Synthesis of N-benzyl-des-D-ring lamellarin K via an acyl-Claisen/Paal-Knorr approach

Lamellarin K is a complex pyrrole natural product and member of the lamellarin family – a group of natural products known for their potent biological activities, such as, antiproliferative activity and inhibition of P-gp mediated drug efflux pumps. We herein describe the synthesis of the N-benzyl-des-D ring analogue of lamellarin K using a route that centres on an acyl-Claisen reaction to eventually prepare a highly-functionalised 1-aryl-4-methyl-1,4-diketone. Paal-Knorr pyrrole formation using this diketone undergoes auto-oxidation to give a fully-substituted 5-formyl pyrrole which was converted into the natural lactone B ring. Antiproliferative testing of the N-benzyl-des-D ring analogue gave an IC₅₀ of 2.63 μM against the MDA-MB-231 breast cancer cell line.     

Macrocycle Dynamics in a Branched [8]Catenane Controlled by Three Different Stimuli in Three Different Regions

A branched [8]catenane from an efficient one-pot synthesis (72 % HPLC yield, 59 % isolated yield) featuring the simultaneous use of three kinds of templates and cucurbit[6]uril-mediated azide–alkyne cycloaddition (CBAAC) for ring-closing is reported. Design and assembly of the [8]catenane precursors are unexpectedly complex that can involve cooperating, competing and non-influencing interactions. Due to the branched structure, dynamics of the [8]catenane can be modulated in different extent by rigidifying/loosening the mechanical bonds at different regions by using solvent polarity, acid-base and metal ions as the stimuli. This work not only highlights the importance of understanding the delicate interplay of the weak and non-obvious supramolecular interactions in the synthesis of high-order [n]catenane, but also demonstrates a complex control of dynamics and flexibility for exploiting [n]catenanes applications.     

Velocity and turbulence measurements in combustion systems

A laser-Doppler velocimeter is used in the measurement of high-temperature gas flows. A two-stage fluidization particle generator provides magnesium oxide particles to serve as optical scattering centers. The one-dimensional dual-beam system is frequency shifted to permit measurements of velocities up to 300 meters per second and turbulence intensities greater than 100 percent.Exiting flows from can-type gas turbine combustors and burners with pre-mixed oxy-acetylene flames are described in terms of the velocity, turbulence intensity, and temperature profiles.The results indicate the influence of the combustion process on turbulence.List of Symbols A exit area of combustor or burner (m²) - A/F mass air-fuel ratio - D exit diameter of combustor or burner (m) - M mass flow rate of gases (kg/s) - N _D number of Doppler bursts used in each velocity measurement - Q volumetric flow rate at T _r (m³/s) - R exit radius of combustor or burner (m) - R _1/2 distance from centerline to radius where the velocity is one-half of the local centerline velocity (m) - Re exit Reynolds number based on cold flow, QD/A - r distance from centerline of flow (m) - T temperature (°C) - T _CL centerline temperature (°C) - T _r inlet (cold) air temperature of combustor or burner (°C) - T.I. turbulence intensity, - mean velocity (m/s) - U _i instantaneous velocity individually realized by LDV (m/s) - mean velocity at centerline of flow (m/s) - mean square velocity fluctuation (m²/s² - x distance along centerline downstream of exit (m) - absolute viscosity at T _r (kg/(ms)) - density at T _r (kg/m³)     

Measurements of layer depth during baroclinic instability in a two-layer flow

This study investigates the baroclinic instability of a two-layer rotating fluid system. The instability is generated by releasing a cylinder of buoyant fluid at the surface of ambient fluid. The buoyant fluid is dyed so that its depth may be determined from its optical thickness. The system first adjusts until the horizontal density gradient is balanced by a flow along the front, and the adjusted state is then unstable to azimuthal waves. Contours of constant upper layer depth are examined, and the perturbation at each azimuthal wavenumber is determined. The initial wavenumber is well modelled by simple quasi-geostrophic theory. There is a clear high wavenumber cutoff, and a transfer of energy to larger scales with time.     

Non-linear oscillations of a rotor-magnetic bearing system under superharmonic resonance conditions

The effect of non-linear magnetic forces on the non-linear response of the shaft is examined for the case of superharmonic resonance in this paper. It is shown that the steady-state superharmonic periodic solutions lose their stability by either saddle-node or Hopf bifurcations. The system exhibits many typical characteristics of the behavior of non-linear dynamical systems such as multiple coexisting solutions, jump phenomenon, and sensitive dependence on initial conditions. The effects of the feedback gains and imbalance eccentricity on the non-linear response of the system are studied. Finally, numerical simulations are performed to verify the analytical predictions.     

