Nuclear Overhauser effect mechanism

You can often use experimental data, such as Nuclear Overhauser Effect (NOE) signals from 2D NMR studies, as restraints. NOE signals give distances between pairs of hydrogens in a molecule. Use these distances to limit distances during a molecular mechanics geometry optimization or molecular dynamics calculation. Information on dihedral angles, deduced from NMR, can also limit a conformational search. 

Nuclear Overhauser effect (nOe) The change in intensity in the signal of one nucleus when another nucleus lying spatially close to it is irradiated, with the two nuclei relaxing each other via the dipolar mechanism. Nuclear Overhauser effect correlation spectroscopy (NOESY) A 2D... 

The conformation of the mixed p agonist/5 antagonist H-Tyr-c[-D-Orn-2-Nal-D-Pro-Gly-] in comparison to that of H-Tyr-c[-D-Orn-Phe-D-Pro-Gly-] was studied in DMSO-d6 by NMR spectroscopy and by molecular mechanics calculations [62,64]. Neither peptide showed nuclear Overhauser effects between C H protons or chemical exchange cross peaks in spectra obtained by total correlation and rotating frame Overhauser enhance-... 

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. 

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). 

In solution, dipole-dipole interactions constitute a relaxation mechanism, and the dipolar relaxation which is the basis for the well-known nuclear Overhauser effect (NOE), mostly used in the homonuclear H, H case. The 2D HOESY method between H and Li has been used to obtain structural information of many organolithium systems in solution and this field was reviewed in 1995. Li is commonly used as the relaxation is dominated by the dipole-dipole mechanism and the relaxation time is relatively long. Knowledge of the proximity of the lithium cation relative to protons in the substrate is used to derive information about the structure and aggregation of organolithium systems in solution. In a few cases quantitative investigations have been made °. An average error of the lithium position of ca 0.2 A was reported. 

Although one diastereomer 10 was largely favored, the product was obtained as a mixture of diastereomers, and the previously unreported minor diastereomer 11 was also characterized. The stereochemistry of the products was established by nuclear Overhauser effect (NOE) studies. A plausible mechanism assumes the intermediacy of an acetal, and its reaction with 2-methoxypropene generated from 2,2-dimethoxypropane [20]. In order to test this mechanism, the dimethyl acetal of salicylaldehyde was synthesized and reacted independently with both 2,2-dimethoxypropane and 2-methoxypropene. Indeed, both reactions gave the same products as those from the reaction of salicylaldehyde with 2,2-dimethoxypropane (Scheme 4). The condensation of salicylaldehyde and 2,2-dimethoxypropane was also carried out in CD3CN and reaction progress was followed by H NMR spectroscopy. This experiment also confirmed the formation of the acetal from salicylaldehyde (8 5.52, singlet, C//(OMe)2). 

Chemical shift correlated NMR experiments are the most valuable amongst the variety of high resolution NMR techniques designed to date. In the family of homonuclear techniques, four basic experiments are applied routinely to the structure elucidation of molecules of all sizes. The first two, COSY [1, 2] and TOCSY [3, 4], provide through bond connectivity information based on the coherent (J-couplings) transfer of polarization between spins. The other two, NOESY [5] and ROESY [6] reveal proximity of spins in space by making use of the incoherent polarization transfer (nuclear Overhauser effect, NOE). These two different polarization transfer mechanisms can be looked at as two complementary vehicles which allow us to move from one proton atom of a molecule to another proton atom this is the essence of a structure determination by the H NMR spectroscopy. 

Careful choice of solvent and dilution is particularly important for some samples. In general, the spectra of the sulfones show a marked solvent dependence. The line width is especially sensitive to the nature of the solvent. For example, the line widths for 5 mol dm solutions of sulfolane in acetone and water are 16 and 60 Hz, respectively. A shift difference of 6.5 ppm is observed between 5moldm solutions of sulfolane in water and dioxane. Table 50 shows how the chemical shift (quoted relative to that for neat sulfolane) and line width vary with concentration of sulfolane in acetone. No nuclear Overhauser effect is observed for sulfolane, which suggests that sulfur-hydrogen dipolar interactions are not significant as a relaxation mechanism. 

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... 

Polarization Transfers and Reaction Mechanisms. Polarization transfers include the previously mentioned electron-nuclear Over-hauser effect and the nuclear-nuclear Overhauser effect. In this section we will discuss only electron-electron polarization transfer via a secondary chemical reaction involving a primary polarized radical. Again we shall use the photoreduction of quinone (t-butyl-p-benzoquinone) as an example. In solvent containing isopropanol, reaction of triplet quinone by phenols leads to two structural isomers, radicals I and II ... 

Fattorusso and co-workers identified a component of wormwood called artar-borol. Correlation spectroscopy (COSY) and rotating frame nuclear overhauser effect spectroscopy (ROESY) experiments allowed for deduction of four possible diastereomeric structures of artarborol, 2-5. Low energy conformers of 11-14 were obtained through a molecular mechanics (MM) search. These conformers were screened to identify those having a dihedral angle of around 90 for the C-8 and C-9 protons due to a low coupling constant between these protons. Only conformers of 11 and 13 satisfied this criterion. Next, five low energy conformers, two... 

Dipole-dipole relaxation occurs when two nuclei are located close together and are moving at an appropriate relative rate (Section 5-1). Irradiation of one of these nuclei with a Bi field alters the Boltzmann population distribution of the other nucleus and therefore perturbs the inten.sity of its resonance. No J coupling need be present between the nuclei. The original phenomenon was discovered by Overhauser, but between nuclei and unpaired electrons. The nuclear Overhauser effect (when both spins are of nuclei) was observed first by Anet and Bourn and is of more interest to the chemist. It has great structural utility, because the dipole-dipole mechanism for relaxation depends on the distance between the two spins. (See eq. 5-1.)... 

In samples relaxing through nuclear-nuclear dipole-dipole mechanisms, another source of error in quantitative 13C-NMR is the nuclear Overhauser effect. This arises in double resonance experiments when one nucleus (in this case 1h) is irradiated to simplify the spectrum while another (in this case is observed. 

Nonspecific pa.r.r.s affect relaxation through an outer-sphere mechanism. This type of reagent is used primarily to shorten relaxation times and thus increase the speed of data acquisition, or to eliminate nuclear Overhauser effects (n.O.e.s) in order to allow quantitative analysis of data. Cr(acac)3 is... 

There is no straightforward and completely rigorous procedure for determining the relative combinations of the various relaxation mechanisms, except where one mechanism clearly dominates (e.g., if the maximum possible nuclear Overhauser effect (NOE) for a resonance is obtained, dipolar relaxation must dominate its relaxation or an increase in relaxation rate in proportion to the square of the applied field must be due to chemical shift anisotropy). Hence, the study of molecular motion in proteins from relaxation data is performed most readily on nuclei directly bonded to H, and so principally relaxed via dipole-dipole interactions (see Section 4(e)(iii)). 

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