Isotopically labelled mechanistic studies using

Isotopic Studies. In this analysis mode the mass spectrometer Is used to determine the relative abundance of different Isotopes of the same element. SIMS Is the only common surface analysis technique that can distinguish the Isotopes of both the light and heavy elements. This mode Is advantageously used In mechanistic studies using Isotopically labelled samples. By using different Isotopes of the same element experiments can be performed without concern for the differences In chemical effects between the species. 

In another series of experiments, isotopically labelled reactants were used to establish mechanistic details of the various reactions. For one group of these studies, appropriate deuterated reactants were obtained by introducing either ethylene-d4 or ethane-cZc into the first stage of the machine. Reactions 7-10a show the results of these experiments. In cases where a given ion was observed with more than one isotopic composition, the relative yields are noted. 

Mechanistic studies using isotopic labeling have provided additional insights into the details of the mechanism. These studies allowed a complete mechanism to be proposed that accounts for the experimental observations and provides a rational route to the products using established methods [27]. Equation (6.3) shows how one deuterium on the aryl ring in diallylaniline-ds is selectively transferred to the a-methylene of the ethyl group. 

A quite different use of isotopes in mechanistic studies involves their use as labels for ascertaining the location of a given atom involved in a reaction. As in kinetic experiments, the isotopic substitution will not qualitatively affect the course of the reaction. The nuclei most commonly used for isotopic tracer experiments in organic chemistry are deuterium, tritium, and the and isotopes of carbon. There are several means of locating isotopic labels. Deuterium can frequently be located by analysis of NMR spectra. In contrast to the normal isotope, deuterium... 

All the eases presented have been taken from recent literature and deal with the formulation and experimental determination of a mechanistic proposal. They are based on real cases that demonstrate how nowadays organic chemists are still deeply coneemed about insights into a reaetion. Through the book we use any type of information that the authors of the original work considered necessary in the elucidation of the reaction mechanism. This includes spectroscopic data, kinetic and thermodynamic data, isotopic labelling, theoretical studies. .. and of course, the knowledge of the reactivity of organic compounds. 

We said in Section 21.6 that mechanistic studies on ester hydrolysis have been carried out using ethyl propanoate labeled with lsO in the etherlike oxygen. Assume that Odabeled acetic acid is your only source of isotopic oxygen, and then propose a synthesis of the labeled ethyl propanoate. 

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 use of isotopically labelled organogermanium compounds in mechanistic studies... 

In addition to characterization of intermediates, in situ spectroscopic techniques can be applied in kinetic studies, providing additional mechanistic insight. Also, isotopic labeling studies have proven very useful, especially vhen studying the individual steps of a catalytic cycle [5, 6]... 

In this review, we will discuss the use of in situ spectroscopic techniques, in combination with kinetic and isotopic labeling studies, to obtain a detailed mechanistic insight of the rhodium catalyzed hydroformylation. 

For isotopes other than those of hydrogen, equilibrium isotope effects are usually small (ca. <3%), and such isotopes are more often used in labelling studies with their concentrations at a particular position reflecting the probability of a mechanistic pathway, without consideration of the effects of isotopic substitution upon stability of isotopomers. Positional exchange in recovered reactants, for example, provides supporting evidence of intermediates and their nature, and Scheme 9.15 illustrates one dissociative process and one associative process. 

Inorganic chemists, are interested in chemical reactions as well as the static properties of substances. The measurement of thermodynamic quantities for chemical reactions will not concern us, although we will make extensive use of the experimental results elsewhere in this book. In Chapter 9 we will look in more detail at inorganic reactions and their mechanisms blow-by-blow accounts of what actually happens at the atomic level as the reaction proceeds. Some of the spectroscopic methods described in this chapter are important in mechanistic studies they may be used to follow the rate of a reaction or to identify short-lived intermediates. Other techniques (such as isotopic labelling) are useful in the determination of reaction mechanisms. 

More studies of the sulfite oxidase/nitrate reductase catalytic cycles, especially those using carefully isotopically labeled enzyme and substrate, are required before a clear mechanistic picture for (MPT)Mo(0)2(S-cys) family of enzymes will be available. 

Mechanistic studies start with determination of the kinetic rate law and the rate-limiting step information on heat and mass transfer is also needed. These studies may use such techniques as isotopic labeling, chemisorption measurements, surface spectroscopy, temperature-programmed desorption, and kinetic modeling experiments. 

Attempts to use molecular oxygen as the oxidant failed except in solvents that undergo efficient autoxidation to the corresponding hydroperoxide (e.g., THF). Mechanistic studies, including isotopic labeling studies, indicate that fBuOOH is the source of the oxygen atom incorporated into the product, and the reaction proceeds via a hydride-shift pathway that avoids formation of an enol intermediate (Scheme 12). 

Most of the sugars specifically labeled with isotopes of hydrogen that have been synthesized were prepared for use in mechanistic studies of enzymes. 

The amino substituent increases the nucleophilicity of the /Lcarbon due to the electron-donating power of the nitrogen and makes it useful in alkylation reactions368,369. Isotopically labelled enamines have been utilized to study the conjugation of the double bond with nitrogen in these and related compounds by investigating the deuterium isotope effects on 13C and 15N nuclear shielding in enamine derivatives. Mechanistic... 

Synthetic derivatives and analogs of prenyl diphosphates have historically played a key role in defining key featnres of the mechanism of enzymes that ntilize these key intermediates in the isoprenoid pathway. This has also been the case with the investigation of the protein prenyl-transferases. A brief introduction to the protein prenyltransferase enzymes is given along with outlines on the previous use of prenyl diphosphate tools and key aspects of their synthesis. The development of prenyl diphosphate-based FTase inhibitors is described. The use of prenyl diphosphate derivatives as mechanistic and structural probes is next discussed. In particular, the use of fluorinated, isotopically labeled, and photoaffinity derivatives is presented. An overview of the extensive work on the determination of FTase isoprenoid substrate specificity is then given, and the chapter concludes with a section on the development of prenyl diphosphate tools for proteomic studies. 

---