Ligand and Linkage Isomers of Bis(ethylthiocarbamato) Copper Complexes with Cyclic C6H8 Backbone Substituents: Synthesis,Characterization, and Antiproliferation Activity

A series of isomeric bis(alkylthiocarbamate) copper complexes have been synthesized, characterized, and evaluated for antiproliferation activity. The complexes were derived from ligand isomers with 3-methylpentyl (H₂L²) and cyclohexyl (H₂L³) backbone substituents, which each yield a pair of linkage isomers. The thermodynamic products CuL^2a/3a have two imino N and two S donors resulting in three five-member chelate rings (555 isomers). The kinetic isomers CuL^2b/3b have one imino and one hydrazino N donor and two S donors resulting in four-, six-, and five-member rings (465 isomers). The 555 isomers have more accessible Cu^II/I potentials (E_1/2=−811/−768 mV vs. ferrocenium/ferrocene) and lower energy charge transfer bands than their 465 counterparts (E_1/2=−923/-854 mV). Antiproliferation activities were evaluated against the lung adenocarcinoma cell line (A549) and nonmalignant lung fibroblast cell line (IMR-90) using the MTT assay. CuL^2a was potent (^A549EC₅₀=0.080 μM) and selective (^IMR-90EC₅₀/^A549EC₅₀=25) for A549. Its linkage isomer CuL^2b had equivalent A549 activity, but lower selectivity (^IMR-90EC₅₀/^A549EC₅₀=12.5). The isomers CuL^3a and CuL^3b were less potent with ^A549EC₅₀ values of 1.9 and 0.19 M and less selective with ^IMR-90EC₅₀/^A549EC₅₀ ratios of 2.3 and 2.65, respectively. There was no correlation between reduction potential and A549 antiproliferation activity/selectivity.     

Investigation of the “true” extraction recovery of analytes from multiple types of tissues and its impact on tissue bioanalysis using two model compounds

LC-MS/MS has been widely applied to the quantitative analysis of tissue samples. However, one key remaining issue is that the extraction recovery of analyte from spiked tissue calibration standard and quality control samples (QCs) may not accurately represent the “true” recovery of analyte from incurred tissue samples. This may affect the accuracy of LC-MS/MS tissue bioanalysis. Here, we investigated whether the recovery determined using tissue QCs by LC-MS/MS can accurately represent the “true” recovery from incurred tissue samples using two model compounds: BMS-986104, a S1P₁ receptor modulator drug candidate, and its phosphate metabolite, BMS-986104-P. We first developed a novel acid and surfactant assisted protein precipitation method for the extraction of BMS-986104 and BMS-986104-P from rat tissues, and determined their recoveries using tissue QCs by LC-MS/MS. We then used radioactive incurred samples from rats dosed with ³H-labeled BMS-986104 to determine the absolute total radioactivity recovery in six different tissues. The recoveries determined using tissue QCs and incurred samples matched with each other very well. The results demonstrated that, in this assay, tissue QCs accurately represented the incurred tissue samples to determine the “true” recovery, and LC-MS/MS assay was accurate for tissue bioanalysis. Another aspect we investigated is how the tissue QCs should be prepared to better represent the incurred tissue samples. We compared two different QC preparation methods (analyte spiked in tissue homogenates or in intact tissues) and demonstrated that the two methods had no significant difference when a good sample preparation was in place. The developed assay showed excellent accuracy and precision, and was successfully applied to the quantitative determination of BMS-986104 and BMS-986104-P in tissues in a rat toxicology study.     

Inorganic oxidizer detection from propellants,pyrotechnics, and homemade explosive powders using gradient elution moving boundary electrophoresis

Advancement in rapid targeted chemical analysis of homemade and improvised explosive devices is critical for the identification of explosives-based hazards and threats. Gradient elution moving boundary electrophoresis (GEMBE), a robust electrokinetic separation technique, was employed for the separation and detection of common inorganic oxidizers from frequently encountered fuel-oxidizer mixtures. The GEMBE system incorporated sample and run buffer reservoirs, a short capillary (5 cm), an applied electric field, and a pressure-driven counterflow. GEMBE provided a separation format that allowed for continuous injection of sample, selectivity of analytes, and no sample cleanup or filtration prior to analysis. Nitrate, chlorate, and perchlorate oxidizers were successfully detected from low explosive propellants (e.g., black powders and black powder substitutes), pyrotechnics (e.g., flash powder), and tertiary explosive mixtures (e.g., ammonium nitrate- and potassium chlorate-based fuel-oxidizer mixtures). Separation of these mixtures exhibited detection without interference from a plethora of additional organic and inorganic fuels, enabled single particle analysis, and demonstrated semiquantitative capabilities. The bulk counterflow successfully excluded difficult components from fouling the capillary, yielding estimated limits of detection down to approximately 10 μmol/L. Finally, nitrate was separated and detected from postblast debris collected and directly analyzed from two nitrate-based charges.     

