COSY detecting small couplings

For optimum detection of small couplings, the maximum of the coherence transfer signals should occur at the midpoint of each time domain. It may be shown that this maximum arises at a time t where 

When J is small such that JT2 1, the approximation t=T2 holds, and to ensure that the midpoint of each time domain coincides with this maximum, the additional delay A is therefore 

Previous discussions have stressed the need for an antiphase disposition between multiplet vectors for coherence transfer to occur. In COSY, this arises 

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Traditionally, homonuclear 2D double quantum filtered correlation spectroscopy (DQF-COSY) and total correlated spectroscopy (TOCSY) spectra are valuable in the identification of resonances of individual monosaccharide units. In the presence of small couplings, through space connectivities detected by NOESY/ROESY (nuclear Overhauser effect spectroscopy/ rotational nuclear Overhauser effect spectroscopy) experiments are also useful in completing the resonance assignment. When the H NMR spectra of complex oligosaccharides are too crowded to fully elucidate the structure by homonuclear correlation methods, it is efficient to use 2D heteronuclear correlation methods, such as heteronuclear single quantum correlation... 

Long-range COSY experiment for detection of small coupling constants... 

Another ingenious modification of the HNN-COSY scheme involves the replacement of the homonuclear 15N-COSY transfer by a 15N-TOCSY transfer [37]. As the homonuclear TOCSY transfer is twice as fast as the COSY transfer, a significant sensitivity increase is achieved. The application is, however, limited to cases where the 15N donor and acceptor resonances are at similar frequencies, so that the power of the 15N-TOCSY radio frequency pulses needed is not too strong. A very interesting application of this scheme was presented for the sensitive detection of very small (0.14 Hz, Tab. 9.1) h4/NiNi couplings in N1-H1 06=C6-N1 H-bonds of guanosine tetrads. 

Today, a number of one- and two-dimensional NMR experiments are available for the detection of homonuclear Li, Li and Li, Li couplings. Aside from the COSY experiment, the double quantum filtered COSY (COSY-DQF), the TOCSY, and the ID and 2D INADEQUATE experiments [24] have been successfully employed. An attractive feature of all these experiments is their sensitivity for small scalar interactions which give rise to crosspeaks even if line splittings in the corresponding ID spectra are not resolved. This was first demonstrated with COSY experiments for a paramagnetic nickel complex [82] and for quadrupolar nuclei in the case of boron-11 [83]. 

In the case of Li, broad lines can lead to overlap for situations with small chemical shifts and this might give rise to artificial crosspeaks in Li, Li COSY experiments. If the chemical shift is sufficiently large, the larger Li, Li coupling (factor 2.64 compared with 7( Li, Li)) facilitates the experiment. Detection of homonuclear Li, Li coupling was also achieved by the Li, Li INADEQUATE experiment [93]. 

Delayed-COSY Enhances detection of small and long-range couplings (<2 Hz) such as between protons in allylic systems or those in w-relationships. Requires magnitude-mode presentation. Crosspeaks due to larger couplings can be significantly attenuated. 

Correlated spectroscopy (COSY) was among the first two-dimensional (2D) NMR experiment realized [447, 448] and it is still among the most useful NMR experiments. COSY generates cross peaks in the 2D spectrum at the intersection of resonances of coupled spins (Fig. 14.48). In proteins cross peaks are observed for gem-inal, i.e. over two bonds, and vicinal, i.e. over three bonds, protons and in small peptides also couplings over four bonds may be detected. Thus the COSY spectrum allows the identification of spin systems for the assignment. However, apart from peptides, the overlap and degeneracy in chemical shifts is likely to prevent one from obtaining entire spin systems exclusively from the COSY spectrum additional experiments are required. 

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