Bright fluorescent chemosensor platforms for imaging endogenous pools of neuronal zinc

A series of new fluorescent Zinpyr (ZP) chemosensors based on the fluorescein platform have been prepared and evaluated for imaging neuronal Zn(2+). A systematic synthetic survey of electronegative substitution patterns on a homologous ZP scaffold provides a basis for tuning the fluorescence responses of "off-on" photoinduced electron transfer (PET) probes by controlling fluorophore pK(a) values and attendant proton-induced interfering fluorescence of the metal-free (apo) probes at physiological pH. We further establish the value of these improved optical tools for interrogating the metalloneurochemistry of Zn(2+); the novel ZP3 fluorophore images endogenous stores of Zn(2+) in live hippocampal neurons and slices, including the first fluorescence detection of Zn(2+) in isolated dentate gyrus cultures. Our findings reveal that careful control of fluorophore pK(a) can minimize proton-induced fluorescence of the apo probes and that electronegative substitution offers a general strategy for tuning PET chemosensors for cellular studies. In addition to providing improved optical tools for Zn(2+) in the neurosciences, these results afford a rational starting point for creating superior fluorescent probes for biological applications.     

Influence of recent vegetation on labile and recalcitrant carbon soil pools in central Queensland, Australia: evidence from thermal analysis-quadrupole mass spectrometry-isotope ratio mass spectrometry

The effect of a recent vegetation change (<100 years) from C(4) grassland to C(3) woodland in central Queensland, Australia, on soil organic matter (SOM) composition and SOM dynamics has been investigated using a novel coupled thermogravimetry-differential scanning calorimetry-quadrupole.mass spectrometry-isotope ratio mass spectrometry (TG-DSC-QMS-IRMS) system. TG-DSC-QMS-IRMS distinguishes the C isotope composition of discrete SOM pools, showing changes in labile, recalcitrant and refractory carbon in the bulk soil and particle size fractions which track the vegetation changes. Analysis of evolved gases (by QMS) from thermal decomposition, rather than observed weight loss, proved essential in determining the temperature at which SOM decomposes, because smectite and kaolinite clays contribute to observed weight losses. The delta(13)C analyses of the CO(2) evolved at different temperatures for bulk soil and particle size-separates showed that most of the labile SOM under the more recent woody vegetation was C(3)-derived carbon whereas the delta(13)C values in the recalcitrant SOM showed greater C(4) contributions. This indicated a shift from grass (C(4))- to tree (C(3))-derived carbon in the woodland, which was also supported by the two-phase (13)C enrichment with depth, i.e. C(3) vegetation dominated the top soil (0-10 cm), but the C(4) contribution increased with depth (more gradual). This is perturbed by the inclusion of charcoal from forest fires ((14)C age incursions) and by the deep incorporation of C(3) carbon due to root penetration.     

Direct functionalization of labile alkoxyamines

Direct esterification of a labile alkoxyamine R¹R²NOR³, which was previously reported as unsuccessful, is achieved by a Mitsunobu reaction or a nucleophilic substitution. Ester derivatives are obtained under smooth conditions and easily purified. Macrocyclization attempts on ester derivatives were successful for five-membered ring lactones and unsuccessful for 13-membered ring lactones. Moreover, the success of the cyclization was dramatically dependent on the quality of the solution degassing. Poor degassing led to unexpected carbonate alkoxyamine.     

Simultaneous voltammetric determination of cobalt, nickel and labile zinc, using 2-quinolinethiol in the presence of surfactants without prior digestion

2-Quinolinethiol forms very stable cobalt and nickel complexes, which are strongly chemisorbed on the hanging mercury drop electrode (HMDE). This allows the simultaneous determination of cobalt, nickel and labile zinc traces; Co and Ni by differential pulse adsorptive stripping voltammetry (DPAdSV) and Zn by differential pulse sweep voltammetry (DPSV), even in the presence of a large amount of surfactant like Triton X-100. This is advantageous for determining these metals directly in natural waters, without previous UV-irradiation or acid digestion. The surfactant does not only not interfere, but shows a beneficial effect with respect to the resolution between copper and nickel peaks. The method has been tested in estuary waters. The determination limits are 1 nmol/l Ni, 10 nmol/l Co and 1 mol/l Zn, with RSD less than 6.3%.     

