A molecular approach to rationally constructing specific fluorogenic substrates for the detection of acetylcholinesterase activity in live cells,mice brains and tissues

Acetylcholinesterase (AChE) is an extremely critical hydrolase tightly associated with neurological diseases. Currently, developing specific substrates for imaging AChE activity still remains a great challenge due to the interference from butyrylcholinesterase (BChE) and carboxylesterase (CE). Herein, we propose an approach to designing specific substrates for AChE detection by combining dimethylcarbamate choline with a self-immolative scaffold. The representative P10 can effectively eliminate the interference from CE and BChE. The high specificity of P10 has been proved via imaging AChE activity in cells. Moreover, P10 can also be used to successfully map AChE activity in different regions of a normal mouse brain, which may provide important data for AChE evaluation in clinical studies. Such a rational and effective approach can also provide a solid basis for designing probes with different properties to study AChE in biosystems and another way to design specific substrates for other enzymes.

In this work, a new approach was developed for designing the representative P10 with high selectivity and sensitivity for imaging AChE activity in the cells and normal mouse brain.     

Metal-oxygen-metal arrays in lamellar hybrid materials: cobalt and manganese 4-cyclohexene-1,2-dicarboxylates

We have obtained three layered hybrid materials from the hydrothermal reaction of 4-cyclohexene-1,2-dicarboxylic acid with Co and Mn salts: Co(C(8)H(8)O(4))[1], Mn(H(2)O)(C(8)H(8)O(4))[2], and Mn(4)(H(2)O)(C(8)H(8)O(4))(4).0.3(H(2)O)[3]. The structures for all materials were solved by single-crystal XRD ([1]P1, a=4.805(2) A, b=6.650(3) A, c=12.960(6) A, alpha=98.285(7) degrees, beta=98.986(7) degrees, gamma=95.689(7) degrees, V= 401.6(3) A(3), R(1)= 0.0438; [2] P2(1)/c, a=11.151(2) A, b=11.330(2) A, c=7.6560(15) A, beta=108.813(3) degrees , V=915.6(3) A(3), R(1)=0.0412; [3] P1, a= 11.412(3) A, b=12.136(4) A, c=13.809(4) A, alpha=104.703(6) degrees, beta=103.207(6) degrees, gamma=92.468(5) degrees, V=1790.6(9) A(3), R(1)=0.1056). While all three structures are two-dimensional overall, the metal-oxygen-metal dimensionality within the layers varies from isolated metal atoms in the case of [1] to 1D ribbons of vertex sharing MnO(6) octahedra [2] and 2D arrays of edge- and vertex-sharing polyhedra in [3].     

Integral equation theory for two-dimensional polymer melts

The polymer reference interaction site model theory is investigated for two-dimensional polymer melts composed of freely-jointed hard disk chains and tangent-disk rods. Exact results for the intramolecular pair correlation functions are input into the theory, and predictions of the theory for the intermolecular pair correlation functions are tested via comparison with simulation. The theory is not as accurate for this system as it is for three-dimensional polymer melts, and the quantitative predictions are not good except at the highest area fractions. Possible reasons for the deficiency in the theory are discussed.     

Decarbopalladation of pi-allylpalladium intermediates formed from palladium-catalyzed arylations of 3-allen-1-ols

[reaction: see text] Unusual palladium-catalyzed arylative fragmentations of acyclic 3-allen-1-ols were observed. Oxidative addition of Pd(0) to aryl halides would form the arylpalladium halides, which added to the central carbon of allenes via carbopalladation to form the pi-allylpalladium intermediates. The pi-allylpalladium intermediates would be reductively eliminated via carbon-carbon cleavage to give the arylated dienes and the alpha-hydroxyalkylpalladium intermediates, which were further reductively eliminated to the corresponding aldehydes.     

Chlorinated briarane-type diterpenoids from the gorgonian coral Ellisella robusta (Ellisellidae)

Four chlorinated metabolites featuring briarane carbon skeletons have been isolated from the gorgonian coral Ellisella robusta, which was collected off the coast of southern Taiwan: two new natural products, robustolides D (1) and E (2), and two known metabolites, robustolides F (3) and G (4). The structures of metabolites 1–4 were determined by spectroscopic methods, using 1D and 2D NMR in particular. The structures and absolute stereochemistry of robustolides D (1), F (3), and G (4) were directly established by X-ray diffraction analysis. Robustolide D (1) is the first metabolite of briarane-related natural products found to possess two halogen atoms.     

