Isotopes, lead compounds

An important breakthrough in HTS ee assays came from the group of Reetz in late 1990, with the introduction of mass spectroscopy (MS)-based procedures [90]. These methods use special asymmetrically isotope-labeled compounds. Enzymatic transformations of these compounds usually lead to two pseudoenantiomeric compounds whose relative concentration can be estimated using MS techniques. 

Most elements possess stable isotopes. A compound analysed by mass spectrometry will lead to an isotope cluster whose relative intensities can be calculated. 

Of the various analytical techniques, methods using mass spectrometry with isotope dilution play a special role. Initially they were used for determination of inorganic analytes, but later, in the last decades of twentieth century, they were also used for the analysis of organic species. These methods require the use of isotope-labeled compounds, but lead to very good precision and accuracy, as required in definitive procedures [14]. 

The isolation of allantoin (7), after lead peroxide oxidation of uric acid was followed by the recognition of other oxidation products, the main product of which are oxonic acid (8), allantoxaidine (9) and oxaluric acid (HjNOCHNCOCOjH). Their structures have been clarified by comprehensive studies using isotopically labeled compounds. ... 

As already pointed out in chapter 6.2.2.1, isotope abundances, especially of primary products, are primarily fixed by those of their original elemental source. Within a closed system , e.g. a plant, all secondary compounds must be isotopically correlated to the primary assimilation products (carbohydrates), and their isotope abundances or patterns can be characterised by moderate shifts from here in the course of their biosynthesis by isotope effects of the reactions involved. These will only become manifest in the case of metabolic branching and would, depending on material fluxes in different directions, lead to isotopically depleted compounds in one... 

Other isotopes have higher mass isotopes. If a molecule of acetone has an 0 atom, the relative abundance of that o gen isotope is 0.20. This is at the threshold of detectabihty for small molecules, but this ion will appear at mJz 60 for acetone. This ion is two mass units higher than the parent and is called the M42 peak (also known as the P42 peak). Both the M+1 and M+2 peaks are due to formation of compounds using isotopes of lesser abundance. For acetone, the M+1 peak at 59 has an abrmdance of 2.7% relative to the molecular ion, M, for acetone in Figure 14.9. Similarly, the M+2 peak at 60 has an abundance of 0.35% relative to M. The presence of isotopes leads to peaks of higher mass than the molecular ion, M, whose composition is hewed on the most abundant isotopes. 

An isotopic composition can also be used as a tracer to determine the sources of lead pollution. For example, lead compounds (mostly bromides and some chlorides) from the tetraethyl lead used as a gasoline antiknock additive have been the primary source of lead pollution. This source of lead can be distinguished from that derived from the combustion of coal (which contains lead impurities and constitutes the distant second leading source of lead pollution) or various lead-smelting operations. 

The isotope dilution technique is to add to the sample a known mass of a lead compound that contains only ° Pb, and precipitate the PbS as before. The greater amount of precipitate makes it easier to collect. Mass spectrometry can now be used to measure the new relative abundances of 208pb and Pb (which will be the same as in the sample they were precipitated from). Knowing the quantity of extra Pb which has been added, makes it a simple calculation to work back to the quantity of lead in the ice before enrichment. 

Stable isotope labeled compounds can be obtained by chemical modification of the molecule. Many labeled products can be purchased from commercial suppliers and ordered from the catalog or on special request. Organic compounds of interest for clinical research are labeled with H, C, N, and/or 0 at one or more positions. Multilabeled substrates containing two or three different labels are also available. The choice of the type of label and the position(s) of labeling may be critical for the success of the application for two reasons. First, metabolism of the substrate may lead to loss of label, when the label is in the wrong position. Secondly, unfavorable MS fragmentation may be a cause of loss of... 

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