A scalable synthesis of (1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid

A stereoselective and scalable synthesis of (1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid (3a) is described. Key to the success of the devised route was the realization that the stereoselectivity of a cyclopropanation step could be controlled by the composition of the functional group at C-α.     

SYNTHESIS AND CHARACTERIZATION OF NOVEL REACTIVE POLYORGANOSILOXANE CONTAINING NITRO GROUPS*

 A novel reactive polyorganosiloxane containing nitro groups was first prepared by acid-catalyzed equilibration polymerization. The monomer, 3-(4-nitrophenoxy)propylmethyldichlorosilane (NPPMS), was synthesized by hydrosilylation reaction with dicyclopentadienylplatinum(II) chloride (Cp₂PtC1₂) catalyst in high yield. The synthesized polynitroorganosiloxane, which has potential application as a precursor for synthesizing advanced functional polymers, was characterized by FTIR, ¹H-NMR, ¹³C-NMR, ²⁹Si-NMR, vapor pressure osmometry (VPO) and gel permeation chromatography (GPC).     

Selection of suitable operating conditions to minimize the gradient equilibration time in the separation of drugs by Ultra-High-Pressure Liquid Chromatography with volatile (mass spectrometry-compatible) buffers

Reversed phase gradient elution is the method of choice for pharmaceuticals analysis since it allows reducing the analysis time while improving both the quality of the separation and the detection limits. The current trends are towards faster separations which can be achieved thanks to equipments withstanding ultra-high pressures and/or high temperatures. Under such conditions, gradient separations can be carried out within a few minutes or even a few tens of seconds. A long equilibration time in addition to the gradient time can be therefore very detrimental. In this work, we investigated the extent to which the gradient equilibration time can be reduced and which parameters mainly affect the retention variability of ionizable compounds when using volatile buffers. We first found out an excellent repeatability between run-to-run experiments whatever the equilibration time and the operating conditions. We then pointed out the key operating parameters which allow achieving reproducible runs when varying the equilibration time between runs. With a view of reducing the equilibration time, the effects of various conditions were examined. The latter include the type of additive for mobile phase pH adjustment, the initial eluent composition, the type of stationary phase, the temperature and the flow-rate. Although much remains to be understood about the equilibration process, our study allows making progress in the knowledge of this phenomenon. Based on the present results, a beneficial effect of both temperature and flow-rate was highlighted and operating conditions leading to faster column equilibration are suggested.     

Towards an automated, standardized protocol for determination of equilibrium potential of ion-selective electrodes

An automated real-time method for determination of ISE steady state value and response time is developed, following most recent IUPAC recommendations. Specifically, detection of the ‘steady state’ is related to (1) the time derivative of the emf as it reaches a limiting value (ΔE/Δt_limit, e.g., 0.1–1.0 mV min⁻¹) and (2) the duration of time for which the absolute value of the time derivative remains less than this limiting value (stability window, denoted win_st). A suite of representative ISEs, including glass, solid state, and polymer-based electrodes, is examined to determine sensitivity of results to parameterization choice. Measurements taken over a wide range of concentration values and in un-processed samples (i.e., without use of ionic strength adjustment) provide insight into behavior of ISEs in applications where analyte concentrations span a wide range and/or sample pre-processing may not be an option, e.g., use of sensors for in situ environmental sampling. Results show that declared steady state emf is strongly sensitive to variations in ΔE/Δt_limit but relatively unaffected by changes in the stability window when win_st ≥30 s. Linearity of calibration curves produced, quantified by root mean squared error (RMSE) against a linear fit, improves as ΔE/Δt_limit decreases, however the percentage of measurements which reach a declared steady state within the prescribed sample window (∼6.5 min) falls with corresponding decreases in the ΔE/Δt_limit parameter. Response time, defined as the time required to reach declared steady emf, is also a strong function of parameterization. Dependence of response times on sample composition and/or ISE membrane composition and type are also discussed; results for ISEs in samples comprised exclusively of interfering ions are included. In general, limiting emf derivatives of {0.25–0.4 mV min⁻¹} and stability windows of {30–40 s} achieve both good analytical accuracy and compliance with potentially short sampling window requirements. Methodology based on use of these parameters can improve sampling speed and accuracy as well as promote inter-comparison of data and ISE characterizations among research teams.     

Isotope Studies of Hydrogen and Oxygen in Ground Ice - Experiences with the Equilibration Technique

Abstract

Equilibration technique suitable for a large amount ofsamples is described for hydrogen and oxygen isotope analyses of ground ice, especially ice wedges, including the sampling strategy and the analytical procedure as well as the calibration of the Finnigan MAT Delta-S mass spectrometer in June, 1999. Since for future analyses of ice wedges, a higher sampling resolution with limited sample volume is required, the limit of the equliibration technique for small water samples size of between 0.05 and 5 ml was checked. For water samples smaller than 1ml, corresponding to a molar ratio [H₂O]/[H₂] of smaller than 0.994, a balance correction has to be applied. The experimental errors due to partial evaporation during evacuation, the balance calcultion of the isotope equilibration process, the linearity as well as memory effects of the mass spectrometer for smaples with large differences in δ¹⁸O and δD are tackled in this paper. In the polar regions of Northern Siberia without Late Pleistocene and Holocene glaciation, ground ice is used as an archive for paleoclimate studies. First results of stable isotope measurements on ice wedges clearly show a shift towards heavier isotopes and thus warmer winter temperatures as well as a change in the source of the precipitation between Late Pleistocene and Holocene. These results indicate the high potential of ground ice for paleoclimate studies.     

