Characterization and properties of the copper(II/I) complexes of macrocyclic hexathiaether ligand [21]aneS6

The copper(II/I) complexes of hexathiaether macrocyclic ligand, 1,4,8,11,15,18-hexathiacyclohenicosane ([21]aneS₆), were synthesized, and characterized by electrochemical and spectroscopic techniques. Cyclic voltammetric studies indicate that Cu([21]aneS₆)^2+/+ forms a reversible one-electron redox couple. The electrochemical potential obtained for Cu([21]aneS₆)^2+/+ (E^f = 0.89 V, against SHE) was found to be the highest potential reported to date for a Cu^2+/+ macrocyclic system in aqueous solution. By employing the Nernst equation, we can infer that the practical upper limit for formal potential of Cu(II/I)L systems maybe close to this high value. Stability constant data obtained for these complexes indicate that Cu([21]aneS₆)⁺is 12 orders of magnitude greater in stability than that of Cu([21]aneS₆)²⁺ indicating the favorable nature of this large macrocyclic ligand towards formation of Cu(I) complexes over Cu(II) complexes. Crystal structure of Cu([21]aneS₆)⁺ ( Fig. 2) shows that four sulfurs adjacent to one another are coordinated to Cu⁺ ion in this complex. Bond angles and distances calculated for the crystal indicate that it is a distorted tetrahedron, a geometry commonly encountered by Cu(I) complexes. This is the first report of synthesis and characterization of a metal coordinated [21]aneS₆ complex.     

Simultaneous preparation of tritiated uracil and uridine

Summary Tritiated uracil and uridine have been prepared simultaneously from a mixture of their respective halogenated analogues (5-bromouracil and5-bromouridine) by halogen-tritium exchange in a one pot preparation, followed by purification. The tritiated products thus obtained have specific activities of 0.962 TBq/mmol and 1.036 TBq/mmol, respectively.     

Electrochemical Characteristics of “Polyaniline” Cathodes and Anodes in Aqueous Electrolytes

The quinoid-benzenoid-diimine form, (=(C₆H₄)=N-(C₆H₄)-N=)_x of “polyaniline” shows excellent cathode characteristics including recyclability when used in conjunction with a zinc anode in an aqueous electrolyte of (l. 0M ZnCl₂ + 0. 5M NH₄Cl) having a pH of ～ 4. The reduced form of this material, (-(C₆H₄)-N(H)-(C₆H₄)-N(H)-)_x can be used as an anode in conjunction with a Pb0₂ cathode in an aqueous 0.5M Pb(BF₄)₂ electrolyte.     

Profiling primaquine metabolites in primary human hepatocytes using UHPLC‐QTOF‐MS with 13C stable isotope labeling

Therapeutic efficiency and hemolytic toxicity of primaquine (PQ), the only drug available for radical cure of relapsing vivax malaria are believed to be mediated by its metabolites. However, identification of these metabolites has remained a major challenge apparently due to low quantities and their reactive nature. Drug candidates labeled with stable isotopes afford convenient tools for tracking drug‐derived metabolites in complex matrices by liquid chromatography‐tandem mass spectrometry (LC‐MS‐MS) and filtering for masses with twin peaks attributable to the label. This study was undertaken to identify metabolites of PQ from an in vitro incubation of a 1:1 w/w mixture of ¹³C₆‐PQ/PQ with primary human hepatocytes. Acquity ultra‐performance LC (UHPLC) was integrated with QTOF‐MS to combine the efficiency of separation with high sensitivity, selectivity of detection and accurate mass determination. UHPLC retention time, twin mass peaks with difference of 6 (originating from ¹³C₆‐PQ/PQ), and MS‐MS fragmentation pattern were used for phenotyping. Besides carboxy‐PQ (cPQ), formed by oxidative deamination of PQ to an aldehyde and subsequent oxidation, several other metabolites were identified: including PQ alcohol, predictably generated by oxidative deamination of PQ to an aldehyde and subsequent reduction, its acetate and the alcohol's glucuronide conjugate. Trace amounts of quinone‐imine metabolites of PQ and cPQ were also detected which may be generated by hydroxylation of the PQ/cPQ quinoline ring at the 5‐position and subsequent oxidation. These findings shed additional light on the human hepatic metabolism of PQ, and the method can be applied for identification of reactive PQ metabolites generated in vivo in preclinical and clinical studies. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis,ABTS-Radical Scavenging Activity,and Antiproliferative and Molecular Docking Studies of Novel Pyrrolo[1,2-a]quinoline Derivatives

A new 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS)-radical scavenging and antiproliferative agents of pyrrolo[1,2-a]quinoline derivatives have been synthesized. An efficient method for the synthesis of 14 novel diversified pyrrolo[1,2-a]quinoline derivatives has been described using 4-(1,3-dioxolan-2-yl)quinoline and different phenacyl bromides in acetone and followed by reacting with different acetylenes in dimethylformamide/K₂CO₃. The structure of the newly synthesized compounds was determined by infrared, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. The in vitro antioxidant activity revealed that among all the tested compounds 5n exhibited maximum scavenging activity with ABTS. Compound 5b has showed good antiproliferative activity as an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase.     

