Nuclear magnetic resonance isotope effects

First publications on nuclear magnetic resonance and isotope effects appeared almost at the same time. The first NMR spectra, independently recorded in two laboratories by Bloch and Purcell groups, were published in the same issue of Physical Review in 1946.1/2 One year later the idea of isotope effects was introduced by Bigeleisen.3 Isotope shifts on shielding were first discussed by Gutovsky 12 years later.4... 

As the glucose is metabolized, the metabolic derivatives become enriched with the isotopic carbon label and are detected using advanced technologies such as mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. Importantly, incorporation of isotopes into molecules can alter reaction mechanisms including the rate of a reaction-this is termed isotopic substitution and forms the basis of the kinetic isotope effect. 

Altman, L. J., Lauggani, D., Gunnarsson, G., and Wennerstrom, H., Proton, deuterium, and tritium nuclear magnetic resonance of intramolecular hydrogen bonds. Isotope effects and the shape of the potential energy function, J. Am. Chem. Soc. 100, 8264-8266 (1978). 

It has been claimed by some workers that Li is more readily transported into erythrocytes than is Li and that there are differences in their biological effects (72). It has also been postulated that Li may produce fewer side effects or less toxicity than the naturally occurring isotope mixture (73). Li nuclear magnetic resonance (NMR) spectroscopy in vivo has been used to measure tissue lithium levels in humans noninvasively and with safety. These experiments showed tissue lithium concentrations significantly lower than those in the serum (74). The NMR technique has been used also to distinguish the isotopes in transport studies in red blood cells (75, 76) and in other cell types (77). 

The greater availability and cheapness of deuterium compounds, coupled with the large isotope effects, has until recently made this isotope the most widely used in mechanistic studies. However, recent work using nuclear magnetic resonance or mass spectrometry has allowed the determination of heavy atom isotope effects in natural abundance, by... 

The natural stable isotope of fluorine, fluorine-19 (19F), with a spin of one-half and a chemical shift range of around 300 ppm, is a sensitive and useful probe in nuclear magnetic resonance (NMR) studies. Fluorine substitution may be a very effective method for studying the fate of bioactive molecules. Since there are few natural fluorinated materials to create background signals, the analyses are freed from the complications often associated with proton NMR spectroscopy (65). An artificially prepared useful short-lived isotope, fluorine-18 (18F), decays by positron emission. Positron emission tomography (PET) is an especially useful non-invasive... 

Another property for which there is a large amount of experimental information concerning isotopic effects is the nuclear magnetic resonance (NMR) chemical shift. This topic has been reviewed at yearly intervals by Raynes for 1978-79 and Jameson for 1980-85, and so will not be considered here except to mention some recent work. " ... 

Stereochemical and kinetic analyses of the Brpnsted acid-catalysed intramolecular hydroamination/deuterioamination of the electronically non-activated cyclic alkene (13) with a neighbouring sulfonamide nucleophile have been found to proceed as an anh-addition (>90%) across the C=C bond to produce (15). No loss of the label was observed by and NMR (nuclear magnetic resonance) spectroscopies and mass spectrometry (MS). The reaction follows the second-order kinetic law rate = 2 [TfOH] [13] with the activation parameters being = 9.1 0.5 kcal moP and = -35 5 cal moP An inverse a-secondary kinetic isotope effect of d/ h = (1-15 0.03), observed for (13) deuteration at C(2), indicates a partial CN bond formation in the transition state (14). The results are consistent with a mechanism involving concerted, intermolecular proton transfer from an N-protonated sulfonamide to the alkenyl C(3) position coupled with an intramolecular anti-addition by the sulfonamide group. ... 

Dedicated to the memory of the late Victor Gold. He was among the first to use nuclear magnetic resonance for the determination of isotope effects on equilibrating systems. 

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