Louis A. Madsen

Polymer beacons for luminescence and magnetic resonance imaging of DNA delivery

The delivery of nucleic acids with polycations offers tremendous potential for developing highly specific treatments for various therapeutic targets. Although materials have been developed and studied for polynucleotide transfer, the biological mechanisms and fate of the synthetic vehicle has remained elusive due to the limitations with current labeling technologies. Here, we have developed polymer beacons that allow the delivery of nucleic acids to be visualized at different biological scales. The polycations have been designed to contain repeated oligoethyleneamines, for binding and compacting nucleic acids into nanoparticles, and lanthanide (Ln) chelates [either luminescent europium (Eu3+) or paramagnetic gadolinium (Gd3+)]. The chelated Lns allow the visualization of the delivery vehicle both on the nm/μm scale via microscopy and on the sub-mm scale via MRI. We demonstrate that these delivery beacons effectively bind and compact plasmid (p)DNA into nanoparticles and protect nucleic acids from nuclease damage. These delivery beacons efficiently deliver pDNA into cultured cells and do not exhibit toxicity. Micrographs of cultured cells exposed to the nanoparticle complexes formed with fluorescein-labeled pDNA and the europium-chelated polymers reveal effective intracellular imaging of the delivery process. MRI of bulk cells exposed to the complexes formulated with pDNA and the gadolinium-chelated structures show bright image contrast, allowing visualization of effective intracellular delivery on the tissue-scale. Because of their versatility, these delivery beacons posses remarkable potential for tracking and understanding nucleic acid transfer in vitro, and have promise as in vivo theranostic agents.

Ion transport and storage of ionic liquids in ionic polymer conductor network composites

We investigate ion transport and storage of ionic liquids in ionic polymer conductor network composite electroactive devices. Specifically, we show that by combining the time domain electric and electromechanical responses, one can gain quantitative information on transport behavior of the two mobile ions in ionic liquids (i.e., cation and anion) in these electroactive devices. By employing a two carrier model, the total excess ions stored and strains generated by the cations and anions, and their transport times in the nanocomposites can be determined, which all depend critically on the morphologies of the conductor network nanocomposites.

Uniaxial and biaxial nematic liquid crystals

The unusual exhibition of a biaxial nematic phase in nonlinear thermotropic mesogens derived from the 2,5-oxadiazole biphenol (ODBP) core is placed in a general context; the uniaxial nematic phase of the prototypical rod-like mesogen para-quinquephenyl does not follow the classical mean-field behaviour of nematics, thus questioning the utility of such theories for quantitative predictions about biaxial nematics. The nuclear magnetic resonance spectra of labelled probe molecules dissolved in ODBP biaxial nematic phases suggest that a second critical rotation frequency, related to the differences in the transverse diamagnetic susceptibilities of the biaxial nematic, must be exceeded in order to create an aligned two-dimensional powder sample. Efforts to find higher viscosity and lower temperature biaxial nematics (with lower critical rotation rates) to confirm the above conjecture are described. Several chemical modifications of the ODBP mesogenic core are presented.

Uniaxial to biaxial nematic phase transition in a bent-core thermotropic liquid crystal by polarising microscopy

Polarising optical microscopy (POM) shows evidence for a reversible uniaxial nematic (NU) to biaxial nematic (NB) phase transition in a quiescent melt of bent-core mesogens (BCM). A second superimposed Schlieren texture, attributed to a second director field, grows into the NU phase on lowering the temperature and disappears again on heating, indicating a fully reversible NB to NU phase transition. This POM result together with recent X-ray data provides a new signature for the NB phase in this class of BCMs, and offers a new method for assessment of new biaxial nematic phases.

Gd3N@C84(OH)x: a new egg-shaped metallofullerene magnetic resonance imaging contrast agent.

Water-soluble derivatives of gadolinium-containing metallofullerenes have been considered to be excellent candidates for new magnetic resonance imaging (MRI) contrast agents because of their high relaxivity and characteristic encapsulation of the lanthanide ions (Gd(3+)), preventing their release into the bioenvironment. The trimetallic nitride template endohedral metallofullerenes (TNT EMFs) have further advantages of high stability, high relative yield, and encapsulation of three Gd(3+) ions per molecule as illustrated by the previously reported nearly spherical, Gd3N@I(h)-C80. In this study, we report the preparation and functionalization of a lower-symmetry EMF, Gd3N@C(s)-C84, with a pentalene (fused pentagons) motif and an egg-shaped structure. The Gd3N@C84 derivative exhibits a higher (1)H MR relaxivity compared to that of the Gd3N@C80 derivative synthesized the same way, at low (0.47 T), medium (1.4 T), and high (9.4 T) magnetic fields. The Gd3N@C(s)-C84 derivative exhibits a higher hydroxyl content and aggregate size, as confirmed by X-ray photoelectron spectroscopy (XPS) and dynamic light scattering (DLS) experiments, which could be the main reasons for the higher relaxivity.