Pt‐Nanoparticle Incorporated Carbon Paste Electrode for the Determination of Cu(II) Ion by Anodic Stripping Voltammetry

Pt‐nanoparticles were synthesized and introduced into a carbon paste electrode (CPE), and the resulting modified electrode was applied to the anodic stripping voltammetry of copper(II) ions. The synthesized Pt‐nanoparticles were characterized by cyclic voltammetry, scanning electron microscopy and X‐ray photoelectron spectroscopy techniques to confirm the purity and the size of the prepared Pt‐nanoparticles (ca. 20 nm). This incorporated material seems to act as catalysts with preconcentration sites for copper(II) species that enhances the sensitivity of Cu(II) ions to Cu(I) species at a deposition potential of ?0.6 V in an aqueous solution. The experimental conditions, such as, the electrode composition, pH of the solution, pre‐concentration time, were optimized for the determination of Cu(II) ion using as‐prepared electrode. The sensitivity changes on the different binder materials and the presence of surfactants in the test solution. The interference effect of the coexisted metals were also investigated. In the presence of surfactants, especially TritonX‐100, the Cu(II) detection limit was lowered to 3.9×10^?9 M. However, the Pt‐nanoparticle modified CPE begins to degrade when the period of deposition exceeds to 10 min. Linear response for copper(II) was found in the concentration range between 3.9×10^?8 M and 1.6×10^?6 M, with an estimated detection limit of 1.6×10^?8 M (1.0 ppb) and relative standard deviation was 4.2% (n=5).     

Polymerizable benzophenone derivatives for labeling vinyl acetate‐butylacrylate latex particles

We describe the synthesis and characterization of three new polymerizable benzophenone derivatives [2‐acryloxy‐5‐methyl benzophenone ( 8 ), 4′‐dimethylamino‐2‐acryloxy‐5‐methyl benzophenone ( 9 ), and 4′‐dimethylamino‐2‐(β‐acryloxyethyl)oxy‐5‐methyl benzophenone ( 10 )]. We show that these monomers can successfully be incorporated into vinyl acetate (VAc) copolymer latex particles. These particles were prepared by semicontinuous emulsion polymerization and mini‐emulsion polymerization of VAc with butylacrylate (BA) for VAc/BA = 4/1 by weight. The two monomers 9 and 10 bearing the 4′‐dimethylamino group satisfy the important spectroscopic criteria required of a dye to serve as an acceptor chromophore for nonradiative energy transfer from phenanthrene (Phe) as the donor. Their UV absorption spectra suggest significant overlap with the emission spectrum of Phe, which can be incorporated into P(VAc‐co‐BA) latex through copolymerization with 9‐acryloxymethyl Phe ( 2 ). In addition, these chromophores provide a window in their absorption spectra for excitation of the Phe chromophore at 300 nm. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3001–3011, 2002     

Binding and photoreactivity of psoralen linked to triple helix-forming oligonucleotides

Triple helix-forming oligonucleotides conjugated to a psoralen (psoTFO) have been designed to bind to three distinct purine-rich sequences within the human interstitial collagenase (MMP1) gene. Gel mobility shift assays indicate that these psoTFO bind to and photoreact with model target DNA sequences following ultraviolet A (UVA) irradiation. The dissociation constants for binding of the psoTFO to their targets range from 0.3 to 4 microM. Psoralen monoadducts with the purine-rich target strand and interstrand crosslinks are efficiently formed on targets containing either 5'-ApT-3' or 5'-TpA-3' sequences adjacent to the TFO binding sequence. The dependence of adduct formation on UVA dose has provided quantitative estimates of the overall rate constants for psoralen monoadduct and crosslink formation in the presence of a TFO. When psoralen is tethered to a TFO, the rate of monoadduct formation exceeds that of crosslinking for all sequences studied. This contrasts with the relatively low rate of monoadduct formation that has been reported for free psoralens, suggesting that the bound TFO facilitates the initial photochemistry that generates monoadducts, but does not significantly affect interstrand crosslink formation. psoTFO and UVA treatment inhibit DNA cleavage by a restriction endonuclease when the psoralen covalently reacts directly at the endonuclease site. The particular TFO studied do not completely inhibit endonuclease activity when they are noncovalently bound or when the covalent psoralen adduct does not coincide with the endonuclease site. Our findings confirm that TFO are capable of directing psoralen photoadducts to specific DNA targets and suggest that TFO can significantly modulate psoralen photoreactivity and DNA-protein interactions.     

Theoretical studies on the mechanism of acid-promoted hydrolysis of N-formylaziridine in comparison with formamide

[reaction: see text] We present an ab initio study of the acid-promoted hydrolysis reaction mechanism of N-formylaziridine in comparison with formamide. Since the rate of amide hydrolysis reactions depends on the formation of the tetrahedral intermediate, we focused our attention mainly on the reactant complex, the tetrahedral intermediate, and the transition state connecting these two stationary points. Geometries were optimized using the density functional theory, and the energetics were refined using ab initio theory including electron correlation. Solvent effects were investigated by using polarizable continuum method calculations. The proton-transfer reaction between the O-protonated and N-protonated amides was investigated. In acidic media, despite that the N-protonated species is more stable than the O-protonated one, it is predicted that both N-protonated and O-protonated pathways compete in the hydrolysis reaction of N-formylaziridine.