Homonuclear Overhauser enhancements

The homonuclear Overhauser enhancements explained in section 4.2.1 may also in principle be exploited for spatial and conformational information. However, this is only possible when the proton shifts are unusually sensitive to tacticity, because otherwise they cannot be resolved. They can be investigated by either 1-D or 2-D methods. The 1-D method involves selective irradiations, but is relatively quick and easy to quantify. The 2-D method, NOESY [38], is more elegant. In both cases one must take precautions to avoid spin-diffusion if quantitative information is required. Spin-diffusion is discussed in chapters 6 and 7 in the context of solid-state NMR, where its effects are more serious. What happens, in brief, is that the Wq term in (equation 4.6) can become very large for a proton pair, so that spin energy flows freely between most of the protons in the sample. Thus all selectivity is lost. In practice, spin diffusion is not too serious in a typical semi-mobile polymer solution, so that qualitative distance information may easily be obtained. The method is particularly promising for random copolymers, where more resonances are available for selective irradiation, because of the many variations of local sequence, as well as of tacticity. 

The quantitative measurement of homonuclear (interproton) Overhauser enhancements [1, 2] is usually a very important tool for the structure determination of organic molecules, in particular when dealing with stereochemical aspects such as configuration and conformation, due to the dependence of the enhancements. 

The terms pc and py correspond to 1/Tic and 1/Tih, respectively, and CTCH is the cross-relaxation rate. It should be stressed that the simplicity of the above equation is a consequence of the rareness of the I spins and of the dominant strength of the dipolar interaction between directly bonded nuclei. The situation for homonuclear proton spin systems is often more complicated, since the protons usually constitute a much larger spin system, and a separation into distinct two-spin systems may be not valid in this case. The broadband irradiation of the protons yields, in a steady state, Mhz = 0 and M z = Mj (1 rj). The factor 1 + 77 is called, as introduced above, the nuclear Overhauser enhancement factor. The NOE factor is related in a simple way to the equilibrium magnetizations of the I- and S-spins (which are proportional to the magnetogyric ratios 71 and 7s), the cross-relaxation rate and the relaxation rate of the I-spin ... 

Even before the common use of Fourier transform NMR, it was known that the homonuclear nuclear Overhauser enhancement (NOE) could be used to identify pairs of protons separated by a few angstroms in space.2 It was also clear, however, that many such distances and accurate assignments to specific protons would be needed to define a solution structure fully. The advent of two-dimensional NMR was a major step toward providing the necessary data,3-4 but the introduction of the two-dimensional NOE measurement (NOESY)5-6 truly revolutionized the ability both to assign spectral peaks and to acquire large quantities of distance information. 

Mismatch-optimized IS transfer Nuclear Overhauser enhancement Nuclear Overhauser effect spectroscopy Numerically optimized isotropic-mbdng sequence Preservation of equivalent pathways Pure in-phase correlation spectroscopy Planar doubly selective homonuclear TACSY Relayed correlation spectroscopy Radiofrequency... 

Homonuclear correlation via the nuclear Overhauser effect (NOESY). The NOESY experiment correlates peaks by means of the nuclear Overhauser enhancement and so identifies pairs of nuclei which are sufficiently close together in space to relax by their dipole-dipole interaction. This technique is not so applicable in determining stereochemical assignments as those described previously, but may be extremely useful in determining the chain conformation as demonstrated by Mirau et al. in a study of the alternating copolymer of styrene and methyl methacrylate [45] (see chapter 4). 

Equation 4.17 shows that the maximum enhancement is 50% for homonuclear decoupling. As dipole-dipole relaxation depends on distances between nuclei, molecular conformations can be studied by measuring Overhauser enhancements. Normally apphed to H H experiments, the procedure involves... 

As a matter of fact, the vast majority of experimental studies focuses on a relatively well-defined set of parameters. Taking as an example the important case of NMR spectroscopy of organic molecules, the characterization is usually based on measurements of proton and carbon chemical shifts in solution, homonuclear (and possibly heteronuclear) coupling constants, and proton-proton nuclear Overhauser enhancements [or the corresponding rotating-frame effects (ROEs)]. This set of data is certainly reductive if compared with the information content potentially accessible by NMR measurements however, it does represent a reasonable balance of such factors as operator and instrument time, apparatus availabihty, costs, amounts of material required, completeness of information, and ease of interpretation. 

In order to isolate and structurally identify the remaining bryostatins earlier detected only in microgram or less quantities and to obtain enough bryostatin 1 for homonuclear correlation (COSY), two dimensional carbon-proton chemical shift correlations ( H- C 2D), 2D-J-resolved experiments, proton-proton differential nuclear Overhauser enhancement (NOEDS, or H-[ H] NOE) experiments, and additional biological evaluation, a 4000-L recollection (1981) of Bugula neritina... 

NMR is the tool most widely used to identify the structure of triterpenes. Different one-dimension and two-dimension techniques are usually used to study the structures of new compounds. Correlation via H-H coupling with square symmetry ( H- H COSY), homonuclear Hartmann-Hahn spectroscopy (HOHAHA), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple bond correlation (HMBC), distortionless enhancement by polarisation transfer (DEPT), incredible natural abundance double quantum transfer experiment (INADEQUATE) and nuclear Overhauser effect spectroscopy (NOESY) allow us to examine the proton and carbon chemical shift, carbon types, coupling constants, carbon-carbon and proton-carbon connectivities, and establish the relative stereochemistry of the chiral centres. 

The nuclear Overhauser effect (NOE), caused by dipole-dipole crossrelaxation, has great potential in the elucidation of the molecular structure and conformation (Noggle and Shirmer, 1971 Hall and Sanders, 1980). A homonuclear NOE can theoretically be as large as 50%, but is usually much smaller, and depends on the inverse sixth power of the distance between the nuclei, so that the relative magnitudes of enhancements reflect the spatial relationships of the atoms involved. 

---