Where is the sodium in self-assembled monolayers of single-stranded DNA?

Monolayers of single-stranded DNA (ssDNA) immobilized on surfaces form the basis of a number of important biotechnology applications, including DNA microarrays and biosensors. The organization of ssDNA as layer on a solid substrate allows one to investigate various properties of the DNA in a controlled manner and to use DNA for analytical applications as well as for exploring futuristic schemes for molecular electronics. It is commonly assumed that the adsorbed DNA layer contains some structural water and the cations. Here we show, based on XPS studies, that when monolayers of ssDNA are formed from sodium phosphate buffer and washed thoroughly, no Na+ signal is detected. A finite concentration of ions is observed when the DNA is made from a solution of Mg2+ ions, but it is still only a fifth of what it would be if all the phosphate ions were fully neutralized by the metal cations.     

A Two‐Dimensional Coordination Compound as a Zinc Ion Selective Luminescent Probe for Biological Applications

A 2D coordination compound {[Cu₂(HL)(N₃)]?ClO₄}_∞ ( 1 ; H₃L=2,6‐bis(hydroxyethyliminoethyl)‐4‐methyl phenol) was synthesized and characterized by single‐crystal X‐ray diffraction to be a polymer in the crystalline state. Each [Cu₂(HL)(N₃)]⁺ species is connected to its adjacent unit by a bridging alkoxide oxygen atom of the ligand to form a helical propagation along the crystallographic a axis. The adjacent helical frameworks are connected by a ligand alcoholic oxygen atom along the crystallographic b axis to produce pleated 2D sheets. In solution, 1 dissociates into [Cu₂(HL)₂(H₃L)]?2H₂O ( 2 ); the monomer displays high selectivity for Zn²⁺ and can be used in HEPES buffer (pH 7.4) as a zinc ion selective luminescent probe for biological application. The system shows a nearly 19‐fold Zn²⁺‐selective chelation‐enhanced fluorescence response in the working buffer. Application of 2 to cultured living cells (B16F10 mouse melanoma and A375 human melanoma) and rat hippocampal slices was also studied by fluorescence microscopy.     

Kinetics and mechanism of the reaction oftrans-cyclohexane-1,2-diamine-N N N' N'-tetra-acetatomanganate(III) with substituted thioureas in aqueous medium

Summary The kinetics of reduction of [Mn^III(cydta)]^– (where H₄cydta=trans-cyclohexane-1,2-diamine-N N N' N'-tetraacetic acid) by some thiourea reductants have been studied in aqueous solution by stopped-flow techniques in the pH ranges 2.5–4.5 and 9.2–10.2. An initial increase in absorbance followed by a steady decrease indicated the formation of a precursor complex prior to the electron transfer step. The reactions are first order in both oxidant and reductant. The observed increase in rate in going from low to high pH is attributed to the difference in reactivities of the aqua and hydroxo species of the Mn^III complex; the higher reactivity of the latter is consistent with the formation of a ligand-bridged activated species prior to electron transfer. The reactivity order for the thiourea derivatives follows the order of their reported substituent effects.     

Silicon clusters: chemistry and structure

The chemical reactions of size selected silicon cluster ions (containing up to 70 atoms) have been studied with a number of different reagents using injected ion drift tube techniques. Both kinetic and equilibrium measurements have been performed as a function of temperature, and the influence of cluster annealing on chemical reactivity explored. Unlike metal clusters, where bulk behavior appears to be approached with around 30 atoms, large silicon clusters (n up to 70) are much less reactive than bulk silicon surfaces. These results suggest that the clusters in the size range examined here are not small crystals of bulk silicon, but have compact, high coordination number structures with few dangling bonds.     

A high yielding, one-pot synthesis of O,S-dialkyl dithiocarbonates from alcohols using Mitsunobu’s reagent

A novel Mitsunobu-based protocol has been developed for the synthesis of O,S-dialkyl dithiocarbonates from a variety of primary, secondary and tertiary alcohols using carbon disulfide, in good to excellent yields. This protocol is mild and efficient compared to other reported methods.     

Enantiomeric separation and quantification of fluoxetine (Prozac) in human plasma by liquid chromatography/tandem mass spectrometry using liquid-liquid extraction in 96-well plate format

Fluoxetine (Prozac) is currently one of the widely prescribed selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression. A high-throughput sample preparation procedure using liquid-liquid extraction (LLE) in a 96-well plate format in conjunction with liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed and validated for quantification of fluoxetine enantiomers in human plasma. After addition of internal standard and ammonium hydroxide, samples were extracted with ethyl acetate. The organic extract was evaporated to dryness and reconstituted in methanol. Where possible, sample transfer and LLE steps were automated using a Tomtec Quadra 96 workstation. Adequate separation of fluoxetine enantiomeric pairs (resolution of 1.17) was achieved on a vancomycin column eluted with methanol containing 0.075% (by weight) ammonium trifluoroacetate. A triple quadrupole mass spectrometer, operated in the multiple reaction monitoring mode at m/z 310-->44 for fluoxetine enantiomeric pairs and m/z 287-->241 for oxazepam (internal standard), was used. Analysis was performed in the positive ion mode using atmospheric pressure chemical ionization (APCI). The standard curve range was 2.0-1000 ng/mL for each fluoxetine enantiomer. The intra- and inter-day precision and accuracy of the quality control (QC) samples were <12.5% (CV) and <13.6% (CV), respectively, for each fluoxetine enantiomer; the correlation coefficient was >0.990. Method ruggedness was demonstrated by the reproducible performance of the assay during a three-day validation period.     

