faculty

Assistant Professor of Chemistry
Ph.D., University Mainz, Germany

Bioinorganic Chemistry, Physical Inorganic Chemistry, Spectroscopy, Bioorganometallic Chemistry, Heme-Nitrosyl Model Complexes, Porphyrins, Nitric Oxide, Denitrification, Density-Functional Calculations

Phone:  734 615-3673   
E-mail: lehnertn@umich.edu

Research Group

Research projects that are currently pursued in my group relate to the biological nitric oxide (NO) metabolism; i.e. the synthesis, function and degradation of nitric oxide in the biosphere. Nitric oxide is a poisonous gas, which, however, has proven to be of great biological significance. In 1992, it was therefore voted as 'the molecule of the year' by the magazine Science. These pioneering results triggered further research and up to this day, it is known that NO plays a key role in nerve signal transduction, vasodilation, blood clotting and immune response by white blood cells. New biological functions of NO and the corresponding, one electron reduced nitroxyl ion are still discovered. Many of the biologically important reactions of nitric oxide are mediated by heme proteins. NO is produced in vivo by the nitric oxide synthase (NOS) family of enzymes. The cardiovascular regulation by NO (produced by endothelial(e-) NOS) is then mediated by soluble guanylate cyclase (sGC), which is activated by coordination of NO to its ferrous heme active site. In addition, 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 intermediate in dissimilatory denitrification, which corresponds to the stepwise reduction of nitrate to dinitrogen in the following equation.

NO is produced by nitrite reductase (NIR) and further reduced to nitrous oxide by the nitric oxide reductases (NOR). We are especially interested in the latter class of enzymes.

Bacterial NOR (NorBC) reduces NO to nitrous oxide (N2O) 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. Hence, the bacterial and fungal enzymes catalyze the same reaction, but utilize different mechanisms. Central research goals are the elucidation of the reaction mechanisms of these enzymes and the properties of heme-nitrosyls in general as a function of porphyrin substitutions and trans-ligands to NO. To this end, a dual strategy is applied. Firstly, "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. Complementarily, we are working on the synthesis of sophisticated model complexes for both NorBC and P450nor. These compounds are then investigated using a variety of spectroscopic techniques (see below) 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 various biological functions of NO related to nitric oxide synthase (NOS), soluble guanylate cyclase (sGC), and NO transport proteins in blood-sucking insects (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 nitrous oxide, the product of NO reductase activity, is explored using Ru(II) complexes. The synthesized model complexes are then investigated using a multitude of spectroscopic techniques (see below).

Besides the research on the biological role of nitric oxide, we are also very interested in the fields of (a) Bioorganometallic Chemistry; i.e. the conduction of organometallic chemistry in aqueous solution using proteins with modified active sites. In this respect, I am especially interested in the usage of small heme proteins for organometallic reactions; and (b) Anti-Cancer Drugs based on Ru-NO compounds, especially their interaction with DNA, their photophysical properties, and their mechanisms of activation. These research areas are currently developed in my group.

Research projects in my group usually involve:

• the synthesis of model complexes which serve as structural or functional models for the enzymes that we are interested in;
• the detailed spectroscopic investigation of these model complexes or the enzymes themselves using vibrational (FT-IR and resonance Raman), magnetic circular dichroism (MCD), electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), and Mössbauer spectroscopy coupled to the simulation of obtained data to extract insightful spectroscopic parameters (force constants, zero-field splitting parameters, polarizations of electronic transitions, etc.);
• the application of density functional theory (DFT) calculations to further evaluate the spectroscopic results, to define the electronic structures of the systems under investigation, and to explore potential reactivities of these metal sites.

These studies ultimately aim at elucidating the catalytic mechanism of the respective enzyme on a molecular level.

REPRESENTATIVE PUBLICATIONS

1. 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


2. F. Paulat, N. Lehnert, "Detailed Assignment of the Magnetic Circular Dichroism and UV-Vis Spectra of Five-Coordinate High-Spin Ferric [Fe(TPP)(Cl)]", Inorg. Chem. 2008 , 47 , in press


3. N. Lehnert, "Electron Paramagnetic Resonance and Low-Temperature Magnetic Circular Dichroism Spectroscopy of Ferrous Heme Nitrosyls"; in: "The Smallest Biomolecules: Perspectives on Heme-Diatomic Interactions"; Ghosh, A., ed., Elsevier, Amsterdam, 2008


4. N. Lehnert, U. Cornelissen, F. Neese, T. Ono, Y. Noguchi, K. Okamoto, K. Fujisawa, "Synthesis and Spectroscopic Characterization of Cu(II)-Nitrito Complexes with Hydrotris(pyrazolyl)borate and related Coligands", Inorg. Chem. 2007 , 46 , 3916-3933


5. F. Paulat, N. Lehnert, "Electronic Structure of Ferric Heme Nitrosyl Complexes with Thiolate Coordination", Inorg. Chem. 2007 , 46 , 1547-1549


6. N. Lehnert, V. K. K. Praneeth, F. Paulat, "Electronic Structure of Fe(II)-Porphyrin Nitroxyl Complexes: Molecular Mechanism of fungal Nitric Oxide Reductase (P450nor)" , J. Comput. Chem. 2006 , 27 , 1338-1351 (special issue: Theoretical Bioinorganic Chemistry)


7. F. Paulat, V. K. K. Praneeth, C. Näther, N. Lehnert, "Quantum Chemistry-Based Analysis of the Vibrational Spectra of Five-Coordinate Metalloporphyrins [M(TPP)Cl]", Inorg. Chem. 2006 , 45 , 2835-2856


8. V. K. K. Praneeth, C. Näther, G. Peters, N. Lehnert, "Spectroscopic Properties and Electronic Structure of Five- and Six-Coordinate Iron(II)-Porphyrin NO Complexes: Effect of the axial N-Donor Ligand", Inorg. Chem. 2006 , 45 , 2795-2811


9. F. Paulat, T. Kuschel, C. Näther, V. K. K. Praneeth, O. Sander, N. Lehnert , "Spectroscopic Properties and Electronic Structure of Pentammineruthenium(II) Dinitrogen Oxide and corresponding Nitrosyl Complexes: Binding Mode of N 2 O and Reactivity", Inorg. Chem. 2004 , 43 , 6979-6994


10. K. Fujisawa, N. Lehnert, Y. Ishikawa, K. Okamoto, "Diazene Complexes of Copper: Synthesis, Spectroscopic Analysis, and Electronic Structure", Angew. Chem. 2004 , (Int. Ed.) , 43 , 4944-4947