Proton relaxation enhancement

Fig. 5.6. Water H NMRD profiles for a solution of methemoglobin ( ) and fluoro-methe-moglobin ( ) at 279 K. In the latter case, fast exchange is responsible for water proton relaxation enhancements which are quenched by slow exchange in the former case [12].

In the 9-coordinate TTHA complexes of the heavier Ln3+ ions, the situation is more complex, since there also the terminal N-atom bearing the uncoordinated acetate moiety is chiral. 170 NMR [49, 50], luminescence [47, 51] and NMRD measurements [46] have shown that, for both 9- and 10-coordinate Ln(TTHA)3 complexes, the inner coordination sphere of the metal ion is fully occupied by donating groups of the ligand, leaving no space for the coordination of water. Consequently, the water proton relaxation enhancement has no inner sphere contribution and the [Gd(TTHA)]3 complex is not very suitable for application... 

Nicollai, N., Rossi, C., Valensin, G., Mascagni, P., and Gibbons, W. A. (1984) An investigation of the mechanisms of nitroxide-induced proton relaxation enhancements in biopolymers. J. Phys. Chem. 88, 5689-5692. 

This modified CR is targeted for blood. This modified CR designated as MS-325 exploits the relaxivity, r, the coefficient which relates the H20 T to the concentration of CR in vitro. The r of free MS-325 is 6.6 (mM) 1 S-1 but the value increases to SOSO (mM) 1 S 1 when the CR is bound to albumin. This means that the CR is reversibly activated on binding to human serum albumin and is very much more effective in reducing H20 T value. Hence the detection is made easy at much lower levels. This effect, known as proton relaxation enhancement (or the receptor-induced magnetization enhancement), is due to the reduced rate of rotation of CR molecule bound to a macromolecule, and in this case, the rotation rate may be reduced by two orders of magnitude. 

The binding affinity (Kp,) (Equation 10.14) and relaxivity (rj) of the adducts that form between complexes and macromolecules can be measured by the proton relaxation enhancement (PRE) method [65, 66], PRE is based on the titration of complexes against the binding substrate of macromolecules, such as HSA. The binding of complexes to HSA influences the XR, Tm, Tie, and Tim of complexes. If a Gd complex (GdL) binds to HSA, then adducts form and r is usually higher than ri. 

Jenkins, B.G., Armstrong, E., and Lauffer, R.B. (1991) Site-specific water proton relaxation enhancement of iron(III) chelates noncovalently bound to human serum albumin. Magnetic Resonance in Medicine, 17, 164-178. 

Aime, S., Botta, M., Fasano, M., et al. (1996) Gd(III) complexes as contrast agents for magnetic resonance imaging a proton relaxation enhancement study of the interaction with human serum albumin. Journal of... 

Paramagnetic ion probes have been successfully used to study the binding characteristics and solution conformations of a number of biochemically important molecules. These include vitamin D, (533) penicillins, (534) and the antibiotics tetracycline, (535-537) vancomycin, (632) and bacitracin. (633) Antibodies and antibody fragments (immunoglobulins, IgG) have been studied by proton relaxation enhancement methods when lanthanide ions, particularly Gd(m), are bound to the proteins. (746-748). 

Proton relaxation enhancement by means of serum albumin and poly-lysine labeled with DTPA-Gd relaxivities as a function of molecular weight and conjugation efficiency. Magn. Reson. Imaging 10(6) 913-917... 

An interesting study of potential dendrimer-based MRI contrast agents, that was not based upon the proton relaxation enhancing properties of gadolinium, was carried out by Meijer and co-workers [46]. Proton relaxation studies were carried out on nitroxyl bearing PPI dendrimers (Figure 8.6) and revealed that as a result of an increased rotational correlation time, the dendrimer architecture conferred an enhanced proton relaxation on the nitroxyl moieties when compared to mononitroxyl species. 

Figure 8.6 The nitroxyl terminated dendrimer proton relaxation enhancement agent for potential use in MRI [46],...

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