A Selective Electrochemical Sensor for the Detection of Cd(II) Based on a Carbon Paste Electrode Impregnated with a Novel Ion-imprinted Hybrid Polymer

An electrochemical sensor (CPE-IIHP) was developed for Cd(II) using a carbon paste electrode (CPE) impregnated with an ion-imprinted hybrid polymer (IIHP). A CPE-NIHP was also prepared for comparison. DPASV was used to optimize the sensor response and quantify Cd(II). The sensor presented a wide linear range from low concentrations of Cd(II): 1 to 100 μg L⁻¹ and high concentrations of Cd(II): 2.75 to 5.0 mg L⁻¹. Ions such as Co(II), Pb(II), Ni(II), Zn(II), Fe(II), Fe(III), Sn(II) and Cu(II), showed no variation in the Cd(II) signal. The CPE-IIHP was successfully applied in river and drinking water analysis, revealing the great potential for its application.     

Determination of pamidronate in human whole blood and urine by reversed-phase HPLC with fluorescence detection

Pamidronate is a bisphosphonate that is effective in treating bone disease including osteopenia and osteoporosis in adults. A sensitive and reliable method for the analysis of pamidronate in whole blood and urine is key to the development of this drug for use in children. A previously described method for pamidronate analysis serum and urine did not consistently detect the drug at satisfactory levels in whole blood. The procedure involves co-precipitation of the bisphosphonates with calcium phosphate, pre-column derivitization with fluorescamine, HPLC utilizing a Nucleosil C(18) column, and fluorescence detection with excitation at 395 nm and emission at 480 nm.Changes to the original protocol included the use of a new internal standard (alendronate), the optimization of the concentration of ethylenediaminetetraacetic acid (EDTA) for dissolving the precipitate, and the elimination of the acidification step prior to deproteinization. The optimum EDTA concentration, which had a significant effect on the labeling capability of fluorescamine, was determined to be 20 mm.A good separation between pamidronate and alendronate was achieved using a heated (40 degrees C ) Nucleosil C(18), 10 micro m particle size column. The mobile phase was an aqueous solution of 1 mm Na(2)EDTA-methanol (97:3, v/v) adjusted to pH 6.5 using a fl ow-rate of 1 mL/min. Fluorescence detection was set at 395 nm for excitation and at 480 nm for emission. The limit of quantitation for pamidronate was 0.5 micro g/mL in whole blood and 0.1 micro g/mL in urine. The method was applied to both whole blood and urine samples from pediatric patients.     

Protonated silanoic acid HSi(OH)2+ and its neutral counterpart: a tandem mass spectrometric and CBS-QB3 computational study

Protonated silanoic acid, HSi(OH)₂⁺, 1a ⁺, is cleanly generated by the dissociative electron ionization of triethoxysilane, HSi(OC₂H₅)₃, and tetraethoxysilane, Si(OC₂H₅)₄. This follows from tandem mass spectrometric experiments and CBS-QB3 model chemistry calculations. The calculations predict that 1a ⁺ (ΔH_f(298 K) = 205 kJ mol⁻¹) is separated by high barriers from its isomers HOSiOH₂⁺, 1b ⁺ and HSi(O)OH₂⁺, 1c ⁺. Low-energy (metastable) ions 1a ⁺ dissociate by loss of H₂O via the pathway 1a ⁺ → 1b ⁺ → SiOH⁺ + H₂O. Analysis of the metastable peak for this process confirms that the isomerization step 1a ⁺ → 1b ⁺ is rate determining. The calculations further predict that the incipient ions 1b ⁺ communicate via a low barrier with the proton-bound dimer SiO···H···OH₂⁺, 1d ⁺. This dimer ion is much lower in energy than its counterpart OSi···H···OH₂⁺, 1e ⁺, which is calculated to be only marginally stable. A comparison of the potential energy diagram for the silicon-containing ions 1a ⁺– 1e ⁺ with that of their carbon analogues reveals that the dissociation chemistries of HSi(OH)₂⁺ and HC(OH)₂⁺ are only superficially similar. Neutralization–reionization experiments confirm the theoretical prediction that the HSi(OH)₂^• radical (ΔH_f(298 K) = −455 kJ mol⁻¹) is a stable species in the rarefied gas phase. However, owing to a mismatch of Franck–Condon factors a large fraction of the neutralized ions dissociates by loss of H^• yielding Si(OH)₂. Copyright © 2004 John Wiley & Sons, Ltd.     

