Gd@C60[C(COOH)2]10 and Gd@C60(OH)x:: Nanoscale aggregation studies of two metallofullerene MRI contrast agents in aqueous solution

Derivatized water-soluble Gd-based metallofullerenes are excellent MRI contrast agents with unusually large proton relaxivities for agents with no direct Gd-OH2 bonding. In this study, dynamic light scattering (DLS), static light scattering (SLS), and transmission electron microscopy (TEM) have been used to characterize the propensity of two such species, Gd@C-60[C(COOH)(2)](10) and Gd@C-60(OH)(x), to aggregate in aqueous solution, since aggregation is known to enhance proton relaxivities of MRI contrast agents by increasing their rotational correlation times (via more slowly tumbling aggregates). The present aggregation study has been conducted as a function of concentration, temperature, and pH and has revealed that both compounds aggregate at pH = 9 to form spherical and irregular clusters having sizes between 30 and 90 nm, with little concentration or temperature dependency. Below pH = 9, the aggregate sizes increase steadily and dramatically, reaching hydrodynamic diameters of 600-1000 nm by pH = 5. Additionally, the intermolecular forces holding the aggregates together are weaker for Gd@C-60[C(COOH)(2)] than for Gd@C-60(OH)(x). We conclude that the tendency of these metallofullerene species to self-assemble into nanoscale aggregates in aqueous solution likely produces their unusually large, outer-sphere, pH-sensitive proton relaxivities.