Patrick J. FarmerProfessor, Chemistry |
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Research Interests |
Inorganic and Bioinorganic Chemistry | |
| URL | www.chem.uci.edu/~pfarmer/grp2/index.htm | |
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Academic Distinctions |
American Cancer Society Research Scholar, 2003 Chancellor's Award for Excellence in Undergraduate Research, 1999 NSF CAREER Award, 1997 Hoechst Celanese Research Excellence Award, 1993 |
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| Appointments |
NSF/Nato Postdoctoral Fellow, 1993, Ecole Normale Suprieure, Paris NSF Postdoctoral Fellow, 1994, California Institute of Technology, Pasadena |
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Research Abstract |
Nature is an amazing chemist that is constantly synthesizing and transforming the world around us. Much of this work is done by enzymes, amazing little catalysts made of protein, just like you and me. Unlike industrial catalysts, enzymes work in water at mild temperatures and pressures. In many cases, enzymes with very similar active sites perform very different functions-- for example, indentical Fe-heme cofactors bind and transport oxygen in hemoglobin and myoglobin, reduce oxygen in the cytochromes P450s and cytochrome oxidase, or nitrogen oxides in the nitrite and nitric oxide reductases. The substrate specificities and reactivity of the heme in the various enzymes is controlled by the protein environment around it, and small changes can have large effects. Likewise, the flow of electrons to a redox-active heme is also largely controled by the protein matrix it is contained in. Nature has amazing control over these electron transfers; redox sites are typically oriented so as to "aim" the electron towards its acceptor site, and triggering the flow to a specific chemical event. Like nature, we try to use a controlled flow of electrons to initiate redox catalysis in hybrid heme enzymes. By varying the structures and environments of the hemes, we hope to make unique catalysts for different reactivities. These tailor-made enzymes are intended to perform useful chemical transformations driven simply by electricity or light. For example, by affixing the oxygen-binding protein myoglobin to an electrode we can make it catalyze the multi-electron reduction of nitrite to ammonia, a reaction that is important in plant metabolism. Using a P450, we can reduce carbon tetrachloride to methane, and amazing eight electron reduction that detoxifies this potent halocarbon. Binding photo-active Ru complexes to the surface of a protein allows us to photo-initiate electron flow into the heme active-site, and to control the reactions that occur there on the time-scale of a laser-pulse. We are also interested in the redox chemistry of melanin, the black pigment in hair and skin. Melanins are catecholic pigments formed in melanocytes by oxidative polymerization of tyrosine. Melanins have very interesting photochemical properties, they are redox-active and tight binders of metal ions. Our recent work shows that they both mediate and generate reduced oxygen species. We are exploring the unique chemistry of melanins as a means of targeting melanoma, a cancer of the cells that make melanin. |
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| Publications | Coordination Chemistry of the HNO Ligand with Hemes and Synthetic Coordination Complexes Farmer, P.J.; Sulc, F. J. Inorg. Biochem. 2005, 99, 166-184. | |
| Bonding in HNO-Myoglobin as Characterized by X-Ray Absorbance and Resonance Raman Spectroscopies Immoos, C.E.; Sulc, F.; Farmer, P.J.; Czarnecki, K.; Bocian, D.F.; Levina, A.; Aitken, J.B.; Armstrong, R.S.; Lay, P.A. J. Am. Chem. Soc. 2005, 127, 814 815. | ||
| Disulfiram causes intracellular Cu uptake and induces apoptosis in human melanoma cells Cen, D.; Brayton, D.; Shahandeh, B.; Meyskens, F.L.; Farmer, P.J. J. Med. Chem. 2004, 47, 6914-6920. | ||
| Multiple pathways for the oxygenation of a Ru(II) dithiocarbamate complex: S-Oxygenation and S-Extrusion Ng, S.; Ziller, J.; Farmer, P.J. Inorg. Chem. 2004, 43, 8301-8309. | ||
| "High Temperature Electrocatalysis Using Thermophilic P450 CYP119: Dehalogenation of CCl4 to CH4" Blair, E.; Greaves, J.; Farmer, P.J. J. Amer. Chem. Soc. 2004, 126, 8632-8633. | ||
