Mary Elizabeth Williams

Controlling transport and chemical functionality of magnetic nanoparticles.

A wide range of metal, magnetic, semiconductor, and polymer nanoparticles with tunable sizes and properties can be synthesized by wet-chemical techniques. Magnetic nanoparticles are particularly attractive because their inherent superparamagnetic properties make them desirable for medical imaging, magnetic field assisted transport, and separations and analyses. With such applications on the horizon, synthetic routes for quickly and reliably rendering magnetic nanoparticle surfaces chemically functional have become an increasingly important focus. This Account describes common synthetic routes for making and functionalizing magnetic nanoparticles and discusses initial applications in magnetic field induced separations. The most widely studied magnetic nanoparticles are iron oxide (Fe2O3 and Fe3O4), cobalt ferrite (CoFe 2O4), iron platinum (FePt), and manganese ferrite (MnFe 2O4), although others have been investigated. Magnetic nanoparticles are typically prepared under either high-temperature organic phase or aqueous conditions, producing particles with surfaces that are stabilized by attached surfactants or associated ions. Although it requires more specialized glassware, high-temperature routes are generally preferred when a high degree of stability and low particle size dispersity is desired. Particles can be further modified with a secondary metal or polymer to create core-shell structures. The outer shells function as protective layers for the inner metal cores and alter the surface chemistry to enable postsynthetic modification of the surfactant chemistry. Efforts by our group as well as others have centered on pathways to yield nanoparticles with surfaces that are both easily functionalized and tunable in terms of the number and variety of attached species. Ligand place-exchange reactions have been shown quite successful for exchanging silanes, acids, thiols, and dopamine ligands onto the surfaces of some magnetic particles. Poly(ethylene oxide)-modified phospholipids can be inserted into nonpolar surface monolayers of as-prepared nanoparticles as a method for modifying the surface chemistry that induces water solubility. In general, reactive termini can subsequently be used to append a range of chemical groups. For example, surfactants with trifluoroethylester or azide termini have been used to attach a range of amine- or alkyne-containing species, respectively. Chemically functionalized magnetic nanoparticles are promising as advanced materials for analytical separations and analysis. Magnetic field flow fractionation leverages the size-dependent magnetic moments to purify and separate the components of a complex mixture of particles. Similarly, magnetic field gradients are useful for manipulating transport and separation in simple microfluidic devices. By either approach, magnet-induced transport of the particles is a simple method in which an attached reagent, catalyst, or bioanalytical tag can be moved between flow streams within a lab on a chip device.

The use of magnetic nanoparticles in analytical chemistry.

Magnetic nanoparticles uniquely combine superparamagnetic behavior with dimensions that are smaller than or the same size as molecular analytes. The integration of magnetic nanoparticles with analytical methods has opened new avenues for sensing, purification, and quantitative analysis. Applied magnetic fields can be used to control the motion and properties of magnetic nanoparticles; in analytical chemistry, use of magnetic fields provides methods for manipulating and analyzing species at the molecular level. In this review, we describe applications of magnetic nanoparticles to analyte handling, chemical sensors, and imaging techniques.

Purification and Magnetic Interrogation of Hybrid Au-Fe3O4 and FePt-Fe3O4 Nanoparticles†

Purifying heterodimers: differential magnetic catch and release separation is used to purify two important hybrid nanocrystal systems, Au-Fe(3)O(4) and FePt-Fe(3)O(4). The purified samples have substantially different magnetic properties compared to the as-synthesized materials: the magnetization values are more accurate and magnetic polydispersity is identified in morphologically similar hybrid nanoparticles.

Differential magnetic catch and release: analysis and separation of magnetic nanoparticles.

