Dipolar coupling NOESY experiments

The main source of conformational information for biopolymers are the easy-to-obtain chemical shifts that can be translated into dihedral restraints. In addition, for fully 13C labeled compounds, proton-driven spin diffusion between carbons [72] can be used to measure quantitatively distances between carbons. The CHHC experiment is the equivalent of the NOESY in solution that measures distances between protons by detecting the resonances of the attached carbons. While both techniques, proton-driven spin diffusion and CHHC experiment [73], allow for some variation in the distance as determined from cross-peak integrals, REDOR [74] experiments in selective labeled compounds measure very accurate distances by direct observation of the oscillation of a signal by the dipolar coupling. While the latter technique provides very accurate distances, it provides only one piece of information per sample. Therefore, the more powerful techniques proton-driven spin diffusion and CHHC have taken over when it comes to structure determination by ss-NMR of fully labeled ligands. 

Nuclei that undergo mutual relaxation via dipolar coupling are said to be dipolar coupled and give rise to the nuclear Overhauser effect. Whether the nuclei in question also may be scalar (or spin) coupled is not pertinent to the discussion (Section 5-4). NOE experiments can be either homonuclear or heteronuclear in nature, although the former, involving protons, are much more common. One-dimensional homonuclear Overhauser experiments are discussed in Section 7-3 their 2D versions, NOESY and ROESY, are treated in this section. 

Concatenation of the 3H—15N HSQC (or HMQC) sequence with a JH—JH NOESY gives rise to the 3D 15N-edited NOESY-HSQC (or 3D NOESY-HMQC) experiment.66-68 Here, two of the frequency dimensions represent the amide JH and 15N chemical shifts, while the third dimension provides information about the chemical shift of protons with which each amide proton is dipolar coupled (i.e., separated by <5.5 A). The spectrum is routinely viewed as narrow 2D (JH—JH) strips taken at the 15N chemical shift of each crosspeak in the JH—15N HSQC spectrum (see Figure 14). 

The resolntion that is gained by the additional freqnency dimension (N in this case) is illnstrated in Figure 3.6. The two-dimensional NOESY spectrnm of a 50 residne a-helical protein is shown in the left part of this fignre. In this experiment, the magnetization is transferred from proton H to proton Hy by dipolar coupling. The first freqnency dimension corresponds to the chemical shift of H and the second frequency dimension corresponds to the chemical shift of Hy. As with the NOESY-HSQC described previously, the intensity of the peak is related to the distance between H and Hy. Note the large number of unresolved overlapping peaks in the... 

Spectral spin diffusion in the solid state involves simultaneous flipflop transitions of dipolar-coupled spins with different resonance frequencies 11,39,63-76], whereas spatial spin diffusion transports spin polarization between spatially separated equivalent spins. In this review we deal only with the first case. The interaction of spins undergoing spin diffusion with the proton reservoir provides compensation for the energy imbalance (extraneous spins mechanism) [68,70,73,74]. Spin diffusion results in an exchange of magnetization between the nuclei responsible for resolved NMR signals, which can be conveniently detected by observing the relevant cross-peaks in the 2D spin-diffusion spectrum [63-65]. This technique, formally analogous to the NOESY experiment in liquids, is already well established for solids and can also be applied to the study of catalysts. 

MAS NOESY experiments have been widely used in SSNMR to study peptide-lipid interactions because of the fast axially rotation and segmental motion of membrane lipids in the liquid crystalline phase which average out efficiently the H- H dipolar couplings, resulting in a high resolution spectrum of membrane lipids under the slow MAS frequencies [166], which leads to the rapid applications of the NOESY-type [167] of solution NMR methods to study peptide-membrane interactions in MAS SSNMR [168-170]. 

The principle purpose of correlation experiments is to establish a one-to-one mapping from the signal to its source i.e. to the particular atomic nucleus in the molecule. This assignment task involves identification of the members in the coupling network, referred to as the spin system. In addition, correlation experiments, as such or with modifications, are suitable for measurements of scalar and dipolar couplings. Correlation in the two dimensions is the most natural dimensionality because the spin-spin interactions are pair wise. Three-dimensional or experiments of higher dimensionality are constructed from concatenated two-dimensional experiments. Homonuclear three-dimensional experiments, such as TOCSY-NOESY, are not considered here because in many cases the multidimensional heteronuclear experiments are superior. 

NOE is widely used in three-dimensional structure determination of molecules, especially for proteins in solution. NOE-based NMR experiments provide an effective means to investigate nanostructural organizations in ionic Hquids. Homonuclear NOE experiments (NOESY) and heter-onuclear NOE experiments (HOESY) have been extensively appfred to probe intra- and intermolecular interactions within ILs and interaction of ILs with solvents and inorganic salts. Due to the abihty to probe dipolar coupled through space interactions, NOE is a perfect choice to probe interionic interactions to understand ion-pair dynamics. Since quantum chemical calculations are a convenient method to study ion-pair interactions and spatial information about them [76-78], combinations of this with NOE experiments would be a powerful approach to understand site-specific ion-pair interactions. 

Other basic 2-D experiments include J spectroscopy, which displays scalar-coupled multiplets along the second dimension, and nuclear Overhauser effect spectroscopy (NOESY, pronounced nosy ), which exploits through-space dipolar couplings to provide conformational information. In the NOESY experiment, protons are selectively irradiated as data are acquired, and the effect of neighboring nuclei is monitored by their mutual enhancement. NOESY is one example of an exchange experiment, in which magnetization is transferred from spin to spin. 

There are several other sources of cross peaks in the 2D EXSY experiment. Dipolar coupling with nearby nuclei (nuclear Overhauser effects) produces cross peaks, as observed in standard Nuclear Overhauser Enhancement Spectroscopy, NOESY. These can be identified because exchange usually has a larger temperature dependence than dipolar coupling. Scalar coupling interferes with 2D EXSY by producing so-called J cross peaks that can be eliminated by phase cycling. ... 

NOESY data (Figure 35) is also very valuable as it allows one to observe the molecule in its spatial environment. To this end, the data can provide supportive information to the structure that has been assembled by the rest of the ID and 2D data. In addition, the dipolar coupling data can be used to imderstand regiochemistry as well is some stereochemical issues. In addition, if properly set up the dipolar coupling experiments can allow one to observe chemical exchange processes. 

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