The nuclear Overhauser effect (NOE) is the transfer of nuclear spin polarization from one population of spin-active nuclei (e.g. 1H, 13C, 15N etc.) to another via cross-relaxation. A phenomenological definition of the NOE in nuclear magnetic resonance spectroscopy (NMR) is the change in the integrated intensity (positive or negative) of one NMR resonance that occurs when another is saturated by irradiation with an RF field. The change in resonance intensity of a nucleus is a consequence of the nucleus being close in space to those directly affected by the RF perturbation. The NOE is particularly important in the assignment of NMR resonances, and the elucidation and confirmation of the structures or configurations of organic and biological molecules. The 1H two-dimensional NOE SpectroscopY (NOESY) experiment and its extensions are important tools to identify stereochemistry of proteins and other biomolecules in solution, whereas in solid form crystal x-ray diffraction typically used to identify stereochemistry. The heteronuclear NOE is particularly important in 13C NMR spectroscopy to identify carbons bonded to protons, to provide polarization enhancements to such carbons to increase signal-to-noise, and to ascertain the extent the relaxation of these carbons is controlled by the dipole-dipole relaxation mechanism. History The NOE developed from the theoretical work of American physicist Albert Overhauser who in 1953 proposed that nuclear spin polarization could be enhanced by the microwave irradiation of the conduction electrons in certain metals. The electron-nuclear enhancement predicted by Overhauser was experimentally demonstrated in 7Li metal by T. R. Carver and C. P. Slichter also in 1953. A general theoretical basis and experimental observation of an Overhauser effect involving only nuclear spins in the HF molecule was published by Ionel Solomon in 1955. Another early experimental observation of the NOE was used by Kaiser in 1963 to show how the NOE may be used to determine the relative signs of scalar coupling constants, and to assign spectral lines in NMR spectra to transitions between energy levels. In this study, the resonance of one population of protons (1H) in an organic molecule was enhanced when a second distinct population of protons in the same organic molecule was saturated by RF irradiation. The application of the NOE was used by Anet and Bourn in 1965 to confirm the assignments of the NMR resonances for β,β-dimethylacrylic acid and dimethyl formamide, thereby showing that conformation and configuration information about organic molecules in solution can be obtained. Bell and