical requirements of loading priority and weight distribution along the main dimension of the container are incorporated into the model. A heuristic solution strategy is proposed and used to control the computation time by pre-setting the search increments. Three case examples are presented. The first and third examples show that the proposed model can produce a better solution than the manual schedulers. The second example is taken from the literature and is compared with the solution generated by the proposed model, demonstrating that the practical considerations incorporated into the model do not necessarily lead to increased shipping costs.