NOE effect

The nuclear Overhauser effect occurs when a proton, whose ratio of nuclei with spin +1/2 and –1/2 is altered (which is achieved with strong proton irradiation) interacts by dipole coupling with a neighboring proton, altering its ratio. of nuclei with spin +1/2 and –1/2 and thus changing the intensity of the absorption. The chemical shift is not altered. It is used to detect protons that are close to each other. It is very sensitive to distance because the dipole interaction depends on r ^-6 . The NOE effect only works at distances less than 5Å and the number of chemical bonds that separate the two protons does not matter.

Figure 1. Example NOE

1- Where does the NOE come from?

Consider two nuclei, I and S, that share a dipole (through-space) coupling. These dipolar couplings depend on the relative orientation of I and S. In solution, molecular flipping averages these couplings, so they do not appear in typical NMR spectra. However, magnetization can still be transferred between them.

Figure 2. lys represented.

Now if we consider the effect of perturbing the equilibrium populations of spin S in some way on the intensity of the spin I signal. The NOE is defined as:

For simplicity, suppose that I and S do not share a scalar coupling (J). The simplest NOE experiment is the steady state experiment. One selectively saturates spin S, and then applies a 90° pulse to observe the effect this has on the spin population at spin I:

Figure 3. Pulse in NMR schematized at 90

Remember that saturation means that the population of alpha and beta energy levels in the S spin equalizes. In this case, the amount of time the saturation is applied is the mixing time for the experiment; In a general sense, longer mixing times allow more time for magnetization transfer.

At equilibrium, the population differences between energy levels are determined by the Boltzmann distribution. Let's call difference the population difference for spin I: roughly speaking, the number of excess nuclei in the lower energy state. Because the chemical shifts are much smaller than the Larmor frequency, the increment is also the population difference for spin S (assuming, as we are here, that I and S are both protons).

For 4N nuclei, the energy diagram is:

NOE Example

For historical reasons a bit should be said about NOE difference experiments. The idea is to take pairs of scans, one where the selective presaturation is applied to the resonance and one where it is not. Presaturation is not just turned off in the control experiment to have conditions that are as similar as possible. The more non-NOE differences there are, the more noise. Off-resonance presaturation is typically applied at the edge of the spectrum.

 

Here are some spectra (top: NOE., Bottom: regular 1D):

In the above example, it appears that NOE was used to assign the 2,5-cis geometry in this five-membered ring. I don't know the details of this case, but in general, using NOEs to assign relative configuration in five-membered rings is dangerous since they are conformationally flexible.

As a result, the COZY and NOESY (and EXSY) pulse sequences are basically the same. In COZY, the transfer of magnetization through bonds is of interest; at NOESY, we are interested in the transfer of magnetization through space. HOST correlations arise from zero quantum coherence, which we will discuss in detail later in future blogs. These cannot be removed by gradients or phase cycling, but some special methods such as "z-filtering" have been developed to remove them. (I'll tell you about that later in another blog of this NMR content.) The point is that COZY crossovers are easy to identify because they have an "up-down" phase. They are particularly common when J is large; for example, between two transdiaxial protons in a cyclohexane.

 

Here is a NOESY spectrum without any zero quantum artifact removal:

Here, a sophisticated method called "swept frequency inversion" was used to remove anti-phase COZY signals:

 

ROESY wraiths are also not immune to artifacts. Instead of COZY widgets, they have TOCSY widgets. found that the "cross-ROESY" experiment, or t-ROESY, can get rid of most of these annoying TOCSY cross-peaks. The price is that there is some loss of sensitivity (none for small molecules, 2x for intermediate molecules, and 4x for very large molecules). It works by alternating the phase of the twist lock gear:

 

 

 

 References 

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