E. Liepinsh, A. Jacobson, and G. Otting
Karolinska Institute, S-171 77 Stockholm, Sweden
The water relaxation rates in tissue are greatly enhanced by the interaction with biological macromolecules. The origin of the "magnetic coupling" between the water and the macromolecular phase is widely believed to arise from intermolecular NOEs with hydration water molecules with long residence times on the immobile surface. In contrast, we argue for a different model, where the magnetization transfer is primarily mediated by chemical exchange of protons from hydroxyl and amino groups bonded to the macromolecular phase. This view implies that contrast obtained in MR imaging depends more strongly on a chemical property of the tissue (number of hydroxyl and amino protons), than a structural property (hydration sites containing water molecules with long residence times).
To support the argument by an example, a DNA hydration study is presented using novel 2D NOE-NOESY and ROE-NOESY pulse sequences. The experiments detect a few hydration water molecules with residence times longer than 0.5 ns in the minor groove of AT base pairs by negative NOEs to adenine 2 protons and 1' sugar protons. Most of the hydration water molecules, however, exchange more rapidly as evidenced by positive NOEs. The integrated intensity of the positive NOEs is larger than that of the negative NOEs. Chemical exchange between the water and labile protons of the DNA is detected by the same experiments. More magnetization is transferred between the water and the DNA by the chemical exchange of imino and amino protons than by the hydration water molecules.
In addition, the proton exchange rates from amino acid side chains were measured as a function of temperature, pH and the presence of different proton exchange catalysts. The results indicate that hydroxyl and amino protons exchange sufficiently rapidly under physiological conditions that the overall magnetization transfer between the macromolecular phase and the water is rate limited by the NOE between the OH and NH groups and the non-labile protons of the macromolecular phase rather than by thechemical exchange.
The proton exchange hypothesis explains the experimentally observed increased water relaxation rates in white over grey matter in brain by the different lipid composition with more hydroxyl and amino group containing lipids in white matter.