Voltammetry of Organic Microparticles

 Solid microparticles of several different insoluble organic compounds were mechanically immobilized on the surface of graphite electrodes and immersed into a liquid electrolyte in order to study their electrochemical reactions. Cyclic staircase voltammetry and square-wave voltammetry were used. Quinhydrone was found to be a stable intermediate in the reversible redox reaction of solid quinone and hydroquinone on the electrode surface. The reaction occurs on the surface of the solid particle which is in contact with water. Indigo can be reduced to leucoindigo and oxidized to dehydroindigo in two separate reversible redox reactions. In strongly basic medium indigo dissolves in water upon electroreduction. A hydroacridine radical was detected as a stable intermediate in the electrochemically irreversible redox reaction of acridine and dihydroacridine. Famotidine can be electrooxidized and the product of this reaction can be electroreduced in two separate chemically irreversible reactions. Probucol is oxidized to a semiquinone radical which can be re-reduced in an electrochemically irreversible redox reaction. Propyl- thiouracil can be also oxidized to an unknown product which can be re-reduced in a chemically reversible, but slow solid state surface redox reaction. Reductions of solid thionicotinoylanilide and nicotinoylanilide are totally irreversible. Received September 22, 1998. Revision March 19, 1999.     

Microwave-assisted three-component synthesis of 7-aryl-2-alkylthio-4,7-dihydro-1,2,4-triazolo[1,5-a]-pyrimidine-6-carboxamides and their selective reduction

Multicomponent reactions (MCRs) and microwave-assisted organic synthesis (MAOS) have been used as key methods for the synthesis of fused dihydropyrimidine derivatives. The three-component condensation of 3-amino-5-alkylthio-1,2,4-triazoles with aromatic aldehydes and acetoacetamides under microwave irradiation was developed as a rapid and efficient solution-phase method for the high-yielding preparation of 7-aryl-2-alkylthio-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxamide libraries. In addition, the selective reduction of the formed dihydrotriazolopyrimidines to trans-trans-2-alkylthio-7-aryl-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxamides was established. The described synthetic protocols provide rapid access to novel and diversely substituted dihydroazolopyrimidine libraries.     

Structural Comparison of Oligoribonucleotides and Their 2′-Deoxy-2′-fluoro Analogs by heteronuclear NMR spectroscopy

1-(2′-Deoxy-2′-fluororibofuranosyl)pyrimidines were synthesized and incorporated into an RNA oligonucleotide to give 5′-r[C_fGC_f(U_fU_fC_fG)GC_fG]-3′ (C_f: short form of C = 2′-deoxy-2′-fluorocytidine; U_f: short form of U = 2′-deoxy-2′-fluorouridine). The oligomer was investigated by means of UV, CD, and NMR spectroscopy to address the question of how F-labels can substitute ¹³C-labels in the ribose ring. Through-space (NOE) and through-bond (scalar couplings) experiments were performed that make use of the ameliorated chemical-shift dispersion induced by ¹⁹F as an alternative heteronucleus. A comparison of the structures of fluorinated vs. unmodified oligomer is given. It turns out that the fluorinated oligonucleotide exists in a 14:3 equilibrium between a hairpin and a duplex conformation, in contrast to the unmodified oligonucleotide which predominantly adopts the hairpin conformation. Furthermore, the fluorinated hairpin structure adopts two distinct conformations that differ in the sugar conformation of the U and C nucleoside units, as detected by the ¹⁹F-NMR chemical shifts. The role of the 2′-OH group as stabilizing element in RNA secondary structure is discussed.     

Dilatational rheology of beta-casein adsorbed layers at liquid-fluid interfaces

The rheological behavior of beta-casein adsorption layers formed at the air-water and tetradecane-water interfaces is studied in detail by means of pendant drop tensiometry. First, its adsorption behavior is briefly summarized at both interfaces, experimentally and also theoretically. Subsequently, the experimental dilatational results obtained for a wide range of frequencies are presented for both interfaces. An interesting dependence with the oscillation frequency is observed via the comparative analysis of the interfacial elasticity (storage part) and the interfacial viscosity (loss part) for the two interfaces. The analysis of the interfacial elasticities provides information on the conformational transitions undergone by the protein upon adsorption at both interfaces. The air-water interface shows a complex behavior in which two maxima merge into one as the frequency increases, whereas only a single maximum is found at the tetradecane interface within the range of frequencies studied. This is interpreted in terms of a decisive interaction between the oil and the protein molecules. Furthermore, the analysis of the interfacial viscosities provides information on the relaxation processes occurring at both interfaces. Similarly, substantial differences arise between the gaseous and liquid interfaces and various possible relaxation mechanisms are discussed. Finally, the experimental elasticities obtained for frequencies higher than 0.1 Hz are further analyzed on the basis of a thermodynamic model. Accordingly, the nature of the conformational transition given by the maximum at these frequencies is discussed in terms of different theoretical considerations. The formation of a protein bilayer at the interface or the limited compressibility of the protein in the adsorbed state are regarded as possible explanations of the maximum.     

Formation of Superoxo Species by Interaction of O2 with Na Atoms Deposited on MgO Powders: A Combined Continuous‐Wave EPR (CW‐EPR), Hyperfine Sublevel Correlation (HYSCORE) and DFT Study

The formation of O₂^? radical anions by contact of O₂ molecules with a Na pre‐covered MgO surface is studied by a combined EPR and quantum chemical approach. Na atoms deposited on polycrystalline MgO samples are brought into contact with O₂. The typical EPR signal of isolated Na atoms disappears when the reaction with O₂ takes place and new paramagnetic species are observed, which are attributed to different surface‐stabilised O₂^? radicals. Hyperfine sublevel correlation (HYSCORE) spectroscopy allows the superhyperfine interaction tensor of O₂^?Na⁺ species to be determined, demonstrating the direct coordination of the O₂^? adsorbate to surface Na⁺ cations. DFT calculations enable the structural details of the formed species to be determined. Matrix‐isolated alkali superoxides are used as a standard to enable comparison of the formed species, revealing important and unexpected contributions of the MgO matrix in determining the electronic structure of the surface‐stabilised Na⁺? O₂^? complexes.     

