Transfer of magnetization

The transfer of magnetization from the proton spins to the carbon spins occurs now when the Hartmann-Hahn condition, Eq. (2), is fulfilled. 

The process of spin-lattice relaxation involves the transfer of magnetization between the magnetic nuclei (spins) and their environment (the lattice). The rate at which this transfer of energy occurs is the spin-lattice relaxation-rate (/ , in s ). The inverse of this quantity is the spin-lattice relaxation-time (Ti, in s), which is the experimentally determinable parameter. In principle, this energy interchange can be mediated by several different mechanisms, including dipole-dipole interactions, chemical-shift anisotropy, and spin-rotation interactions. For protons, as will be seen later, the dominant relaxation-mechanism for energy transfer is usually the intramolecular dipole-dipole interaction. 

Many subspectral editing techniques alternative to DEPT, such as SEMUT (Subspectral Editing using a Multiple Quantum Trap) (Bildsoe et al., 1983) and SEMUT GL, have been developed that utilize the fact that the transfer of magnetization to unobservable multiple-quantum coherence for CH, CHj, and CH spin systems is dependent on the last flip angle 0. However, these experiments have not been widely used. 

Both homonuclear and heteronuclear versions of relayed nOe experiments are known. The homonuclear relayed NOESY experiment involves both an incoherent transfer of magnetization between two spins H and H/ that are not coupled but close in space, and a coherent transfer of magnetization between two spins H(and H that are /-coupled together. The magnetization pathway may be depicted as... 

Oil and 0)2, and (b) 2D shift-correlation spectra, involving either coherent transfer of magnetization [e.g., COSY (Aue et al, 1976), hetero-COSY (Maudsley and Ernst, 1977), relayed COSY (Eich et al, 1982), TOCSY (Braunschweiler and Ernst, 1983), 2D multiple-quantum spectra (Braun-schweiler et al, 1983), etc.] or incoherent transfer of magnedzation (Kumar et al, 1980 Machura and Ernst, 1980 Bothner-By et al, 1984) [e.g., 2D crossrelaxation experiments, such as NOESY, ROESY, 2D chemical-exchange spectroscopy (EXSY) (Jeener et al, 1979 Meier and Ernst, 1979), and 2D spin-diffusion spectroscopy (Caravatti et al, 1985) ]. 

F ure 6.5 (a) Schematic representation of a 3D spectrum of a linear spin syv tern ABC with identical mixing processes Mi and M2. In a linear spin system, the transfer of magnetization between A and C is forbidden for both Mi and M2, (b) Schematic representation of a 3D spectrum of a linear spin system ABC, where transfer via Mi is possible only between A and B and transfer via M2 occurs only between B and C. (Reprinted from J. Mag. Reson. 84, C. Griesinger, et al., 14, copyright (1989), with permission from Academic Press, Inc.)... 

A 90° Gaussian pulse is employed as an excitation pulse. In the case of a simple AX spin system, the delay t between the first, soft 90° excitation pulse and the final, hard 90° detection pulse is adjusted to correspond to the coupling constant JJ x (Fig- 7.2). If the excitation frequency corresponds to the chemical shift frequency of nucleus A, then the doublet of nucleus A will disappear and the total transfer of magnetization to nucleus X will produce an antiphase doublet (Fig. 7.3). The antiphase structure of the multiplets can be removed by employing a refocused ID COSY experiment (Hore, 1983). 

Figure 7.3 One-dimensional COSYspectram for an AX system, (a) A common ID sjjectrum. (b) Selective excitation of spin A leads to a ID COSY spectrum with antiphase X lines and maximum transfer of magnetization from A to X. (Reprinted from Mag. Reson. Chem. 29, H. Kessler et at, 527, copyright (1991), with permission from John Wiley and Sons Limited, Baffins Lane, Chichester, Sussex P019 lUD, England.)...

Fig. 9.1 The internuclear transfer of magnetization via NOE cross-relaxation in an isolated spin-pair. (A) Build-up curves for the cross-peak intensity in a 2D NOESY experiment for various internuclear distances r. The dashed line indicates a typical mixing time tm = 300rns used for drug-like molecules.

The first such experiment (Fig. 21a), introduced independently by Gan [258] and Bodenhausen et al. [259], used 13C as the so-called spy nuclei in a 2D experiment similar to the HMQC scheme used in solution NMR [260], The transfer of magnetization occurred by a combination of weak ]JCN (through-bond) couplings and second-order quadrupolar-dipolar (through-space) cross-terms between 14N and 13C, which contain the isotropic and anisotropic terms l = 0, 2, and 4 and are referred to as residual dipolar splittings (RDS) [261-263], Under MAS, the 1 = 0 term results in isotropic coupling, which for NH3 groups is expected to be... 

