Precise structural control is critical for scientists to harness the optical, magnetic, chemical and biological properties of nanomaterials and nanomedicines. In nanoscience, precise bottom-up synthesis bridging the microscopic and macroscopic world is an ultimate goal. To this end, identifying precise building blocks and understanding how their functionalization are fundamental. Fullerenes and their close relatives, endohedral metallofullerenes (EMFs) reside at the boundary between inorganic and organic worlds, and between small-molecules and nanomaterials. They have defined molecular structures, and can be functionalized with robust C-C bonds. Our group focuses on the chemistry of these molecules, and the application of them as functional materials.

Research Area #1: Chemistry of fullerenes and EMFs.

As the fundamental component of our group, we work on new chemistry on fullerenes and metallofullerenes. We are especially interested in the aspects that are different from well-established “traditional” fullerene chemistry, including unusual regioselectivity, unusual reactivity, approaches to regioselectively synthesize multi-adducts, and new properties of the products.


Research Area #2: Fullerene as a core for precise “designer nanoparticles”.

A central theme in our work is to use the hexakisadduct of fullerene C60 as a modular scaffold to build biomedical imaging probes. Recent advancements in nanoparticles have yielded biomedical tools that excel in navigating the heterogeneous biological systems, microenvironments, and cellular barriers to achieve powerful probes, diagnostics, and therapeutics. However, conventional nanoparticles are inherently polydisperse and pose challenges in reproducibility, quantification and quality control required in biology and medicine. In our group, we develop systematic methodology to use fullerene hexakisadducts as a core to construct precise molecular nanoparticles with functional ligands by choice.

In Bingel-Hirsch reactions, each addition can bring a pair of ligands, so hexakisadduct would have 12 ligands, but the number can be increased by further branching. With different chemistry we can build them in different combinations (a “6+6” model is exemplified in the figure below). With the chemistry, we will use bottom-up design to develop new chemical probes to enable many biological studies, including FISH (fluorescence in-situ hybridization) imaging probes, ratiometric probes, single molecule Förster resonance energy transfer (smFRET) imaging probes, and therapeutic agents.

C60 as a core

Research Area #3: The metallobuckytrio (MBT).

EMFs provide an ideal template for lanthanide-based nanomedicine as the carbon cage is robust to confine the toxic metal ions but still reactive enough to allow functionalization. One perfect case in point is their application as MRI contrast agents. Current clinical contrast-enhanced MRI exams are using GBCAs based on chelating complexes, but the Gd3+ ions can escape from the chelates under complex conditions, causing significant safety concerns. EMFs can confine them in the cage which would definitively preclude the leak of Gd3+ ions.

The limitation for EMF based medicine, including Gd EMF based MRI contrast agents, is the lack of structurally defined water-soluble EMF derivatives. Current approaches introduce hydrophilic groups give a mixture of products with batch-to-batch variations and limited control over their metabolic behavior. We created a new platform that can systematic develop water-soluble EMFs with hydrophilic ligands by choice, dubbed the “metallobuckytrio” (MBT). They consist of three buckyballs, with a fullerene C60 core, 2 EMFs on the periphery, and 10 ligands to ensure water solubility and to introduce biological functions. We are actively exploring the how different ligands will affect the T1 relaxivity and their biological properties of Gd MBTs, and how to use the MBT system to develop new agents for photodynamic therapy.

Figure 1 just MBT