PubMed Health⌕ Search

Biomedical subjects

R L Belford

Publications and source records attributed to R L Belford.

9 recordsLinked to original sources
PubMed1999

Interaction of Gd(III) MRI contrast agents with membranes: a review of recent EPR studies.

Rational development of new selective paramagnetic contrast agents (PCAs) requires a detailed understanding of their interactions with biological macromolecules. This report shows how some of these interactions can be studied with electron paramagnetic resonance (EPR) through examples of Gd3+ complexes interactions with model phospholipid membranes. It is shown that the spin label EPR method can be used to detect: (i) presence and possible location of lipophilic contrast agents in the model membranes, (ii) changes and distortions in membrane organization upon interaction with the PCAs, and (iii) changes in the local polarity of the bilayer and its phase behavior due to addition of Gd3+ complexes. This work demonstrates that interaction of Gd3+ complexes with phospholipid bilayers can be observed directly from changes in their continuous wave (CW) EPR spectra obtained at frequencies higher than X-band (9.5 GHz), where signals arising from aqueous and lipid-bound Gd3+ complexes become resolved. Analysis of frequency dependence of the effective g-factors of the EPR signal provides estimates of zero-field splitting (ZFS) parameter for these complexes at physiological conditions and information on how this parameter is affected by interaction with lipids. Multifrequency EPR experiments at high magnetic fields are also useful in providing data on the frequency dispersion of electronic relaxation caused mainly by a modulation of the electron-electron dipolar interaction (ZFS) of these high spin ions.

Chelating Agents↗
PubMed1998

Molecular diffusion and DNP enhancement in aqueous char suspensions.

The heterogeneous 1H dynamic nuclear polarization (DNP) effect is studied at low magnetic fields for a system consisting of several newly synthesized carbon chars suspended in water. By using Fourier Transform pulsed-field-gradient spin-echo NMR spectroscopy, several different self-diffusion coefficients have been observed in aqueous char suspensions, corresponding to regions of differing water mobility in the porous structure. Proton spin-lattice relaxation data generally confirm the results of molecular diffusion measurements. Through utilization of the Torrey model, the influence of "cage effects" on DNP enhancement in porous media is discussed. Results suggest that short-range nuclear-electronic interactions in pores have a dominant effect on DNP enhancement in char suspensions.

Algorithms↗
PubMed1998

Electron paramagnetic resonance and dynamic nuclear polarization of char suspensions: surface science and oximetry.

Carbon chars have been synthesized in our laboratory from a variety of starting materials, by means of a highly controlled pyrolysis technique. These chars exhibit electron paramagnetic resonance (EPR) line shapes which change with the local oxygen concentration in a reproducible and stable fashion; they can be calibrated and used for oximetry. Biological stability and low toxicity make chars good sensors for in vivo measurements. Scalar and dipolar interactions of water protons at the surfaces of chars may be utilized to produce dynamic nuclear polarization (DNP) of the 1H nuclear spin population in conjunction with electron Zeeman pumping. Low-frequency EPR, DNP and DNP-enhanced MRI all show promise as oximetry methods when used with carbon chars.

Biophysical Phenomena↗
PubMed1997

Interaction of MRI gadolinium contrast agents with phospholipid bilayers as studied by 95 GHz EPR.

Interactions of two MRI gadolinium contrast agents, gadolinium ethoxybenzyl-diethylenetriaminepentaacetate (Gd-EOB-DTPA) and gadolinium N-pentyl-1,4,7,10-tetraazacyclododecane-N',N",N'"- triacetic acid (Gd-DOTA-P), with multibilayer phospholipid dispersions prepared from 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) have been investigated with high resolution EPR spectroscopy at 95 GHz. At a resonance field of 3.3 T, EPR spectra of a small nitroxide probe, 2,2,6,6-tetramethyl-1-piperidinyloxyl (Tempo), partitioned between aqueous and membrane phases are clearly resolved, making measurements of dynamics parameters of the probe accurate and unambiguous. Results show that although the presence of the more lipophilic contrast agent, Gd-DOTA-P, can be detected within the bilayer, the structural organization of the membrane remains unaffected even at physiologically high (5 mM) concentrations. The temperature of the main phase transition of the bilayer was also unaffected to within the 0.4 degree C accuracy of its determination.

Contrast Media↗
PubMed1996

EPR linewidth (T2) method to measure oxygen permeability of phospholipid bilayers and its use to study the effect of low ethanol concentrations.

