Determination of the antiretroviral drug nevirapine in diluted alkaline electrolyte by adsorptive stripping voltammetry at the mercury film electrode

This paper describes a stripping method for the determination of nevirapine at the submicromolar concentration levels. The method is based on controlled adsorptive accumulation of nevirapine at thin-film mercury electrode, followed by a linear cyclic scan voltammetry measurement of the surface species. Optimal experimental conditions include a 2.0 x 10(-3) mol L(-1) NaOH solution (supporting electrolyte), an accumulation potential of -0.20 V, and a scan rate of 100 mV s(-1). The response of nevirapine is linear over the concentration range 0.01-0.14 ppm. For an accumulation time of 6 minutes, the detection limit was found to be 0.87 ppb (3.0 x 10(-9) mol L(-1)). More convenient methods to measure the nevirapine in presence of the efavirenz, acyclovir, didanosine, indinavir, nelfinavir, saquinavir, lamivudine, zidovudine and metals ions were also investigated. The utility of this method is demonstrated by the presence of nevirapine together with ATP or DNA.     

The Reaction of the Bis-spirocyclic Phosphazene [N 3 P 3 (O 2 C 12 H 8 ) 2 Cl 2 ] (O 2 C 12 H 8 = 2,2′-Dioxybiphenyl) with Thiophenols,in the Presence of Alkali Carbonates

The reactions of the spirocyclic phosphazene [N 3 P 3 (O 2 C 12 H 8 ) 2 Cl 2 ] (O 2 C 12 H 8 = 2,2'-dioxybiphenyl) with the thiophenols HS--C 6 H 4 --R and M 2 CO 3 (M = K or Cs) in refluxing acetone gave respectively the spirocyclic substituted derivatives [N 3 P 3 (O 2 C 12 H 8 ) 2 (SC 6 H 4 --R) 2 ] R = H ( 2a ), Br ( 2b ), OMe ( 2c ), NO 2 ( 2d ). The reaction is a two-step process the second of which is much faster than the first and the monosubstituted intermediate [N 3 P 3 (O 2 C 12 H 8 ) 2 (SC 6 H 4 --R)Cl] cannot be detected. By contrast, in the analogous reactions with the phenols HO--C 6 H 4 --R and M 2 CO 3 (M = K or Cs) in acetone or THF, to give the known derivatives [N 3 P 3 (O 2 C 12 H 8 ) 2 (OC 6 H 4 --R) 2 ], the first step is faster although both are very dependent on R, M and the solvent. Thus, in the case of the phenol HO--C 6 H 4 --OMe the reaction conditions could be adjusted to give the useful synthetic intermediate monosubstituted derivative [N 3 P 3 (O 2 C 12 H 8 ) 2 (OC 6 H 4 --OMe)Cl] ( 3 ). The reaction of [N 3 P 3 (O 2 C 12 H 8 ) 2 Cl 2 ] with the bifunctional reagent mercaptophenol HS--C 6 H 4 --OH was not specific and led to mixtures of cyclic and oligomeric products.     

Impact of pulsed electric field on electrodialysis process performance and membrane fouling during consecutive demineralization of a model salt solution containing a high magnesium/calcium ratio

Pulsed electric fields (PEFs), hashed modes of current consisting in the application of a constant current density during a fixed time (Ton) followed by a pause lapse (Toff), were recently demonstrated as an effective alternative for mineral fouling mitigation and process intensification during electrodialysis (ED) treatments. Recent ED studies have continuously reported a considerable mineral fouling formation on ion-exchange membranes, especially during the demineralization of solutions containing a high Mg/Ca ratio and a basified concentrate solution. The aim of this study was to evaluate the process performance under two different PEF conditions on a mineral solution containing a mineral mixture giving a high Mg(2+)/Ca(2+) ratio of 2/5. Two different pause-lapse durations (PEF ratio 1 (Ton/Toff 10s/10s); PEF ratio 0.3 (Ton/Toff 10s/33.3 s)) during consecutive ED treatments and their comparison with dc current were evaluated at a current density of 40 mA/cm(2). Our results showed that PEFs resulted in an intensification of ED process, enhancing the demineralization rates (DRs), reducing the system resistance (SR), and reducing the fouling and energy consumption (EC). PEF ratio 1 was the most optimal condition among the current regimes applied, leading to faster and higher demineralization rates due to a lower fouling and with low energy consumption during all consecutive runs.     