Multiwall carbon nanotube absorber on a thin-film lithium niobate pyroelectric detector

Multiwall carbon nanotubes (MWNTs) were applied in a bulk layer to a pyroelectric film to increase the detector sensitivity nearly fourfold without a substantial penalty to the low-frequency response (4-100 Hz). In addition, the spectral sensitivity over the wavelength range from 600 to 1800 nm was uniformly enhanced, with variations less than 1%. The results demonstrate the suitability of MWNTs as an efficient thermal absorber having low thermal mass.     

Tyrosine nitration site specificity identified by LC/MS in nitrite-modified collagen type IV

Non-enzymatic nitrite induced collagen cross-linking results in changes reminiscent of age-related damage and parallels the well-known model system, non-enzymatic glycation. We have recently observed that nitrite modification of basement membrane proteins can induce deleterious effects on overlying retinal pigment epithelial cells in studies relevant to age-related macular degeneration. The present work was undertaken in order to confirm 3-nitro-tyrosine (3-NT) as a product of the reaction and to identify the site specificity of nitration in collagen IV, a major component of basement membranes. Human collagen type IV was modified via incubation with 200 mM NaNO(2) (pH=7.38) for one week at 37(o)C. The modified protein was prepared in 2 different ways, including acid hydrolysis and trypsin digestion for site specificity determination. The samples were analyzed by LC/MS using a C(12) RP column. Site specificity was determined from tandem MS/MS data utilizing TurboSEQUEST software and the Swiss-Prot sequence database. 3-NT was detected in protein digests and acid hydrolysates of nitrite modified collagen IV. Positive identification with standard 3-NT was confirmed by identical R(t), lambda(max)=279 nm and 355 nm, and m/z=227. Analyses of tryptic digests identified four sites of tyrosine nitration, alpha1(IV)Y348, alpha1(IV)Y534, alpha2(IV)Y327, and alpha2(IV)Y1081. These sites are located in the triple-helical region of the protein and provide clues regarding potential sites for nitrite modification in collagen type IV.     

Facile, fast, and inexpensive synthesis of monodisperse amorphous nickel-phosphide nanoparticles of predefined size

Monodisperse, size-controlled Ni-P nanoparticles were synthesised in a single step process using triphenyl-phosphane (TPP), oleylamine (OA), and Ni(II)acetyl-acetonate. The nanoparticles were amorphous, contained ~30 at% P and their size was controlled between 7-21 nm simply by varying the amount of TPP. They are catalytically active for tailored carbon nanotube growth.     

FRET detection of proteins using fluorescently doped electrospun nanofibers and pattern recognition

This paper reports the fabrication of solid-state nanofiber sensor arrays and their use for detection of multiple proteins using principal component analysis (PCA). Four cationic and anionic fluorescently embedded nanofibers are generated by an electrospinning method, yielding unique patterns of fluorescence change upon interaction with protein samples. Five metal and nonmetal containing proteins, i.e., hemoglobin, myoglobin, cytochrome c, BSA, and avidin, have been investigated; and the results show that distinct fluorescent patterns can be formed upon the addition of protein samples to the array of solid nanofiber substrates, allowing their unambiguous identification. The nanofiber films are highly repeatable with a batch-to-batch variation of approximately 5% and demonstrated outstanding reusability with less than a 15% loss of fluorescence intensity signal after 5 regenerations of test cycles. For a more practical visualization, a cluster map was generated using PCA of the change-in-fluorescence (ΔI) composite patterns, demonstrating the potential of the method for diagnostic applications.     

Identifying attributes and insecurity of a public-channel key exchange protocol using chaos synchronization

Klein et al. proposed a key exchange protocol using chaos synchronization. The first protocol comprises two parties with chaotic dynamics that are mutually coupled and undergo a synchronization process, at the end of which they can use their identical dynamical state as an encryption key. From cryptographic point of view, their key exchange protocol is a key agreement protocol. Klein et al. claimed that their key agreement can be carried out over a public channel. In order to increase the key space and decrease the precision of the calculation, they made an extension of the system to a network of N Lorenz equations. In this paper, we will provide a cryptanalysis of their key agreement protocol. We will first point out some weaknesses, and then show that their protocol is not secure against several attacks including impersonation attack.     

Polarization switching without domain formation at the intrinsic coercive field in ultrathin ferroelectric PbTiO₃

Polarization switching in ferroelectrics has been thought to occur only through the nucleation and growth of new domains. Here we use in situ synchrotron x-ray scattering to monitor switching controlled by applied chemical potential. In sufficiently thin PbTiO? films, nucleation is suppressed and switching occurs by a continuous mechanism, i.e., by uniform decrease and inversion of the polarization without domain formation. The observed lattice parameter shows that the electric field in the film during switching reaches the theoretical intrinsic coercive field.