| "Electron Transfer Chemistry of Ru-linker-(heme)-modified Myoglobin: Rapid Intraprotein Reduction of a Photogenerated Porphyrin Cation Radical" Immoos, C.E.; Di Bilio, A.J.; Cohen, M.S.; Van der Veer, W.; Gray, H.B.; Farmer, P.J. Inorg. Chem. 2004, 43, 3593 3596. | ||
| "Electrocatalytic reductions of nitrite, nitric oxide and nitrous oxide by Cytochrome P450 CYP 119" Immoos, C.E.; Chou, J.; Bayachou, M.; Blair, E.; Farmer, P.J. J. Amer. Chem. Soc. 2004, 126, 4934-4942. | ||
| "Etiologic Pathogenesis of Melanoma: A Unifying Hypothesis for the Missing Attributable Risk" Meyskens, F.L.; Farmer, P.J.; Anton-Culver, H. Clin. Canc. Res. 2004, 10, 2581-2583. | ||
| "Trapping of Nitroxyl by Deoxy Myoglobin" Sulc, F.; Immoos, C.; Pervitsky, D. Farmer, P.J. J. Amer. Chem. Soc. 2004, 125,1096-1101. | ||
| "Melanin as a target for melanoma chemotherapy: pro-oxidant effect of oxygen and metals on melanoma viability." Farmer, P.J.; Gidanian, S.; Shahandeh, B.; Di Bilio, A.J.; Tohidian, N.; Meyskens, F.L. Pigment Cell. Res. 2003, 16, 273-279. | ||
| "A Novel Heme and Peroxide-Dependent Tryptophan-Tyrosine Cross-link in a Mutant of Cytochrome c Peroxidase" Bhaskar, B.; Immoos, C.E.; Shimizu, H.; Sulc, F.; Farmer, P.J.; Poulos, T.L. J. Mol. Biol. 2003, 328, 157-166. | ||
| "1H NMR Structure of the Heme Pocket of HNO-Myoglobin" Sulc, F.; Fleischer, E.; Farmer, P.J.; Ma, D.; La Mar, G. J. Biol. Inorg. Chem. 2003, 8, 348-352. | ||
| "Direct Assessment of the Reduction Potential of the [4Fe-4S]1+/0 Couple of the Nitrogenase Fe Protein from Azotobacter vinelandii" Guo, M.; Sulc, F.; Ribbe, M.W.; Immoos, C.E.; Chou, J.; Farmer, P.J.; Burgess, B.K. J. Amer. Chem. Soc. 2002, 124, 2100-12101. | ||
| "The reduction potential of nitric oxide (NO) and its importance to NO biochemistry" Bartberger, M.D.; Liu, W.; Ford, E.; Miranda, K.M.; Switzer, C.; Fukuto, J.M.; Farmer, P.J.; Wink, D.A.; Houk K. N. Proc. Nat. Acad. Sci. 2002, 99, 10958-10963. | ||
| "Mesopone Cytochrome C Peroxidase: Functional Model of Heme Oxygenated Oxidases" Immoos, C.E.; Bhaskar, B.; Cohen, M.S.; Barrows, T.P.; Farmer, P.J.; Poulos, T.L. J. Inorg. Biochem. 2002, 91, 635-643. | ||
| "O Atom Transfer from Nitric Oxide Catalyzed by Fe(TPP) "Lin, R.; Farmer, P. J. J. Am. Chem. Soc. 2001,123, 1143 -1150 | ||
| "Metal Binding by Melanins: Studies of Colloidal DHI-Melanin, and its Complexation by Cu(II), and Zn(II) Ions " Szpoganicz, B.; Kong, P.; Farmer, P. J. J. Inorg. Biochem. 2001, 89, 61. | ||
| "Redox Behavior of Melanins: Direct Electrochemistry of DHI-melanin and its Cu and Zn Adducts " Gidanian, S.; Farmer, P. J. J. Inorg. Biochem. 2001, 89, 54. | ||
| "Redox Regulation in Human Melanocytes and Melanoma" Meyskens, F.L.; Farmer, P. J.; Fruehauf, J. Pigm. Cell Res. 2001, 14, 148-154. | ||
| "The HNO Adduct of Myoglobin: Synthesis and Characterization" Lin, R.; Farmer, P. J. J. Am. Chem. Soc. 2000, 122, 2393 -2394. | ||
| "Electron Transfer in the Ruthenated Heme Domain of Cytochrome P450BM-3" Sevrioukova, I.F.; Immoos, C.E.; Poulos, T.L.; Farmer, P. J. Isr. J. Chem. 2000, 40, 47-53. | ||
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"Electrochemical Reduction of NO by Myoglobin in Surfactant Film: Characterization and Reactivity of the Nitroxyl (NO-) Adduct," Bayachou, M.; Lin, R.; Cho, W.; Farmer, P. J. J. Am. Chem. Soc. 1998, 120, 9888. |
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| "Nitrite Reduction by Myoglobin in Surfactant Films," Lin, R.; Baychou, M.; Farmer, P. J. J. Am. Chem. Soc. 1997, 119, 12689. | ||
| Grants | "Reductive Heme Protein Catalysis" Granting Agency: National Science Foundation | |
| "S-Oxygenation of Dithiocarbamate Metal Complexes" Granting Agency: Petroleum Research Fund | ||
| "Targeting Melanoma by Metal-Induced Oxidative Stress" Granting Agency: American Cancer Society | ||
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Professional Societies |
American Chemical Society Electrochemical Society Society of Biological Inorganic Chemistry Panamerican Society of Pigment Cell Researchers Society for Free Radical Biology and Medicine |
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| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=2093 | |
| Last updated | 01/26/2006 | |
| (This faculty member is (or was) affiliated with UCI, but does not currently have an active appointment with UCI.) | ||
