Strategies for the Controlled Covalent Double Functionalization of Graphene Oxide.

Graphene oxide (GO) is a versatile platform with unique properties that have found broad applications in the biomedical field. Double functionalization is a key aspect in the design of multifunctional GO with combined imaging, targeting, and therapeutic properties. Compared to noncovalent functionalization, covalent strategies lead to GO conjugates with a higher stability in biological fluids. However, only a few double covalent functionalization approaches have been developed so far. The complexity of GO makes the derivatization of the oxygenated groups difficult to control. The combination of a nucleophilic epoxide ring opening with the derivatization of the hydroxyl groups through esterification or Williamson reaction was investigated. The conditions were selective and mild, thus preserving the structure of GO. Our strategy of double functionalization holds great potential for different applications in which the derivatization of GO with different molecules is needed, especially in the biomedical field.