Ting Cai

High Relaxivity Trimetallic Nitride (Gd3N) Metallofullerene MRI Contrast Agents with Optimized Functionality

Water-soluble poly(ethylene glycol) (PEG) functionalized and hydroxylated endohedral trimetallic nitride metallofullerene derivatives, Gd(3)N@C(80)[DiPEG(OH)(x)], have been synthesized and characterized. The (1)H MRI relaxivities in aqueous solution were measured for the derivatives with four different molecular weights of PEG (350-5000 Da) at 0.35, 2.4, and 9.4 T. The 350/750 Da PEG derivatives have the highest relaxivities among the derivatives, 237/232 mM(-1) s(-1) for r(1) and 460/398 mM(-1) s(-1) for r(2) (79/77 mM(-1) s(-1) and 153/133 mM(-1) s(-1) based on Gd(3+) ion), respectively, at a clinical-range magnetic field of 2.4 T. These represent some of the highest relaxivities reported for commercial or investigational MRI contrast agents. Dynamic light scattering results confirm a larger average size for 350/750 Da PEGs derivatives (95/96 nm) relative to longer chain length derivatives, 5000 Da PEG derivatives (37 nm). Direct infusion of the optimized 350 Da PEG derivatives into live tumor-bearing rat brains demonstrated an initial uniform distribution, and hence, the potential for effective brachytherapy applications when the encapsulated Gd(3+) ions are replaced with radioactive (177)Lu.

Selective Formation of a Symmetric Sc3N@C78 Bisadduct: Adduct Docking Controlled by an Internal Trimetallic Nitride Cluster

In this paper we report a regioselective Bingel−Hirsch reaction of Sc3N@C78 yielding a single mono- and a dominate bis-ethyl malonate derivative for the first time. The Cs-symmetric monoadduct 1 and C2v-symmetric bisadduct 2 were isolated by HPLC and characterized by MS, UV−vis, and NMR spectroscopy. The symmetric bisadduct 2 clearly demonstrate the remarkable regioselectivity control exerted by the encapsulated Sc3N cluster. We have employed a LUMO electron density surface computational approach to predict multiadduct docking sites on the ellipsoidal fullerene cage surface.

Highly Regioselective Derivatization of Trimetallic Nitride Templated Endohedral Metallofullerenes via a Facile Photochemical Reaction

Photochemically generated benzyl radicals react with Sc(3)N@C(80)-I(h) to produce a dibenzyl adduct [Sc(3)N@C(80)(CH(2)C(6)H(5))(2)] in 82% yield and high regioselectivity. The adducts (1)H spectrum revealed high symmetry: only one AB pattern was observed for the methylene protons. The (13)C NMR spectrum suggested a C(2)-symmetrical structure. DFT calculations reveal that a 1,4-adduct is more favorable than a 1,2-adduct by >10 kcal/mol. The 1,4-structure on [566] ring junctions was unambiguously confirmed by X-ray crystallographic analysis. UV-vis spectra revealed that the removal of two p orbitals from the pi system of the cage together with the benzylic substituents change the electronic properties of the metallofullerene in a manner similar to those reported for disilirane and trifluoromethyl moieties. Under the same conditions from Lu(3)N@C(80)-I(h) we prepared (63% yield) Lu(3)N@C(80)(CH(2)C(6)H(5))(2), which demonstrated properties similar to the 1,4-dibenzyl adduct of Sc(3)N@C(80)-I(h).

Synthesis and characterization of the first trimetallic nitride templated pyrrolidino endohedral metallofullerenes

New pyrrolidino derivatives of both diamagnetic and paramagnetic trimetallic nitride templated endohedral metallofullerenes were synthesized by the Prato reaction, isolated and characterized by means of MALDI-TOF MS, NMR and UV-vis spectroscopies.