Retention studies of 2′-2′-difluorodeoxycytidine and 2′-2′-difluorodeoxyuridine nucleosides and nucleotides on porous graphitic carbon: Development of a liquid chromatography–tandem mass spectrometry method

The development of a method for the separation of 2′-2′-difluorodeoxycytidine (gemcitabine, dFdC), 2′-2′-difluorodeoxyuridine (dFdU) and their mono-, di- and triphosphates using a porous graphitic carbon column (Hypercarb), without ion-pairing agent, is described. The retention of dFdC and dFdU could be controlled with an organic modifier (acetonitrile, CH₃CN) and the retention of the anionic nucleotides with an eluting ion (bicarbonate). Separation of all analytes was achieved using a 0–25 mM ammonium bicarbonate gradient in CH₃CN–H₂O (15:85, v/v). Under these conditions, however, very long re-equilibration times were required. Injection of an acidic solution (100 μL 10% formic acid in H₂O, v/v; 2.65 M) after running a gradient directly restored the separation capabilities of the column. Still, separation between the analytes slowly deteriorated over a period of months. These problems were solved by preconditioning the column with a pH buffered hydrogen peroxide (H₂O₂) solution (0.05% H₂O₂ in CH₃CN–H₂O (15:85, v/v), pH 4) before starting an analytical run. The oxidation of the stationary phase with H₂O₂ prevented its slow reduction, which most likely caused the decreasing retention times. The analytes were detected using tandem mass spectrometry.     

Optimally chosen Nakajima–Zwanzig master equation for mean field approximation

We define an ensemble of projection operators, each of which has an exact associated Nakajima–Zwanzig master equation for quantum open system evolution. A mean field approximation for the memory kernels is introduced that yields a completely determined inhomogeneous master equation for every projection operator. A specific projection operator is then chosen so that the master equation optimally matches an abstract mathematical form which preserves positivity, complete positivity, and correctly equilibrates. We study a nitrogen vacancy center in diamond interacting with ¹³C impurities to illustrate the method.     

Equilibration implies asymptotic stationarity for open quantum systems

We use the exact Nakajima–Zwanzig form of the master equation to show that open quantum systems which exhibit equilibration (or thermalization) by evolving to a time independent asymptotic state, have under certain conditions a reduced density matrix for the system which commutes with the effective system Hamiltonian. We also show that if the initial system–bath density matrix is of product form then the asymptotic reduced density matrix of the system depends only on the diagonal elements of the initial system density matrix in the eigenbasis of the effective Hamiltonian.     

An evaluation of solid-phase microextraction for analysis of volatile organic compounds in drinking water

Solid-phase microextraction (SPME) has been applied to the quantitative analysis of 60 volatile organic compounds (VOCs) in drinking water. Equilibration curves for the partitioning of the VOCs between the fiber coating and fortified water obtained at 20, 50, and 80 °C are found between the theoretical curves for completely agitated and non-agitated samples. Two important factors for the amount adsorbed by the SPME fiber coating are the extraction time and the fiber coating/water distribution coefficient, K_FW . Both depend on the sample temperature, but in a counteracting manner: Increasing the temperature shortened the equilibration times, especially for the heavier VOCs, but also lead to lower K_FW values, and consequently a lower sensitivity of the method. K_FW values are determined for 33 of the VOCs at 40, 60, and 80°C and the heats of adsorption,–ΔH, are calculated. The nature of the adsorption is found to be exothermic which explains the decreasing sensitivity of the method with increasing temperature. Detection limits were typically from 20 ng/l to 200 ng/l, except for the very light VOCs with which detection difficulties were encountered. For all of the VOCs the linear range extended from the lowest concentration at which they were actually detected to at least 5 mg/l. The precision, 3% average standard deviation when an internal standard was used, was satisfactory for most quantitative routine analysis. SPME was also applied to head-space (HS) analysis of drinking water through the coupled equilibrium between water/head-space/fiber coating. HS-SPME is demonstrated to have shorter equilibration times than SPME directly from the water and equal sensitivities, except for the very light VOCs. Water samples from a drinking water plant contaminated in the low μg/l range with 1,1,1-trichloroethane, trichloroethene and tetrachloroethene were analyzed. There seems to be a reasonable agreement between results obtained by SPME and purge & trap. It is concluded that SPME has a great potential for drinking water analysis.     

Polyethylene/Poly(Butyl Methacrylate-co-Styrene) Copolymers Interpenetrating-Like Networks. I. Influence of the Copolymer Composition on Interpenetrating Polymer Network Properties

Abstract

IPN-like systems, consisting of low-density polyethylene (PE) and poly[butyl methacrylate (BMA)-co-styrene (S)] copolymer networks, were prepared in situ by a procedure described in previous papers. The initial PE/copolymer molar ratio was kept equal to 1 for all samples. The initial molar BMA/S ratio of the copolymer was varied over a composition range from pure S to pure BMA in order to investigate its influence on IPN properties. The samples obtained were analyzed by DSC; WAXS; tensile mechanical, dynamic-mechanical, and impact tests; swelling in CCl₄; and by some optical and electronic observations. The materials, became more and more brittle after undergoing mechanical and impact tests, even in the rubbery state, with increasing copolymer BMA content. The morphology consisted of a two-phase system. Good optical properties were obtained for the transparent specimens at relatively high BMA molar contents in the copolymer (70–80% BMA). Reversible changes of the optical properties were induced by temperature variations. A matching/mismatching of the refractive indexes of PE and the copolymer was found to be the cause of the optical behavior of these materials. Work is in progress to improve the mechanical behavior of these systems.