This article reports the purification and separation of magnetic nanoparticle mixtures using differential magnetic catch and release (DMCR). This method applies a variable magnetic flux orthogonal to the flow direction in an open tubular capillary to trap and controllably release magnetic nanoparticles. Magnetic moments of 8, 12, and 17 nm diameter CoFe2O4 nanoparticles are calculated using the applied magnetic flux and experimentally determined force required to trap 50% of the particle sample. Balancing the relative strengths of the drag and magnetic forces enables separation and purification of magnetic CoFe2O4 nanoparticle samples with <20 nm diameters. Samples were characterized by transmission electron microscopy to determine the average size and size dispersity of the sample population. DMCR is further demonstrated to be useful for separation of a magnetic nanoparticle mixture, resulting in samples with narrowed size distributions.

Full disclosure: the practical side of nanoscale total synthesis.

Colloidal hybrid nanoparticles merge multiple distinct materials into single particles, producing nanostructures that often exhibit synergistic properties and multifunctionality. As the complexity of such nanostructures continues to expand and the design criteria become increasingly stringent, the synthetic pathways required to access such materials are growing in sophistication. Multistep pathways are typically needed to generate complex hybrid nanoparticles, and these synthetic protocols have important conceptual analogies to the total synthesis framework used by chemists to construct complex organic molecules. This issue of ACS Nano includes a new nanoscale total synthesis: a five-step route to Co(x)O(y)-Pt-(CdSe@CdS)-Pt-Co(x)O(y) nanorods, a material which consists of CdSe@CdS nanorods that have Pt and cobalt oxide (Co(x)O(y)) at the tips. In addition to the conceptual analogies between molecular and nanoparticle total syntheses, there are practical analogies, as well, which are important for ensuring the reproducible and high-yield production of multicomponent nanostructured products with the highest possible purities. This Perspective highlights some of the practical considerations that are important for all nanoparticle syntheses but that become magnified significantly when multiple sequential reactions are required to generate a target product. These considerations include detailed reporting of reaction setups, experimental and workup procedures, hazards, yields of all intermediates and final products, complete data analysis, and separation techniques for ensuring high purity.

The effects of nigericin, valinomycin, and 2,4-dinitrophenol on intracellular pH, glycolysis, and K+ concentration of ehrlich ascites tumor cells

Abstract The effects of nigericin, valinomycin, 2,4-dinitrophenol, and combinations of these drugs on intracellular pH (pH i ), glycolysis, and K + concentrations of Ehrlich ascites tumor cells have been studied. All of the drugs and combinations raised extracellular pH (pH e ) and lowered pH i in non-glycolyzing cells. All drugs administered with glucose except nigericin increased the rate of glycolysis and produced lower values of pH e and pH i than did glucose alone. Nigericin caused some increase in the rate of lactate production with little if any effect on glucose utilization. The values of pH e and pH i obtained with glycolyzing cells treated with nigericin alone and in combination with valinomycin indicate effective transfer of H + from the external medium into the cells, presumably in exchange for K + . All drugs and combinations caused loss of cellular K + that was partially inhibited by glucose. The effects of nigericin and valinomycin on K + loss were additive. Those of dinitrophenol and valinomycin were not. The effects of dinitrophenol and valinomycin are attributed to depletion of ATP required for Na + -K + membrane transport. An additional effect of nigericin may be promotion of K + -H + exchange across the plasma membrane. The combination of valinomycin plus dinitrophenol does not have an effect equivalent to that of nigericin on the plasma membrane.

Effects of valinomycin, ouabain, and potassium on glycolysis and intracellular pH of Ehrlich ascites tumor cells.

SummaryBoth valinomycin and ouabain block reaccumulation of K+ by Ehrlich ascites tumor cells depleted of K+ and cause loss of K+ from high-K+ cells. Glucose largely reverses the effect of valinomycin and to a lesser extent that of ouabain.In cells depleted of K+, glucose utilization and lactate production are impaired. Neither extracellular pH (pHe) nor intracellular pH (pHi) falls to the extent seen in non-depleted glycolyzing cells. Addition of K+ to depleted cells reverses these effects. Valinomycin increases glycolysis in K+-depleted cells but to a greater extent in nondepleted or K+-repleted cells. The increase in lactate production caused by valinomycin is accompanied by a correspondingly greater fall in pHe and pHi. Valinomycin, unlike other uncoupling agents, does not abolish the pH gradient across the plasma membrane. Increased utilization of glucose resulting from addition of K+ to K+-depleted cells or addition of valinomycin either to depleted or non-depleted cells can be entirely accounted for by increased lactate production. Ouabain blocks the stimulatory effect of added K+ on K+-depleted cells and has an inhibitory effect on glycolysis in non-depleted cells. It does not obliterate the difference in glycolytic activity between K+-depleted and nondepleted cells. Ouabain does not completely block the effect of valinomycin in augmenting glycolysis in depleted or non-depleted cells. Increased accumulation of glycolytic intermediates, particularly dihydroxyacetone phosphate, is found in glycolyzing K+-depleted cells. The most marked accumulation was found in ouabain-treated K+-deficient cells.

