Shift correlation, heteronuclear inverse-detected

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. 

Inverse experiments Heteronuclear shift-correlation experiments in which magnetization of the less sensitive heteronucleus (e.g., C) is detected through the more sensitive magnetization (e.g., H). 

NMR probes are designed with the X-coil closest to the sample for improved sensitivity of rare nuclei. Inverse detection NMR probes have the proton coil inside the X-coil to afford better proton sensitivity, with the X-coil largely relegated to the task of broadband X-nucleus decoupling. These proton optimized probes are often used for heteronuclear shift correlation experiments. 

Direct heteronuclear chemical shift correlation Conceptually, the 2D J-resolved experiments lay the groundwork for heteronuclear chemical shift correlation experiments. For molecules with highly congested 13C spectra, 13C rather than XH detection is desirable due to high resolution in the F% dimension [40]. Otherwise, much more sensitive and time-efficient proton or so-called inverse -detected heteronuclear chemical shift correlation experiments are preferable [41]. 

Homonuclear as well as heteronuclear 2D shift correlation experiments ( H/ H-COSY, H/ C-COSY, H/C COSY- H/ H-TOCSY), involving the perturbation of either one or two types of nuclei respectively and in the heteronuclear case including both the conventional, direct C detection, as well as the more sensitive, indirect ( inverse or reverse ) H-detection. 

In the case of an unknown chemical, or where resonance overlap occurs, it may be necessary to call upon the full arsenal of NMR methods. To confirm a heteronuclear coupling, the normal H NMR spectrum is compared with 1H 19F and/or XH 31 P NMR spectra. After this, and, in particular, where a strong background is present, the various 2-D NMR spectra are recorded. Homonuclear chemical shift correlation experiments such as COSY and TOCSY (or some of their variants) provide information on coupled protons, even networks of protons (1), while the inverse detected heteronuclear correlation experiments such as HMQC and HMQC/TOCSY provide similar information but only for protons coupling to heteronuclei, for example, the pairs 1H-31P and - C. Although interpretation of these data provides abundant information on the molecular structure, the results obtained with other analytical or spectrometric techniques must be taken into account as well. The various methods of MS and gas chromatography/Fourier transform infrared (GC/FTIR) spectroscopy supply complementary information to fully resolve or confirm the structure. Unambiguous identification of an unknown chemical requires consistent results from all spectrometric techniques employed. 

Beginning with the report of the HMQC experiment in 1986 by Bax and Subramanian- the utilization of proton- or inverse-detected heteronuclear shift correlation experiment was essentially ushered in. Despite reports that have demonstrated the superior resolution of single quantum-based heteronuclear shift correlation methods,-" the HMQC experiment still remains the most widely employed, proton-detected heteronuclear shift correlation method. Gradients were incorporated into the HMQC experiment in 1991 by Hurd and John- and are discussed in the excellent contribution of Ruiz-Cabello and co-workers- and... 

Heteronucleus-detected shift correlation experiments have now been largely supplanted by far more sensitive proton- or inverse -detected methods. The heteronu-cleus-detected experiments are now largely reserved, in laboratories with modem NMR spectrometers, for those occasions when very high digital resolution is needed in the carbon frequency domain because of high spectral congestion [109, 110]. The remainder of this section will focus on the now widely utihzed proton-detected heteronuclear shift correlation methods. 

NMR has been a powerful technique for structural analyses of macromolecules. However, ID NMR spectra of PDMS are usually complicated due to signal overly. Their complete characterization often requires combinations of several techniques. Multidimensional NMR techniques, especially inversely detected 3D heteronuclear shift correlation experiments, offer the opportunity to obtain the complete structural characterization by using NMR experiments alone. Biological 3D-NMR experiments are usually performed in conjunction with uniform and isotopic labeling. In polymer chemistry, when isotopic labeling is possible, it is often very difficult and expensive. By modifying the 3D-pulse sequence used for biopolymers, triple resonance 3D-NMR techniques have been adapted for sbufying the structures of polymers, which involve H- C- P, H- C- Si spin... 

Clearly the development and dissemination of two-dimensional NMR techniques has had a profound impact in natural products structure elucidation. Some techniques, COSY and variants of the C-detected heteronuclear chemical shift correlation (variously referred to as HETCOR, HC-COSY, etc.) experiment, have been widely used by the natural products chemistry community. Inverse-detected heteronuclear shift correlation techniques are becoming recognized as a powerful adjunct to the COSY experiment and a replacement for their less sensitive and, in some cases, less versatile C-detected predecessor experiments (Martin and Crouch 1991). 

Inverse-Detected One-Bond Heteronuclear Shift Correlation Experiments... 

At present, several experiments are available for inverse-detected one-bond heteronuclear shift correlation. The HMQC experiment described by Bax and Subramanian (1986) has probably been most widely employed. Alternatives, however, are available in the form of DEPT-HMQC (Kessler et al. 1989b) and the HSQC or so-called Overbodenhausen experiment (Boden-hausen and Ruben 1980). For alkaloids with highly congested proton spectra, DEPT-HMQC may be a useful alternative to HMQC, because it allows the acquisition of edited correlation spectra. For investigators interested in correlation of protons to alkaloidal nitrogen atoms via one or two bonds, HSQC or a doubly refocused variant may be the preferred choice. 

Quite probably, HMQC (Bax and Subramanian 1986) is the most widely employed inverse-detected heteronuclear chemical shift correlation experi-... 

To date, the only inverse-detected heteronuclear chemical shift correlation experiment available for multiple-bond correlation is the HMBC experiment of Bax and Summers (1986). The pulse sequence is shown in Fig. 5 and... 

Navelbine . The most recent application of inverse-detected 2D NMR methods to a bis-indole was the reported assignment of the proton and carbon NMR spectra of Navelbine (24) reported by the authors (Spitzer et al. 1992). Direct proton-carbon shift correlations were established using an HMQC spectrum. The authors also reported the comparative evaluation of the recently reported GEM-COSY technique (Domke et al. 1991), which affords a heteronuclear correlation spectrum of only the methylenes of a molecule, with the HMQC spectrum. Based on their assessment, GEM-COSY, while useful, did not offer any advantage over the HMQC experiment. In addition, the nature of the experiment required high levels of... 

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