Pulse sequence quantum correlation

HC HMQC (heteronuclear multiple quantum coherence) and HC HSQC (heteronuclear single quantum coherence) are the acronyms of the pulse sequences used for inverse carbon-proton shift correlations. These sensitive inverse experiments detect one-bond carbon-proton connectivities within some minutes instead of some hours as required for CH COSY as demonstrated by an HC HSQC experiment with a-pinene in Fig. 2.15. 

HSQC Heteronuclear single quantum coherence, e.g. inverse CH correlation via one-bond coupling providing the same result as HMQC but using an alternative pulse sequence... 

Figure 1. Pulse sequences of some typical 2D-NMR experiments. COSY = correlation SpectroscopY, DQFCOSY = Double Quantum Filtered COSY, RELAY = RELAYed Magnetization Spectroscopy, and NOESY = Nuclear Overhauser Effect SpectroscopY.

The SELINCOR experiment is a selective ID inverse heteronuclear shift-correlation experiment i.e., ID H,C-COSYinverse experiment) (Berger, 1989). The last C pulse of the HMQC experiment is in this case substituted by a selective 90° Gaussian pulse. Thus the soft pulse is used for coherence transfer and not for excitation at the beginning of the sequence, as is usual for other pulse sequences. The BIRD pulse and the A-i delay are optimized to suppress protons bound to nuclei As is adjusted to correspond to the direct H,C couplings. The soft pulse at the end of the pulse sequence (Fig. 7.8) serves to transfer the heteronuclear double-quantum coherence into the antiphase magnetization of the protons attached to the selectively excited C nuclei. 

To be fair, we must point out that this type of experiment is extremely sensitive to the parameters chosen. Various pulse sequences are available, including the original COLOC (Correlation by means of Long range Coupling) as well as experiments variously referred to as HMBC (Heteronuclear Multiple-Bond Correlation) and HMQC (Heteronuclear Multiple-Quantum Correlation). Depending on the parameters chosen, it is often not possible to suppress correlations due to one-bond coupling ... 

Fig. 2 (a) DRAMA pulse sequence (using % = t/2 = rr/4 in the text) and a representative calculated dipolar recoupled frequency domain spectrum (reproduced from [23] with permission), (b) RFDR pulse sequence inserted as mixing block in a 2D 13C-13C chemical shift correlation experiment, along with an experimental spectrum of 13C-labeled alanine (reproduced from [24] with permission), (c) Rotational resonance inversion sequence along with an n = 3 rotational resonance differential dephasing curve for 13C-labeled alanine (reproduced from [21] with permission), (d) Double-quantum HORROR experiment along with a 2D HORROR nutation spectrum of 13C2-2,3-L-alanine (reproduced from [26] with permission)... 

Fig. 5 Symmetry-based dipolar recoupling illustrated in terms of pulse sequences for the CN (a) and RNvn (b) pulse sequences, a spin-space selection diagram for the Cl symmetry (c) (reproduced from [118] with permission). Application of POST-CVj [31] as an element in a H- H double-quantum vs 13C chemical shift correlation experiment (d) used as elements (B panel) in a study of water binding to polycrystalline proteins (reproduced from [119] with permission)...

Fig. 10.14. Gradient-enhanced HMQC pulse sequence described in 1991 by Hurd and John derived from the earlier non-gradient experiment of Bax and Subramanian. For 1H-13C heteronuclear shift correlation, the gradient ratio, G1 G2 G3 should be 2 2 1 or a comparable ratio. The pulses sequence creates heteronuclear multiple quantum of orders zero and two with the application of the 90° 13C pulse. The multiple quantum coherence evolves during the first half of ti. The 180° proton pulse midway through the evolution period decouples proton chemical shift evolution and interchanges the zero and double quantum coherence terms. Antiphase proton magnetization is created by the second 90° 13C pulse that is refocused during the interval A prior to detection and the application of broadband X-decoupling.

Fig. 10.15. Pulse sequence for the multiplicity-edited gradient HSQC experiment. Heteronuclear single quantum coherence is created by the first INEPT step within the pulse sequence, followed by the evolution period, t . Following evolution, the heteronuclear single quantum coherence is reconverted to observable proton magnetization by the reverse INEPT step. The simultaneous 180° XH and 13C pulses flanked by the delays, A = l/2( 1 edits magnetization inverting signals for methylene resonances, while leaving methine and methyl signals with positive phase (Fig. 16A). Eliminating this pulse sequence element affords a heteronuclear shift correlation experiment in which all resonances have the same phase (Fig. 16B).

A sequence suitable for measurement of J(H, P) and J(C, P) couplings is shown in Fig. 7.9a. The pulse sequence is a constant-time [13C, H]-HSQC (heteronuclear single-quantum correlation), in which 31P decoupling is applied in ot, in the first experiment and in co2 in the second. 

The method relies on the measurement of cross-correlated relaxation rates in a constant time period such that the cross-correlated relaxation rate evolves during a fixed time r. In order to resolve the cross-correlated relaxation rate, however, the couplings need to evolve during an evolution time, e.g. tt. The first pulse sequence published for the measurement of the cross-correlated relaxation rate between the HNn and the Ca j,Ha i vector relied on an HN(CO)CA experiment, in which the Ca chemical shift evolution period was replaced by evolution of 15N,13C double and zero quantum coherences (Fig. 7.20). 

Despite the very different mechanism, the HSQC sequence (//eteronuclear Single Quantum Correlation) yields results equivalent to an HMQC sequence except that HSQC offers an additional benefit—the cross-peaks do not exhibit homonuclear JH—XH couplings along the FI axis. These splittings reduce sensitivity and resolution along this axis in HMQC spectra. On the other hand, the HSQC sequence contains more pulses and is more sensitive to errors in calibrations etc. The sequence is209 ... 

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... 

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