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Washington University Department of Chemistry
Liviu M. Mirica
mirica
Assistant Professor

Biological Chemistry, Inorganic Chemistry, Bioinorganic Chemistry

Department of Chemistry
Washington University in St. Louis
St. Louis, MO 63130-4899

NIH Postdoctoral Fellow, University of California, Berkeley (2005-8)
Ph.D., Stanford University (2005)
B.S., California Institute of Technology (1999)

Young Investigator Award, Division of Inorganic Chemistry, ACS (2006)
Franklin Veatch Memorial Fellowship (2004-2005)
Stanford Graduate Fellowship (1999-2003)
Taube Prize (2000), Merck Index Award (1999), Carnation Merit Award (1997)
Gold and Silver Medals, International Chemistry Olympiad (1994,1995)
Postdoctoral Position Available! A postdoctoral position is available in the Mirica Group. Applicants should possess a Ph.D. in chemistry or a related field and should have experience in one of the following areas: inorganic chemistry, biochemistry, or organic chemistry. To apply for this position, please send your CV and names of three references to mirica@wuchem.wustl.edu

Research

Our research program uses inorganic chemistry, organic chemistry, and biological chemistry to address important metal-mediated processes with energy, biological, and medical relevance. An interdisciplinary, problem-based approach will be employed to synthesize and characterize new organic molecules and inorganic complexes, with the ultimate goal to tackle unsolved problems with broad implications to our society. Three main research areas will be pursued, which are expected to attract students and postdocs with different research interests and to provide them with a broad knowledge base applicable in most chemistry careers.

Non-Heme Iron Enzymes. Non-heme iron enzymes catalyze a wide range of oxidation and oxygenation reactions that have environmental, pharmaceutical, and medical significance. These enzymes, although exhibit a similar overall fold, exhibit different substrate specificity. This project aims to design and synthesize specific inhibitors of O2-activating non-heme iron enzymes by taking advantage of the enzyme’s substrate specificity. While the proposed approach is applicable to any metalloenzyme, of particular interest are histone demethylases, a new class of enzymes that play an important role in regulating transcription and epigenetic inheritance. The developed inhibitors could be used as tools for studying the role of histone demethylases in cell function and development. Insights into the specificity of these enzymes will provide opportunities to advance therapeutics related to stem cell technology and cancer treatment.

Renewable Energy Catalysis. The global energy consumption is expected to at least double in the next fifty years due to population and economic growth. Given the dramatic increase of CO2 levels from fossil fuel consumption, development of carbon-neutral energy production is greatly needed, with solar energy being the largest exploitable renewable energy resource. In this context, there is a large interest in developing molecular systems that can capture solar energy and used it to produce oxygen and hydrogen from water. This project regards the design, synthesis, and characterization of polymetallic complexes as potential catalysts for water oxidation. If successful, the developed catalysts capable of water oxidation can potentially be used in tandem with photovoltaic cells to construct artificial photosynthetic centers.

Amyloid b Peptides in Alzheimer’s Disease. Alzheimer’s Disease (AD) is the most common neurodegenerative disease. Presently around five million people are diagnosed with AD in the US and the number is expected to reach fourteen million by 2050. The brains of patients with AD are characterized by the deposition of amyloid b (Ab) peptide plaques, which accumulate unusually high concentrations of copper, iron, and zinc. This project is directed toward the investigation of the interaction of transition metal ions with Ab peptides and the study of the role of metal ions in amyloid plaque and reactive oxygen species (ROS) formation. Additionally, a novel bifunctional strategy will be used to develop inhibitors of Ab peptide aggregation, which could provide improved strategies for the prevention, diagnosis, and treatment of AD.

Selected Publications

  • Mirica, L. M.; Klinman, J. P. “The Nature of O2 Activation by the Ethylene-Forming Enzyme ACC Oxidase.” Proc. Natl. Acad. Sci. U. S. A., 2008, 105, 1814.
  • Thrower, J. T.; Mirica, L. M.; McCusker, K. P.; Klinman, J. P. “Mechanistic Investigations of 1-Aminocylcyclopropane 1-Carboxylic Acid Oxidase with Alternate Cyclic and Acyclic Substrate” Biochemistry, 2006, 45, 13108.
  • Mirica, L. M.; Rudd, D. J.; Vance, M.; Solomon, E. I.; Hedman, B.; Hodgson, K. O.; Stack, T. D. P. “A m-h2:h2-Peroxodicopper(II) Complex with a Secondary Diamine Ligand: A Functional Model of Tyrosinase.” J. Am. Chem. Soc., 2006, 128, 2654.
  • Mirica, L. M.; Vance, M.; Rudd, D. J.; Hedman, B.; Hodgson, K. O.; Solomon, E. I.; Stack, T. D. P. “Tyrosinase Reactivity in a Model Complex: An Alternative Hydroxylation Mechanism.” Science, 2005, 308, 1890.
  • Mirica, L. M.; Stack, T. D. P. “A Tris(m-hydroxy)tricopper(II) Complex as a Model of the Native Intermediate in Laccase and Its Relationship to a Binuclear Analogue.” Inorg. Chem., 2005, 44, 2131.
  • Mirica, L. M.; Ottenwaelder, X.; Stack, T. D. P. “Structure and Spectroscopy of Copper–Dioxygen Complexes.” Chem. Rev., 2004, 104, 1013.
  • Mirica, L. M.; Vance, M.; Rudd, D. J.; Hedman, B.; Hodgson, K. O.; Solomon, E. I.; Stack, T. D. P. “A Stabilized m-h2:h2-Peroxodicopper(II) Complex with a Secondary Diamine Ligand and Its Tyrosinase-like Reactivity.” J. Am. Chem. Soc., 2002, 124, 9332.
Page Last Updated: July 13th, 2008