Nuclear Overhauser effect cross-relaxation

As with the COSY experiment, the sequence starts with a pulse followed by an evolution period, but now the mechanism that couples the two spins (which must be in close proximity, typically <6 A) is the Nuclear Overhauser Effect (NOE). The second pulse converts magnetization into population disturbances, and cross-relaxation is allowed during the mixing time. Finally, the third pulse transfers the spins back to the x-y-plane, where detection takes place. The spectrum will resemble a COSY spectrum, but the off-diagonal peaks now indicate through-space rather than through-bond interactions. 

Nuclear Overhauser effect Occurs as a result of cross-relaxation between dipolar-coupled spins resulting from spin spin interactions through space. Phase diagram Summarizes the pressure and temperature conditions at which each phase of a homogeneous material is most stable. 

The principle source of experimental conformational data in an NMR structure determination is constraints on short interatomic distances between hydrogen atoms obtained from NMR measurements of the nuclear Overhauser effect (NOE). NOEs result from cross-relaxation mediated by the dipole-dipole interaction between spatially proximate nu-... 

Exchange of magnetization due to cross-relaxation (NOE, nuclear Overhauser effect) does lead to intensity changes of individual resonances which provide valuable information about spatial and motional characteristics of the spins involved [4, 5]. It is currently mostly measured in two-dimensional NMR, where the NOE is measured as cross-peak intensity. Cross-relaxation is caused by mutual spin flips in dipolar coupled spin pairs. 

Since the discovery of the nuclear Overhauser effect (NOE, see previous section) [4, 5] and scalar coupling constants [36, 37] decades ago, NMR-derived structure calculations of biomolecules largely depended on the measurement of these two parameters [38]. Recently it became possible to use cross-correlated relaxation (CCR) to directly measure angles between bond vectors [39] (see also Chapt 7). In addition, residual dipolar couplings of weakly aligned molecules were discovered to measure the orientation of bond vectors relative to the alignment tensor (see Sect 16.5). Measurement of cross-correlated relaxation was described experimentally earlier for homonuclear cases [40, 41] and is widely used in solid-state NMR [42 14]. 

Hence, provided that I g is known and that R has been determined by means of an independent experiment, provides the cross-relaxation rate ct. This enhancement is called nuclear Overhauser effect (nOe) (17,19) from Overhauser (20) who was the first to recognize that, by a related method, electron spin polarization could be transferred to nuclear spins (such a method can be worked out whenever EPR lines are relatively sharp it is presently known as DNP for Dynamic Nuclear Polarization). This effect is usually quantified by the so-called nOe factor p... 

The basis for the determination of solution conformation from NMR data lies in the determination of cross relaxation rates between pairs of protons from cross peak intensities in two-dimensional nuclear Overhauser effect (NOE) experiments. In the event that pairs of protons may be assumed to be rigidly fixed in an isotopically tumbling sphere, a simple inverse sixth power relationship between interproton distances and cross relaxation rates permits the accurate determination of distances. Determination of a sufficient number of interproton distance constraints can lead to the unambiguous determination of solution conformation, as illustrated in the early work of Kuntz, et al. (25). While distance geometry algorithms remain the basis of much structural work done today (1-4), other approaches exist. For instance, those we intend to apply here represent NMR constraints as pseudoenergies for use in molecular dynamics or molecular mechanics programs (5-9). 

The pulse sequence shown in Fig. 10.4 is sometimes used to study exchange, but more than 99% of the use of this sequence is to study the effect of dipolar cross relaxation via the NOE. As a result, this type of study is given the name nuclear Overhauser effect spectroscopy, NOESY, and the pulse sequence of Fig. 10.4... 

Under continuous uv irradiation, the observed steady-state polarization (whether by cw or by FT spectrometers) may be substantially modified by various nuclear relaxation processes. For example, Closs and Czeropski (35,36) have demonstrated that CIDNP can be transferred from a group of polarized nuclei to another group not originally polarized. Both the dipolar and the scalar relaxation mechanisms (of the nuclear Overhauser effects) can be operative. The extremely interesting case of intramolecular dipolar nuclear cross relaxation reported by Closs and Czeropski (35) involves the thermal reaction of... 

