Isotope Effects in NMR Spectroscopy

The research on isotope effects in organic chemistry is based on the vibrational theory [1]. Kinetic isotope effects in chemical reactions and equilibrium isotope effects have been dealt with on the basic assumption that the only important difference between isotopes is their mass and any effects from isotopic substitution ultimately should be traced back to this difference. Thus, within the Born-Oppenheimer approximation the electronic potential of a C–D bond is believed to be identical with the potential of a C–H bond. Isotope effects therefore are thought to stem from the anharmonicity of this potential and the different zero point energy of the heavier isotope within this potential.

The term “isotope effect” in NMR spectroscopy refers to changes of NMR spectral parameters that may arise due to isotopic substitution (^mX/ⁿX) of element X. Molecules A^mX and AⁿX, differing in isotopes of element X, with A being an invariable part of the molecules are called isotopomers. Thus, isotope effects may be defined as: where θ is the measured spectral characteristics.

Isotope effects may be broadly classified as intrinsic isotope effects (either primary isotope effects or secondary isotope effects), equilibrium isotope effects, or solvent isotope effects. In nuclear magnetic resonance (NMR) spectroscopy the most intensely studied and widely used of these isotope effects are the (intrinsic) secondary isotope effects, which arise because isotopic substitution in a molecule changes the shielding of other nuclei in the molecule. Thus, NMR signals of chemically identical nuclei in different isotopomers may have different chemical shifts. In general, the chemical shifts of nuclei in isotopomers with the heavier isotopes are upfield with respect to the lighter isotopes within a series, as for example the isotopes of hydrogen, the isotopes of oxygen, etc. The magnitudes of these secondary isotope effects are calculated as the differences in the chemical shifts for the different isotopomers, and are called isotope effects, isotope-induced shifts, or simply, isotope shifts.

Since the time this review had been finished (April 1987) a number of investigations dealing with NMR isotope effects have been published, among them several comprehensive reviews [139–141].