COSY, Homonuclear Correlated Spectroscopy

Figures 13.7 and 13.8 are two examples of two-dimensional NMR spectroscopy applied to polymers. Figure 13.7 is the proton homonuclear correlated spectroscopy (COSY) contour plot of Allied 8207A poly(amide) 6 [29]. In this experiment, the normal NMR spectrum is along the diagonal. Whenever a cross peak occurs, it is indicative of protons that are three bonds apart. Consequently, the backbone methylenes of this particular polymer can be traced through their J-coupling. Figure 13.8 is the proton-carbon correlated (HETCOR) contour plot of Nylon 6 [29]. This experiment permits the mapping of the proton resonances into the carbon-13 resonances.

Fig. 13.7 Proton homonuclear correlated spectroscopy (COSY) contour plot of Allied 8207A, a poly(amide) 6.

Wemmer, D. E., Homonuclear Correlated Spectroscopy (COSY). Concepts in Magnetic Resonance An Educational Journal, 1989,1, (No 2)... 

Homonuclear correlation spectroscopy (COSY) experiments (see Chapter 9) substantiate the theoretical predictions, based on molecular orbital calculation, of the pattern of spin delocalization in the 3e orbitals of low-spin Fe(III) complexes of unsymmetrically substituted tetraphenylporphyrins [46]. Furthermore, the correlations observed show that this n electron spin density distribution is differently modified by the electronic properties of a mono-orf/io-substituted derivative, depending on the distribution of the electronic effect over both sets of pyrrole rings or only over the immediately adjacent pyrrole rings [46]. No NOESY cross peaks are detectable, consistently with expectations of small NOEs for relatively small molecules and effective paramagnetic relaxation [47]. 

By way of example, useful 2-D techniques are homonuclear correlation spectroscopy (COSY), total correlation spectroscopy (TOCSY), heteronuclear multiple quantum coherence (HMQC) spectroscopy, and heteronuclear multiple quantum coherence/total... 

The number of sugar residues and constituent monosaccharides are determined by a combination of COSY (two-dimensional homonuclear correlation spectroscopy), HOHAHA (2D homonuclear Hartman-Hann spectroscopy) and HETCOR (direct heteronuclear correlation spectroscopy)... 

The second way to improve the resolution of proton resonances is with homonuclear correlation spectroscopy, or COSY, experiment. In the basic form of the experiment the magnetization is excited with a 90° pulse. During the consequent fi period the chemical shift and homonuclear / couplings evolve, until a second 90° pulse is applied prior to acquisition. This pulse causes polarization transfer to take place between protons that are coupled to each other. If we consider a proton H coupled to another proton H, then the observable terms of the proton H magnetization for the COSY experiments are... 

H homonuclear correlation spectroscopy (COSY). The connection between the benzyltetraisoquinoline and pavine moieties in 66 was located at C-10 and C-7 through an ether bridge as a result of the unambiguous assignments of H and 13C NMR signals by the heteronuclear multiple-bond quantum coherence (HMQC) and heteronuclear multiple-bond coherence (HMBC) NMR techniques. The EIMS of 66 confirmed the presence of a hydroxybenzyl moiety due to the observed complementary peaks at m/z 545 and 107 [11]. Furthermore, the structure of 66 was substantiated by the formation of herveline C (68) after 66 was treated with diazomethane in ethyl ether solution overnight [11]. 

Two-dimensional homonuclear correlation spectroscopy (COSY) is well established for the study of liquids [24,25] and has recently been shown to be effective with solid samples [8,26-38], many of which are of catalytic interest [30,37]. The COSY spectrum contains diagona] peaks and off-diagonal cross-peaks. The cross-peaks arise because of coherence transfer between spins, and they indicate that the resonances at the relevant shift positions on the two axes are coupled. In the solid state, the necessary coherence transfer may occur through dipolar or scalar interactions. Experiments based on scalar couplings have been more popular, because in favorable circumstances they allow the spectroscopist to establish unambiguously the atomic connectivities within molecules in solid samples [8,27-38] including complex zeolitic frameworks [8,30-37]. 

Homonuclear correlation spectroscopy (COSY) offers a way to identify spin-coupled pairs of nuclei, even when structural information for the specific molecule under study is completely lacking. Correlation is established using homonuclear coupling, so the technique essentially shows the same information in one plot as in ID homonuclear decoupling experiments. A potentially useful application for this class of analysis is the spin-spin correlation of C- C, but there are two main problems with this approach. The first one is related to the need of the presence of C nuclei in two adjacent atoms. In natural abundance, this probability is too low, so the experiment is highly insensitive and suitable only for concentrated samples rich in carbon content. The second one relates to the relative weakness of the spin-coupled peaks from C- C pairs when compared with the peaks from isolated C nuclei. 