Polymerization of vinylcarbazole on copper(II)-13X molecular sieves: Role of copper(II) salts

Copper(II)-exchanged-13X molecular sieves, prepared from four copper(II) salts, namely, sulfate, nitrate, chloride, and acetate, and their activities in the polymerization of N-vinylcarbazole at a fixed copper ion exchange level were studied. From the kinetic characteristics of polymerization it was established that the variation in activities of the Cu-exchanged sieves is due primarily to the difference in the pH of the original salt solution, which is responsible for the varying degree of proton exchange with the zeolite during copper ion exchange. A first-order dependence of the rate of polymerization was observed with respect to H⁺ ion concentration of the original copper-salt solution. It was further established that the rate of polymerization of exchanged copper ion, at a hypothetical zero proton concentration, is low. A mechanism of polymerization of NVC on copper-exchanged-13X zeolite was suggested on the basis of the results obtained.     

<Superscript>90</Superscript>Y-DOTA-Lanreotide: A potential agent for targeted therapy

Several human tumors such as neuroendocrine tumors, medullary thyroid carcinoma, etc., express somatostatin receptors which specifically bind somatostatin and its analogues such as lanreotide, octreotide, etc. In order to prepare a therapeutic agent for targeting such tumors, attempts were made to prepare ⁹⁰Y-DOTA-Lanreotide. Lanreotide could be successfully conjugated with the macrocyclic chelating agent DOTA (1,4,7,10-tetraaza cyclododecane tetracetic acid) which forms stable complexes with ⁹⁰Y. ⁹⁰Y-DOTA-Lanreotide could be prepared in >98% radiochemical purity and remained stable for 72 hours at room temperature. The tracer showed specific binding to A431 cells. Biodistribution studies in C57BL6 mice bearing melanoma showed ∼1.3% uptake pergram of tumor at 24-hour p.i.     

Supramolecular peptide helix from a novel double turn forming peptide containing a β-amino acid

A single-crystal X-ray diffraction study of the terminally protected tetrapeptide Boc-β-Ala-Aib-Leu-Aib-OMe 1 (Aib: α-aminoisobutyric acid; β-Ala: β-Alanine) reveals that it adopts a new type of double turn structure which self-associates to form a unique supramolecular helix through intermolecular hydrogen bonds. Scanning electron microscopic studies show that peptide 1 exhibits amyloid-like fibrillar morphology in the solid state.     

Stereocontrolled synthesis of cis-dibenzoquinolizine chlorofumarates: curare-like agents of ultrashort duration

The quaternizations of dibenzoquinolizines 9 and 14 with 3-halo-1-propanols are highly cis-selective (94-100% cis), results consistent with the N-methylation of O-methylcapaurine (7b), but in contrast to the proposed trans-stereochemistry of dibenzo[a,h]quinolizine methiodide 10 and the analogous quaternizations of 1-benzyl- and 1-phenylisoquinoline congeners 5b and 5c. In this report, we describe stereoselective preparation of the unique cis-dibenzoquinolizinium propanols 15 and 16and their transformation into bis- and mixed-onium chlorofumarates 19, 20ab, and 26. Dibenzo[a,g]quinolizinium propanol 15 was prepared enantioselectively in three steps from dihydroisoquinoline 11. Asymmetric transfer hydrogenation of 11 in the presence of triethylamine/formic acid and Noyori's chiral ruthenium catalyst 12 produced R-(-)-5',8-dimethoxynorlaudanosine (13) in 98% yield and 87% ee. Pictet-Spengler cyclization of 13 in formalin/formic acid afforded the dibenzo[a,g]quinolizine 14 in 65% yield. Quaternization of 14 with 3-chloro-1-propanol under Finkelstein conditions generated cis-dibenzoquinolizinium propanol 15 in 85% yield with >94% cis-selectivity. The cis-dibenzo[a,h]quinolizinium propanol 16 was obtained as a single stereoisomer by reaction of the known tetramethoxyquinolizine 9 with neat 3-iodo-1-propanol. Bis-onium chlorofumarates 18 and 19 and the mixed-onium derivative 20ab were prepared by a pool synthesis procedure from (1R)-trans-6a, 16, and chlorofumaryl chloride (17). Mixed-onium alpha-chlorofumarate 26 was synthesized from (1S)-trans-6d, 15 and (+/-)-trans-2,3-dichlorosuccinic anhydride (22), employing a recently disclosed chlorofumarate mixed-diester synthesis. The title compounds (19, 20ab, and 26) displayed curare-like effects of ultrashort duration in rhesus monkeys.