Electrochemical Detection of TNT at Cobalt Phthalocyanine Mediated Screen‐Printed Electrodes and Application to Detection of Airborne Vapours

We describe the use of cobalt phthalocyanine as a mediator to improve the sensitivity for the electrochemical detection of TNT. Commercial screen‐printed electrodes containing cobalt phthalocyanine were employed for determination of TNT. Improved sensitivities compared to screen‐printed carbon electrodes without phthalocyanine were observed, current response for cyclic voltammetric measurements at modified electrodes being at least double that of unmodified electrodes. A synergistic effect between oxygen and TNT reduction was also observed. Correlation between TNT concentrations and sensor output was observed between 0–200 µM TNT. Initial proof‐of‐concept experiments combining electrochemical determinations, with the use of an air‐sampling cyclone, are also reported.     

Viscoelastic properties of poly(ε‐caprolactone) – hydroxyapatite micro‐ and nano‐composites

Various composites have been proposed in the literature for the fabrication of bioscaffolds for bone tissue engineering. These materials include poly(ε‐caprolactone) (PCL) with hydroxyapatite (HA). Since the biomaterial acts as the medium that transfers mechanical signals from the body to the cells, the fundamental properties of the biomaterials should be characterized. Furthermore, in order to control the processing of these materials into scaffolds, the characterization of the fundamental properties is also necessary. In this study, the physical, thermal, mechanical, and viscoelastic properties of the PCL‐HA micro‐ and nano‐composites were characterized. Although the addition of filler particles increased the compressive modulus by up to 450%, the thermal and viscoelastic properties were unaffected. Furthermore, although the presence of water plasticized the polymer, the viscoelastic behavior was only minimally affected. Testing the composites under various conditions showed that the addition of HA can strengthen PCL without changing its viscoelastic response. The results found in this study can be used to further understand and approximate the time‐dependent behavior of scaffolds for bone tissue engineering. Copyright © 2012 John Wiley & Sons, Ltd.     

Self-assembly and aggregation of ATRP prepared amphiphilic BAB tri-block copolymers contained nonionic ethylene glycol and fluorescent 9,10-di(1-naphthalenyl)-2-vinyl-anthracene/1-vinyl-pyrene segments

Two novel amphiphilic BAB-type block copolymers, ADN-PEG3400-ADN and Py-PEG3400-Py containing deep blue and bluish-green fluorescent moieties were prepared using atom transfer radical polymerization (ATRP) (where, ADN = poly(9,10-di(1-naphthalenyl)-2-vinylanthracene), Py = poly(1-vinyl pyrene) and PEG3400 = poly(ethylene glycol) with M_n = 3400 g/mol). The GPC number averaged molecular weights (MW) of the block copolymers were M_n = 9600 and 13,800 g/mol, respectively, based on polystyrene MW standards. The PEG3400 segment has a melting temperature (T_m peak) at 64–65 °C, whereas the glass transition temperatures (T_g midpoint) of the ADN and Py segments were found to be 230 °C and 193 °C, respectively, and are similar to their respective homopolymers indicating complete microphase segregration. The photoluminescence (PL) emission of the copolymers ADN-PEG3400-ADN exhibited two maxima at 423.5 nm and 441.5 nm while Py-PEG3400-Py has a maximum at 488.5 nm. Both copolymers form individual spherical micelles with diameter from 30 to 90 nm for Py-PEG3400-Py and 40–160 nm for ADN-PEG3400-ADN. The micelles, however, transform into cross-linked pearl-necklace-like aggregates at polymer concentrations above 1000 ppm, which may be attributed to the physical cross-linking between adjacent spherical micelles caused by the PEG3400 segments.     

Photodynamic Tumor Eradication With a Novel Targetable Photosensitizer: Strong Vascular Effects and Dependence on Treatment Repetition Versus Potentiation

A novel pyropheophorbide‐a (PPa) derivative, Ac‐sPPp, was developed in our lab for targeted photodynamic therapy (PDT) and combination therapies. Its versatile peptide moiety, high water‐solubility, amphiphilicity, and micellar aggregation allow efficient coupling to targeting moieties and convenient mixing with other therapeutics. Photosensitizer immunoconjugate (PIC) targeted PDT, using Ac‐sPPp conjugated to therapeutic anti‐epidermal growth factor receptor (EGFR) antibody cetuximab, and PDT + chemotherapy combination treatment, using Ac‐sPPp mixed with stealth liposomal doxorubicin (Doxil), were investigated as promising strategies for potentiating PDT and improving target specificity. Passively targeted PDT with Ac‐sPPp only or surfactant‐solubilized PPa was also investigated for comparison. The A‐431 human vulvar squamous cell carcinoma, xenografted in nude mice, was chosen as a tumor model because of its high EGFR expression and sensitivity to liposomal doxorubicin in vitro. Fluorescence imaging and PDT experiments showed that Ac‐sPPp formulations circulated far longer and provided superior tumor contrast and superior tumor control compared to PPa. Strong PDT vascular effects were observed by laser Doppler imaging regardless of whether Ac‐sPPp was passively or actively targeted. Passively targeted Ac‐sPPp PDT gave equivalent or better tumor control than PIC‐targeted PDT or PDT + Doxil combination therapy, and when treatments were repeated, it also yielded the highest cure rate.