Engineered Bacteriorhodopsin May Induce Lung Cancer Cell Cycle Arrest and Suppress Their Proliferation and Migration

Highly expressible bacteriorhodopsin (HEBR) is a light-triggered protein (optogenetic protein) that has seven transmembrane regions with retinal bound as their chromophore to sense light. HEBR has controllable photochemical properties and regulates activity on proton pumping. In this study, we generated HEBR protein and incubated with lung cancer cell lines (A549 and H1299) to evaluate if there was a growth-inhibitory effect with or without light illumination. The data revealed that the HEBR protein suppressed cell proliferation and induced the G₀/G₁ cell cycle arrest without light illumination. Moreover, the migration abilities of A549 and H1299 cells were reduced by ~17% and ~31% after incubation with HEBR (40 μg/mL) for 4 h. The Snail-1 gene expression level of the A549 cells was significantly downregulated by ~50% after the treatment of HEBR. In addition, HEBR significantly inhibited the gene expression of Sox-2 and Oct-4 in H1299 cells. These results suggested that the HEBR protein may inhibit cell proliferation and cell cycle progression of lung cancer cells, reduce their migration activity, and suppress some stemness-related genes. These findings also suggested the potential of HEBR protein to regulate the growth and migration of tumor cells, which may offer the possibility for an anticancer drug.     

Computational Screening for the Anticancer Potential of Seed-Derived Antioxidant Peptides: A Cheminformatic Approach

Some seed-derived antioxidant peptides are known to regulate cellular modulators of ROS production, including those proposed to be promising targets of anticancer therapy. Nevertheless, research in this direction is relatively slow owing to the inevitable time-consuming nature of wet-lab experimentations. To help expedite such explorations, we performed structure-based virtual screening on seed-derived antioxidant peptides in the literature for anticancer potential. The ability of the peptides to interact with myeloperoxidase, xanthine oxidase, Keap1, and p47^phox was examined. We generated a virtual library of 677 peptides based on a database and literature search. Screening for anticancer potential, non-toxicity, non-allergenicity, non-hemolyticity narrowed down the collection to five candidates. Molecular docking found LYSPH as the most promising in targeting myeloperoxidase, xanthine oxidase, and Keap1, whereas PSYLNTPLL was the best candidate to bind stably to key residues in p47^phox. Stability of the four peptide-target complexes was supported by molecular dynamics simulation. LYSPH and PSYLNTPLL were predicted to have cell- and blood-brain barrier penetrating potential, although intolerant to gastrointestinal digestion. Computational alanine scanning found tyrosine residues in both peptides as crucial to stable binding to the targets. Overall, LYSPH and PSYLNTPLL are two potential anticancer peptides that deserve deeper exploration in future.     

Hexacoordinate Phosphorus. 7. Synthesis and Characterization of Neutral Phosphorus(V) Compounds Containing Divalent Tridentate Diphenol Imine, Azo, and Thio Ligands

The reactions of bis(trimethylsilyl)ated forms of the Schiff base ligands N-(2-hydroxyphenyl)salicylideneamine {(HO)C(6)H(4)N(CH)C(6)H(4)(OH)}, N-(4-tert-butyl-2-hydroxyphenyl)salicylideneamine {(HO)((t)Bu)C(6)H(3)N(CH)C(6)H(4)(OH)}, N-(2-hydroxy-4-nitrophenyl)salicylideneamine {(HO)(O(2)N)C(6)H(3)N(CH)C(6)H(4)(OH)}, and the structurally related ligand 2,2'-azophenol with halogeno- and (trifluoromethyl)halogenophosphoranes yield a series of neutral hexacoordinate phosphorus(V) compounds by means of trimethylsilyl halide elimination. In all of these cases the ligands chelate in a meridional conformation in which bicyclic five- and six-membered chelate rings are formed through structures containing two phenolic P-O bonds and one N-P bond. The hexacoordinate nature of these compounds is evidenced by their high-field (31)P NMR chemical shifts and their characteristic J(PF) coupling patterns and is further substantiated by the crystal structures of {O((t)Bu)C(6)H(3)N(CH)C(6)H(4)O}PCl(3) and {OC(6)H(4)N=NC(6)H(4)O}PF(3). Crystal data for {O((t)Bu)C(6)H(3)N(CH)C(6)H(4)O}PCl(3): triclinic, space group P&onemacr; (No. 2), a = 11.167(1) ?, b = 15.684(1) ?, c = 17.047(2) ?, V = 2840(1) ?(3), Z = 2. Final R and R(w) values were 0.051 and 0.079, respectively. Crystal data for {OC(6)H(4)N=NC(6)H(4)O}PF(3): monoclinic, space group P2(1)/c (No. 14), a = 6.9393(8) ?, b = 12.450(2) ?, c = 13.907(2) ?, V = 1190.7(6) ?(3), Z = 4. Final R and R(w) values were 0.045 and 0.056, respectively. The molecular structures of {O((t)Bu)C(6)H(3)N(CH)C(6)H(4)O}PCl(3) and {OC(6)H(4)N=NC(6)H(4)O}PF(3) show that in both cases the Schiff base ligand chelates occupy the meridional plane about the six-coordinate phosphorus atom. In the case of {OC(6)H(4)N=NC(6)H(4)O}PF(3) the equivalent nitrogen atoms in the chelate rings are disordered to form half-occupancy pairs. The silylated form of the related thiobis(phenol), 2,2'-thiobis(4,6-tert-butylphenol), reacted similarly with pentavalent halides to form the six-coordinate complex [{2-O-3,5-((t)Bu)(2)C(6)H(2)}(2)S]PCl(3) which was also verified by a crystal structure. Crystal data for [{2-O-3,5-((t)Bu)(2)C(6)H(2)}(2)S]PCl(3): monoclinic P2(1)/n, a = 13.989(2), b = 13.594(2), c = 16.483(2) ?, beta = 97.98(2) degrees, V = 3104(2) ?(3), Z = 4; final R and R(w)() values were 0.039 and 0.052, respectively. In contrast to the above six coordinate complexes, this compound possesses a facial structure in which two phenoxy substituents form planar chelates centered on the bridging sulfur and intersecting at the P-S axis. The P-S bond length, 2.331(1) ?, is slightly shorter than has been previously observed in the example wherein the ligand possesses two tert-butyl groups and the phosphorus carries three OCH(2)CF(3 )substituents indicating stronger interaction between P and S in the present case.     