It is well known that continuous-wave EPR spectra of nitroxide probes (labels) introduced into phospholipid bilayers are sensitive to molecular oxygen. However, accurate determination of oxygen broadening from these experiments is complicated by the complex shapes of EPR spectra, which are strongly influenced by anisotropic restricted motion of the probe molecules. An accurate method is presented to extract the oxygen broadening from the spectra measured with and without oxygen and at the same temperature. The method is based on a fast convolution algorithm with Levenberg-Marquardt optimization. This method was previously applied to EPR oximetry with nitroxides exhibiting rotational motion in the fast limit. It is shown that for several membrane spin probes, the oxygen broadening can be described as homogeneous; thus, a one-linewidth-parameter fitting model is appropriate. The method is applied to measure permeability profiles of model membranes composed from 1,2-dimyristoyl-sn-glycero-3-phosphocholine above and below the main phase transition. For both membrane phases, the broadening of doxyl- and sterol-type labels is found to be homogeneous, a finding consistent with the model of Heisenberg exchange between molecular oxygen and spin probes. As an example, the method is applied to study the ethanol effect on local oxygen permeability of a phospholipid bilayer. It is shown that ethanol concentrations as low as 1% (v/v) increase oxygen permeability of the bilayer. The effect is larger at the surface of the membrane than at its center, indicating that ethanol molecules interact primarily within the polar head region of the bilayer.

Cell Membrane Permeability↗
PubMed1995

Accuracy of oxygen measurements in T2 (line width) EPR oximetry.

EPR oximetry is used for in vivo and in vitro measurements of oxygen in biological systems, including experimental animals. The accuracy of oxygen measurements in T2 (line width) EPR oximetry is significantly improved if least-squares simulation is used to extract the line width parameters. The oxygen effect on the EPR spectra of nitroxide solutions and aqueous suspensions of fusinite can be described as an additional homogeneous broadening that modifies the EPR spectrum of the oxygen-free probe. This allows one to use a one-parameter line width model in most cases. The simulations were carried out with the use of a fast-convolution algorithm followed by Levenberg-Marquardt optimization. The validity of error estimates provided by this method was tested on sets of experimental spectra taken under common conditions. It is shown that the accuracy of oxygen measurements in line width (T2) oximetry is determined not only by the probe sensitivity (rate of line width change versus oxygen concentration), but also by the signal-to-noise ratio, inhomogeneous contribution to the line shape (e.g., unresolved proton superhyperfine structure), and the spectral window. The accuracy of oxygen measurements is compared for aqueous solutions of two nitroxide radicals with different superhyperfine structure and for aqueous suspensions of fusinite.

Carbon↗
PubMed1993

Solvate structures in water-methanol solutions of MRI contrast agents: electron spin echo envelope modulation in gadolinium chelates.

Electron Spin Echo Envelope Modulation (ESEEM) data are reported for three gadolinium (III) chelates, Gd-EDTA, Gd-DTPA, and Gd-TTHA, in frozen D2O/CH3OD glasses. This series includes Gd-DTPA, an MRI contrast agent that is in clinical use. Three-pulse electron spin echo modulation patterns can be modeled to yield geometrical information; e.g., distances and numbers of Gd+3-OD interactions. Interpreted by a spherical shell model, the data for Gd-TTHA are accounted for by Gd+3 surrounded by seven deuterons at an effective distance of 3.9 A. We attribute these deuterons to second-coordination sphere solvent molecules, since it is likely that Gd+3 is fully coordinated by a TTHA ligand. For analysis of ESEEM from Gd-EDTA and Gd-DTPA, the second-sphere structures of Gd-EDTA, Gd-DTPA, and Gd-TTHA are assumed equivalent. 2H-ESEEM from inner-sphere solvent molecules gives the effective distance between deuterons and Gd+3 to be approximately 2.7 A for the inner-sphere water in both EDTA and DTPA complexes. The results of simulations also give the isotropic hyperfine and quadrupole coupling constants for solvent deuterium in these systems. Possible sources of error in the determination of r and q by this method are discussed.

Chelating Agents↗
PubMed1972

Dynamics of fluorescence polarization in macromolecules.

Reexamination of the theory of fluorescence time dependence owing to rotational diffusion of rigid macromolecules reveals deficiencies or hidden restrictions in each of the previous treatments. The correct master equation has five exponential decay terms, with preexponential factors that depend upon the diffusion constants and, in a completely symmetrical fashion, upon the orientations of absorbing and emitting dipoles.

Diffusion↗