Shift correlation

A H(detected)- C shift correlation spectrum (conmion acronym HMQC, for heteronuclear multiple quantum coherence, but sometimes also called COSY) is a rapid way to assign peaks from protonated carbons, once the hydrogen peaks are identified. With changes in pulse timings, this can also become the HMBC (l eteronuclear multiple bond coimectivity) experiment, where the correlations are made via the... 

Figure Bl.ll.13. C- Fl shift correlation via This spectrum of metliyl-a-...

A second 2D NMR method called HETCOR (heteronuclear chemical shift correlation) is a type of COSY in which the two frequency axes are the chemical shifts for different nuclei usually H and With HETCOR it is possible to relate a peak m a C spectrum to the H signal of the protons attached to that carbon As we did with COSY we 11 use 2 hexanone to illustrate the technique... 

HETCOR (Section 13 19) A 2D NMR technique that correlates the H chemical shift of a proton to the chemical shift of the carbon to which it is attached HETCOR stands for heteronuclear chemical shift correlation Heteroatom (Section 1 7) An atom in an organic molecule that IS neither carbon nor hydrogen Heterocyclic compound (Section 3 15) Cyclic compound in which one or more of the atoms in the nng are elements other than carbon Heterocyclic compounds may or may not be aromatic... 

Although the natural abundance of nitrogen-15 [14390-96-6] leads to lower sensitivity than for carbon-13, this nucleus has attracted considerable interest in the area of polypeptide and protein stmcture deterrnination. Uniform enrichment of is achieved by growing protein synthesi2ing cells in media where is the only nitrogen source. reverse shift correlation via double quantum coherence permits the... 

Heteronuclear chemical shift-correlated spectroscopy, commonly called H-X COSY or HETCOR has, as the name implies, different and F frequencies. The experiment uses polarization transfer from the nuclei to the C or X nuclei which increases the SNR. Additionally, the repetition rate can be set to 1—3 of the rather than the longer C. Using the standard C COSY, the ampHtude of the C signals are modulated by the... 

Figure 2.11. Proton-Proton shift correlations of a-pinene (1) [purity 99 %, CDCls, 5 % v/v, 25 °C, 500 MHz, 8 scans, 256 experiments], (a) HH COSY (b) HH TOCSY (c) selective one-dimensional HH TOCSY, soft pulse irradiation at Sh = 5.20 (signal not shown), compared with the NMR spectrum on top deviations of chemical shifts from those in other experiments (Fig. 2.14, 2.16) arise from solvent effects...

Two-dimensional carbon-proton shift correlation m one-bond CH coupling... 

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. 

These two-dimensional CH shift correlations indicate CH relationships through two and more bonds (predominantly Jch and Jch connectivities) in addition to more or less suppressed Jch relationships which are in any case established from the CH COSY contour diagram. Format and analysis of the CH COLOC or HMBC plots correspond to those of a C//COSY or HSQC experiment, as is shown for a-pinene (1) in Figs. 2.14 - 2.17. 

COSY Correlated spectroscopy, two-dimensional shift correlations via spin-spin coupling, homonuclear (e.g. HH) or heteronuclear (e.g. CH)... 

CH COSY Correlation via one-bond CH coupling, also referred to as HETCOR (heteronuclear shift correlation), provides carbon-13- and proton shifts of nuclei in C//bonds as cross signals in a 5c versus 8h diagram, assigns all C//bonds of the sample... 

HETCOR (Section 13.19) A 2D NMR technique that correlates the H chemical shift of a proton to the C chemical shift of the carbon to which it is attached. HETCOR stands for heteronuclear chemical shift correlation. 

NMR chemical shift data from die protons ortho or para to the electron-withdrawing group can be used to determine the reactivity of the monomer indirecdy.58 Carbon-13 and 19F NMR can be used to probe the chemical shift at the actual site of nucleophilic reaction. In general, lower chemical shifts correlate widi lower monomer reactivity. Carter reported that a compound might be appropriate for nucleophilic displacement if the 13 C chemical shift of an activated Buoride ranges from 164.5 to 166.2 ppm in CDC1359. 

Some of the most important 2D experiments involve chemical shift correlations between either the same type of nuclei (e.g., H/ H homonu-clear shift correlation) or between nuclei of different types (e.g., H/ C heteronuclear shift correlation). Such experiments depend on the modulation of the nucleus under observation by the chemical shift frequency of other nuclei. Thus, if H nuclei are being observed and they are being modulated by the chemical shifts of other H nuclei in the molecule, then homonuclear shift correlation spectra are obtained. In contrast, if C nuclei are being modulated by H chemical shift frequencies, then heteronuclear shift correlation spectra result. One way to accomplish such modulation is by transfer of polarization from one nucleus to the other nucleus. Thus the magnitude and sign of the polarization of one nucleus are modulated at its chemical shift frequency, and its polarization transferred to another nucleus, before being recorded in the form of a 2D spectrum. Such polarization between nuclei can be accomplished by the simultaneous appli-... 

