Understanding Paramagnetic Relaxation Phenomena for Water-Soluble Gadofullerenes

• Published in: Journal of physical chemistry. C 2007-04, Vol.111 (15), p.5633-5639
• Main Authors: Laus, Sabrina, Sitharaman, Balaji, Tóth, Éva, Bolskar, Robert D, Helm, Lothar, Wilson, Lon J, Merbach, André E
• Format: Article
• Language: English
• ISSN: 1932-7447; 1932-7455
• DOI: 10.1021/jp070458o

Water-soluble, endohedral gadofullerenes exhibit considerably higher relaxivities than clinically used Gd3+-chelates and are currently explored as potential magnetic resonance imaging (MRI) contrast agents. The relaxivities of Gd@C60(OH) x (x ≈ 27) and Gd@C60[C(COOH y Na1- y )2]10 were previously found to vary with pH because of pH-dependent aggregation. By relaxometric measurements, we proved that aggregation can be suppressed by salt addition (75−100 equiv of sodium phosphate). In the aim of better understanding paramagnetic relaxation mechanisms in water-soluble gadofullerenes, we recorded variable-temperature and multiple-field 17O and 1H relaxation rates for Gd@C60(OH) x and Gd@C60[C(COOH y Na1- y )2]10 in both aggregated and disaggregated state (monomers). In the aggregated solutions, the 17O T 1 and T 2 values are very different. This proves the confinement of water molecules in the interstices of the aggregates which is more important for the OH than for the malonate derivative. The rapid exchange of these water molecules with bulk contributes to the high relaxivity of the aggregated gadofullerenes. After disruption of the aggregates into distinct gadofullerene molecules, the temperature-dependent proton relaxivities could be described as the sum of an outer-sphere and an inner-sphere-like mechanism. The inner-sphere-like term originates from proton exchange between the bulk and protonated OH or COOH sites. The relaxivity peak observed between 10 and 300 MHz in the nuclear magnetic relaxation dispersion (NMRD) profile evidences that the malonate groups are at least partially protonated at pH 7.4. The rotational correlation times are long (∼1.2 ns) and identical for the two gadofullerenes. The larger relaxivity of Gd@C60(OH) x as compared to Gd@ C60[C(COOH x Na1- x )2]10 at frequencies above 20 MHz is related to the larger number of protonated sites.