add contact to address book

Nicolai Lehnert

Associate Professor of Chemistry and Biophysics, College of Literature, Science, and the Arts

Office Location(s): 2807 Chemistry
Phone: 734.615.3673
lehnertn@umich.edu
Research Group
Bioinorganic Chemistry

  • About

    Research projects that are currently pursued in my group relate to the biological role of nitric oxide (bioinorganic chemistry and biophysics), the development of homogeneous catalysts for the generation of the sustainable energy carrier hydrogen (organometallic chemistry and energy sciences), and recently, porphyrin-based materials for non-linear optics.

    Historically, nitric oxide (nitrogen monoxide, NO) has always been viewed as an environmental pollutant, generated from the burning of fossil fuels, due to its toxic and corrosive properties. Together with its homolog nitrogen dioxide (NO2), it is one of the main contributors to smog. NO is in fact poisonous to humans at very low concentrations of only 100 ppm in air. This general view of NO as an environmental pollutant and toxin changed dramatically in the 1980’s when it was realized first that humans are capable of NO biosynthesis for the purpose of immune defense and signaling. In humans, NO is generated by the nitric oxide synthase (NOS) isozymes, which belong to the cytochrome P450 family. For the purpose of signaling, NO is produced by endothelial (e-) NOS in the endothelial cells that line the inner surface of arteries (blood pres¬sure control), or by neuronal (n-) NOS in the brain for nerve signal transduction. The important cardiovascular and neuronal regulation by NO is then mediated by soluble guanylate cyclase (sGC), which serves as the general biological NO sensor/receptor protein in mammals. NO is also pro¬duced in macrophages by inducible (i ) NOS for immune defense. In 1992, NO was therefore voted the molecule of the year by the magazine Science, followed by the Nobel Prize in Medicine in 1998.

    Interestingly, the role of nitric oxide in vasodilation is exploited by certain blood-sucking insects that inject NO into the bites of their victims using small NO-carrier heme proteins, the so-called Nitrophorins (Np). Furthermore, nitric oxide occurs as an intermediate in dissimilatory denitrification, which corresponds to the stepwise reduction of nitrate to dinitrogen for the purpose of anaerobic respiration by soil-dwelling bacteria and fungi. New biological functions of NO and its oxidized and reduced derivatives (nitrite, nitroxyl, peroxynitrite, etc.) are still discovered. Importantly, many of the biologically important reactions of nitric oxide are mediated by heme proteins.

    In summary, nitric oxide is a double-edged sword in biological systems: on the one-hand side, it is a primary signaling molecule in the human body, but on the other hand, higher concentrations of NO as they appear in certain disease states (chronic inflammations, septic shock) are detrimental as NO is also a highly toxic molecule. Because of this, the concentration of free NO is tightly controlled in the human body, and the mechanisms for this regulation are currently heavily investigated. One central pathway for the detoxification of NO in biological systems is the reduction to nitrous oxide (laughing gas, N2O) as catalyzed by the NO reductase (NOR) enzyme family. Prominent examples for these enzymes are found in denitrifying bacteria and fungi, and many pathogens. Bacterial NOR (NorBC) reduces NO to nitrous oxide at a mixed heme/non-heme active site, where the heme shows axial histidine coordination. In comparison, the same reaction is performed by fungal nitric oxide reductase (P450nor) at a single heme active site, which, in contrast, has an axial cysteine ligand. Finally, flavodiiron proteins in pathogenic bacteria use a dinuclear non-heme iron active site to catalyze this reaction. We are investigating the electronic structures and reactivities of iron-NO complexes (in particular iron porphyrins) to elucidate the reaction mechanisms of these NORs using a two-pronged approach. Biophysical studies in collaboration with the Ballou laboratory (Department of Biological Chemistry, University of Michigan) focus on cytochrome P450s and flavodiiron proteins, using enzyme expression and purification, site-directed mutagenesis, and spectroscopic studies applying UV-Vis absorption, electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), resonance Raman, nuclear resonance vibrational spectroscopy (NRVS), and stopped-flow absorption spectroscopy. In our biomimetic inorganic studies, we are developing synthetic inorganic model systems for these NOR enzymes to study their reaction mechanisms. First, "simple" model complexes of type [Fe(TPP*)(L)(NO)]n+ (TPP* = tetraphenylporphyrin type ligand; L = N-donor, thiolate, etc.) are synthesized, which allow for the routine investigation of the porphyrin substituent and trans-ligand effect on the coordinated NO. This is followed by the design and synthesis of specifically tailored model systems for these enzymes that capture key features of their active sites. These compounds are then investigated using a variety of spectroscopic techniques (see above) in correlation with DFT calculations. The obtained results are not only important for the understanding of the mechanisms of these enzymes, but are also relevant for the various other biological functions of NO mentioned above, as mediated by nitric oxide synthase (NOS), soluble guanylate cyclase (sGC), and nitrophorins. In dissimilatory denitrification, nitric oxide is produced by the reduction of nitrite (see above), which (amongst others) is performed by a Cu enzyme (CuNIR). In collaboration with Prof. Dr. K. Fujisawa (University of Tsukuba, Japan), model studies on this enzyme are performed using hydrotris(pyrazolyl)borate, tris(pyrazolyl)¬methane, and bis(pyrazolyl)methane ligands. Finally, the coordination chemistry of Ru(III) complexes with NO is also explored as a means of NO-delivery and photochemical release in vivo. The synthesized model complexes are investigated using the multitude of spectroscopic techniques mentioned above.

