title: Quantitative measurement of ligand exchange on iron oxides via radiolabeled oleic acid.
abstract: Ligand exchange of hydrophilic molecules on the surface of hydrophobic iron oxide nanoparticles produced via thermal decomposition of chelated iron precursors is a common method for producing aqueous suspensions of particles for biomedical applications. Despite the wide use, relatively little is understood about the efficiency of ligand exchange on the surface of iron oxide nanoparticles and how much of the hydrophobic ligand is removed. To address this issue, we utilized a radiotracer technique to track the exchange of a radiolabeled (14)C-oleic acid ligand with hydrophilic ligands on the surface of magnetite nanoparticles. Iron oxide nanoparticles functionalized with (14)C-oleic acid were modified with poly(ethylene glycol) with terminal functional groups including, L-3,4-dihydroxyphenylalanine, a nitrated L-3,4-dihydroxyphenylalanine, carboxylic acid, a phosphonate, and an amine. Following ligand exchange, the nanoparticles and byproducts were analyzed using liquid scintillation counting and inductively coupled plasma mass spectroscopy. The labeled and unlabeled particles were further characterized by transmission electron microscopy and dynamic light scattering to determine particle size, hydrodynamic diameter, and zeta potential. The unlabeled particles were characterized via thermogravimetric analysis and vibrating sample magnetometry. Radioanalytical determination of the (14)C from (14)C-oleic acid was used to calculate the amount of oleic acid remaining on the surface of the particles after purification and ligand exchange. There was a significant loss of oleic acid on the surface of the particles after ligand exchange with amounts varying for the different functional binding groups on the poly(ethylene glycol). Nonetheless, all samples demonstrated some residual oleic acid associated with the particles. Quantification of the oleic acid remaining after ligand exchange reveals a binding hierarchy in which catechol derived anchor groups displace oleic acid on the surface of the nanoparticles better than the phosphonate, followed by the amine and carboxylic acid groups. Furthermore, the results show that these ligand exchange reactions do not necessarily occur to completion as is often assumed, thus leaving a residual amount of oleic acid on the surface of the particles. A thorough analysis of ligand exchange is required to develop nanoparticles that are suitable for their desired application.
authors.affiliation: Department of Materials Science and Engineering, ‡Center for Optical Materials Science and Engineering Technologies (COMSET), §Department of Chemical and Biomolecular Engineering, and ∥Department of Environmental Engineering and Earth Sciences, Clemson University , Clemson, South Carolina 29634, United States.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Davis
authors.forename: Bin
authors.initials: B
authors.lastname: Qi
authors.forename: Michael
authors.initials: M
authors.lastname: Witmer
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Kitchens
authors.forename: Brian A
authors.initials: BA
authors.lastname: Powell
authors.forename: O Thompson
authors.initials: OT
authors.lastname: Mefford
mesh_terms: D002247:Carbon Isotopes; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D019301:Oleic Acid / Q000032:analysis* / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D013499:Surface Properties
chemical_list: D002247:Carbon Isotopes; D008024:Ligands; D058185:Magnetite Nanoparticles; D019301:Oleic Acid; D011092:Polyethylene Glycols