Medicinal Organometallic Chemistry: Designing Metal Arene Complexes as Anticancer Agents

The field of medicinal inorganic chemistry is rapidly advancing. In particular organometallic complexes have much potential as therapeutic and diagnostic agents. The carbon‐bound and other ligands allow the thermodynamic and kinetic reactivity of the metal ion to be controlled and also provide a scaffold for functionalization. The establishment of structure–activity relationships and elucidation of the speciation of complexes under conditions relevant to drug testing and formulation are crucial for the further development of promising medicinal applications of organometallic complexes. Specific examples involving the design of ruthenium and osmium arene complexes as anticancer agents are discussed.     

On the dynamic electromechanical loading of dielectric elastomer membranes

Dielectric elastomer actuators (DEAs) have received considerable attention recently due to large voltage-induced strains, which can be over 100%. Previously, a large deformation quasi-static model that describes the out-of-plane deformations of clamped diaphragms was derived. The numerical model results compare well with quasi-static experimental results for the same configuration. With relevance to dynamic applications, the time-varying response of initially planar dielectric elastomer membranes configured for out-of-plane deformations has not been reported until now. In this paper, an experimental investigation and analysis of the dynamic response of a dielectric elastomer membrane is reported. The experiments were conducted with prestretched DEAs fabricated from 0.5 mm thick polyacrylate films and carbon grease electrodes. The experiments covered the electromechanical spectrum by investigating membrane response due to (i) a time-varying voltage input and (ii) a time-varying pressure input, resulting in a combined electromechanical loading state in both cases. For the time-varying voltage experiments, the membrane had a prestretch of three and was passively inflated to various predetermined states, and then actuated. The pole strains incurred during the inflation were as high as 25.6%, corresponding to slightly less than a hemispherical state. On actuation, the membrane would inflate further, causing a maximum additional strain of 9.5%. For the time-varying pressure experiments, the prestretched membrane was inflated and deflated mechanically while a constant voltage was applied. The membrane was cycled between various predetermined inflation states, the largest of which was nearly hemispherical, which with an applied constant voltage of 3 kV corresponded to a maximum polar strain of 28%. The results from these experiments reveal that the response of the membrane is a departure from the classical dynamic response of continuum membrane structures. The dynamic response of the membrane is that of a damped system with specific deformation shapes reminiscent of the classical membrane mode shapes but without same-phase oscillation, that is to say all parts of the system do not pass through the equilibrium configuration at the same time. Of particular interest is the ability to excite these deformations through a varying electrical load at constant mechanical pressure.     

Experimental Evaluation of Strain Shielding in Distal Femur in Revision TKA

Theoretical concerns about the use of cemented and press-fit stems in revision total knee arthroplasty (TKA) include stress shielding with adverse effects on prosthesis fixation. Radiological studies have showed distal femoral bone resorption after revision TKA. The revision with use of stems can place abnormal stresses. These stresses can promote the effect of bone stress shielding and may contribute to bone loss. Experimental quantification of strain shielding in the distal synthetic femur following TKA is the main purpose of the present study. Three different constructs of TKA were assessed. The first construct included a stemless femoral component. The other two included a press-fit and a cemented femoral stem. Cortical bone strains were measured experimentally with tri-axial strain gauges in synthetic femurs before and after in-vitro knee surgery. The difference between principal strains of implanted and intact femur was calculated for each strain gauge position. This study indicates that the use of stems in distal femur changes the distribution and magnitude of bone strains. The press-fit stem provoked relevant bone area (stem length) subjected to strain shielding and also originated the highest reduction of strains in the distal region, which can potentially induce bone resorption. The stemless implanted femur produced minor bone strain changes relatively to the intact femur. The use of distal femur stems increases initial stability in the bone, but the observed reduction of strains in this region, relative to the intact femur, provokes strain shielding that can induce bone resorption and may compromise the long term implant stability.     

An Experimental Investigation into the Acoustic Characteristics of Fluid-filled Porous Structures—A Simplified Model of the Human Skull Cancellous Structure

In nature, shape and structure evolve from the struggle for better performance. Often, biological structures combine multiple beneficial properties, making research into mimicking them very complex. Presented here is a summary of observations from a series of experiments performed on a material that closely resembles the human skull bone’s cancellous structure under acoustic loads. Transmission loss through flat and curved open-cell polyurethane foam samples is observed using air and water as the two interstitial fluids. Reduction in strength and stiffness caused by porosity can be recovered partially by filling the interstitial pores with a fluid. The test findings demonstrate the influence of the interstitial fluid on the mechanical characteristics of a porous structure in a quantitative manner. It is also demonstrated that the transmission loss does not depend only on the mass per unit area of the structure as predicted by acoustic mass law. Current tests also demonstrate that the transmission loss is more sensitive to the interstitial fluid than the shape and support conditions of the structures. Test observations thus support the concepts of “moisture-sensitivity of biological design” and the “law of hierarchy in natural design”.     