    Political leaders around the world are calling to move from the total reliance on fossil fuel to an energy economy based on alternatives to petroleum. In this respect, hydrogen is the ultimate clean fuel with the highest achievable energy density, and its use as primary energy source is therefore desirable. However, ~95% of the current hydrogen production stems from natural gas reforming, and hence, from fossil fuels. Hydrogen could be produced electrochemically from water; however, current catalysts for hydrogen production are either inefficient or based on expensive (unsustainable) platinum catalysts. Besides the substantial cost factor, the global platinum production would not be sufficient to support the demand for electrochemical catalysts for a global hydrogen economy. Catalysts based on inexpensive and abundant metals are desperately needed for (a) electrochemical production of hydrogen as energy carrier, and (b) energy extraction (utilization) of hydrogen via oxidation in fuel cells to power, for example, automobiles. In particular, catalysts that are able to activate H2 for energy extraction are very rare. Nature provides a model for the design of such catalysts in the form of the hydrogenase enzymes, which are extremely efficient in catalyzing the generation and oxidation of hydrogen using dinuclear Fe-Fe and Ni-Fe clusters as catalysts. In our research, we are developing dinuclear Fe-Fe and mixed-metal clusters that are suitable for practical applications in fuel cells in collaboration with the Thompson laboratory (Department of Chemical Engineering, University of Michigan). These catalysts are organometallic analogs of the active sites of the hydrogenases, and hence, are biologically-inspired but not biomimetic in order to increase their stability and adapt them to the envisioned application conditions.

    Finally, we have started a new project that is focused on the development of porphyrin-based materials for optically-limiting and non-linear optical applications. Here, we put our expertise in the synthesis of functionalized porphyrins to work to generate materials that contain linked porphyrin building blocks.

    Awards
    • LS&A Award for Outstanding Contributions to Undergraduate Education, 2014
    • 3M Nontenured Faculty Grant, 2011
    • NSF Career Award, 2009
    • Japan Society for the Promotion of Science Invitation Fellowship, 2008
    • Dow Corning Assistant Professor of Chemistry, 2007
    Representative Publications

    M. G. I. Galinato, J. G. Kleingardner, S. E. J. Bowman, E. E. Alp, J. Zhao, K. L. Bren, N. Lehnert, "Heme-Protein Vibrational Couplings in Cytochrome c provide a Dynamic Link that Connects the Heme-Iron and the Protein Surface", Proc. Nat. Acad. Sci. U.S.A. 2012, 109, 8896 - 8900