Gas chromatography/ion trap mass spectrometry applied for the determination of polybrominated diphenyl ethers in soil

A gas chromatography/ion trap mass spectrometry (GC/ITMS) method was developed for the determination of polybrominated diphenyl ethers (PBDEs). ITMS parameters were optimized in order to achieve the best sensitivity for the PBDE analysis. Tandem mass spectrometry, along with an isotope dilution internal standard method, was used for the quantitation. Chromatographic windows were developed for mono- to hepta-BDEs, depending on the retention times when a 30-m GC column was used. A different 15-m column was used to analyze deca-BDE. Environmental soil samples collected from an electronic waste recycling site were prepared by using Soxhlet extraction and column chromatographic cleanup. Average recoveries of 61-118% were obtained for the 13C-labeled PBDE internal standards spiked in the samples prior to sample preparation. The accuracy represented by relative analytical errors was -24% to 18%, and the precision (relative standard deviation) was 11-26% (n=8). The method detection limits ranged from 0.013-0.25 ng/g for the PBDEs in soil.     

Polymer translocation through a cylindrical channel

A formalism of polymer translocation through a cylindrical channel of finite diameter and length between two spherical compartments is developed. Unlike previous simplified systems, the finite diameter of the channel allows the number of polymer segments inside the channel to be adjusted during translocation according to the free energy of possible conformations. The translocation process of a Gaussian chain without excluded volume and hydrodynamic interactions is studied using exact formulas of confinement free energy under this formalism. The free energy landscape for the translocation process, the distribution of the translocation time, and the average translocation time are presented. The complex dependencies of the average translocation time on the length and diameter of the channel, the sizes of the donor and receptor compartments, and the chain length are illustrated.     

Biotransformations of Anticancer Ruthenium(III) Complexes: An X‐Ray Absorption Spectroscopic Study

An anti‐metastatic drug, NAMI‐A ((ImH)[Ru^IIICl₄(Im)(dmso)]; Im=imidazole, dmso=S‐bound dimethylsulfoxide), and a cytotoxic drug, KP1019 ((IndH)[Ru^IIICl₄(Ind)₂]; Ind=indazole), are two Ru‐based anticancer drugs in human clinical trials. Their reactivities under biologically relevant conditions, including aqueous buffers, protein solutions or gels (e.g, albumin, transferrin and collagen), undiluted blood serum, cell‐culture medium and human liver (HepG2) cancer cells, were studied by Ru K‐edge X‐ray absorption spectroscopy (XAS). These XAS data were fitted from linear combinations of spectra of well‐characterised Ru compounds. The absence of XAS data from the parent drugs in these fits points to profound changes in the coordination environments of Ru^III. The fits point to the presence of Ru^IV/III clusters and binding of Ru^III to S‐donor groups, amine/imine and carboxylato groups of proteins. Cellular uptake of KP1019 is approximately 20‐fold higher than that of NAMI‐A under the same conditions, but it diminishes drastically after the decomposition of KP1019 in cell‐culture media, which indicate that the parent complex is taken in by cells through passive diffusion.     

Inspiration from Old Dyes: Tris(stilbene) Compounds as Potent Gram‐Positive Antibacterial Agents

Herein we describe the preparation and structure‐activity relationship studies on range of stilbene based compounds and their antibacterial activity. Two related compounds, each bearing carboxylic acid moieties, exhibit good activity against several bacterial strains, including methicillin‐resistant Staphylococcus aureus MRSA (ATCC 33592 and NCTC 10442). Compound 10 was most active against Moraxella catarrhalis with minimum inhibitory concentrations (MICs) of 0.12–0.25 μg mL^?1 and against Staphylococcus spp. with MICs ranging from 2–4 μg mL^?1. The derivative 17 showed increased activity with MICs of 0.06–0.25 μg mL^?1 against M. catarrhalis and 0.12–1 against Staphylococcus spp. This level of activity is similar to that reported for S. aureus for antibiotics, such as vancomycin, with MICs of ≤2.0 μg mL^?1 and clindamycin with MICs of ≤0.5 μg mL^?1. As an indicator of toxicity, 17 was tested for its ability to lyse sheep erythrocytes, and showed low haemolytic activity. Such results highlight the value of tris(stilbene) compounds as antibacterial agents providing suitable properties for further development.