Encapsulation of Pt(iv) prodrugs within a Pt(ii) cage for drug delivery

This report presents a novel strategy that facilitates delivery of multiple, specific payloads of Pt(iv) prodrugs using a well-defined supramolecular system. This delivery system comprises a hexanuclear Pt(ii) cage that can host four Pt(iv) prodrug guest molecules. Relying on host–guest interactions between adamantyl units tethered to the Pt(iv) molecules and the cage, four prodrugs could be encapsulated within one cage. This host–guest complex, exhibiting a diameter of about 3 nm, has been characterized by detailed NMR spectroscopic measurements. Owing to the high positive charge, this nanostructure exhibits high cellular uptake. Upon entering cells and reacting with biological reductants such as ascorbic acid, the host–guest complex releases cisplatin, which leads to cell cycle arrest and apoptosis. The fully assembled complex displays cytotoxicity comparable to that of cisplatin against a panel of human cancer cell lines, whereas the cage or the Pt(iv) guest alone exhibit lower cytotoxicity. These findings indicate the potential of utilising well-defined supramolecular constructs for the delivery of prodrug molecules.     

Binuclear and trinuclear complexes of exoO(2)-cyclam

Complexes of the ligand 2,3-dioxo-1,4,8,11-tetraaza-cyclotetradecane (exoO(2)-cyclam) have been prepared of formula [M(1){M(2)(exoO(2)-cyclam)}(2)][BPh(4)](2) where M(1)M(2) = CoCo (3), ZnZn (4), MnCu (5), FeCu (6), CoCu (7), NiCu (8), ZnCu (9), and [(bipy)(2)Ru{Cu(exoO(2)-cyclam)}][NO(3)](2) (10). Complex 10 crystallised in the space group C2/c and shows Jahn-Teller distorted Cu(II) with axial nitrate ligands. The {Cu(exoO(2)-cyclam)} moiety chelates to the Ru with Ru-O distances of 2.082(5) A. Complexes 5-10 show a Cu(II)/Cu(III) redox process and additional metal-centred (6, 8, 10) processes and ligand-centred (10) processes. The electrochemical and UV-Vis spectroelectrochemical study of suggested two closely-spaced oxidations based on the Cu and Ru centres which suggests that substituted derivatives of will be of interest for enhanced charge separation in dye-sensitised solar cells. Magnetic susceptibility measurements revealed dominant antiferromagnetic coupling within the trinuclear species 3, 5-8. Complex 10 showed Curie-Weiss behaviour with weak intermolecular interactions.     

The synthesis of monomeric terminal lead aryloxides: dependence on reagents and conditions

The successful synthesis of terminal lead aryloxides is shown to be dependent upon reaction conditions, including choice of solvent and alkali metal aryloxide precursor.     

Surface‐sampled simulations of turbulent flow at high Reynolds number

A new approach to turbulence simulation, based on a combination of large eddy simulation (LES) for the whole flow and an array of non–space‐filling quasi‐direct numerical simulations (QDNS), which sample the response of near‐wall turbulence to large‐scale forcing, is proposed and evaluated. The technique overcomes some of the cost limitations of turbulence simulation, since the main flow is treated with a coarse‐grid LES, with the equivalent of wall functions supplied by the near‐wall sampled QDNS. Two cases are tested, at friction Reynolds number Re_τ=4200 and 20000. The total grid point count for the first case is less than half a million and less than 2 million for the second case, with the calculations only requiring a desktop computer. A good agreement with published direct numerical simulation (DNS) is found at Re_τ=4200, both in the mean velocity profile and the streamwise velocity fluctuation statistics, which correctly show a substantial increase in near‐wall turbulence levels due to a modulation of near‐wall streaks by large‐scale structures. The trend continues at Re_τ=20000, in agreement with experiment, which represents one of the major achievements of the new approach. A number of detailed aspects of the model, including numerical resolution, LES‐QDNS coupling strategy and subgrid model are explored. A low level of grid sensitivity is demonstrated for both the QDNS and LES aspects. Since the method does not assume a law of the wall, it can in principle be applied to flows that are out of equilibrium.     