Dispersion modeling by kinematic simulation: Cloud dispersion model

A new technique has been developed to compute mean and fluctuating concentrations in complex turbulent flows (tidal current near a coast and deep ocean). An initial distribution of material is discretized into any small clouds which are advected by a combination of the mean flow and large scale turbulence. The turbulence can be simulated either by kinematic simulation (KS) or direct numerical simulation. The clouds also diffuse relative to their centroids; the statistics for this are obtained from a separate calculation of the growth of individual clouds in small scale turbulence, generated by KS. The ensemble of discrete clouds is periodically re-discretized, to limit the size of the small clouds and prevent overlapping. The model is illustrated with simulations of dispersion in uniform flow, and the results are compared with analytic, steady state solutions. The aim of this study is to understand how pollutants disperses in a turbulent flow through a numerical simulation of fluid particle motion in a random flow field generated by Fourier modes. Although this homogeneous turbulent is rather a “simple” flow, it represents a building block toward understanding pollutant dispersion in more complex flow. The results presented here are preliminary in nature, but we expect that similar qualitative results should be observed in a genuine turbulent flow.     

Fatigue Loading and Life Prediction in Three Fretting Fatigue Fixtures

Three fixtures for conducting laboratory fretting fatigue tests are described and their respective testing methods and the results of the analysis are compared. Each of these fixtures has been used to investigate the effects of various parameters of interest in fretting fatigue. These fixtures include a unique apparatus in which all load applied to the specimen is transferred to the fretting pads, an apparatus similar to many found in the literature where partial load transfer occurs across the pads, and a simplified dovetail fixture in which the clamping load, P, and the shear load, Q, are varied in phase. Select test conditions from prior experiments performed on identical material and resulting in similar lives ranging from one to ten million cycles from these fixtures are identified. The various testing conditions were used to compute the unique stress field for each case. The resulting contact stresses were used to calculate crack initiation based criteria, and to calculate stress intensity factors. The three fixtures were shown to be able to accommodate a range of loads, fretting pad contours, and specimen geometries that produced a variety of stress fields. A crack-initiation-based criterion was shown to predict the failure lives of thinner specimens accurately. The stress intensity factor calculations showed the possibility of a crack arresting for a stress field that decays rapidly and the possibility of a local minimum for K as a function of depth. The fixtures are shown to be complementary in generating data for development of robust fretting fatigue models that use these criteria.     

Hydrophilic segmented block copolymers based on poly(ethylene oxide) and monodisperse amide segments

Segmented block copolymers based on poly(ethylene oxide) (PEO) flexible segments and monodisperse crystallizable bisester tetra‐amide segments were made via a polycondensation reaction. The molecular weight of the PEO segments varied from 600 to 4600 g/mol and a bisester tetra‐amide segment (T6T6T) based on dimethyl terephthalate (T) and hexamethylenediamine (6) was used. The resulting copolymers were melt‐processable and transparent. The crystallinity of the copolymers was investigated by differential scanning calorimetry (DSC) and Fourier Transform infrared (FTIR). The thermal properties were studied by DSC, temperature modulated synchrotron small angle X‐ray scattering (SAXS), and dynamic mechanical analysis (DMA). The elastic properties were evaluated by compression set (CS) test. The crystallinity of the T6T6T segments in the copolymers was high (>84%) and the crystallization fast due to the use of monodisperse tetra‐amide segments. DMA experiments showed that the materials had a low T_g, a broad and almost temperature independent rubbery plateau and a sharp flow temperature. With increasing PEO length both the PEO melting temperature and the PEO crystallinity increased. When the PEO segment length was longer than 2000 g/mol the PEO melting temperature was above room temperature and this resulted in a higher modulus and in higher compression set values at room temperature. The properties of PEO‐T6T6T copolymers were compared with similar poly(propylene oxide) and poly(tetramethylene oxide) copolymers. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4522–4535, 2007     

Synthesis of vanadium-phosphorus oxide catalysts deposited onto silica-carbon supports

Effect of conditions of hydrothermal and microwave synthesis of supported vanadium-phosphorus oxide catalysts in an aqueous medium on the physicochemical properties of the vanadyl hydrophosphate obtained was studied. The transformations occurring in the system were examined using X-ray phase and differential-thermal analyses, adsorption-structural method, and scanning electron microscopy.     

Globally anisotropic high porosity silica aerogels

We discuss two methods by which high porosity silica aerogels can be engineered to exhibit global anisotropy. First, anisotropy can be introduced with axial strain (i.e. axial compression). In addition, intrinsic anisotropy can result during growth and drying stages and, suitably controlled, it can be correlated with preferential radial shrinkage in cylindrical samples. We have performed small angle X-ray scattering (SAXS) to characterize these two types of anisotropy. We show that global anisotropy originating from either strain or shrinkage leads to optical birefringence and that optical cross-polarization studies are a useful characterization of the uniformity of the imposed global anisotropy.