Fig. 8.10 Pulse sequence for homonuclear correlation spectroscopy, COSY/GCCOSY [46-48]. Although the gradient version of the experiment is shown, the pulse sequences are the same except for the two gradients and their associated delays. The non-gradient experiment employs a four-step phase cycle the gradient experiment allows the acquisition of data with a...

Homonuclear NMR Structural elucidation becomes much more difficult as spectral complexity increases. Under these circumstances, proton NMR spectroscopy has benefited considerably from the use of 2D NMR techniques. For example, homonuclear correlation spectroscopy (COSY) identifies spin-coupled pairs of nuclei as well as spin-coupled networks of nuclei in a molecule, even without prior structural information. The 2D /-resolved spectroscopy method permits even highly overlapping resonances to be resolved into readily interpretable multiplets. This enables chemical shift assignments to be made in a very straightforward manner. Both of... 

D-correlation experiments are almost invariably presented in a contour plot. Homonuclear correlation spectroscopy, in the form of COSY (proton correlation spectroscopy) (25, 28) or SECSY (2D-spin echo-correlated spectroscopy) (279) pulse sequences, is routinely employed in modern natural products structure determination (198, 328). 

The pathway for homonuclear correlation spectroscopy (COSY) is shown in Figure 2 and provides a simple example. The first pulse creates coherence with orders -l-l and -1 and leaves some z magnetization as coherence order 0. Thus, there are three pathways by which the coherence can reach the receiver after the second RF pulse, namely [0 0 -1], [0 + I -1] and [0 -1 -1]. If the RF carrier is placed on one side of the F2 spectrum, all of the peaks in the 2D spectrum corresponding to the [0 -1 -1] coherence pathway will lie on one side of Fi = 0 and the peaks from [0 -hi -1] will lie on... 

The most useful experiment of all is the homonuclear COSY (two-dimensional homonuclear Correlated SpectroscopY) experiment. This yields a square matrix of data. The diagonal, projected onto either frequency axis, is the normal one-dimensional spectrum, and off-diagonal multiplets appear with the x coordinate of resonance A and the y coordinate of resonance B or vice versa, when A and B are mutually spin-coupled. A two-dimensional spectrum of this type is most conveniently presented as a contour diagram, as viewed from above, even though such maps seem at first strange to one-dimensional spectroscopists. 

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

TOCSY Total correlation spectroscopy, in the homonuclear COSY format, e.g. HH TOCSY traces out all proton-proton coimectivities of a partial structure in addition to the coimectivities (V, V, V, J) as detected by HH COSY... 

Figure 1.45 Coherence transfer pathways in 2D NMR experiments. (A) Pathways in homonuclear 2D correlation spectroscopy. The first 90° pulse excites singlequantum coherence of order p= . The second mixing pulse of angle /3 converts the coherence into detectable magnetization (p= —1). (Bra) Coherence transfer pathways in NOESY/2D exchange spectroscopy (B b) relayed COSY (B c) doublequantum spectroscopy (B d) 2D COSY with double-quantum filter (t = 0). The pathways shown in (B a,b, and d) involve a fixed mixing interval (t ). (Reprinted from G. Bodenhausen et al, J. Magn. Resonance, 58, 370, copyright 1984, Rights and Permission Department, Academic Press Inc., 6277 Sea Harbor Drive, Orlando, Florida 32887.)...

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... 

The HOHAHA spectrum (100 ms) of podophyllotoxin is presented. The HOHAHA, or TOCSY (total correlation spectroscopy), spectrum (100 ms) shows coupling interactions of all protons within a spin network, irrespective of whether they are directly coupled to one another or not. As in COSY spectra, peaks on the diagonal are ignored as they arise due to magnetization that is not modulated by coupling interactions. Podophyllotoxin has only one large spin system, extending from the C-1 proton to the C4 and 015 protons. Identify all homonuclear correlations of protons within this spin system based on the crosspeaks in the spectrum. 

Homonuclear shift-correlation spectroscopy (COSY) is a standard method for establishing proton coupling networks. Diagonal and off-diagonal peaks appear with respect to the two frequency dimensions. 

Homonuclear 19F-19F experiments are the most commonly carried out, and they are also the most easily implemented on conventional NMR spectrometers. Among such experiments, 19F COSY correlation spectroscopy is probably the 2D 19F NMR technique most frequently encountered, mainly because of through space couplings that can make it otherwise difficult to infer definitive structural information from the presence or magnitude of observed correlations. It has been found to be particularly useful in the analysis of fluoropolymers. 

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