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

Abstract

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.

Nitroxide TEMPO: A genotoxic and oxidative stress inducer in cultured cells

“…Nitroxides have a reducible nitroxide group ( · N-O) as part of a five-or six-carbon ring (Soule et al, 2007;Wilcox and Pearlman, 2008). Piperidine nitroxides are a diverse group of stable free radicals classically used as spin probes in electron paramagnetic resonance spectroscopy (Matsumoto et al, 2004), as paramagnetic contrast agents in nuclear magnetic resonance imaging (Bennett et al, 1987), and as oxygen-sensitive probes in biological systems (Strzalka et al, 1990). TEMPO (2,2,6,C 9 H 18 NO,MW 156.25), one of the most commonly used members of the nitroxide family, is a stable nitroxyl radical that has a variety of uses related to its role as radical scavenger and stabilizer.…”

Cholesterol enhances surface water diffusion of phospholipid bilayers

“…5-7, 61, 64-70 In order to quantify the τ value from ξ , the appropriate model governing the dynamic parameters of the solvent molecules interacting with the spin labels has to be applied. For nitroxide radicals free in water, as well as nitroxide radicals tethered on the surface of liposomes, the force-free hardsphere model 71 has been shown to give a good fit to field cycling relaxometry data [72][73][74][75] and can be used to model the spectral density function. This method becomes especially convenient, when translation diffusion is the dominant modulator of the electron spin-mediated nuclear spin relaxation that is driven via dipolar coupling between the electron and 1 H nuclear spins.…”

A numerical prediction of spin-lattice relaxation enhancement of water protons by paramagnetic metal ions and free radicals. A contribution to the basic principles of relaxometry in MRI

“…The relaxation enhancement of protons by paramagnetic metal ions [7,11,14,23,[33][34][35][37][38][39] and nitroxyl (aminoxyl) radicals [15,36,41] was theoritized to be caused by dipole-dipole interactions involving fluctuating magnetic fields of unpalred electrons of the paramagnetic metal ions, and the fluctuating magnetic fields of water protons in a stationary magnetic field. The fluctuations were believed to originate from Brownian motions of the interacting species possessing a magnetic moment.…”

“…with organic species possessing one or more [15,[18][19]21,24,28,29] odd electrons, although the detailed relaxation mechanisms induced by radicals and metal ions may not be identical. The va¡ factors to be considered in the longitudinal relaxation phenomena of water proton can be pictorially presented (Fig.1), and were, in part, mathematically expressed by Solomon and Bloembergen in their equation, and by other equations [23,[36][37][38][39][40][41]. The combined Solomon-Bloembergen equations ate almost never presented in literature in their original form.…”

“…All these equations are not amenable to rapid numerical assessments of the relaxation of water. More suitable for this purpose are several shorter equations which have been published over the years, notably by Bloembergen, PurceU and Pound [33], Pople, Schneider and Bernstein [38], Abragam [39], Wehrli [40], and Bennett, Brown, Koenig and Swartz [41]. However, although these equations are all similar to that of BPP equation, they differ from each other somewhat.…”