Campus Box 1134
Inorganic Chemistry, Bioinorganic Chemistry, Organometallic Chemistry, Organic Chemistry, Biological Chemistry, Biomimetic Oxidations, Renewable Energy Catalysis, Oxygen-Activating Metalloenzymes, Role of Transition Metal Ions in Neurodegenerative Diseases
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. Several 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.
1. Catalysis of Energy-Related Processes. The global energy consumption is expected to at least double in the next fifty years and development of efficient chemical transformations for efficient fossil fuel utilization and energy production from renewable sources will be greatly needed. Methane – the main constituent of natural gas, is found in large quantities on earth and could become a significant source of energy as petroleum reserves diminish. The conversion of methane into liquid fuels (e.g., higher alkanes) would allow for a more efficient use of natural gas reserves as an inexpensive energy resource. In this regard, we are interesting in the development of novel catalysts for the oxidative oligomerization of methane using green oxidants such as O2 that should have a major impact on our society and the environment. In addition, we are also interested in developing catalytic systems for CO2 reduction, which would constitute an important step in employing CO2 as a renewable source for the generation of liquid fuels and thus potentially impact the global carbon balance. In our catalyst development we aim to combine successful approaches from organometallic chemistry for the functionalization of unactivated organic molecules with strategies from bioinorganic chemistry for the activation of small molecules (i.e., O2 and CO2). While initial studies have focused on Pd complexes – given their extensive use in catalysis, current research efforts focus on earth abundant Ni complexes. The proposed research will take advantage of our ability to judiciously design ligands that tune the electronic properties and catalytic reactivity of metal ions in various oxidation states. We are also uniquely equipped to study the electronic properties and reactivity of both paramagnetic and diamagnetic systems through an extensive series of spectroscopic, mechanistic, and computational approaches to characterize in detail the electronic properties and reactivity of the investigated systems.
Angew. Chem. Int. Ed., 2011, 50, 5532
Chem. Comm., 2012, 48, 1532
Organometallics, 2013, 32, 3343
Coord. Chem. Rev., 2013, 257, 299
Inorg. Chem., 2014, 53, 13112
J. Am. Chem. Soc., 2010, 132, 7303; 2012, 134, 2414
Organometallics, 2012, 31, 4627; 2012, 31, 6690
Chem. Comm., 2014, 50, 3036
Another approach for the production of carbon-neutral energy production is to use sunlight, 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. We are interested in 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.
Inorg. Chem., 2011, 50, 6152; 2013, 52, 3920
In addition, we have recently been able to isolate and characterize in detail organometallic NiIII complexes containing various organic ligands. These are the first isolated NiIII species that undergo transmetallation and/or reductive elimination reactions to form new C-C or C-heteroatom bonds, and are also competent catalysts for Kumada and Negishi cross-coupling reactions, providing strong evidence for the direct involvement of organometallic NiIII species in cross-coupling reactions and oxidatively-induced C-heteroatom bond formation reactions. Importantly, successful development of earth abundant Ni-based catalysts for such key chemical transformations would replace the currently used precious metal catalysts employing Pd, Rh, Ir, and Ru systems.
J. Am. Chem. Soc., 2014, 136, 6499
Chem. Comm., 2015, 51, 3113
2. Metal-Amyloid β Peptide Interactions 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 β (Aβ) peptide plaques, which accumulate unusually high concentrations of copper, iron, and zinc. This project aims to investigate the interaction of transition metal ions with Aβ peptides and the study of the role of metal ions in Aβ oligomerization and amyloid plaque formation. In addition, we are developing novel metal-binding bifunctional compounds as potential therapeutic and diagnostic agents for AD.
J. Am. Chem. Soc., 2012, 134, 6625;
Proc. Natl. Acad. Sci. U.S.A., 2013, 110, 14604;
Metallomics, 2013, 5, 1519;
Inorg. Chem., 2014, 53, 11367.
