Heteronuclear single-bond correlations

Figure 15.1. (A) COSY, (B) TOCSY, (C) 1H-1T HSQC or HMQC, (D) dl- Y HMBC, for 4-oxopentanal. For clarity, only key assignments have been given as an example. Note that the double-ended arrows indicate how to interpret the spectra. In the case of COSY and TOCSY the information is represented as cross-peaks that are symmetrically oriented with respect to the central diagonal. In the single-bond correlation (HSQC/HMQC) a cross-peak represents in one dimension the carbon chemical shift and in the other dimension the proton chemical shift. Note there is no diagonal in heteronuclear NMR experiments. In the HMBC, lines are drawn vertically to connect the cross-peaks. In HMBC 2-4 bonds, H-13C correlations are often observed. Note that the 4-bond correlation is less common in NMR but has been included here as an example, and 1-bond correlation is commonly filtered from the HMBC experiment to improve detection limits for the weaker 2-4 bond correlations.

Other strategies that show great promise in reducing NMR acquisition time utilise methods to obtain multiple sets of data from one experiment through a concept known as time-shared evolution. An example of this process that should find utility in natural products elucidation was demonstrated by a pulse sequence called CN-HMBC.93 Traditionally, a separate 13C-HMBC and 15N-HMBC were acquired independently. However, the CN-HMBC allows both 13C- and 15N-HMBC spectra to be obtained simultaneously. By acquiring both data sets simultaneously, an effective 50% time reduction can be achieved.93 This approach has also been demonstrated for a sensitivity-enhanced 2D HSQC-TOCSY (heteronuclear multiple bond correlation total correlation spectroscopy) and HSQMBC (heteronuclear single quantum... 

Introducing a heteronuclear dimension reduces the signal overlap by using the additional chemical shift dispersion of the heteronuclei and facilitates assignment of biomolecules. The Heteronuclear Single Quantum Correlation (HSQC) experiment yields a spectmm that correlates the chemical shift of a spin with that of a covalently bound or spin (55). In a HSQC spectrum, every peak represents the correlation of an amide bond, which shows correlations... 

Figure 2. Heteronuclear Single Quantum Correlation Spectra of I N-rCRALBP with and without 11-c/s-retinaldehyde. Results are shown from a gradient-enhanced sensitivity-enhanced heteronuclear single quantum correlation (GESE-HSQC) NMR experiment. The experiment correlates directly bonded pairs in rCRALBP. The correlation map for rCRALBP (29 mg/ml) with bound 11-c/s-retinaidehyde (heavy lines)...

Fourier transform or transformation heteronuclear chemical-shift correlation heteronuclear multiple bond correlation heteronuclear multiple quantum correlation heteronuclear single quantum correlation... 

The assignment of heteronuclei generally requires acquisition of a heteronuclear single quantum coherence (HSQC) experiment and a heteronuclear multiple bond correlation (HMBC) experiment, and these are described in more detail below. 

The heteronuclear multiple-quantum correlation (HMQC) experiment is one of the two commonly employed proton-detected single-bond correlation experiments. Although this was suggested many years ago [1,2], the experiment lacked widespread use until a scheme was presented [3] that was able to overcome the technical difficulties associated with proton observation described above. Since then, and particularly since the advent of PFGs, the technique has come to dominate organic NMR spectroscopy. 

The main emphasis of current carbohydrate structural analysis is the applicability of modern multi-dimensional NMR for solving the two crucial problems in complex carbohydrate structural analysis, namely, the elucidation of the sequence of glycosyl residues and the solution conformation and dynamics of a carbohydrate (150). Techniques include 2D Total Correlation Spectroscopy (TOCSY), Nuclear Overhauser effect spectroscopy (NOESY), rotational nuclear Overhauser effect spectroscopy (ROES Y),hetero-nuclear single quantum coherence (HSQC), heteronuclear multiple quantum correlation (HMQC), heteronuclear multiple bond correlation (HMBC), and (pseudo) 3D and 4D extensions. 

In the heteronuclear experiment category, the experiments of interest are the heteronuclear multiple quantum correlation (HMQC) experiment, the heteronuclear single quantum correlation (HSQC) experiment, and the heteronuclear multiple bond correlation (HMBC, including the gradient-selected version gHMBC) experiment. Both the HMQC and HSQC produce similar results, but each has its own unique advantages and disadvantages. 

HMBC. Heteronuclear multiple bond correlation. HMQC. Heteronuclear multiple quantum correlation. HSQC. Heteronuclear single quantum correlation. INADEQUATE. Incredible natural abundance double quantum transfer. 

M. Takasaki, K. Kimura, Y. Nakagawa, N. Sato, B. Bae, K. Miyatake, M. Watanabe, Complete NMR assignment of a stdfonated aromatic block copolymer via heter-onuclear single-quantum correlation, heteronuclear multiple-bond correlation and heteronuclear single-quantum correlation total correlation spectroscopy, Polym. J. 44 (2012) 845-849. 

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