The magnetic field dependence of the nuclear spin-lattice relaxation rate constant provides the Magnetic Relaxation Dispersion profile (MRD). The MRD contains most of the dynamical information that is available from a nuclear magnetic resonance experiment because it maps spectral power densities as a function of Larmor frequency over very wide ranges. The spectral densities report intra and intermolecular motions that modulate magnetic couplings. We have constructed MRD spectrometers that overcome the low sensitivity and low resolution usually associated with current switched instruments by utilizing a magnet pair and pneumatically moving a sample between a polarization/detection field and a variable evolution field. The finite sample transit time limits the relaxation rates that may be measured making it difficult to measure nonlabile spins in macromolecules because the large low-field rates destroy magnetization during transit through low field regions. We solve this problem using an exchange dilution method employing a thermodynamically stable metal site with which an observed ligand exchanges rapidly. The diamagnetic metal site in combination with an electron magnetic moment may define a unique vector the fluctuations of which we map over the time range from 10 ms to 0.5 ps. We propose to apply this technology to the study of molecular dynamics in soluble proteins, membrane-bound proteins, and small molecule systems utilizing localization of spin pairs based on cysteine double mutants. We propose: to examine localized translational diffusion constants for small molecules in the immediate vicinity of membrane bound channel proteins; to characterize fluctuations of specific vectors in channel protein MscL initially utilizing an extensive mutant library; to characterize fluctuations within the soluble protein T4 lysozyme utilizing a considerable mutant library, to characterize the local dynamics and ordering of quadrupolar nuclear spin bearing molecules in semisolid or membrane-bound protein systems. We propose to develop a fringe-field probe that may be utilized in commercial NMR spectrometers. We propose experimental tests of the new theory that accounts well for the magnetic field dependence of spin-lattice rate constants in dynamically heterogeneous materials like tissues and examine the electron relaxation properties of metal ions in these systems to understand effects of targeting contrast agents in MRI to rotationally nonlabile sites.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
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Biophysical Chemistry Study Section (BBCB)
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Mclaughlin, Alan Charles
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University of Virginia
Schools of Arts and Sciences
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Diakova, Galina; Korb, Jean-Pierre; Bryant, Robert G (2012) The magnetic field dependence of water T1 in tissues. Magn Reson Med 68:272-7
Diakova, Galina; Goddard, Yanina; Korb, Jean-Pierre et al. (2011) Water-proton-spin-lattice-relaxation dispersion of paramagnetic protein solutions. J Magn Reson 208:195-203
Goddard, Yanina A; Korb, Jean-Pierre; Bryant, Robert G (2009) Water molecule contributions to proton spin-lattice relaxation in rotationally immobilized proteins. J Magn Reson 199:68-74
Grebenkov, Denis S; Goddard, Yanina A; Diakova, Galina et al. (2009) Dimensionality of diffusive exploration at the protein interface in solution. J Phys Chem B 113:13347-56
Bhowmik, Anshu; Ellena, Jeffrey F; Bryant, Robert G et al. (2008) Spin-diffusion couples proton relaxation rates for proteins in exchange with a membrane interface. J Magn Reson 194:283-8
Korb, Jean-Pierre; Diakova, Galina; Goddard, Yanina et al. (2007) Relaxation of protons by radicals in rotationally immobilized proteins. J Magn Reson 186:176-81
Diakova, Galina; Goddard, Yanina A; Korb, Jean-Pierre et al. (2007) Changes in protein structure and dynamics as a function of hydration from (1)H second moments. J Magn Reson 189:166-72