Effects of nitroxides on the magnetic field and temperature dependence of 1/T1 of solvent water protons.

We report a study of the longitudinal NMRD profiles (proton longitudinal relaxation rates as a function of field strength) over a broad range of magnetic field (0.01 to 50 MHz proton Larmor frequency) and temperature (-9.6 to 37 degrees C) for aqueous solutions of (i) a fatty acid-nitroxide/albumin complex and (ii) 10 low molecular weight nitroxides. Analysis of the NMRD profile for the fatty acid-nitroxide/albumin complex provides a lower bound estimate for the rotational correlation time of the complex, which permits the calculation of an upper bound on the inner sphere contribution to relaxation of the uncomplexed nitroxides. Inner sphere processes, ostensibly due to water molecules hydrogen bonded to the nitroxide moiety, dominate the relaxation effects of the slowly rotating macromolecular nitroxide/albumin complex. By extrapolation, the contribution of these inner sphere processes are negligible for rapidly tumbling nitroxides free in solution, which affect solvent proton relaxation almost entirely through outer sphere processes (i.e., translational diffusion). A comparison of the relaxation data for aqueous solutions of the uncomplexed nitroxides with the theory of outer sphere relaxation of J.H. Freed (J. Chem. Phys. 68, 4034 (1978] yields values for the distance of closest approach of the water and nitroxide molecules, as well as for their relative diffusion constants, at five different temperatures. Our results indicate that the rather modest relaxivities of aqueous solutions of nitroxides increase substantially with increased solvent viscosity and with protein binding, supporting the potential utility of nitroxides for enhancement of contrast in nuclear magnetic resonance images.