The Gadolinium(III)-Water Hydrogen Distance in MRI Contrast Agents

The ion-nuclear distance of Gd(III) to a coordinated water proton, rGd-H, is central to the understanding of the efficacy of gadolinium-based MRI contrast agents. The dipolar relaxation mechanism operative for contrast agents has a 1/r^6 dependence. Estimates in the literature for this distance span 0.8 (angstrom) (2.5-3.3 (angstrom)). This study describes a direct determination of rGd-H using the anisotropic hyperfine constant T determined from pulsed ENDOR spectra. Five Gd(III) complexes were examined: [Gd(H2O)8]^3+, [Gd(DTPA)(H2O)]^2-, [Gd(BOPTA)(H2O)]^2-, MS-325, and [Gd(HPDO3A)(H2O)]. The distance, rGd-H, was the same within error for all five complexes: 3.1 (plus+minus) 0.1 (angstrom). These distance estimates should aid in the design of new contrast agents, and in the interpretation of other molecular factors influencing relaxivity.