Awards & Honors
2014, Organometallics Young Investigator Fellowship, ACS Division of Organic Chemistry
2014, Saltman Lectureship, Metals in Biology Gordon Research Conference
2013-2018, NSF CAREER Award
2012, Undergraduate Research Mentor of the Year Award, Washington University
2012, Alfred P. Sloan Foundation Research Fellowship
2011, Outstanding Faculty Member Nominee, Freshman Class Council & First Year Center
2011, Sony Electronics Award for Excellence in Teaching
2010-2011, Ralph E. Powe Junior Faculty Award, Oak Ridge Associated Universities
2007-2008, NIH-NRSA Postdoctoral Fellowship
2006, Young Investigator Award, Division of Inorganic Chemistry, ACS
2004-2005, Franklin Veatch Memorial Fellowship, Stanford University
1999-2003, Stanford Graduate Fellowship, Stanford University
1999, Taube Prize, Stanford University
1999, Merck Index Award for Excellence in Chemistry, California Institute of Technology
1997-1998, Carnation Merit Award, California Institute of Technology
1995, Silver Medal, International Chemistry Olympiad, Beijing, China
1994, Gold Medal, International Chemistry Olympiad, Oslo, Norway
2013-present Associate Professor, Department of Chemistry, Washington University
2011-present Member, International Center for Advanced Renewable Energy & Sustainability (I-CARES), Washington University
2008-present Member, Division of Biological and Biomedical Sciences (DBBS), Washington University
2008-present, Assistant Professor of Chemistry, Washington University
2005-2008, NIH Postdoctoral Fellow, University of California, Berkeley
Tang, F.; Rath, N. P.; Mirica, L. M.* “Stable Bis(trifluoromethyl)Nickel(III) Complexes”, Chem. Comm., 2015, 51, 3113-3116; DOI: 10.1039/c4cc09594d.
Khusnutdinova, J. R.; Rath, N. P.; Mirica, L. M.* “The Conformational Flexibility of the Tetradentate Ligand tBuN4 is Essential for the Stabilization of (tBuN4)PdIII Complexes”, Inorg. Chem., 2014, 53, 13112-13129, DOI: 10.1021/ic5023054.
Sharma, A. K.; Kim, J.; Prior, J. T.; Hawco, N. J.; Rath, N. P.; Kim, J.; Mirica, L. M.;* “Small Bifunctional Chelators that Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity”, Inorg. Chem., 2014, 53, 11367-11376, DOI: 10.1021/ic500926c.
Zheng, B.; Tang, F.; Luo, J.; Schultz, J. W.; Rath, N. P.; Mirica, L. M.* “Organometallic Nickel(III) Complexes Relevant to Cross-Coupling and Carbon-Heteroatom Bond Formation Reactions”, J. Am. Chem. Soc., 2014, 136, 6499-6504; DOI: 10.1021/ ja5024749.
Qu, F.; Khusnutdinova, J. R.; Rath, N. P.; Mirica, L. M.* “An Organometallic Pd(IV)-OH Complex Formed upon Aerobic Oxidation of a Pd(II) Precursor and Its C-O Bond Formation Reactivity”, Chem. Comm., 2014, 50, 3036-3039; DOI: 10.1039/c3cc49387c.
Sharma, A. K.; Pavlova, S. T.; Kim, J.; Kim, J.; Mirica, L. M.;* “The Effect of Cu2+ and Zn2+ on the Ab42 Peptide Aggregation and Cellular Toxicity”, Metallomics, 2013, 5, 1519-1536; DOI: 10.1039/c3mt00161j.
Zhang, Y.; Rempel, D. L.; Zhang, J.; Sharma, A. K.; Mirica, L. M.;* Gross M. L.* “Pulsed hydrogen-deuterium exchange mass spectrometry probes conformational changes in amyloid beta (Aβ) peptide aggregation”, Proc. Natl. Acad. Sci. U. S. A., 2013, 110, 14604-14609; DOI: 10.1073/pnas.1309175110.
Luo, J.; Rath, N. P.; Mirica, L. M.* “Oxidative Reactivity of (N2S2)PdRX Complexes (R = Me, Cl; X = Me, Cl, Br): Involvement of Palladium(III) and Palladium(IV) Intermediate”, Organometallics, 2013, 32, 3343-3353; DOI: 10.1021/om400286j.
Khusnutdinova, J. R.; Luo, J.; Rath, N. P.; Mirica, L. M.* “Late First Row Transition Metal Complexes of a Tetradentate Pyridinophane Ligand: Electronic Properties and Reactivity Implications”, Inorg. Chem., 2013, 52, 3920-3932, DOI: 10.1021/ic400260z.
Mirica, L. M.;* Khusnutdinova, J. R., “Structure and Electronic Properties of Pd(III) Complexes”, Coord. Chem. Rev., 2013, 257, 299-314. DOI: 10.1016/j.ccr.2012.04.030.
