Isotopic labelling applications

Troost and Olavesen investigated the application of an internal standardization to the quantitative analysis of polynuclear aromatic hydrocarbons. The following results were obtained for the analysis of the analyte phenanthrene using isotopically labeled phenanthrene as an internal standard... 

Some advantages of this reaction are high yield if the tosylate is in a sterically accessible position excellent isotopic purity of the product (usually higher than-95%) and perhaps most important, access to stereospecifically labeled methylene derivatives. For example, deuteride displacement of 3j -tosylates (183) yields the corresponding Sa-d derivative (185) in 96-98% isotopic purity. Application of this method to the labeled sulfonate (184), obtained. by lithium aluminum deuteride reduction of a 3-ketone precursor (see section HI-A) followed by tosylation, provides an excellent synthesis of 3,3-d2 labeled steroids (186) without isotopic scrambling at the adjacent positions. The only other method which provides products of comparable isotopic purity at this position is the reduction of the tosyl-hydrazone derivative of 3-keto steroids (section IV-B). 

The most frequently encountered examples of cyclopropyl ring opening reactions in the steroid field are usually associated with angular or side chain methylation sequences. In fact, isotope labeling of the C-19 angular methyl group is the only reported application of this reaction for deuteration or tritiation pui poses. 

Isotope labeling by derivative formation with deuterated reagents is useful for the preparation of analogs such as dg-acetonides, da-acetates, da-methyl ethers, dg-methyl esters, etc. The required reagents are either commercially available or can be easily prepared. (The preparation of da-methyl iodide is described in section IX-F. Various procedures are reported in the literature for the preparation of dg-acetone, da-diazometh-ane57.i63.i73 and da-acetyl chloride. ) These reactions can be carried out under the usual conditions and they need no further discussion. A convenient procedure has been reported for the da-methylation of sterically hindered or hydrogen bonded phenolic hydroxyl functions by using da-methyl iodide and sodium hydroxide in dimethyl sulfoxide solution. This procedure should be equally applicable to the preparation of estradiol da-methyl ether derivatives. 

Trager, W.F. (1988). Isotope effects as mechanistic probes of cytochrome P450-catalysed reactions. In Synthesis and Application of Isotopically Labelled Compounds Proceedings of the Third International Symposium T.A. Baillie and J.R. Jones (Eds.) Amsterdam Elsevier 333-340. 

The application of substrates isotopically labeled in specific positions makes it possible to follow the fate of individual atoms during the microbial degradation of xenobiotics. Under optimal conditions, both the kinetics of the degradation, and the formation of metabolites may be followed— ideally when samples of the labeled metabolites are available. Many of the classical studies on the microbial metabolism of carbohydrates, carboxylic acids, and amino acids used radioactive... 

The first etCCR application has been reported for a partially C— N-labeled phosphotyrosine peptide derived from interleukin-4 receptor ligated to STAT-6 [107] and subsequent studies involve nucleotide cofactors ligated to human recombinant deoxycytidine kinase [108] and epothilone A bound to tubulin [109]. Since etCCR usually involves isotope-labeling schemes for the ligand, its applicability is limited to specific molecular classes. 

Kingston, L. P., Lockley, W. J. S., Mather, A. N., Spink, E., Thompson, S. P., Wilkinson, D. J., Hydrogen isotope labelling novel applications of parallel chemistry techniques, International Isotope Society Symposium, Dresden, June 2000. 

The approach recruited to chemical proteomics in Reference [17] is called SILAC (stable isotope labeling with amino acids in cell culture) and is important in comparative proteomics (Figure 1). SILAC works well with cultured mammalian cells, but prokaryotes defeat it by metabolizing the label (usually supplied in lysine and arginine) into other amino acids. For applications beyond cultured eukaryotic cells, the reductive methylation route to differential labeling [18] is among the alternatives [15]-... 

The synthesis, analysis and applications of labeled compounds is an area in which basic and applied research go hand-in-hand. Over the last quarter of a century the field has seen considerable expansion as reflected in the emergence of a specific journal (Journal of Labeled Compounds and Radiopharmaceuticals) and the publication of the proceedings of international conferences held at three-yearly intervals. The formation of the International Isotope Society is also an indication of the increasing importance of isotopes and isotopically labeled compounds. 

H. Zhang, J. Joseph, J. Vasquez-Vivar, H. Karoui, C. Nsanzumuhire, P. Martasek, P. Tordo, and B. Kalyanaraman, Detection of superoxide anion using an isotopically labeled nitrone spin trap potential biological applications. FEBS Lett. 473, 58-62 (2000). 

R. N. Hanson, in Proceedings of the Third International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds (Eds. T. A. Bailie and J. R. Jones), Elsevier, Amsterdam, 1989, pp. 275-281. 

ESI represents a powerful method by which to transfer organometallic ions from catalytically active solutions into the gas phase. ESI-MS systems allow the characterization of the gas-phase ions using CID, reactivity, and isotope-labeling studies. The application of ESI-tandem-MS systems allows gas-phase preparations and isolation of desired organometallic ions in the first ESI-octopole-quad-rupole, followed by characterization or reactivity studies in the second octopole-quadrupole. 

The first mode of the high resolution C-NMR of adsorbed molecules was recently reviewed Q-3) and the NMR parameters were thoroughly discussed. In this work we emphasize the study of the state of adsorbed molecules, their mobility on the surface, the identification of the surface active sites in presence of adsorbed molecules and finally the study of catalytic transformations. As an illustration we report the study of 1- and 2-butene molecules adsorbed on zeolites and on mixed tin-antimony oxides (4>3). Another application of this technique consists in the in-situ identification of products when a complex reaction such as the conversion of methanol, of ethanol (6 7) or of ethylene (8) is run on a highly acidic and shape-selective zeolite. When the conversion of methanol-ethylene mixtures (9) is considered, isotopic labeling proves to be a powerful technique to discriminate between the possible reaction pathways of ethylene. 

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