List of Faculty
|
Cassandra
L. FraserPolymeric Metal Complexes. Metallobiomaterials for Medicine and Biotechnology. Bio-inspired and Sustainable Design. Responsive Nanoscale Assemblies.
Research in the Fraser Lab is concerned with the synthesis, properties and applications of metal complexes with polymeric ligands. Like metalloproteins, polymeric metal complexes feature site-isolated metal centers in well-defined macromolecular environments. These multifunctional targets are prepared via combination of coordination chemistry with living polymerization methodologies and offer many opportunities for further modification. The development of new synthetic methodologies involving main group, transition metal and lanthanide complexes with bipyridine and diketonate macroligands has paved the way for the discovery of some fascinating and unexpected properties and reactivity. The resulting hybrid materials can function as soluble agents, films, nanoparticles, or bulk materials, and block copolymers can form higher order nanoscale assemblies. Presently, we are exploring uses for these metallobiomaterials as optical imaging agents, oxygen sensors, drug delivery systems, and responsive materials in biomedicine and sustainable design.
For example, difluoroboron dibenzoylmethane polylactide, BF2dbmPLA, is a multi-emissive material exhibiting both intense blue fluorescence and unusual long lived, room and body temperature green phosphorescence, the latter of which serves as the basis for optical oxygen sensing via a quenching mechanism. When fabricated as nanoparticles and tested in cell, tissue and in vivo mouse models, 2-photon absorbing, fluorescent boron systems are very stable to photobleaching compared to other common imaging agents such as green fluorescent protein or FITC and very bright compared to quantum dots. Given high sensitivity in low oxygen environments, boron biomaterials may serve as hypoxia or anoxia sensors in tumors, vascular blockage relevant to strokes and heart disease, organ transplantation, and many other medical contexts. Emission color tuning is achievable via modification of the diketonate ligand, polymer composition, or molecular weight. Efforts are underway to better understand the properties of boron diketonate compounds and fully exploit the potential of these impressive, single-component, multi-emissive biomaterials for a wide range of imaging and sensing applications.
We have also explored polymeric iron, ruthenium and europium complexes, including block copolymer systems. Multifunctional iron dibenzoylmethane initiators also serve as catalysts for lactide ring opening polymerization and introduce acid responsive features into the resulting biomaterial. Entirely unexpected air sensitivity is noted for iron tris(bipyridine) complexes in poly(ethylene glycol) environments and other iron bipyridine polymers are reversibly thermochromic. Akin to biomineralization processes in nature, hierarchically structured iron block copolymer films function as both metal delivery systems and nanoscale templates for controlled iron cluster formation upon annealing. Coupling triggered changes at the metal center with structural transformations in ordered films in lanthanide systems introduces unique dynamic features into nanoscale materials. Luminescent ruthenium systems have been tested as gene delivery vectors. Because the properties and stabilities of metal complexes are highly tunable through variation of the metal ion, the ligand set, and other molecular parameters, this makes the coordinate bond a remarkably versatile platform for macromolecular assembly.
Representative Publications:
Boron
"Multi-Emissive Difluoroboron Dibenzoylmethane Polylactide Exhibiting Intense Fluorescence and Oxygen Sensitive Room Temperature Phosphorescence" Zhang, G.; Chen, J.; Payne, S. J.; Kooi, S. E.; Demas, J. N.; Fraser, C. L. J. Am. Chem. Soc. 2007, 129, 8942-3.
"Emission Color Tuning with Polymer Molecular Weight for Boron Dibenzoylmethane-Polylactide" Zhang, G.; Kooi, S. E.; Demas, J. N.; Fraser, C. L. Adv. Mater. 2008, 20, 2099-104.
"Boron Polylactide Nanoparticles Exhibiting Fluorescence and Phosphorescence in Aqueous Medium" Pfister, A.; Zhang, G.; Zareno, J.; Horwitz, A. F.; Fraser, C. L. ACS Nano 2008, 2, 1252-8.
Iron
“Synthesis and Unexpected Reactivity of Iron Tris(bipyridine) Complexes with Poly(ethylene glycol) Macroligands” Pfister, A.; Fraser, C. L. Biomacromolecules 2006 , 7, 459-68.
“Iron Tris(dibenzoylmethane)-centered Polylactide Stars: Multiple Roles for the Metal Complex in Lactide Ring Opening Polymerization” Gorczynski, J. L.; Chen, J.; Fraser, C. L. J. Am. Chem. Soc. 2005, 127, 14956-7.
