2219-51-4Relevant articles and documents
Tandem Mass Spectrometric Approaches for the Analysis of Alkylguanines in Human Urine
Cushnir, J. R.,Naylor, S.,Lamb, J. H.,Farmer, P. B.
, p. 552 - 558 (1993)
Human exposure to carcinogenic alkylating agents can lead to the formation of covalently bound adducts in DNA, some of which are excreted in urine as alkylated purines following DNA degradation and repair.Tandem mass spectrometric methods have been developed for the qualitative and quantitative determination of such alkylpurines in human urine.Short-chain alkyl- and hydroxyalkylguanines have been synthesized with the substituents at the N-7, O6- and N2-positions of guanine.Examination of the product ion scans of their molecular ions (electron impact (EI) ionization) revealed that the ion at m/z 151, +, was common to all of the alkylguanines studied, with the exception of the methylated analogues.Precursor ion scans of this ion on partially purified human urine extracts showed the presence of several ions (e.g. m/z 179, 195) which were consistent with molecular ions for alkylguanines.The presence of these and other constituents was confirmed by product ion spectra of molecular ions (EI and fast atom bombardement), and by high-performance liquid chromatographic separation prior to tandem mass spectrometry (MS/MS).Evidence was obtained for the presence of N-7-methyl-, N2-methyl, N2-dimethyl-, N2-ethyl- and N-7-(2-hydroxyethyl)guanine.Quantitative methods were established for these five alkylguanines using gas chromatography mass spectrometry (GC/MS) and GC/MS/MS.Deuterated internal standards were synthesized and added to the urine prior to extraction of alkylpurines by Sep-Pak cartridge chromatography.The products were converted into their tert-butyldimethylsilyl derivatives and analysed by selected ion monitoring (SIM) of + or by multiple reaction monitoring (MRM) of the fragmentation M+. -> +.The MRM method yielded values for N-7-methylguanine of 2.57 +/- S.D. 1.32 mg day-1 (n=6), N2-methylguanine of 0.31 +/- 0.10 mg day-1 (n=10) and N2-dimethylguanine of 0.21 +/- 0.23 mg day-1 (n=10).N2-Ethyl- and N-7-(2-hydroxyethyl)guanine could only be detected by SIM at levels of ca. 0.5 and 2 μg day-1, respectively.The MRM analyses, although inherently less sensitive than the SIM analyses, exhibit greater selectivity and consequently fewer contaminant ions.
Regioselective deuteration of alcohols in D2O catalysed by homogeneous manganese and iron pincer complexes
Kar, Sayan,Goeppert, Alain,Sen, Raktim,Kothandaraman, Jotheeswari,Surya Prakash
supporting information, p. 2706 - 2710 (2018/07/05)
We report a convenient and cost-effective protocol for the regioselective deuteration of primary and secondary alcohols using Earth abundant homogeneous first row transition metal pincer catalysts. D2O is utilized as both a deuterium source and a solvent, allowing for a benign inexpensive process. Depending on the metal selected (Mn or Fe), a high degree of deuterium incorporation was observed selectively either at the α and β position (Mn) or exclusively at the α position (Fe), for primary alcohols. This simple, efficient, and cost-effective protocol for alcohol C-H bond deuteration constitutes a powerful tool for the large scale synthesis of deuterated molecules.
CYCLOPROPYL MODULATORS OF P2Y12 RECEPTOR
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Page/Page column 46-47, (2011/02/24)
The present invention relates to new cyclopropyl modulators of P2Y12 receptor activity, pharmaceutical compositions thereof, and methods of use thereof.
Oxidation of some vicinal and non-vicinal diols by tetrakis(pyridine)silver dichromate: A kinetic and mechanistic study
Meena,Daiya,Sharma,Banerji,Kotai,Sharma, Vinita
experimental part, p. 1887 - 1893 (2012/04/04)
The kinetics of oxidation of four vicinal, four non-vicinal diols and two of their monoethers by tetrakis(pyridine)-silver dichromate (TPSD) have been studied in dimethylsulphoxide (DMSO). The main product of oxidation is the corresponding hydroxycarbonyl compound. The reaction is first order in TPSD. Michaelis-Menten type of kinetics is observed with respect to the diols. The reaction is catalysed by hydrogen ions. The hydrogen ion dependence has the form : kobs = a + b (H+]. The oxidation of [1,1,2,2- 2H4] ethanediol exhibits a substantial primary kinetic isotope effect (kH/kD = 5.91 at 298 K). The reaction has been studied in nineteen different organic solvents and the solvent effect has been analysed using Taft's and Swain's multiparametric equations. The temperature dependence of the kinetic isotope effect indicates the presence of a symmetrical transition state in the rate-determining step. A suitable mechanism has been proposed.
