MOLECULAR-DYNAMICS OF ION-CHELATE COMPLEXES ATTACHED TO DENDRIMERS

We studied the molecular dynamics of vanadyl-chelate complexes covalen tly attached to the surface of cascade polymers, dendrimers. The rotat ional correlation times of the ion-chelate complex were determined fro m computer simulations of their EPR spectra. The chelate anatobenzyl)- 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 matrice s were determined from the rigid limit spectra using the SIMPOW progra m. Spectra were fitted with modification of the slow-motional line-sha pe theory. Our results indicate that the rotational correlation times of the surface chelate increase with molecular weight and resemble tho se of ''internal'' segmental motions found in PAMAMs. For this macromo lecular 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 contra st agents in the response of their relaxivity to molecular weight part ially result from differing responses of their rotational correlation time to increases in molecular weight. A comparison of isotropic and a nisotropic tumbling models indicates anisotropic tumbling of the ion-c helate complex at physiological temperatures, which is consistent with a model that incorporates segmental motions of the dendrimer side cha ins.