“Iron Tris(bipyridine)-Centered Star Block Copolymers: Chelation of Triblock Macroligands Generated by ROP and ATRP” Johnson, R. M.; Fraser, C. L. Macromolecules 2004, 37, 2718-27.
“Iron Cluster and Microstructure Formation in Metal-Centered Star Block Copolymers: Metal-Centered Iron Tris(bipyridine)-Centered Polyoxazolines” Park, C.; McAlvin, J. E.; Fraser, C. L.; Thomas, E. L. Chem. Mater. 2002, 14, 1225-30.
“Biocompatible Polyester Macroligands: New Subunits for the Assembly of Star-Shaped Polymers with Luminescent and Cleavable Metal Cores” Corbin, P. S.; Webb, M. P.; McAlvin, J. E.; Fraser, C. L. Biomacromolecules 2001, 2, 223-32.
Ruthenium
“Ruthenium Tris(bipyridine) Complexes with Sulfur Substituents: Model Studies for PEG Coupling” Fiore, G. L.; Goguen, B. N.; Klinkenberg, J. L.; Payne, S. J.; Demas, J. N.; Fraser, C. L. Inorg. Chem. 2008, 47, 6532-40.
“Ruthenium Tris(bipyridine)-centered PEI for Gene Delivery” Fiore, G. L.; Edwards, J. M.; Klinkenberg, J. L.; Payne, S. J.; Demas, J. N.; Gioeli, D. G.; Fraser, C. L. Biomacromolecules 2007, 8, 2829-35.
“Metalloinitiation Routes to Biocompatible Poly(lactic acid) and Poly(acrylic acid) Stars with Luminescent Ruthenium Tris(bipyridine) Cores” Johnson, R. M.; Fraser, C. L. Biomacromolecules 2004, 5, 580-8.
“Metal Template-Assisted Block Copolymer Synthesis: Use of Solvent Polarity to Control Chain Conformation and Reactivity at the Metal Core” Fraser, C. L.; Smith, A. P.; Wu, X. J. Am. Chem. Soc. 2000, 122, 9026-7.
Europium
“Site-Isolated Luminescent Europium Complexes with Polyester Macroligands: Metal-Centered Heteroarm Stars and Nanoscale Assembles with Labile Block Junctions” Bender, J. L.; Corbin, P. S.; Fraser, C. L.; Metcalf, D. H.; Richardson, F. S.; Thomas, E. L.; Urbas, A. M. J. Am. Chem. Soc. 2002, 124, 8526-7.
“Poly(epsilon-caprolactone) Macroligands with Beta-diketonate Binding Sites: Synthesis and Coordination Chemistry” Bender, J. L.; Shen, Q.-D.; Fraser, C. L. Tetrahedron 2004, 60, 7277-85. Invited paper. Issue honoring Robert H. Grubbs.
Bipyridine Ligands
“Synthesis of 4-, 5-, and 6-Methyl-2,2’-bipyridine by a Negishi Cross-Coupling Strategy: 5-Methyl-2,2’-bipyridine,” Smith, A. P.; Savage, S. A.; Love, J. C.; Fraser, C. L. in Thematic Collections of Organic Synthesis, Vol. 1, Palladium, Nickel and Iron-Catalyzed Reactions, Danheiser, R., Ed., Wiley: New York, 2008.
“Bipyridines” Fraser, C. L.; Smith, A. P; Comprehensive Coordination Chemistry II; Meyer, T. J.; McCleverty, J. A., Eds; Elsevier Ltd.: Oxford, UK, 2004; Vol. 1, Ch. 1, pp. 1-23.
“Synthesis of Bipyridine-Centered Diblock Copolymers” Smith, A. P.; Fraser, C. L. Macromolecules 2003, 36, 2654-60.
“Efficient Synthesis of Halomethyl-2,2'-Bipyridines” Smith, A. P.; Lamba, J. J. S.; Fraser, C. L. Org. Synth. 2001, 78, 82-90.
Review
“Metal Complexes with Polymeric Ligands: Chelation and Metalloinitiation Approaches to Metal Tris(bipyridine)-Containing Materials” Fraser, C. L.; Smith, A. P. J. Polym. Sci. Part A Polym. Chem. 2000, 38, 4704-16.