Professor
B.S. 1966 (Iowa State);
Ph.D. 1971 (U. of Washington).
NIH Postdoctoral Fellow (University of Illinois)
NSF Foreign Exchange Fellow (Institute for Inorganic Chemistry,
Florence, Italy)
Our research program involves the transition
metals and lies at the interfaces of organic chemistry, inorganic chemistry
and biochemistry. We are concerned with the role of metal ions in
biological processes and their use in medicine.
Ours is one of the few research groups
in the world with routine access to endohedral metallofullerene materials
where metal ions are trapped inside all-carbon fullerene cages. Interest
in such fascinating molecules as Gd@C82, Ho@C82 and
Tm@C82 (M@C82 denotes an internally-trapped metal
ion inside a cage of eighty-two carbon atoms) arises from their potential
application in diagnostic and therapeutic medicine. For example,
water-solublized forms like [M@C82(OH)30] are being
explored for use as magnetic resonance imaging (MRI) contrast agents (M
= Gd3+), x-ray contrast agents (M = Ho3+) and radiopharmaceuticals
(M = 166Ho3+ and 170Tm2+).
In Figure 1, [Gd@C82(OH)30] is seen acting as a MRI
contrast agent by simultaneously relaxing many water protons on its 200
Å2 paramagnetic surface.
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Metallofullerene MRI Contrast Agent |
A Cytochrome c Oxidase (CcO) Model Compound |
At present, a model compound approach is being employed to probe the active sites of plastocyanin (Cu, MW = 10 KDa, electron transfer) and cytochrome c oxidase (Cu/Fe, MW = 200 KDa, 4e- reduction of O2). The function of these metalloproteins varies dramatically and so do their known active-site structures. One such model compound currently under development for the CcO site is shown in Figure 2. Such model compounds represent a strong synthetic challenge to both organic chemistry (free ligands) and inorganic chemistry (metallated ligands), and each molecule is known, or believed, to reproduce essential architectural features associated with the specific chemistry promoted by the metal-containing sites in the proteins. Much remains to be learned from these types of biomimicry studies, and we believe that the field of "Bioinorganic Chemistry" offers an exciting approach toward an understanding of complex biomolecules where unique chemistry revolves around metal-ion centers.
Representative Publications
New Non-Ionic Water-Soluble Porphyrins: Evaluation of Manganese(III) Polyhydroxylamide Porphyrins as MRI Contrast Agents, with J. E. Bradshaw, K. A. Gillogly, K. Kumar, X. Wan, M. F. Tweedle, G. Hernandez and R. G. Bryant, Inorg. Chim. Acta. 1998, 275-276, 106-116.
Internal Reorganization Energies for Copper Redox Couples: The Slow-Electron Transfer Reactions of the [CuII/I(bib)2]2+/+ Couple, with B. Xie, T. Elder and D. M. Stanbury, Inorg. Chem. 1999, 38, 12-19.
In Vivo Studies of Fullerene-Based Materials Employing Endohedral Metallofullerene Radiotracers," with D. W. Cagle, S. J. Kennel, S. Mirzadeh, and J. M. Alford, Proc. Nat. Acad. Sci. USA 1999, 96, 5182-5187.
Toward Fullerene-Based Radiopharmaceuticals: High Yield Neutron Activation of Endohedral 165Ho Metallofullerenes, with T. P. Thrash, D. W. Cagle, J. M. Alford, G. J. Ehrhardt, and S. Mirzadeh, Chem. Phys. Lett. 1999, 308, 329-336.
Metallofullerene Drug Design, with D. W. Cagle, T. P. Thrash, S. J. Kennel, S. Mirzadeh, J. M. Alford and G. J. Ehrhardt, Coord. Chem. Rev.1999, 190-192, 199-207.
Synthesis, Characterization and Neutron Activation of Holmium Metallofullerenes, with D. W. Cagle, T. P. Thrash, M. Alford, L. P. F. Chibante and G. J. Ehrhardt, J. Am. Chem. Soc. 1996, 118, 8043-8047.
Reversible Fullerene Electrochemistry: Correlation with the HOMO-LUMO Energy Difference for C60, C70, C76, C78 and C84, with Y. Yang, F. Arias, L. Echegoyen, L. P. F. Chibante, S. Flanagan and A. Robertson, J. Am. Chem. Soc., 1995, 117, 7801.
Spin-State Isomerism in Crystalline [FeIII(TPP)(OSO2CF3)], with J. A. González, Inorg. Chem., 1994, 33, 1543.
An Electron Self-Exchange Study of the Coordination-Number-Invariant
Pentacoordinate Copper(I/II) Couple, [CuI,II((5-MeimidH)2DAP)]+/2+,
with D. K. Coggin, J. A. González, A. M. Kook, W. R. Scheidt and
D. M. Stanbury, Inorg. Chem., 1991, 30, 1125.