RESUMO
The study of intermolecular collisions and bonding interactions in solutions is of critical importance in understanding and predicting solute/solvent properties. Previous work has established that stable paramagnetic nitroxide molecules are excellent probes of intermolecular interactions for hydrogen bonding in polar solvents. In this study, 1H, 2H, 13C, 15N NMR and liquid/liquid intermolecular transfer dynamic nuclear polarization (L2IT DNP) results are obtained for the paramagnetic probe molecule, TEMPO, interacting with the common aprotic and protic polar solvents, CH3CN and CH3CONH2, yielding a profile of both dipolar and scalar interactions. A significant scalar contact hyperfine is observed for the N-O...H-C interaction (13CH3 hyperfine, a/h=0.66 MHz) in the CH3CN/TEMPO system, whereas the N-O...H-C and N-O...H-N interactions for the TEMPO/CH3CONH2 system yield 13CH3 and 15N hyperfine couplings of a/h=0.16 and -0.50 MHz, respectively. The distance and attitude of the scalar interaction for the nitroxide hydrogen bonding at the methyl group in CH3CN and the amino group in CH3CONH2 are computed using density functional theory (DFT), yielding good agreement with the experimental results. These results show that the hyperfine coupling provides a sensitive probe of weak hydrogen-bonding interactions in solution.
RESUMO
PURPOSE: To evaluate the effectiveness of a functionalized trimetallic nitride endohedral metallofullerene nanoparticle as a magnetic resonance (MR) imaging proton relaxation agent and to follow its distribution for in vitro agarose gel infusions and in vivo infusions in rat brain. MATERIALS AND METHODS: The animal study was approved by the animal care and use committee. Gd(3)N@C(80) was functionalized with poly(ethylene glycol) units, and the carbon cage was hydroxylated to provide improved water solubility and biodistribution. Relaxation rate measurements (R1 = 1/T1 and R2 = 1/T2) of water solutions of this contrast agent were conducted at 0.35-, 2.4-, and 9.4-T MR imaging. Images of contrast agent distributions were produced following infusions in six agarose gel samples at 2.4 T and from direct brain infusions into normal and tumor-bearing rat brain at 2.4 T. The relaxivity of a control functionalized lutetium agent, Lu(3)N@C(80), was also determined. RESULTS: Water hydrogen MR imaging relaxivity (r1) for this metallofullerene nanoparticle was markedly higher than that for commercial agents (eg, gadodiamide); r1 values of 102, 143, and 32 L . mmol(-1) . sec(-1) were measured at 0.35, 2.4, and 9.4 T, respectively. In studies of in vitro agarose gel infusion, the use of functionalized Gd(3)N@C(80) at concentrations an order of magnitude lower resulted in equivalent visualization in comparison with commercial agents. Comparable contrast enhancement was obtained with direct infusions of 0.013 mmol/L of Gd(3)N@C(80) and 0.50 mmol/L of gadodiamide in live normal rat brain. Elapsed-time studies demonstrated lower diffusion rates for Gd(3)N@C(80) relative to gadodiamide in live normal rat brain tissue. Functionalized metallofullerenes directly infused into a tumor-bearing brain provided an improved tumor delineation in comparison with the intravenously injected conventional Gd(3+) chelate. A control lutetium functionalized Lu(3)N@C(80) nanoparticle exhibited very low MR imaging relaxivity. CONCLUSION: The new functionalized trimetallic nitride endohedral metallofullerene species Gd(3)N@C(80)[DiPEG5000(OH)(x)] is an effective proton relaxation agent, as demonstrated with in vitro relaxivity and MR imaging studies, in infusion experiments with agarose gel and in vivo rat brain studies simulating clinical conditions of direct intraparenchymal drug delivery for the treatment of brain tumors.
