Nathan A. Oyler

Supramolecular Structure in Full-Length Alzheimer's β-Amyloid Fibrils: Evidence for a Parallel β-Sheet Organization from Solid-State Nuclear Magnetic Resonance

Abstract We report constraints on the supramolecular structure of amyloid fibrils formed by the 40-residue β -amyloid peptide associated with Alzheimers disease (A β 1–40 ) obtained from solid-state nuclear magnetic resonance (NMR) measurements of intermolecular dipole-dipole couplings between 13 C labels at 11 carbon sites in residues 2 through 39. The measurements are carried out under magic-angle spinning conditions, using the constant-time finite-pulse radiofrequency-driven recoupling (fpRFDR-CT) technique. We also present one-dimensional 13 C magic-angle spinning NMR spectra of the labeled A β 1–40 samples. The fpRFDR-CT data reveal nearest-neighbor intermolecular distances of 4.8±0.5A for carbon sites from residues 12 through 39, indicating a parallel alignment of neighboring peptide chains in the predominantly β -sheet structure of the amyloid fibrils. The one-dimensional NMR spectra indicate structural order at these sites. The fpRFDR-CT data and NMR spectra also indicate structural disorder in the N-terminal segment of A β 1–40 , including the first nine residues. These results place strong constraints on any molecular-level structural model for full-length β -amyloid fibrils.

Properties of Disorder-Engineered Black Titanium Dioxide Nanoparticles through Hydrogenation

The recent discovery of “black” TiO2 nanoparticles with visible and infrared absorption has triggered an explosion of interest in the application of TiO2 in a diverse set of solar energy systems; however, what a black TiO2 nanoparticle really is remains a mystery. Here we elucidate more properties and try to understand the inner workings of black TiO2 nanoparticles with hydrogenated disorders in a surface layer surrounding a crystalline core. Contrary to traditional findings, Ti3+ here is not responsible for the visible and infrared absorption of black TiO2, while there is evidence of mid-gap states above the valence band maximum due to the hydrogenated, engineered disorders. The hydrogen atoms, on the other hand, can undergo fast diffusion and exchange. The enhanced hydrogen mobility may be explained by the presence of the hydrogenated, disordered surface layer. This unique structure thus may give TiO2, one of the most-studied oxide materials, a renewed potential.

Hydrogenated TiO2 Nanocrystals: A Novel Microwave Absorbing Material

Here, we report, for the first time, hydrogenated TiO2 nanocrystals as a novel and exciting microwave absorbing material, based on an innovative collective-movement-of-interfacial-dipole mechanism which causes collective-interfacial-polarization-amplified microwave absorption at the crystalline/disordered and anatase/rutile interfaces. This mechanism is intriguing and upon further exploration may trigger other new concepts and applications.

Strong Microwave Absorption of Hydrogenated Wide Bandgap Semiconductor Nanoparticles

Electromagnetic interactions in the microelectronvolt (μeV) or microwave region have numerous important applications in both civil and military fields, such as electronic communications, signal protection, and antireflective coatings on airplanes against microwave detection. Traditionally, nonmagnetic wide-bandgap metal oxide semiconductors lack these μeV electronic transitions and applications. Here, we demonstrate that these metal oxides can be fabricated as good microwave absorbers using a 2D electron gas plasma resonance at the disorder/order interface generated by a hydrogenation process. Using ZnO and TiO2 nanoparticles as examples, we show that large absorption with reflection loss values as large as -49.0 dB (99.99999%) is obtained in the microwave region. The frequency of absorption can be tuned with the particle size and hydrogenation condition. These results may pave the way for new applications for wide bandgap semiconductors, especially in the μeV regime.

Spray Drying Tenofovir Loaded Mucoadhesive and pH-Sensitive Microspheres Intended for HIV Prevention

PURPOSE To develop spray dried mucoadhesive and pH-sensitive microspheres (MS) based on polymethacrylate salt intended for vaginal delivery of tenofovir (a model HIV microbicide) and assess their critical biological responses. METHODS The formulation variables and process parameters are screened and optimized using a 2(4-1) fractional factorial design. The MS are characterized for size, zeta potential, yield, encapsulation efficiency, Carrs index, drug loading, in vitro release, cytotoxicity, inflammatory responses and mucoadhesion. RESULTS The optimal MS formulation has an average size of 4.73μm, zeta potential of -26.3mV, 68.9% yield, encapsulation efficiency of 88.7%, Carrs index of 28.3 and drug loading of 2% (w/w). The MS formulation release 91.7% of its payload in the presence of simulated human semen. At a concentration of 1mg/ml, the MS are noncytotoxic to vaginal endocervical/epithelial cells and Lactobacillus crispatus when compared to control media. There is also no statistically significant level of inflammatory cytokine (IL1-α, IL-1β, IL-6, IL-8, and IP-10) release triggered by these MS. Their percent mucoadhesion is 2-fold higher than that of 1% HEC gel formulation. CONCLUSION These data suggest the promise of using such MS as an alternative controlled microbicide delivery template by intravaginal route for HIV prevention.

The local physical structure of amorphous hydrogenated boron carbide: insights from magic angle spinning solid-state NMR spectroscopy

Magic angle spinning solid-state nuclear magnetic resonance spectroscopy techniques are applied to the elucidation of the local physical structure of an intermediate product in the plasma-enhanced chemical vapour deposition of thin-film amorphous hydrogenated boron carbide (B(x)C:H(y)) from an orthocarborane precursor. Experimental chemical shifts are compared with theoretical shift predictions from ab initio calculations of model molecular compounds to assign atomic chemical environments, while Lee-Goldburg cross-polarization and heteronuclear recoupling experiments are used to confirm atomic connectivities. A model for the B(x)C:H(y) intermediate is proposed wherein the solid is dominated by predominantly hydrogenated carborane icosahedra that are lightly cross-linked via nonhydrogenated intraicosahedral B atoms, either directly through B-B bonds or through extraicosahedral hydrocarbon chains. While there is no clear evidence for extraicosahedral B aside from boron oxides, ∼40% of the C is found to exist as extraicosahedral hydrocarbon species that are intimately bound within the icosahedral network rather than in segregated phases.

