Isotopes s. Compounds, labeled

IR-4.5.3.2 Specifically labelled compounds An isotopically labelled compound is called a specifically labelled compound when a unique isotopically substituted compound is added formally to the analogous isotopically unmodified compound. A specifically labelled compound is indicated by enclosing the appropriate nuclide symbol(s) and multiplying subscript (if any) in square brackets. 

We have tried to emphasize not only the importance of the problem of the availability, but also that of the precise specifications of C, S, (etc.) labelled compounds, namely the specificity of the labelling position and the radiochemical purity. These two parameters are of vital importance for the future application of the labelled molecule in medicine, biology and the environmental sciences. Furthermore, two factors must be considered for the reliability of metabolic studies of drugs and pesticides correct choice of labelling position, since a position that is too exposed can result in loss of the label and consequently incomplete results the other factor is that of stable isotopes and the so-called isotopic effect. 

In isotope-labeled compounds, one or more of the atoms of the molecules are replaced with a detectable quantity of radioactive or stable isotope(s) of the... 

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... 

Out of this arsenal of synthetic procedures, only Michael and Diels-Alder additions have been exploited so far for the preparation of e.p. compounds labeled with isotopic carbon or hydrogen. For applications in 1,4-additions, starting materials derived from Oppolzer s and Helmchen s auxiliaries have shown some superiority to the original Evans derivatives, though most weak points of the latter have been overcome by utilizing the C4-phenyl auxiUary (Xcpo) instead of the isopropyl (Xqpo) or benzyl (Xcbo) analogs. Nevertheless, the latter two have been more commonly used. 

Adequate precision and accuracy are only likely to be achieved if some standardization procedure is employed and the nature of this, internal or external standards or the method of standard additions, needs to be chosen carefully. If internal standardization procedures are adopted then appropriate compound(s) must be chosen and their effect on the chromatographic and mass spectrometry methods assessed. The ideal internal standard is an isotopically labelled analogue of the analyte but, although there are a number of commercial companies who produce a range of such molecules, these are not always readily available. An analytical laboratory is then faced with the choice of carrying out the synthesis of the internal standard themselves or choosing a less appropriate alternative with implications on the accuracy and precision of the method to be developed. 

Elements such as C, N, O, S, and Cl that are components of many organic compounds exist naturally as mixtures of stable isotopes. The ratios of these in a compound reflect the different rates of reaction at isotopically labeled positions, and therefore reflect the fractionation—biotic or abiotic—by which it was synthesized or to which the compound has been subjected. Techniques have been developed whereby the ratios C/ C (5 C), (5 N), (5 0),... 

A wide range of other isotopic labels, e.g. 3H (or T), 13C, I4C, 15N, 32P, 35S, 37C1, 1311, etc., have also been used to provide important mechanistic information. The major difficulties encountered in such labelling studies have always been (a) ensuring that the label is incorporated only into the desired position(s) in the test compound and (b) finding exactly where the label has gone to in the product(s) after the reaction being studied has taken place. 

The basic idea of isotope filtering/editing techniques is to selectively observe the subspectra of the labeled or unlabeled components only. A prerequisite for the application is of course the different isotopic composition of the different components. In an ideal case, we will have one compound which is completely labeled with the NMR active iso-tope(s) of one (or several) elements, and the other compound completely devoid of these isotopes (see Fig. 17.1). 

---