New Quantization Method for Evaluation of Eigenenergies

A quantum dynamical equation is constructed as the limit of a sequence of functions (called Semiquantum momentum functions or SQMF). The quantum action variable J is defined as the limit of the sequence of contour integrals of SQMFs such that the quantization condition is J = n, where n is a nonnegative integer for eigenvalues and a noninteger for off eigenvalues. This quantization condition is exact and J is an analytic function of energy. Based on new definitions, an accurate numerical method is developed for obtaining eigenenergies. The method can be applied to both real and PT symmetric complex potentials. The validity and the accuracy of this new method is demonstrated with three illustrations.     

Preparation of tritiated fluorenone and fluorenol

Summary Tritiated fluorenone 2 was prepared from 2-iodofluorenone 1 by halogen-tritium exchange. The product had specific activity of 17 Ci/mmol. The product 2(after dilution with unlabeled congener) on reduction with NaBH₄gave the corresponding tritiated fluorenol 3.     

Analysis of primaquine and its metabolite carboxyprimaquine in biological samples: enantiomeric separation, method validation and quantification

The clinical formulation of primaquine (PQ) is a mixture of (−)‐(R)‐ and (+)‐(S)‐ primaquine enantiomers which may show different pharmacokinetic and pharmacodynamic properties. To assess the efficacy and toxicity of primaquine enantiomers, a method using LC‐MSD‐TOF has been developed. The enantiomers were well separated using a Chiralcel OD column (250 × 4.6 mm, 10 µm) with a linear gradient of mobile phase consisting of acetonitrile (0.1% formic acid) and aqueous ammonium formate (20 mm ; 0.1% formic acid) adjusted to pH 5.9 at a flow rate of 0.7 mL/min. The method was validated for linearity, precision, accuracy and limits of detection and quantification. The calibration curves were linear with all correlation coefficients being >0.999. The average recoveries of (−)‐(R)‐ and (+)‐(S)‐primaquine and (−)‐(R)‐ and (+)‐(S)‐carboxyprimaquine were 88 and 92%, respectively, in spiked human plasma and 89 and 93% respectively in spiked mouse plasma samples. The RSD of (−)‐(R)‐ and (+)‐(S)‐primaquine and (−)‐(R)‐ and (+)‐(S)‐carboxyprimaquine were 2.15, 1.74, 1.73 and 2.31, respectively, in spiked human plasma and 2.21, 1.09, 1.95 and 1.17% in spiked mouse plasma, respectively. The intra‐day and inter‐day precisions expressed as RSD were lower than 10% in all analyzed quality control levels. The method as reported is suitable for study of the pharmacokinetic and pharmacodynamic properties of the enantiomers of primaquine. The method was successfully applied to study plasma pharmacokinetic profile of enantiomers of primaquine and carboxyprimaquine in mice administered with primaquine in racemic form. The analytical method was found to be linear, accurate, precise and specific. Copyright © 2010 John Wiley & Sons, Ltd.     

A liquid drop RC filter apparatus for detection

A new analytical detector based on a liquid drop resistor–capacitor (RC) filter is described, in which transformed gain vs. frequency curves are used to analyze compounds. This detector can be used to detect either charged or neutral species (that are dielectrically different) which are dissolved in a liquid (e.g., water, alcohol, solvent mixtures, etc.). This device was fabricated by modifying an electrowetting on dielectric (EWOD)-based experimental setup. When a liquid drop is placed on a dielectric surface, the system acts as a RC filter. At a given frequency, gain is a function of conductivity, surface tension, dielectric constant, double-layer thickness of the solid–liquid drop interface, as well as the applied voltage. Since different liquids and solutions have different physical properties, each liquid/solution has a unique curve (peak) in gain vs. frequency plot. This is the basic principle behind the detector. Different amounts of zinc chloride dissolved in water, benzalkonium chloride in water, 1-methylimidazole in water, cetyltrimethyl-ammonium chloride (CTAC) in water, and CTAC dissolved in ethylene glycol solutions were tested with the detector as proof of principle. The device can be used as a stand-alone detector or can easily be coupled with droplet based microfluidic lab-on-a-chip systems such as EWOD-based microfluidic chips.     

New Semiclassical and Numerical Approaches to Locate Zeros of Wave Functions Asiri Nanayakkara

A new semiclassical method is presented for evaluating zeros of wave functions. In this method, locating zeros of the wave functions of Schrodinger equation is converted to finding roots of a polynomial. The coefficients of this polynomial are evaluated using WKB and semi quantum action variable methods. For certain potentials WKB expressions for moments are obtained exactly. Almost explicit formulae for moments are obtained for the potential V (x) = xN. Examples are given to illustrate both methods. Using semi quantum action variable method, complex zeros of the wave functions of the PT symmetric complex system V(x) = x4 iAx are obtained. These zeros exhibit complex version of interlacing.