Electrophoretic NMR studies of polymer and surfactant systems

The aim of this tutorial review is to introduce to a broader readership the emerging technique of electrophoretic NMR (eNMR). The "electrophoretic" element of the technique refers to the fact that charged particles are induced to flow by the application of an electric field. This flow is measured using pulsed-gradient spin-echo NMR (PGSE-NMR). The great potential of this experimental approach is the fact that NMR is chemically selective and non-invasive. eNMR, especially when combined with the more established PGSE-NMR experiment, may therefore be used to quantify the structure of multi-component systems via the dynamics and charge of each species within a complex mixture. Accordingly, eNMR is likely to be of great significance for colloid scientists, biologists, technologists and formulation scientists.     

Encodable activators of SRC family kinases

There is considerable current interest in the design of encodable molecules that regulate intracellular protein circuitry and/or activity, ideally with a high level of specificity. Src homology 3 (SH3) domains are ubiquitous components of multidomain signaling proteins, including many kinases, and are attractive drug targets because of the important role their interactions play in diseases as diverse as cancer, osteoporosis, and inflammation. Here we describe a set of miniature proteins that recognize distinct SH3 domains from Src family kinases with high affinity. Three of these molecules discriminate effectively between the SH3 domains of Src and Fyn, which are expressed ubiquitously, and two of these three activate Hck kinase with potencies that rival HIV Nef, one of the most potent kinase activators known. These results suggest that miniature proteins represent a viable, encodable strategy for selective activation of Src family kinases in a variety of cell types.     

Metallosurfactants: interfaces and micelles

Incorporating a metal cation as an integral component of the headgroup of a surfactant--a metallosurfactant--offers a route to concentrate these ions and their associated functionality at interfaces. To reduce the lability of the metal, various chelating or macrocyclic ligands may be employed leading to a family of homologous series of related metallosurfactants with a structural diversity that is arguably broader than is inherently possible with conventional surfactants. This review discusses the small number of key papers that are quantifying the physico-chemical properties of metallosurfactants and highlights their "classical" as well as "non-classical" surfactant behaviour, providing an insight into the structure of micelles and films formed from these novel materials.     

NMR method for the determination of solute hydrogen bond acidity

It is shown that the difference in the 1H NMR chemical shift of a protic hydrogen in DMSO and CDCl3 solvents is directly related to the overall, or summation, hydrogen bond acidity for a wide range of solutes. This provides a new and direct method of measuring the hydrogen bond acidity. For 54 compounds, the observed shifts for 72 protic hydrogens could be correlated to the Abraham solute hydrogen bond acidity parameter, A, with a correlation coefficient squared, R2, of 0.938 and a standard deviation, SD, of 0.054 units in A. A training equation that used half the data could predict A values for the remaining data with an average error of 0.001 and a standard deviation, SD, of 0.053 units, thus demonstrating the predictive power of the method. Unlike any previous method for the determination of solute hydrogen bond acidities, the NMR method allows the determination of A values for individual protic hydrogens in multifunctional solutes.     

Separation of viscothermal losses and scattering in ultrasonic characterization of porous media

This paper presents a method for separating viscothermal and scattering losses in ultrasonic characterization of porous media. This method is based on variations of the static pressure of the saturating fluid. Experimental results were already presented in previous papers and the losses separation was verified experimentally. The aim of this paper is to present an analytic justification of this losses separation in the case of this experimental method and to show that it is possible to estimate acoustic parameters without the knowledge of scattering characteristics. The standard scattering length is used to renormalize speed and transmission through the porous medium, described as an equivalent fluid. Under certain assumptions corresponding to a weak scattering regime, it is shown how viscothermal and scattering losses can be separated easily without knowing scattering characteristics. Application of this model is presented in the case of weak scattering in a polyurethane foam and in the limit case of stronger scattering in a glass beads sample.     

MRI studies of the evaporation of a single liquid droplet from porous surfaces

A combination of in situ one-dimensional profiling and two-dimensional 1H magnetic resonance imaging has been applied to study the shape and subsequent dynamic evaporation behavior of a single liquid droplet after impact onto a porous surface in a carefully controlled atmosphere. Aspects of the porous media permeability and particle shape are shown to affect considerably the observed drying regime. Variation in the shape, spread ratio, and penetration depth of the liquid droplet following impact are attributed to the different types of porous media used. A comparison of numerical simulations with the MRI data for the droplet shape, spread factor, and penetration depth show good agreement though larger deviations between simulated and experimental results occur in certain cases where the surface of the porous medium is disrupted by the impact of the liquid droplet. Initial results examining the effect of a reduced liquid surface tension show a significantly increased evaporation rate.     

Microfluidic platform for combinatorial synthesis in picolitre droplets

This paper presents a droplet-based microfluidic platform for miniaturized combinatorial synthesis. As a proof of concept, a library of small molecules for early stage drug screening was produced. We present an efficient strategy for producing a 7 × 3 library of potential thrombin inhibitors that can be utilized for other combinatorial synthesis applications. Picolitre droplets containing the first type of reagent (reagents A(1), A(2), …, A(m)) were formed individually in identical microfluidic chips and then stored off chip with the aid of stabilizing surfactants. These droplets were then mixed to form a library of droplets containing reagents A(1-m), each individually compartmentalized, which was reinjected into a second microfluidic chip and combinatorially fused with picolitre droplets containing the second reagent (reagents B(1), B(2), …, B(n)) that were formed on chip. The concept was demonstrated with a three-component Ugi-type reaction involving an amine (reagents A(1-3)), an aldehyde (reagents B(1-7)), and an isocyanide (held constant), to synthesize a library of small molecules with potential thrombin inhibitory activity. Our technique produced 10(6) droplets of each reaction at a rate of 2.3 kHz. Each droplet had a reaction volume of 3.1 pL, at least six orders of magnitude lower than conventional techniques. The droplets can then be divided into aliquots for different downstream screening applications. In addition to medicinal chemistry applications, this combinatorial droplet-based approach holds great potential for other applications that involve sampling large areas of chemical parameter space with minimal reagent consumption; such an approach could be beneficial when optimizing reaction conditions or performing combinatorial reactions aimed at producing novel materials.     

Quantum Counterfactuals and Locality

Stapp’s counterfactual argument for quantum nonlocality based upon a Hardy entangled state is shown to be flawed. While he has correctly analyzed a particular framework using the method of consistent histories, there are alternative frameworks which do not support his argument. The framework dependence of quantum counterfactual arguments, with analogs in classical counterfactuals, vitiates the claim that nonlocal (superluminal) influences exist in the quantum world. Instead it shows that counterfactual arguments are of limited use for analyzing these questions.     

Thermodynamic Limit for Polydisperse Fluids

We examine the thermodynamic limit of fluids of hard core particles that are polydisperse in size and shape. In addition, particles may interact magnetically. Free energy of such systems is a random variable because it depends on the choice of particles. We prove that the thermodynamic limit exists with probability 1, and is independent of the choice of particles. Our proof applies to polydisperse hard-sphere fluids, colloids and ferrofluids. The existence of a thermodynamic limit implies system shape and size independence of thermodynamic properties of a system.