Electrochemical dissolution of magnetite in acid solutions

The present paper deals with the electrochemical behavior of magnetite microcrystals in an acid medium. A voltammetric method employing a carbon-paste electroactive electrode (CPEE) with an organic binder was used. It was found that the cathodic voltammograms, which were recorded at different scan rates, formed a set bounded in the space of i–E parameters by a generalizing voltammetric curve corresponding to the effective potential scan rate _eff. In other words, all curves are situated under one enveloping curve, just as the smaller dolls sit in the largest doll of a Russian doll. Reverse currents (a cathodic current in the anodic direction of the potential scan) were observed on the cyclic voltammogram. Forward and reverse currents obey the same laws and have one and the same generalizing curve, which could be taken as the magnetite characteristic.     

Kinetics and Mechanism of Mineral Respiration: How Iron Hemes Synchronize Electron Transfer Rates

Anaerobic microorganisms of the Geobacter genus are effective electron sources for the synthesis of nanoparticles, for bioremediation of polluted water, and for the production of electricity in fuel cells. In multistep reactions, electrons are transferred via iron/heme cofactors of c‐type cytochromes from the inner cell membrane to extracellular metal ions, which are bound to outer membrane cytochromes. We measured electron production and electron flux rates to 5×10⁵ e s^?1 per G. sulfurreducens. Remarkably, these rates are independent of the oxidants, and follow zero order kinetics. It turned out that the microorganisms regulate electron flux rates by increasing their Fe²⁺/Fe³⁺ ratios in the multiheme cytochromes whenever the activity of the extracellular metal oxidants is diminished. By this mechanism the respiration remains constant even when oxidizing conditions are changing. This homeostasis is a vital condition for living systems, and makes G. sulfurreducens a versatile electron source.     

Photochromic Free MOF‐Based Near‐Infrared Optical Switch

We demonstrate herein an all‐optical switch based on stimuli‐responsive and photochromic‐free metal–organic framework (HKUST‐1). Ultrafast near‐infrared laser pulses stimulate a reversible 0.4 eV blue shift of the absorption band with up to 200 s^?1 rate due to dehydration and concomitant shrinking of the structure‐forming [Cu₂C₄O₈] cages of HKUST‐1. Such light‐induced switching enables the remote modulation of intensities of photoluminescence of single crystals of HKUST‐1 as well visible radiation passing through the crystal by 2 order of magnitude. This opens up the possibility of utilyzing stimuli‐responsive MOFs for all‐optical data processing devices.     

Probing the Brønsted Acidity of the External Surface of Faujasite-Type Zeolites

We outline two methodologies to selectively characterize the Brønsted acidity of the external surface of FAU-type zeolites by IR and NMR spectroscopy of adsorbed basic probe molecules. The challenge and goal are to develop reliable and quantitative IR and NMR methodologies to investigate the accessibility of acidic sites in the large pore FAU-type zeolite Y and its mesoporous derivatives often referred to as ultra-stable Y (USY). The accessibility of their Brønsted acid sites to probe molecules (n-alkylamines, n-alkylpyridines, n-alkylphosphine- and phenylphosphine-oxides) of different molecular sizes is quantitatively monitored either by IR or ³¹P NMR spectroscopy. It is now possible, for the first time to quantitatively discriminate between the Brønsted acidity located in the microporosity and on the external surface of large pore zeolites. For instance, the number of external acid sites on a Y (LZY-64) zeolite represents 2 % of its total acid sites while that of a USY (CBV760) represents 4 % while the latter has a much lower framework Si/Al ratio.     

Development and validation of an HPLC-MS/MS method to quantify clopidogrel acyl glucuronide, clopidogrel acid metabolite, and clopidogrel in plasma samples avoiding analyte back-conversion

A new sensitive and fast quantitative analytical method for the simultaneous determination of clopidogrel, its main metabolite clopidogrel carboxylic acid, and the newly described acyl glucuronide metabolite, in human plasma samples, is presented. The analytical procedures (plasma storage, handling, and extract storage in the autosampler) were optimized in order to avoid back-conversion; a known drawback in measurements of clopidogrel. Clopidogrel acyl glucuronide was confirmed as a major source of back-conversion to the parent drug in the presence of methanol, and thorough stability experiments were carried out to find the most appropriate conditions for an accurate analysis of clopidogrel and the two metabolites. The method was validated by assessing selectivity, sensitivity, linearity, accuracy, and precision for all three analytes, in accordance to Food and Drug Administration guidelines. Spiked quality controls in plasma as well as incurred samples were used to verify back-conversion in the selected conditions, with results meeting European Medicines Agency acceptance criteria (concentrations within 80–120% of the first reading). The method was then applied to a pharmacokinetic study, and for the first time, a pharmacokinetic curve of clopidogrel acyl glucuronide in human plasma is presented. The concentrations ranged up to 1,048.684 ng/mL, with a mean of 470.268 ng/mL, while clopidogrel had a mean C _max of 1.348 ng/mL; these orders of magnitude show how much the back-conversion of this metabolite may influence clopidogrel quantification if it is not properly controlled.