Force-detected magnetic resonance without field gradients

A novel method of nuclear magnetic resonance (NMR) is described which promises to be preferable to known general methods at sample length scales below approximately 100 microm. Its advantages stem from the seemingly paradoxical combination of a homogeneous static magnetic field and detection of a mechanical force between a spin-bearing sample and a magnet assembly. In contrast to other methods of force-detected nuclear magnetic resonance (FDNMR), the method is characterized by better observation of magnetization, enhanced resolution, and no gradient (BOOMERANG), and it is generally applicable with respect to sample composition, pulse sequence, and magnetic field strength. Further advantages of portability and low cost stem from the small instrument volume and mass and promise to extend the use of NMR to new applications and environments. A sensitivity analysis, relevant to spectroscopy or imaging, quantifies the advantage of BOOMERANG relative to magnetic induction using microcoils and to FDNMR methods that rely on large gradients of the magnetic field at the sample.

Influence of Zn2+ and water on the transport properties of a pyrrolidinium dicyanamide ionic liquid

In order to expand our understanding of a potential zinc-based battery electrolyte, we have characterized the physical and transport properties of the ionic liquid (IL) 1-butyl-1-methylpyrrolidinium dicyanamide ([C4mpyr][dca]) containing various levels of both Zn(2+) and H2O. Detailed measurements of density, viscosity, conductivity, and individual anion and cation diffusion coefficients using pulsed-field-gradient (PFG) NMR combined with NMR chemical shifts and spin-lattice relaxation (T1) NMR experiments provide insights into the motion and chemical environment of all molecular species. We find that the various techniques for probing ion transport and dynamics form a coherent picture as a function of electrolyte composition. Zn(2+) addition causes a moderate reduction in the self-diffusion of the IL anion and cation, whereas the addition of H2O increases ion mobility by increasing the liquids overall fluidity. Temperature-dependent (13)C T1 experiments of the dca carbon analyzed using Bloembergen-Purcell-Pound fits show monotonic slowing of anion dynamics with Zn(2+) addition, suggesting increased Zn(2+)/dca(-) association. T1 experiments show minimal change in the spin-lattice relaxation of cation or anion upon H2O addition, suggesting that H2O is playing no significant role in Zn(2+) speciation. Finally, we employ a novel electrophoretic NMR technique to directly determine the electrophoretic mobility of the C4mpyr cation, which we discuss in the context of impedance-based conductivity measurements.

The biaxial nematic phase of oxadiazole biphenol mesogens

Herein we review the attributes of the cluster biaxial nematic exhibited by bent-core mesogens derived from the oxadiazole biphenol mesogenic core. We present an array of static 2H NMR spectra as well as 2D powder spectra generated by rotating the nematic phase of directly labelled mesogens. Analysis of these motionally averaged NMR observations requires the nematic phase to have monoclinic symmetry. X-ray diffraction data, in particular the effects of electric and magnetic field effects, are also consonant with the cluster picture of this biaxial nematic phase.

The role of water in transport of ionic liquids in polymeric artificial muscle actuators

Ionic liquid (IL) based polymeric mechanical actuators show promise for providing an important and unprecedented combination of electromechanical and soft material properties. Measurement of ion transport in an ionomer/IL membrane is essential for understanding and designing these “artificial muscle” actuators. Furthermore, water forms a ubiquitous part of these hydrophilic membrane systems when used in open air, greatly affecting electrochemical and physical properties including the ion conductivity critical for actuation performance. Here we present the first study quantifying the delicate interplay between water and an IL absorbed in an ionomer membrane as used in ionic polymer actuators. We use 1H and 19F NMR diffusometry to investigate cation and anion diffusion of 1-ethyl-3-methyl-imidazolium trifluoromethanesulfonate (EMI-Tf), swollen into a perfluorosulfonate ionomer membrane. The EMI cation diffuses faster than the Tf anion in both the neat state and inside the membrane. We quantitatively evaluate the effects of temperature, IL uptake, and water content. A key factor is the co-existing water content, quantified by in situ1H NMR, which dramatically accelerates the diffusive motion of the IL. When water content, χH2O, drops from 1 to 0.5 water molecules per EMI-Tf, IL diffusion coefficients decrease by 36–60%. Our experiments provide critical feedback for optimizing actuator performance via novel materials, device development, and control of operation conditions.

Humidity-Modulated Phase Control and Nanoscopic Transport in Supramolecular Assemblies

Supramolecular assembly allows for enhanced control of bulk material properties through the fine modulation of intermolecular interactions. We present a comprehensive study of a cross-linkable amphiphilic wedge molecule based on a sulfonated trialkoxybenzene with a sodium counterion that forms liquid crystalline (LC) phases with ionic nanochannel structures. This compound exhibits drastic structural changes as a function of relative humidity (RH). Our combined structural, dynamical, and transport studies reveal deep and novel information on the coupling of water and wedge molecule transport to structural motifs, including the significant influence of domain boundaries within the material. Over a range of RH values, we employ (23)Na solid-state NMR on the counterions to complement detailed structural studies by grazing-incidence small-angle X-ray scattering. RH-dependent pulsed-field-gradient (PFG) NMR diffusion studies on both water and the wedge amphiphiles show multiple components, corresponding to species diffusing within LC domains as well as in the domain boundaries that compose 10% of the material. The rich transport and dynamical behaviors described here represent an important window into the world of supramolecular soft materials, carrying implications for optimization of these materials in many venues. Cubic phases present at high RH show fast transport of water (2 × 10(-10) m(2)/s), competitive with that observed in benchmark polymeric ion conductors. Understanding the self-assembly of these supramolecular building blocks shows promise for generating cross-linked membranes with fast ion conduction for applications such as next-generation batteries.