Targeting and photodynamic killing of a microbial pathogen using protein cage architectures functionalized with a photosensitizer

The selectivity of antimicrobial photodynamic therapy (PDT) can be enhanced by coupling the photosensitizer (PS) to a targeting ligand. Nanoplatforms provide a medium for designing delivery vehicles that incorporate both functional attributes. We report here the photodynamic inactivation of a pathogenic bacterium, Staphylococcus aureus, using targeted nanoplatforms conjugated to a photosensitizer (PS). Both electrostatic and complementary biological interactions were used to mediate targeting. Genetic constructs of a protein cage architecture allowed site-specific chemical functionalization with the PS and facilitated dual functionalization with the PS and the targeting ligand. These results demonstrate that protein cage architectures can serve as versatile templates for engineering nanoplatforms for targeted antimicrobial PDT.     

fac-[Re(CO)(3)L](+) complexes with N-CH(2)-CH(2)-X-CH(2)-CH(2)-N tridentate ligands. synthetic, X-ray crystallographic, and NMR spectroscopic investigations

Polyamine ligands (L) have excellent binding characteristics for the formation of fac-99mTc(CO)3-based radiopharmaceuticals. Normally, these L are elaborated so as to leave pendant groups designed to impart useful biodistribution characteristics to the fac-[99mTc(CO)3L] imaging agent. Our goal is to lay a foundation for understanding the features of the bound elaborated ligands by using the fac-[Re(CO)3L]-analogue approach with the minimal prototypical ligands, diethylenetriamine (dien) or simple dien-related derivatives. Treatment of the fac-[Re(CO)3(H2O)3]+ cation with such triamine (NNN) ligands afforded fac-[Re(CO)3L]+ complexes. Ligand variations included having a central amine thioether donor, thus allowing X-ray crystallographic and NMR spectroscopic comparisons of fac-[Re(CO)3L]+ complexes with NNN and NSN ligands. fac-[Re(CO)3L]+ complexes with two terminal exo-NH groups exhibit unusually far upfield exo-NH NMR signals in DMSO-d6. Upon the addition of Cl-, these exo-NH signals move downfield, while the signals of any endo-NH or central NH groups move very little. This behavior is attributed to the formation of 1:1 ion pairs having selective Cl- hydrogen bonding to both exo-NH groups. Base addition to a DMSO-d6 solution of meso-exo-[Re(CO)3(N,N',N'-Me3dien)]PF6 led to isomerization of only one NHMe group, producing the chiral isomer. The meso isomer did not form. The [Re(CO)3(N,N,N',N',N'-pentamethyldiethylenetriamine)]triflate.[Re(CO)3(mu3-OH)]4.3.35H2O crystal, the first structure with a fac-[Re(CO)3L] complex cocrystallized with this well-known cluster, provided parameters for a bulky NNN ligand and also reveals CO-CO interlocking intermolecular interactions that could stabilize the crystal.     

Condensed phase ionic polarizabilities from plane wave density functional theory calculations

A method is presented to allow the calculation of the dipole polarizabilities of ions and molecules in a condensed-phase coordination environment. These values will be useful for understanding the optical properties of materials and for developing simulation potentials which incorporate polarization effects. The reported values are derived from plane wave density functional theory calculations, though the method itself will apply to first-principles calculations on periodic systems more generally. After reporting results of test calculations on atoms to validate the procedure, values for the polarizabilities of the oxide ion and various cations in a range of materials are reported and compared with experimental information as well as previous theoretical results.     

Analysis of O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate (VX) and its degradation products by packed capillary liquid chromatography-electrospray mass spectrometry

Packed capillary column liquid chromatography (LC)-electrospray mass spectrometry (ESI-MS) was used for the first time to detect and identify O-ethyl, S-[2-(diisopropylamino)ethyl] methylphosphonothiolate (VX) and its degradation products, including compounds containing a P-CH3 bond, bis(diisopropylamino)thioalkanes and ureas commonly employed as VX stabilizers. The reported ESI-MS data were generally acquired with a higher sampling cone voltage, a setting that promoted collisionally activated dissociation, and resulted in the acquisition in informative mass spectra containing both molecular and product ion information. The developed method appears to be an attractive alternative to GC-MS for the analysis of aqueous sample containing the degradation products of VX, since they may be analysed directly with little risk of thermal decomposition and without the need for additional sample handling or derivatization. Application of this method to a degraded VX sample resulted in the detection of a number of novel polar and higher-molecular-mass degradation products, not previously associated with VX during GC-MS analysis.     

Zr doping on one-dimensional titania nanomaterials synthesized in supercritical carbon dioxide

The growth mechanism of one-dimensional metal oxide nanotubular structures is of tremendous current interest to tailor materials using "green" synthetic procedures for emerging industries in alternative energy and biomaterials. In this study, ZrO(2)-modified TiO(2) nanorods and tubular structures were successfully synthesized via a surfactant-free sol-gel route using supercritical carbon dioxide (scCO(2)) as the solvent/drying agent. The effect of metal alkoxide concentration (0.35-1.4 mol/L), acid/metal alkoxide ratio (R = 3-7), and Zr ratio (0-20%) was examined on the morphology and crystallinity of the resulting nanostructures as measured by electron microscopy (SEM and TEM), EDX, XPS, and XRD. The electron microscopy results showed that the crystal growth of the synthesized binary Ti-Zr nanomaterials could be tailored by changing the operating variables with nanotubular structure formed at metal alkoxide concentration of 1.2 mol/L, R = 5-6, and Zr ratio between 4% and 20%. Gelation kinetics for this new system was also studied and revealed that increasing alkoxide concentration and R value enhanced the gelation kinetics. In situ and powder FTIR results revealed that this Ti-Zr binary system follows a similar reaction scheme to that of either single-component system, showing the flexibility of this approach for tailoring nanotubular production.     

Compensation of susceptibility-induced signal loss in echo-planar imaging for functional applications

Functional magnetic resonance imaging favors the use of multi-slice gradient-recalled echo-planar imaging due to its short image acquisition times, whole brain coverage and sensitivity to BOLD contrast. However, despite its advantages, gradient-recalled echo-planar imaging also is sensitive to static magnetic field gradients arising primarily from air-tissue interfaces. This can lead to image artifacts such as voxel shifts and complete signal loss. A method to recover signal loss by adjusting the refocusing gradient amplitude in the slice-select direction, preferably axially, is proposed. This method is implemented as an automated computer algorithm that partitions echo-planar images into regions of recoverable signal intensities using a histogram analysis and determines each region's proper refocusing gradient amplitude. As an example, different refocusing gradient amplitudes are interleaved in a fMRI acquisition to maximize the signal to noise ratio and obtain functional activation in normal and dropout regions. The effectiveness of this method is demonstrated by recovering signal voids in the orbitofrontal cortex, parahippocampal/amygdala region, and inferior visual association cortex near the cerebellum.     

Power-law conductivity inside the Mott gap: application to kappa-(BEDT-TTF)2Cu2(CN){3}

The charge dynamics of spin-liquid states described by U(1) gauge theory coupling to fermionic spinons is discussed in this paper. We find that the gapless spinons give rise to a power-law optical conductivity inside the charge gap. The theory is applied to explain the unusual optical conductivity observed recently in the organic compound kappa-(BEDT-TTF)2Cu2(CN){3}. We also propose an optical experiment to search for the in-gap excitations in the kagome spin-liquid insulator.