Metal oxide nanoparticles, in particular magnetic metal oxides, have recently attracted a great deal of attention for their potential wide range of applications including use as cellular delivery carriers, 1 magnetic storage media, 2 and MRI contrast agents. 3a,b In many practical applications, nanoparticle cores must be provided with surface ligands which both prevent aggregation and also provide a handle that conveniently allows functionalization of the final periphery of the system. The harsh conditions generally required for nanoparticle preparation severely limit the use of functionalized ligands during the synthesis. As a result, a common method of functionalizing the nanoparticle surface involves stripping off nonfunctional ligands used for synthesis and then redispersing the particles with functionalized ligands.In this report we demonstrate a strategy for the synthesis of surface functionalized metal oxide nanoparticles through the design of versatile ligands whose structures include the following features: (1) a robust anchor that can bind generally to a variety of metal oxide surfaces, (2) tailored surface groups that act as spacers or branches from the metal oxide surface, and (3) a general method for covalently attaching a functional perimeter to the spacers through "click" chemistry. Ligands which possess the flexibility and synthetic generality of features 1-3 possess the characteristic of "universal" ligands which allow the construction of a broad range of functionalities for the periphery of nanoparticles with good yields and synthetic facility.The copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) has received broad attention because of its unique "click" nature: namely, the reaction proceeds with high yields and no byproducts and exhibits functional group orthogonality. 4a-e As a result, the CuAAC reaction has been employed in a variety of materials synthesis applications including functionalization of polymers and dendrimers, 5a-c polysaccharides, 6,7 DNA, 8 and a variety of bulk surfaces including gold 9 and silica, 10 as well as gold nanoparticle surfaces. 11 In the design of universal ligands which allow simple and efficient functionalization of nanoparticle-ligand complexes with a desired moeity, we found the CuAAC reaction to be ideal because of its click nature. Herein we demonstrate the potential effectiveness of CuAAC for the modification of γ-Fe 2 O 3 nanoparticles with a diverse array of functional species including small molecules and polymers.In the design of functional ligands for nanoparticle surfaces, one must consider both the binding properties as well as the stability of the ligand and, importantly, prevention of particle aggregation. It has been established that organo-phosphates as well as carboxylates bind strongly to the surface of metal oxides. 12a-g For our studies we chose ligands containing either a phosphonic acid group or a carboxylic acid group at one terminus, to serve as anchors which can bind strongly to the surface of the γ-Fe 2 O 3 , and either an azide o...