Figure 3.1 The various time periods in a two-dimensional NMR experiment. Nuclei are allowed to approach a state of thermal equilibrium during the preparation period before the first pulse is applied. This pulse disturbs the equilibrium ptolariza-tion state established during the preparation period, and during the subsequent evolution period the nuclei may be subjected to the influence of other, neighboring spins. If the amplitudes of the nuclei are modulated by the chemical shifts of the nuclei to which they are coupled, 2D-shift-correlated spectra are obtained. On the other hand, if their amplitudes are modulated by the coupling frequencies, then 2D /-resolved spectra result. The evolution period may be followed by a mixing period A, as in Nuclear Overhauser Enhancement Spectroscopy (NOESY) or 2D exchange spectra. The mixing period is followed by the second evolution (detection) period) ij.

There are basically three main types of 2D NMR experiments J-resolved, shift correlation through bonds (e.g., COSY), and shift correlations through space e.g., NOESY). These spectra may be of homonuclear or heteronuclear type involving interactions between similar nuclei (e.g., protons) or between different nuclear species (e.g., H with C). 

In homonuclear-shift-correlated experiments, the Ft domain corresponds to the nucleus under observation in heteronuclear-shift-correlated experiments. Ft relates to the unobserved or decoupled nucleus. It is therefore necessary to set the spectral width SW, after considering the ID spectrum of the nucleus corresponding to the Ft domain. In 2D /-resolved spectra, the value of SW depends on the magnitude of the coupling constants and the type of experiment. In both homonuclear and heteronuclear experiments, the size of the largest multiplet structure, in hertz, determines... 

SWi, which in turn is related to the homonuclear or heteronuclear coupling constants. In homonuclear 2D spectra, the transmitter offset frequency is kept at the center of (i.e., at = 0) and F domains. In heteronuclear-shift-correlated spectra, the decoupler offset frequency is kept at the center (Fi = 0) of thei i domain, with the domain corresponding to the invisible or decoupled nucleus. 

Heteronuclear-shift-correlation spectra, which are usually presented in the absolute-value mode, normally contain long dispersive tails that are suppressed by applying a Gaussian or sine-bell function in the F domain. In the El dimension, the choice of a weighting function is less critical. If a better signal-to-noise ratio is wanted, then an exponential broadening multiplication may be employed. If better resolution is needed, then a resolution-enhancing function can be used. 

The matrix obtained after the F Fourier transformation and rearrangement of the data set contains a number of spectra. If we look down the columns of these spectra parallel to h, we can see the variation of signal intensities with different evolution periods. Subdivision of the data matrix parallel to gives columns of data containing both the real and the imaginary parts of each spectrum. An equal number of zeros is now added and the data sets subjected to Fourier transformation along I,. This Fourier transformation may be either a Redfield transform, if the h data are acquired alternately (as on the Bruker instruments), or a complex Fourier transform, if the <2 data are collected as simultaneous A and B quadrature pairs (as on the Varian instruments). Window multiplication for may be with the same function as that employed for (e.g., in COSY), or it may be with a different function (e.g., in 2D /-resolved or heteronuclear-shift-correlation experiments). 

One-dimensional spectra obtained by projecting 2D spectra along a suitable direction often contain information that cannot be obtained directly from a conventional ID spectrum. They therefore provide chemical shift information of individual multiplets that may overlap with other multiplets in the corresponding ID spectra. The main difference between the projection spectrum and the ID spectrum in shift-correlated spectra is that the projection spectrum contains only the signals that are coupled with each other, whereas the ID H-NMR spectrum will display signals for all protons present in the molecule. 

A more useful type of 2D NMR spectroscopy is shift-correlated spectroscopy (COSY), in which both axes describe the chemical shifts of the coupled nuclei, and the cross-peaks obtained tell us which nuclei are coupled to which other nuclei. The coupled nuclei may be of the same type—e.g., protons coupled to protons, as in homonuclear 2D shift-correlated experiments—or of different types—e.g., protons coupled to C nuclei, as in heteronuclear 2D shift-correlated spectroscopy. Thus, in contrast to /-resolved spectroscopy, in which the nuclei were being modulated (i.e., undergoing... 

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