    N. Lehnert, "Elucidating Second Coordination Sphere Effects in Heme Proteins using Low-Temperature Magnetic Circular Dichroism Spectroscopy", J. Inorg. Biochem. 2012, 110, 83?93

    A. C. Merkle, N. L. Fry, P. K. Mascharak, N. Lehnert, "The Mechanism of NO Photodissociation in Photolabile Manganese NO complexes with Pentadentate N5 Ligands", Inorg. Chem. 2011, 50, 12192-12203

    T. C. Berto, N. Lehnert, "DFT Modeling of the Proposed Nitrite Anhydrase Function of Hemoglobin in Hypoxia Sensing", Inorg. Chem. 2011, 50, 7361-7363

    T. C. Berto, M. B. Hoffman, Y. Murata, K. B. Landenberger, E. E. Alp, J. Zhao, N. Lehnert, "Structural and Electronic Characterization of Non-Heme Fe(II)-Nitrosyls as Biomimetic Models of the FeB Center of Bacterial Nitric Oxide Reductase (NorBC)", J. Am. Chem. Soc. 2011, 133, 16714?16717

    M. G. I. Galinato, T. Spolitak, D. P. Ballou, N. Lehnert, "Elucidating the Role of the Hydrogen Bonding Network in Ferric Cytochrome P450cam and corresponding Mutants using Magnetic Circular Dichroism Spectroscopy". Biochemistry 2011, 50, 1053-1069.

    M. G. I. Galinato, C. M. Whaley, D. Roberts, P. Wang, N. Lehnert, "Favorable protonation of the (mu-edt)[Fe2(PMe3)4(CO)2(H-terminal)] hydrogenase model complex over its bridging mu-H counterpart: a spectroscopic and DFT study". Eur. J. Inorg. Chem, 2011, 1147-1154 (special issue: Hydrogenases)

    N. Lehnert, J. T. Sage, N. Silvernail, W. R. Scheidt, E. E. Alp, W. Sturhahn, J. Zhao, "Oriented Single-Crystal Nuclear Resonance Vibrational Spectroscopy of [Fe(TPP)(MI)(NO)]: Quantitative Assessment of the trans Effect of NO", Inorg. Chem. 2010, 49, 7197-7215

    T. C. Berto, V. K. K. Praneeth, L. E. Goodrich, N. Lehnert, "Iron-Porphyrin NO Complexes with Covalently Attached N-Donor Ligands: The Formation of a Stable Six-Coordinate Species in Solution", J. Am. Chem. Soc. 2009, 131, 17116-17126

    V. K. K. Praneeth, F. Paulat, T. C. Berto, S. DeBeer George, C. Nather, C. D. Sulok, N. Lehnert, "Electronic Structure of Six-Coordinate Iron(III)-Porphyrin NO Adducts: the Elusive Fe(III)-NO(radical) State and Its Influence on the Properties of these Complexes", J. Am. Chem. Soc. 2008, 130, 15288-15303

    K. Fujisawa, A. Tateda, T. Ono, Y. Miyashita, K. Okamoto, F. Paulat, V. K. K. Praneeth, A. Merkle, N. Lehnert, "Structural and Spectroscopic Characterization of Mononuclear Copper(I) Nitrosyl Complexes: End-on versus Side-on Coordination of NO to Copper(I)", J. Am. Chem. Soc. 2008, 130, 1205-1213

  • Education
    • PhD: University Mainz, Germany
      Biophysical Chemistry
      Energy Science
      Inorganic Chemistry
      Physical Chemistry
      Sustainable Chemistry
  • Awards
    • NSF Career Award 2009
  • Research Areas of Interest
    • Bioinorganic Chemistry
      Biophysical Chemistry
      Energy Science
      Inorganic Chemistry
      Organometallic Chemistry
      Physical Chemistry
      Sustainable Chemistry
      Physical Inorganic Chemistry
      Spectroscopy
      Bioorganometallic Chemistry
      Heme-Nitrosyl Model Complexes, Porphyrins, Nitric Oxide, Denitrification, Density-Functional Calculations