A Novel Green TiO2 Photocatalyst with a Surface Charge-Transfer Complex of Ti and Hydrazine Groups

The optical property of TiO2 plays an important role in its various and promising photocatalytic applications. Previous efforts in improving its optical properties include doping with various metal and/or non-metal elements, coupling with other colorful semiconductors or molecules, and hydrogenating to crystalline/disordered core/shell nanostructures. Here, we report a beautiful green TiO2 achieved by forming the charge-transfer complex of colorless hydrazine groups and surface Ti4+ , which extends the optical absorption into the near infrared region (≈1100 nm, 1.05 eV). It shows an enhanced photocatalytic performance in hydrogen generation under simulated sunlight, and degradation of organic pollution under visible light due to an impurity state (about 0.28 eV) resulting in fast electron-hole separation and injection of electrons from the ligand to the conduction band of TiO2 . This study demonstrates an alternative approach to tune the optical, impurity state and photocatalytic properties of TiO2 nanoparticles and we believe this will spur a wide interest in related materials and applications.

Spectroscopic analysis of interactions between alkylated silanes and alumina nanoporous membranes.

Transport across alumina nanoporous membranes can be altered via surface attachment of alkylated trimethoxysilane compounds. The mechanism of attachment has been previously assumed to be monolayer silane coverage through full chemisorption regardless of reaction conditions. This chemisorption arises via covalent Si-O-Al bond formation resulting from condensation between the three putative silanols (due to hydrolysis of the three Si-OCH(3) bonds) and hydroxides present on the alumina surface. If this model was correct, methanol would be produced in large quantities in the reaction solution, and the methoxy moieties would no longer be present on the silane molecule. The results presented in this paper utilized FT-IR and both solution and solid-state NMR to examine the chemical nature of octadecyltrimethoxysilane (ODTMS) present on the alumina surface. The FT-IR results confirm the presence of the silane on the membrane. The (1)H solution NMR results indicate small but detectable methanol production during attachment. The solid-state NMR results demonstrate that the methoxy proton NMR integrated peak intensities remain in nearly the same ratios present in the free silane, concluding that the majority of methoxy groups are intact while the silane is attached to the membrane surface. These three results suggest that monolayer surface coverage and chemisorption through full covalent bonding is not the primary means of attachment for ODTMS on the surface of alumina nanomembranes under these reaction conditions.

Layer-by-Layer Engineered Microbicide Drug Delivery System Targeting HIV-1 gp120: Physico-Chemical and Biological Properties

The purpose of this study was to engineer a model anti-HIV microbicide (tenofovir) drug delivery system targeting HIV-1 envelope glycoprotein gp120 (HIV-1 g120) for the prevention of HIV sexual transmission. HIV-1 g120 and mannose responsive particles (MRP) were prepared through the layer-by-layer coating of calcium carbonate (CaCO3) with concanavalin A (Con A) and glycogen. MRP average particle size ranged from 881.7 ± 15.45 nm to 1130 ± 15.72 nm, depending on the number of Con A layers. Tenofovir encapsulation efficiency in CaCO3 was 74.4% with drug loading of 16.3% (w/w). MRP was non-cytotoxic to Lactobacillus crispatus, human vaginal keratinocytes (VK2), and murine macrophage RAW 264.7 cells and did not induce any significant proinflammatory nitric oxide release. Overall, compared to control, no statistically significant increase in proinflammatory cytokine IL-1α, IL-1β, IL-6, MKC, IL-7, and interferon-γ-inducible protein 10 (IP10) levels was observed. Drug release profiles in the presence of methyl α-d-mannopyranoside and recombinant HIV-1 envelope glycoprotein gp120 followed Hixson-Crowell and Hopfenberg kinetic models, indicative of a surface-eroding system. The one Con A layer containing system was found to be the most sensitive (∼2-fold increase in drug release vs control SFS:VFS) at the lowest HIV gp120 concentration tested (25 μg/mL). Percent mucoadhesion, tested ex vivo on porcine vaginal tissue, ranged from 10% to 21%, depending on the number of Con A layers in the formulation. Collectively, these data suggested that the proposed HIV-1 g120 targeting, using MRP, potentially represent a safe and effective template for vaginal microbicide drug delivery, if future preclinical studies are conclusive.

Solid state 2H NMR analysis of furanose ring dynamics in DNA containing uracil.

DNA damage has been implicated in numerous human diseases, particularly cancer, and the aging process. Single-base lesions, such as uracil, in DNA can be cytotoxic or mutagenic and are recognized by a DNA glycosylase during the process of base excision repair. Increased dynamic properties in lesion-containing DNAs have been suggested to assist recognition and specificity. Deuterium solid-state nuclear magnetic resonance (SSNMR) has been used to directly observe local dynamics of the furanose ring within a uracil:adenine (U:A) base pair and compared to a normal thymine:adenine (T:A) base pair. Quadrupole echo lineshapes, , and relaxation data were collected, and computer modeling was performed. The results indicate that the relaxation times are identical within the experimental error, the solid lineshapes are essentially indistinguishable above the noise level, and our lineshapes are best fit with a model that does not have significant local motions. Therefore, U:A base pair furanose rings appear to have essentially identical dynamic properties as a normal T:A base pair, and the local dynamics of the furanose ring are unlikely to be the sole arbiter for uracil recognition and specificity in U:A base pairs.