A slightly more complicated case of nuclear Overhauser effect was recently observed in our laboratory in the photoreduction of furil. Furil is considered as a weakly coupled AMX three-proton spin system and the dipolar cross relaxation involves the interplay of all three spins. The experiments were done in a light-modulation mode with a FT spectrometer and a detailed theoretical analysis of the experimental data will allow the evaluation of the various different cross-relaxation rates (138). ... 

Most of protein structural information from NMR is obtained in the form of nuclear Overhauser effects or NOEs between pairs of protons that are less than 6 A apart through space. An NOE between a spin pair carries distance information, but only short distances are observed because NOEs have an inverse sixth power dependence on distance. However, the distance cannot be uniquely determined given a measured NOE intensity without making some assumption about the environment of the spin pair and the motion of the vector between them. The simplest model for obtaining a distance from cross peak intensities in a nuclear Overhauser effect spectrum (NOESY) is the isolated ri d spin pair (RRNN - rigid rotor nearest neither) approximation (Jardetzky and Roberts, 1981). In this approximation the observed cross peak intensity, which is proportional to the cross relaxation rate, is related to a sini e intemudear distance, r. 

The NOESY (Nuclear Overhauser Effect SpectrocopY) spectrum is recorded using the same basic sequence. The only difference is that during the mixing time the cross-relaxation is responsible for the exchange of magnetization between different spins. Thus, a cross-peak indicates that two spins are experiencing mutual cross-relaxation and hence are close in space. 

Plainly, there will be no such effect unless relaxation pathways. It will be seen later on that such pathways are only present when there is dipolar relaxation between the two spins and that the resulting cross-relaxation rate constants have a strong dependence on the distance between the two spins. The observation of a nuclear Overhauser effect is therefore diagnostic of dipolar relaxation and hence the proximity of pairs of spins. The effect is of enormous value, therefore, in structure determination by NMR. 

Nuclear Overhauser effect (NOE), the transfer of spin polarization from one spin population to another by cross-relaxation in nuclear magnetic resonance spectroscopy. The NOE in, e.g., NOESY spectra can be used to derive distance information between two nuclei in a molecule and, hence, serves as a tool for structure elucidation. 

Ferrage F, Cowbum D, Ghose R (2009) Accurate sampling of high-frequency motions in proteins by steady-state (15)N- (1)H nuclear Overhauser effect measurements in the presence of cross-correlated relaxation. J Am Chem Soc 131 6048-6049... 

Two-dimensional nuclear Overhauser effect spectroscopy (NOESY) has proven to be a valuable technique in determining the conformations of large polypeptides and oligonucleotides. The slow motional regime in which such molecules lie (where wt> 1) causes the zero quantum transition to be extremely important in determining the rate of cross-relaxation. Crossrelaxation in the homonuclear case is described by the expression ... 

Proton, Proton Cross Relaxation the Nuclear Overhauser Effect (NOE)... 

The elucidation of the scalar coupling network by the correlation experiments is, apart from small molecules, not sufficient for the unambiguous, sequential and stereo-specific assignment. The complementary information of spatially adjacent protons is obtained via cross-relaxation experiments, the laboratory-frame nuclear Overhauser enhancement spectroscopy (NOESY) and the rotating-frame nuclear Overhauser effect spectroscopy (ROESY). These experiments provide also the distance restraints for the structure determination and help to recognize exchange processes. 

Dipolar Couplings and Distance Information. - The nuclear Overhauser effect (NOE) arises from dipolar interactions between magnetic moments associated with nuclear spins and it has become a powerful tool to extract relevant pieces of structural information about small molecules, as well as in molecules of biological interest. As a consequence, accurate NOE measurement is a very crucial issue. Walker et presented a comparison between direct and a new inverse HOESY experiment aimed at the detection of heteronuclear NOE between H and which is particularly well suited for symmetric compounds. It transpires that directly detected data are more suitable for quantitative assessment even if they suffer from lower sensitivity, whereas inverse detection is quite appropriate for a quick and quahtative assessment. In the latter experiment, unwanted cross-correlation effects may hide valuable NOE data (cross-relaxation), this drawback can be circumvented by a slight modification of the pulse sequence. 

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