Magnetic moment measurements in the semi-magic nuclei 94Ru and 95Rh after recoil implantation into iron and nickel

The magnetic moments of the 12⁺ and 11⁻ yrast states in ⁹⁴Ru and of the 25/2⁻, 29/2⁺, and 35/2⁺ levels in ⁹⁵Rh have been measured via the IMPAD technique. The nuclei were produced in the reaction ⁵⁸Ni +⁴⁰Ca and recoil-implanted into polarized Ni and Fe hosts. The g-factors were deduced from the measured time-integral Larmor precessions. The comparison between the experimental results and large-scale shell model calculations suggests that the 12⁺ and 11⁻ states in ⁹⁴Ru and the 25/2⁻ level in ⁹⁵Rh are pure proton states whereas the 29/2⁺ and 35/2⁺ states in ⁹⁵Rh contain a neutron excitation across the N=50 shell gap. This interpretation supports the conclusion drawn from recent lifetime measurements. Received: 2 June 1999     

The rippled β-sheet layer configuration—a novel supramolecular architecture based on predictions by Pauling and Corey

The rippled β-sheet is a peptidic structural motif related to but distinct from the pleated β-sheet. Both motifs were predicted in the 1950s by Pauling and Corey. The pleated β-sheet was since observed in countless proteins and peptides and is considered common textbook knowledge. Conversely, the rippled β-sheet only gained a meaningful experimental foundation in the past decade, and the first crystal structural study of rippled β-sheets was published as recently as this year. Noteworthy, the crystallized assembly stopped at the rippled β-dimer stage. It did not form the extended, periodic rippled β-sheet layer topography hypothesized by Pauling and Corey, thus calling the validity of their prediction into question. NMR work conducted since moreover shows that certain model peptides rather form pleated and not rippled β-sheets in solution. To determine whether the periodic rippled β-sheet layer configuration is viable, the field urgently needs crystal structures. Here we report on crystal structures of two racemic and one quasi-racemic aggregating peptide systems, all of which yield periodic rippled antiparallel β-sheet layers that are in excellent agreement with the predictions by Pauling and Corey. Our study establishes the rippled β-sheet layer configuration as a motif with general features and opens the road to structure-based design of unique supramolecular architectures.

The rippled sheet was proposed by Pauling and Corey in 1953, yet structural foundation remains extremely limited. Here we report on three X-ray crystal structures of rippled β-sheets, thus providing the long-sought structural basis for the field.     

Exact Risk Analysis of Wavelet Regression

Abstract

Wavelets have motivated development of a host of new ideas in nonparametric regression smoothing. Here we apply the too] of exact risk analysis, to understand the small sample behavior of wavelet estimators, and thus to check directly the conclusions suggested by asymptotics. Comparisons between some wavelet bases, and also between hard and soft thresholding, are given from several viewpoints. Our results provide insight as to why the viewpoints and conclusions of Donoho and Johnstone differ from those of Hall and Patil.     

Near-Infrared Study of the Hydrogen Bonding in Acetone-Methanol and Acetone-Ethanol Mixtures: Roles of Mechanical and Electrical Anharmonicities of Hydroxyl Oscillator

Near-infrared spectra of methanol-acetone and ethanol-acetone mixtures in the entire mole fraction range in increments of 0.1 were recorded in the region of 7500–6000 cm^?1. The first overtone bands of the hydroxyl (OH) groups were assigned to the polymeric and oligomeric OH associations. In both solutions, the frequency of the polymeric OH band decreased with the increase in the mole fraction of alcohol, which indicated the increase in the hydrogen bonding strength. The integrated area of the polymeric OH band followed the opposite trend to the frequency with the mole fraction. The nonlinearity of the plot of the integrated band area of the polymeric OH band of methanol versus the mole fraction of acetone revealed the nonideal character of the methanol-acetone mixtures, whereas the opposite was observed for the ethanol-acetone mixtures. These observations have been explained in terms of mechanical and electrical anharmonicities of the OH oscillator.     

Rapid formation of diphenylmethyl ethers and thioethers using microwave irradiation and protic ionic liquids

Using microwave irradiation and protic ionic liquids (pIL) as co-solvent and catalyst for the synthesis of several diphenylmethyl ethers was achieved. The desired ethers were isolated simply by filtration through a silica plug to remove the pIL and proceeded in high yields (60–98%). These reactions were extremely rapid (10–30 min) and occurred under mild conditions (80 °C). This protocol was also successfully applied to the synthesis of thioethers.     

Convexity of the Proximal Average

We complete the study of the convexity of the proximal average by proving it is convex as a function of each of its parameters separately, but not jointly convex as a function of any two of its parameters. We present an interpolation-based plotting algorithm that takes advantage of the partial convexity of the proximal average, and improves the plotting time by a factor of 100, while reducing picture sizes by a factor of 10.