April M. Sawvel

Exceptionally Mild Reactive Stripping of Native Ligands from Nanocrystal Surfaces by Using Meerwein’s Salt†

Native coordinating ligands acquired during the chemical synthesis of colloidal nanocrystals are optimized primarily for their ability to exert control over nanocrystal size, composition, morphology, and dispersibility, and not necessarily for their final application. [1] In general, they are hydrophobic and highly insulating, and constitute a significant barrier for charge or ion transport in devices configured therefrom. Bare nanocrystal surfaces, while desirable for many applications, can be difficult to obtain reliably and without undesirable consequences. For example, removal of native ligands from nanocrystal dispersions usually results in aggregation or etching, [2] while in thin films their chemical displacement (e.g., by hydrazine or formic acid) often gives inefficient removal of surface ligands. [3] Thermal treatments inevitably leave behind an undesirable residue, require lengthy annealing times, or result in particle sintering. [4] Nevertheless, these approaches have demonstrated that near-bare nanocrystal surfaces are useful in a broad spectrum of advanced energy applications, from light-emitting diodes to field-effect transistors and photovoltaics. [5, 6] Dispersions of bare nanocrystals would also be useful as nanoinks and for facilitating their transfer into polar media for biomedical applications and catalysis. [7] In pursuit of a universal reagent for producing

Blood Clot Initiation by Mesocellular Foams : Dependence on Nanopore Size and Enzyme Immobilization

Porous silica materials are attractive for hemorrhage control because of their blood clot promoting surface chemistry, the wide variety of surface topologies and porous structures that can be created, and the potential ability to achieve high loading of therapeutic proteins within the silica support. We show that silica cell-window size variation in the nanometers to tens of nanometers range greatly affects the rate at which blood clots are formed in human plasma, indicating that window sizes in this size range directly impact the accessibility and diffusion of clotting-promoting proteins to and from the interior surfaces and pore volume of mesocellular foams (MCFs). These studies point toward a critical window size at which the clotting speed is minimized and serve as a model for the design of more effective wound-dressing materials. We demonstrate that the clotting times of plasma exposed to MCF materials are dramatically reduced by immobilizing thrombin in the pores of the MCF, validating the utility of enzyme-immobilized mesoporous silicas in biomedical applications.

High performance separation of aerosol sprayed mesoporous TiO2 sub-microspheres from aggregates via density gradient centrifugation

Mesoporous titanium dioxide sub-microspheres were prepared using aerosol techniques with a size distribution from 80 nm to 3 µm. Both theoretical and experimental results showed that non-equilibrium sucrose density gradient centrifugation is an effective way to size-partition these titanium dioxide nanoparticles from a continuous and broad particle size range. The sucrose serves as a multi-functional solution and plays three significant roles during the metal oxide fractionation. First, the high viscosity and density make the sedimentation rate of nanomaterials sensitive to particle size, which leads to particle fractionation in solution. Second, sucrose greatly decreases aggregation among nanoparticles during the separation by acting as a non-ionic capping agent. No other capping agent or surfactant is required. Finally, the density gradient stratifies the nanoparticles with a similar size into well-defined layers, so that the size-selected particles are relatively easy to collect. In addition, the unique biocompatibility of sucrose makes this fractionation method an ideal candidate for biological applications of nanoparticles. Post-aerosol synthesis separation of mesoporous metal oxide nanoparticles using a non-equilibrium density gradient has proven to be an effective, scalable way to access a large fraction of TiO2 sub-microspheres within a narrow size range and a low polydispersity index.

Engineering strategy to improve peptide analogs: from structure-based computational design to tumor homing

We present a chemical strategy to engineer analogs of the tumor-homing peptide CREKA (Cys-Arg-Glu-Lys-Ala), which binds to fibrin and fibrin-associated clotted plasma proteins in tumor vessels (Simberg et al. in Proc Natl Acad Sci USA 104:932–936, 2007) with improved ability to inhibit tumor growth. Computer modeling using a combination of simulated annealing and molecular dynamics were carried out to design targeted replacements aimed at enhancing the stability of the bioactive conformation of CREKA. Because this conformation presents a pocket-like shape with the charged groups of Arg, Glu and Lys pointing outward, non-proteinogenic amino acids α-methyl and N-methyl derivatives of Arg, Glu and Lys were selected, rationally designed and incorporated into CREKA analogs. The stabilization of the bioactive conformation predicted by the modeling for the different CREKA analogs matched the tumor fluorescence results, with tumor accumulation increasing with stabilization. Here we report the modeling, synthetic procedures, and new biological assays used to test the efficacy and utility of the analogs. Combined, our results show how studies based on multi-disciplinary collaboration can converge and lead to useful biomedical advances.

Cytotoxicity and potency of mesocellular foam-26 in comparison to layered clays used as hemostatic agents

Uncontrolled hemorrhage is a leading cause of potentially preventable death. The most effective commercial hemostatic products employ layered clays. Due to safety concerns only a product containing kaolin is currently recommended by the U. S. Department of Defense. A problem related to layered clays, including kaolin, is their cytotoxicity. Also, material left in the wound can lead to thrombosis and other adverse effects. Recently, it has been shown that pure silica mesocellular foams (MCF) with cell window sizes >20 nm are effective in promoting blood clotting. Here, we tested the potency and cytotoxicity of layered clays in comparison to MCF with a cell window size of 26 nm (MCF-26) in vitro. The results showed that the potencies of MCF-26 and layered clays in promoting clotting were comparable. Effects on cell viability were assessed with relevant primary human cell types. The cytotoxic effects of all compounds were cell type-specific and most sensitive were endothelial cells. The IC50 values of MCF-26 were in the mg ml−1 range and its cytotoxicity was ∼1–2 orders of magnitude lower than the cytotoxicity of layered clays. Further, MCF-26 did not adhere strongly to cell surfaces and was not taken up by cells as observed for the layered clays. This suggests that it would be easier to remove MCF-26 from wounds. Altogether, the results suggest that MCF-26 would be effective and safer than currently used hemostatic agents.

Solid State NMR Measurements for Preliminary Lifetime Assessments in λ-Irradiated and Thermally Aged Siloxane Elastomers

Siloxanes have a wide variety of applications throughout the aerospace industry which take advantage of their exceptional insulating and adhesive properties and general resilience. They also offer a wide range of tailorable engineering properties with changes in composition and filler content. They are, however, subject to degradation in radiatively and thermally harsh environments. We are using solid state nuclear magnetic resonance techniques to investigate changes in network and interfacial structure in siloxane elastomers and their correlations to changes in engineering performance in a series of degraded materials. NMR parameters such as transverse ( T{sub 2}) relaxation times, cross relaxation rates, and residual dipolar coupling constants provide excellent probes of changes crosslink density and motional dynamics of the polymers caused by multi-mechanism degradation. The results of NMR studies on aged siloxanes are being used in conjunction with other mechanical tests to provide insight into component failure and degradation kinetics necessary for preliminary lifetime assessments of these materials as well as into the structure-property relationships of the polymers. NMR and MRI results obtained both from high resolution NMR spectrometers as well as low resolution benchtop NMR screening tools will be presented.