A modified electrode for the electrochemical detection of biogenic amines and their amino acid precursors separated by microchip capillary electrophoresis

The use of a mixed-valent ruthenium oxide/hexacyanoruthenate polymeric film electrochemically deposited onto glassy carbon electrodes is proposed here for the detection of biogenic amines and their amino acid precursors, following their separation by microchip capillary electrophoresis. The ability of this ruthenium coating to electrocatalyze the oxidation of aliphatic and heterocyclic amines, as well as their amino acid precursors, was checked by using ethanolamine, tryptamine and tryptophane as prototype compounds and adopting a 25 mM sulphuric acid as the electrolyte in the detection cell, where a constant potential of 1.05 V versus Ag/AgCl, 3 M KCl was applied to the modified working electrode. Optimization of parameters affecting both detection and separation steps led to satisfactory separations when performed by using a 20 mM phosphate running buffer (pH 2.5) and applying a high voltage of 2.5 kV both in the separation and in the electrokinetic injection (duration 4 s). The recorded peaks were characterized by good repeatability (RSD ≤ 3.6%), high sensitivity and a wide linear range. Detection limits of 23 μM (1.4 mg/L), 27 μM (4.3 mg/L) and 34 μM (6.8 mg/L) were inferred for ethanolamine, tryptamine and tryptophane, respectively. The approach proposed here was also applied for the analysis of some double malt dark beers spiked with a controlled amount of the analytes considered.     

Chemoenzymatic asymmetric synthesis of optically active pentane-1,5-diamine fragments by means of lipase-catalyzed desymmetrization transformations

A novel family of prochiral pentane-1,5-diamines has been efficiently synthesized, possessing stabilities significantly higher than those of corresponding propane-1,3-diamine analogues. Diamines have been later desymmetrized using Pseudomonas cepacia lipase as an efficient biocatalyst for the mono- but also stereoselective protection of one of their amino groups. Reaction parameters such as type and loading of enzyme, temperature, solvent, and acyl donor have been exhaustively analyzed, searching for optimal conditions for the production of interesting optically active nitrogenated compounds. Thus, acylation and alkoxycarbonylation processes have been compared in terms of conversion and enantiomeric excess values. The best results were found in the reaction of prochiral diamines with ethyl methoxyacetate as acyl donor and 1,4-dioxane as solvent, yielding (S)-monoamides in 33-59% isolated yield and 54-99% ee, depending on the aromatic pattern substitution.     

Complementary lipase-mediated desymmetrization processes of 3-aryl-1,5-disubstituted fragments. Enantiopure synthetic valuable carboxylic acid derivatives

Desymmetrizaton enzymatic processes have been extensively studied searching for optimal methods of producing enantioenriched monoacetates from prochiral diols and diesters. AK lipase has been found as an excellent biocatalyst for the desymmetriaztion of a series of previously synthesized 3-arylpentane-1,5-diols derivatives. The access to (S)- or (R)-monoacetates in high optical purity (86-99% ee) has been possible by using acetylation or hydrolysis reactions, respectively, where the reaction parameters have been optimized in terms of source and amount of biocatalyst, temperature, solvent, and reaction time. The synthetic potential of enantiopure monoesters has been demonstrated by using these interesting chiral building blocks for the preparation of novel enantiopure carboxylic acid derivatives.     

Extreme gravity tests with gravitational waves from compact binary coalescences: (II) ringdown

The LIGO/Virgo detections of binary black hole mergers marked a watershed moment in astronomy, ushering in the era of precision tests of Kerr dynamics. We review theoretical and experimental challenges that must be overcome to carry out black hole spectroscopy with present and future gravitational wave detectors. Among other topics, we discuss quasinormal mode excitation in binary mergers, astrophysical event rates, tests of black hole dynamics in modified theories of gravity, parameterized “post-Kerr” ringdown tests, exotic compact objects, and proposed data analysis methods to improve spectroscopic tests of Kerr dynamics by stacking multiple events.     

High-Throughput Diversification of Complex Bioactive Molecules by Accelerated Synthesis in Microdroplets

Late-stage diversification of drug molecules is an important strategy in drug discovery that can be facilitated by reaction screening using high-throughput experimentation. Here we present a rapid method for functionalizing bioactive molecules based on accelerated reactions in microdroplets. Reaction mixtures are nebulized at throughputs better than 1 reaction/second and the accelerated reactions occurring in the microdroplets are followed by desorption electrospray ionization mass spectrometry (DESI-MS). Because the accelerated reactions occur on the millisecond timescale, they allow an overall screening throughput of 1 Hz working at the low nanogram scale. Using this approach, an opioid agonist (PZM21) and an antagonist (naloxone) were diversified using three reactions important in medicinal chemistry: sulfur fluoride exchange (SuFEx) click reactions, imine formation reactions, and ene-type click reactions. Some 269 functionalized analogs of naloxone and PZM21 were generated and characterized by tandem mass spectrometry (MS/MS) after screening over 500 reactions.     

Thermolytic behaviour of polybutadienyllithium and polystyryllithium in ethylbenzene at high concentrations

The polymerization of butadiene and styrene with lithium and lithium alkyls has been extensively studied. The kinetics and mechanism of the pyrolysis of alkyllithium compounds has also been investigated thoroughly. The mechanism of these elimination reactions is conveniently elucidated by manometric methods, and mechanistic interpretations have been proposed. However, there are less published accounts of the thermal stability of polymer-lithium systems. There is a need to have kinetic data describing the thermal termination of “living” polymers at lithium concentrations approaching those of commercial polymerization systems. This paper will discuss the thermal stabilities of concentrated solutions in ethylbenzene of polystyryllithium and polybutadienyllithium.