Cascella, B.; Mirica, L. M.* “Kinetic Analysis of Iron-Dependent Histone Demethylases: a-Ketoglutarate Substrate Inhibition and Potential Relevance to the Regulation of Histone Demethylation in Cancer Cells”, Biochemistry, 2012, 51, 8699-8701, DOI: 10.1021/bi3012466.
Tang, F.; Qu, F.; Khusnutdinova, J. R.; Rath, N. P.; Mirica, L. M.* “Structural and Reactivity Comparison of Analogous Organometallic Pd(III) and Pd(IV) Complexes”, Dalton Trans., 2012, 41, 14046-14050, DOI:10.1039/C2DT32127K.
Tang, F.; Zhang, Y.; Rath, N. P.; Mirica, L. M.* “Detection of Pd(III) and Pd(IV) Intermediates during the Aerobic Oxidative C-C Bond Formation from a Pd(II) Dimethyl Complex”, Organometallics, 2012, 31, 6690-6696. DOI: 10.1021/om300752w.
Khusnutdinova, J. R.; Qu, F.; Zhang, Y.; Rath, N. P.; Mirica, L. M.* “Formation of the Pd(IV) Complex [(Me3tacn)PdIVMe3]+ through Aerobic Oxidation of (Me3tacn)PdIIMe2 (Me3tacn = N,N’,N’’-trimethyl-1,4,7-triazacyclononane)”, Organometallics, 2012, 31, 4627-4630, DOI: 10.1021/om300426r. Article featured on the cover.
Sharma, A. K.; Pavlova, S. T.; Kim, J.; Finkelstein, D.; Hawco, N. J.; Rath, N. P.; Kim, J.; Mirica, L. M.* “Bifunctional Metal-Binding Compounds for Controlling the Metal-Mediated Aggregation of the Ab42 Peptide”, J. Am. Chem. Soc., 2012, 134, 6625-6636, DOI: 10.1021/ja210588m.
Khusnutdinova, J. R.; Rath, N. P.; Mirica, L. M.* “The Aerobic Oxidation of a Pd(II) Dimethyl Complex Leads to Selective Ethane Elimination from a Pd(III) Intermediate”, J. Am. Chem. Soc., 2012, 134, 2414-2422, DOI: 10.1021/ja210841f.
Luo, J., Khusnutdinova J. R., Rath N., Mirica L. M.* “Unsupported d8-d8 Interactions in Cationic PdII and PtII Complexes: Evidence for a Significant Metal-Metal Bonding Character” Chem. Comm., Emerging Investigators issue 2012, in press, DOI:10.1039/C1CC15420F.
Luo, J., Rath N., Mirica L. M.* “Dinuclear Co(II)Co(III) Mixed-Valence and Co(III)Co(III) Complexes with N- and O-Donor Ligands: Characterization and Water Oxidation Studies” Inorg. Chem., 2011, 50, 6152-6157.
Khusnutdinova J., Rath N., Mirica L. M.* "Dinuclear PD(III) Complexes with a Single Unsupported Bridging Halide Ligand: reversible Formation from Mononuclear Pd(II) or Pd(IV) Precursors" Agnew. Chem Int. Ed.,2011, 50 5532-5536.
Khusnutdinova J., Rath N., Mirica L. M.* “Stable Mononuclear Organometallic Pd(III) Complexes and Their C-C Bond Formation Reactivity” J. Am. Chem. Soc., 2010, 132, 7303-7305. Featured as “News of the Week” in Chem. & Eng. News, 2010, 88, 21, 9.
Mirica, L. M.; McCusker, K. P.; Munos, J. W.; Liu, H. W.; Klinman, J. P.* “Probing the Nature of Reactive Fe/O2 Intermediates in Non-Heme Iron Enzymes through 18O Kinetic Isotope Effects.” J. Am. Chem. Soc., 2008, 130, 8122-8123.
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, 1814-1819.
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, 2654-2665.
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, 1890-1892. Featured as a perspective in Science, 2005, 308, 1876-1877 and a science concentrate in Chem. & Eng. News, 2005, 83, 26, 38.
Mirica, L. M.; Ottenwaelder, X.; Stack, T. D. P.* “Structure and Spectroscopy of Copper–Dioxygen Complexes.” Chem. Rev., 2004, 104, 1013-1046.
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, 9332-9333.
Chemistry 461, Inorganic Chemistry
Chemistry 112, General Chemistry II
Chemistry 464, Inorganic Biochemistry
Chemistry 452, Special Topics in Inorganic Chemistry: Metal-Catalyzed Reactions in Chemistry and Biology