The concept of cross-polarization as applied to solid state NMR was implemented by Pines et al. [20]. A basic description of the technique is the enhancement of the magnetization of the rare spin system by transfer of magnetization from the abundant spin system. Typically, the rare spin system is classified as 13C nuclei and the abundant system as H spins. This is especially the case for pharmaceutical solids and the remaining discussion of cross-polarization focuses on these two spin systems only. 

As mentioned above, 2D-NMR (or more generally multidimensional NMR) is based on the transfer of magnetization during the evolution/mixing period. 

The transfer of magnetization is not restricted to protons as in the H- H COSY experiment, but can also be applied between other nuclei (i.e., H-13C-correlation or 31P-31P correlation experiments). 

Fig. 10.22. Diagram showing the cross-polarization from protons, H, to a heteronucleus, X, such as carbons. Heteronuclear dipolar coupling enables the transfer of magnetization from H to X, such as protons to carbons. Homonuclear dipolar coupling between the abundant protons enables the redistribution of proton spin energy through spin diffusion.

Fig. 16.2 A simplified scheme of the trNOE concept. The ligand L in the free state has negligible cross-relaxation between protons Hi and H2 because of its rapid tumbling motion. Upon binding to the much slower tumbling protein 7 becomes effective and leads to a transfer of magnetization from Hn to H2. Because of the dynamic equilibrium the ligand is released back into solution where it is still in the magnetization state corresponding to the bound form. The same concept is also applicable to trCCR and trRDC (see Sects. 16.4 and 16.5).

Fig. 16. ID COSY-NOESY experiment on the polysaccharide 6 [77]. The structure of a terminal 3,6-dideoxy-4-C-(l-hydroxyethyl)-D-xylohexose is shown in the inset. The COSY transfer is depicted using the solid line, while a dotted line is used for the NOESY transfer, (a) H spectrum of 6 at 600 MHz and 50°C. (b) ID COSY-NOESY spectrum acquired using the sequence of fig. 13(c) with the initial transfer of magnetization from H-8 and the following parameters = 100 ms, to = 29 ms, Tr = 32 ms, A = 0.5 ms, N = 0, 1,...,64,...

In all CSSF experiments filtration was performed immediately after the COSY step. Should there not be a sufficient chemical shift separation between H-2 protons, the magnetization could be further transferred along the spin system and filtered during one of the later spin-echoes. We note that such extensive transfer of magnetization can bring some signal attenuation due to the relaxation losses and a compromise setting of spin-echo intervals. 

For a spin-1/2 nucleus, such as carbon-13, the relaxation is often dominated by the dipole-dipole interaction with directly bonded proton(s). As mentioned in the theory section, the longitudinal relaxation in such a system deviates in general from the simple description based on Bloch equations. The complication - the transfer of magnetization from one spin to another - is usually referred to as cross-relaxation. The cross-relaxation process is conveniently described within the framework of the extended Solomon equations. If cross-correlation effects can be neglected or suitably eliminated, the longitudinal dipole-dipole relaxation of two coupled spins, such... 

A variety of inverse experiments which require a time delay for transfer of magnetization between H and " Cd spins, such as H-i Cd HMQC, " Cd-edited H- H COSY or H-" Cd hetero-TOCSY experiments and 2D H- N HMQC without Cd excitation pulses, are applied for successful identification of histidines coordinated to Cd(II) metal . The latter technique provides geometrical information for the metal coordination sphere through the determination of 7H-cd and 7n-Cc1 for " Cd-bound imidazole rings . 

From the functional form of Eq. (4.30) it is easy to predict the behavior of saturation transfer as a function of the exchange rate. When the rate constant for the B - A transformation (k i) is much smaller than the longitudinal relaxation rate of the nucleus in the B site (Rf), the saturation transfer tends to zero. When the rate constant is much higher, the saturation transfer tends to —1, i.e. there is a total transfer of magnetization to the B site when the A site is kept saturated. Note that these conditions are referred to as fast exchange, even if the exchange is still slow with respect to the chemical shift separation. Fast exchange conditions on the... 

Indeed, paramagnetic broadening is proportional to the square of the nuclear magnetogyric ratio y. Therefore, the inverse detection of heteronucleus (i.e. the transfer of magnetization from the X nucleus to the proton followed by proton detection) may prevent the observation of X signal because of proton 72 relaxation. In fact, the relative values of y for H, 13C and, 5N nuclei are 1 1/4 1/10, and thus the relative contribution to overall relaxation arising from the hyperfine interaction is 1 1/16 1/100, respectively. Therefore, to identify... 

Eq. (VII. 12) is the starting point to derive not only the equations relevant for the NOE phenomenon (Chapter 7) but also Eq. (3.15) and the following ones (Section 3.4). A somewhat different form of Eq. (VII. 12) has already been encountered when dealing with transfer of magnetization between two sites in chemical exchange (Section 4.3.4). 

---