Molecular Dynamics of Ion−Chelate Complexes Attached to Dendrimers

Abstract

We studied the molecular dynamics of vanadyl−chelate complexes covalently attached to the surface of cascade polymers, dendrimers. The rotational correlation times of the ion−chelate complex were determined from computer simulations of their EPR spectra. The chelate 2-(4-isothiocyanatobenzyl)-6-methyldiethylenetriaminepentaacetic acid was covalently attached to ammonia core poly(amidoamine) (PAMAM) cascade polymers via a thiourea (TU) linkage, resulting in PAMAM−TU−DTPA cascade polymers. X-band EPR spectra of their vanadyl complexes were taken, and the A and g matrices were determined from the rigid limit spectra using the SIMPOW program. Spectra were fitted with modification of the slow-motional line-shape theory. Our results indicate that the rotational correlation times of the surface chelate increase with molecular weight and resemble those of “internal” segmental motions found in PAMAMs. For this macromolecular system, the rotational correlation times alone cannot account for differences in the relaxivity between high and moderate molecular weight species. These data are consistent with the hypothesis that the differences between linear-based and cascade polymer-based MRI contrast agents in the response of their relaxivity to molecular weight partially result from differing responses of their rotational correlation time to increases in molecular weight. A comparison of isotropic and anisotropic tumbling models indicates anisotropic tumbling of the ion−chelate complex at physiological temperatures, which is consistent with a model that incorporates segmental motions of the dendrimer side chains.