Inorganic biomimetic nanostructures

Supramolecular structures modeled after biological systems (DNA and enzymes) are being developed to simultaneously mimic natural biological functions including catalysis, information storage, and self-assembly and to engineer novel electronic and magnetic properties. Structural mimics of nucleic acids containing multiple metal-coordinating ligands, and comprising natural and artificial bases or completely synthetic systems, create stable double-stranded structures with new electronic, spectroscopic, and magnetic properties. Supramolecular inorganic mimics of enzymatic function, including metallonucleases and metalloproteases, have begun to be constructed. Alternatively, metal-organic-frameworks have potential as artificial catalysts with substrate-specificity and size-selectivity analogous to biological processes. This review describes some of the recent themes in inorganic supramolecular systems that aim to mimic and exploit natures ability to self-assemble polyfunctional architectures for new materials and biological applications.

Rodent macrophages metabolize 25-hydroxyvitamin D3in, vitro

Abstract Rodent macrophages metabolized 25-hydroxyvitamin D3 to an unidentified metabolite during in , vitro incubations. The production of this macrophage-derived metabolite of 25-hydroxyvitamin D3 increased as the substrate concentration was raised. A two step high pressure liquid chromatography system revealed a unique elution position of this macrophage-derived metabolite that did not match the elution positions of any of the vitamin D3 metabolites available in this laboratory. This unique metabolite was formed in , vitro within one minute by incubated macrophages although its formation increased gradually up to 60 minutes of incubation.

Aminoethylglycine-Functionalized Ru(bpy)32+ with Pendant Bipyridines Self-Assemble Multimetallic Complexes by Copper and Zinc Coordination

Directed self-assembly using inorganic coordination chemistry is an attractive approach for making functional supramolecular structures. In this article, the synthesis and characterization of Ru(bpy) 3 (2+) compounds derivatized with aminoethylglycine (aeg) substituents containing pendant bipyridine (bpy) ligands is presented. The free bpy ligands in these complexes are available for metal chelation to form coordinative cross-links; addition of Cu (2+) or Zn (2+) assembles heterometallic structures containing two or three transition-metal complexes. Control over relative placement of metal complexes is accomplished using two strategies: two bipyridine-containing aeg strands tethered to Ru(bpy) 3 (2+) allow intramolecular coordination and result in a dimetallic hairpin motif. Ru(bpy) 3 (2+) modified with a single strand forms intermolecular cross-links forming the trimetallic complex. Each of these is characterized by a range of methods, and their photophysical properties are compared. These data, and comparison to an acetyl aeg- modified Ru(bpy) 3 (2+) complex, confirm that the metal ions cross-link bpy-containing aeg strands. Heterometallic complexes containing bound Cu (2+) cause a dramatic reduction in the Ru(bpy) 3 (2+) quantum yields and lifetimes. In contrast, the Ru(bpy) 3 (2+) hairpin with coordinated Zn (2+) has only a slight decrease in quantum yield but no change in lifetime, which could be a result of steric impacts on structure in the dimetallic species. Analogous effects are not observed in the trimetallic Ru-Zn-Ru structures in which this constraint is absent. Each of these heterometallic structures represents a facile and reconfigurable means to construct multimetallic structures by metal-coordination-based self-assembly of modular artificial peptide units.