Determination of the labile species of zinc by anodic stripping staircase voltammetry, with special reference to correlation with the toxicity to tetrahymena

Anodic stripping staircase voltammetry (ASSV) has been tested as a method to determine the concentration of “free” ions and very labile complexes of zinc. These species are thought to be primarily responsible for the toxic effect of zinc on the ciliated protozoan Tetrahymena pyriformis. ASSV and toxicological experiments were performed in an inorganic salt medium and the effects of Cu interference were studied. Even though the ASSV results were encumbered with problems, the results agreed well with the toxicological effects. In contrast, calculations based on the solubility product of Zn₃ (PO₄)₂·4H₂O could lead to erroneous results because kinetic and other effects result in very slow precipitation of zinc phosphate at the concentration levels in the salt medium used. In this medium there is a dose-dependent effect of zinc on Tetrahymena which is in agreement with the ASSV data, which indicate that all the zinc is in a labile form. The study emphasizes the importance of using experimental determinations in preference to theoretical models, which may predict quite erroneous results.     

Electrochemistry of a labile average-valence dicopper system

Electrochemical studies on an average-valent dicopper cryptate demonstrate the existence of a solvent-assisted disproportionation in acetonitrile, which is absent in water. The existence of this process was confirmed via absorption spectroscopy, which allowed the evaluation of thermodynamic parameters. The disproportionation equilibrium is enthalpically controlled, and the results suggest an upper limit for the bond energy of the one-electron Cu-Cu bond of 200 kJ mol(-1).     

Development of tyrosinase labile protecting groups for amines

[reaction: see text] The development of two novel protecting groups for amines is described. Thus, a range of amines have been converted to ureas, and the deprotection of these upon exposure to mushroom tyrosinase (E.C. 1.14.18.1) has been demonstrated.     

Oxidative generation of diarylcarbenium ion pools

"Cation pools" of diarylcarbenium ions have been generated by the oxidative C-H bond dissociation of diarylmethanes using anodic oxidation. "Diarylcarbenium ion pools" thus generated react with various nucleophiles, such as allylsilanes, ketene silyl acetals, and aromatic compounds. The reductive homocoupling of the "diarylcarbenium ion pool" has been achieved. The dimer thus obtained also serves as a precursor of the "diarylcarbenium ion pool" via oxidative C-C bond dissociation. [reaction: see text]     

Intramolecular participation in alkoxycarbenium ion pools

[reaction: see text] Alkoxycarbenium ions having no substituents on the cationic carbon have been accumulated as "cation pools" by the introduction of an ether group in an appropriate position. Intramolecular participation of the ether oxygen is suggested to be responsible for stabilization of the alkoxycarbenium ions.     

Electrochemical generation of glycosyl triflate pools

Glycosyl triflates, which serve as important intermediates in glycosylation reactions, were generated and accumulated by the low-temperature electrochemical oxidation of thioglycosides such as thioglucosides, thiogalactosides, and thiomannosides in the presence of tetrabutylammonium triflate (Bu(4)NOTf) as a supporting electrolyte. Thus-obtained solutions of glycosyl triflates (glycosyl triflate pools) were characterized by low-temperature NMR measurements. The thermal stability of glycosyl triflates and their reactions with glycosyl acceptors were also examined.     

Imidazole derivatives bearing potentially labile groups on the n-atom

A number of N-aminoethyl-, N-hydroxyethyl-, and N-mercapto-ethylbenzimidazoles have been synthesized, and their behavior toward sodamide investigated. The influence of the basicity of the benzimidazoles on the course of the Chichibabin reaction is discussed.For part II, see [20].     

Electrochemiluminescent detection of labile radical intermediates of electrochemical reactions

The article considers the basic principles of electrochemiluminescent spin traps diagnostic method which consists of efficient trapping of intermediate labile radical products (free radicals of complex organic molecules) by electrogenerated radical ions of electrochemiluminescers in different liquid-phase systems including bioobjects. The method permits qualitative and quantitative identification of such particles by measurement of electrolysis radical recombination luminescence (electrogenerated chemiluminescence) intensity which is emitted by electrolyzed solutions of organic electrochemiluminescers. The unique possibilities of the method are illustrated on examples of experimental study of systems with sodium tetraphenylborate and chloride ion.     

Imidazole derivatives with potentially labile groups at the N-atom

A number of N-aminomerhyl and N-alkoxy(aroxy)methylbenzimidazoles are prepared. These compounds are decomposed in acid solution, giving benzimidazole. Sodamide reacts with them to give N-aminomethylbenzimidazole, and not the corresponding 2-amino derivative. The facility with which the compounds investigated decompose decreases in the order N-aminomethyl > N-aroxymethyl > N-alkoxymethylbenzimidazole. The mechanism of splitting is considered.     

A base labile handle for solid phase organic chemistry

Several arylsulfonamides have been synthesised on solid phase using a new base labile handle. Cleavage from the solid support is accomplished by oxidation of the sulfide to the sulfone, followed by β-elimination in base media.