Deuterium isotopic labelling with

The first mass spectrometric investigation of the thiazole ring was done by Clarke et al. (271). Shortly after, Cooks et al., in a study devoted to bicydic aromatic systems, demonstrated the influence of the benzo ring in benzothiazole (272). Since this time, many studies have been devoted to the influence of various types of substitution upon fragmentation schemes and rearrangements, in the case of alkylthiazoles by Buttery (273) arylthiazoles by Aune et al. (276), Rix et al. (277), Khnulnitskii et al. (278) functional derivatives by Salmona el al. (279) and Entenmann (280) and thiazoles isotopically labeled with deuterium and C by Bojesen et al. (113). More recently, Witzhum et al. have detected the presence of simple derivatives of thiazole in food aromas by mass spectrometry (281). 

Reduction of aldonolactones and their derivatives with isotopically modified reducing agents leads to sugars labeled at the anomeric center. Glycosides substituted with deuterium or labeled with tritium are widely employed for kinetic isotope-effect measurements, mechanistic studies, isotope-tracing experiments, and so on. 

In addition to the nature of the cation at the adsorption site, the superhyperfine tensor can also give information on neighboring atoms further away. For example, OJ adsorbed on MgO exhibits a superhyperfine tensor ascribed to the presence of a nearby proton, presumably as a hydroxyl group (68) and this has been confirmed by isotopic labeling with deuterium (see Section IV,A). Superhyperfine tensors indicating the presence of nearby protons have also been reported for O J adsorbed on ferrocene deposited on porous Vycor glass (PVG) (120) and for alkylperoxy radicals supported on Ti02 (90). 

PROBLEM 15.12 The mechanism of enzymatic oxidation has been studied by isotopic labeling with the aid of deuterated derivatives of ethanol. Specify the number of deuterium atoms that you would expect to find attached to the dihydropyridine ring of the reduced form of the nicotinamide adenine dinucleotide coenzyme following enzymatic oxidation of each of the alcohols given ... 

This reduction almost certainly proceeds via the activation of the aldehyde carbonyl both by bond polarization in the ground-state and by stabilization of bonding interactions in the transition state. Although deuterium isotope labeling experiments show that hydrogen transfer is direct, comparison of kinetic isotope effects with isotope discrimination studies (23) suggest that the transition state of this reaction may not be a simple transfer of hydride ion (see Section IV—2). 

An irreversible j6-H elimination is observed in the decomposition of PCP-based rhodium(III)-alkyl complexes (Eq. 6.15) [72], Isotopic labeling with C proves that there is no incorporation of C in the methyl end of the ethyl ligand, discounting fast reversible /1-H elimination. This occurs in an irreversible fashion. Deuterium labeling reveals a kinetic isotope effect of kn/ko = 1.4 for ethyl, supporting that /1-H elimination is rate determining. The activation parameters in toluene were A// = 21.2 kcal/mol, A5 = —21.1 eu, and AG gg = 27.5 kcal/mol. 

Several syntheses of carotenoids isotopically labelled with deuterium have been reported [65-68]. The total synthesis of spheroidenes (97) specifically labelled with deuterium in the central part is based on the synthetic scheme discussed above for the C-labelled spheroidenes [68]. When deuterium-enriched compounds are used, a few modifications are necessary to avoid scrambling and isotope dilution (Scheme 28). 

Only a year later, Gagosz and coworkers [32] published a synthesis of 10-membered medium-sized cycloalkynes 28 from 1,10-diynes 27. Like in the earlier investigation of Houk and Toste, the ligand was a bulky phosphane ligand. Two important mechanistic proposals were included in this publication the one shown in Scheme 4.10a which is based on the proposal of Houk and Toste [31], and also the alternative pathway shown in Scheme 4.10b. Both pathways are in accordance with the deuterium isotope labeling experiments conducted. The Houk/Toste catalyst transfer step was not considered by Gagosz. On the other hand, Gagosz already addressed a possible role of the counterion as a proton acceptor, a motive later discussed by Corma [33] and Widenhoefer [34] for the formation of species related to I and Q. 

These three key findings, along with a series of deuterium isotope labeling experiments and the important additional computational results of Zhang s group, led to the following new mechanistic cycle for the formation of 35 (Scheme 4.15). 

Isotopic labelling with deuterium ( H) can be used to provide spectral editing. For example, specific incorporation of a deuterium atom into methylene or methyl groups of amino acids can be used to obtain detailed structural and dynamic information. Dramatic increases in proton NMR resolution for larger proteins can be achieved through random labelling of the protein with deuterium, at levels between 50 and 85%, by growth on substrates in which the ratio of to is controlled. 

In order to obtain some detail about this transformation, a series of deuterium isotope-labeling experiments were conducted. By the treatment of diphenylacetylene with D2O instead of H2O, the deuterated indanone was... 

Sometimes the strongly basic properties of Gngnard reagents can be turned to synthetic advantage A chemist needed samples of butane specifically labeled with deuterium the mass 2 isotope of hydrogen as shown... 

Substitution of deuterium for hydrogen at the a carbon atom of an aldehyde or a ketone is a convenient way to introduce an isotopic label into a molecule and is readily carried out by treating the carbonyl compound with deuterium oxide (D2O) and base... 

A disadvantage of this technique is that isotopic labeling can cause unwanted perturbations to the competition between pathways through kinetic isotope effects. Whereas the Born-Oppenheimer potential energy surfaces are not affected by isotopic substitution, rotational and vibrational levels become more closely spaced with substitution of heavier isotopes. Consequently, the rate of reaction in competing pathways will be modified somewhat compared to the unlabeled reaction. This effect scales approximately as the square root of the ratio of the isotopic masses, and will be most pronounced for deuterium or... 

Further evidence for different reaction pathways is obtained in isotope labelling experiments, illustrated in fig.6. Here we present a comparison of the effects of preadsorbing various amounts of deuterium with methyl groups cm the two metal surfaces. 

As nuclear reactions are isotope specific, NRA may be used, for example, to distinguish the distribution of binary blends of polymers in a polymer film, where one of the polymers is labelled with deuterium. The depth distribution of the deuterium atoms can be established and hence that of the labelled polymers. 

Figure 16.2 The original design of the ICAT compound. The iodoacetyl group provides reactivity with thiol groups. The isotopically labeled spacer arm typically is substituted with eight deuterium atoms.

The use of a deuterium-labeled organosilicon hydride and location of the deuterium isotope in the reduced product shows that 1,2-hydride shifts also occur. Thus, reduction of 1-bromohexane with triethylsilane-A yields hexane with all of the deuterium at C2 (Eq. 51) similar treatment of cyclohexylmethyl bromide produces melhyIcyclohexane-1 -di (Eq. 52).186... 

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