Bioinorganic Chemistry

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).

Our research focuses on model systems for denitrifying enzymes, especially the nitrite (NO₂^-), nitric oxide (NO) and nitrous oxide (N₂O) reductases. One major goal of this research is the investigation of the different mechanisms of activation of complex bound NO. In this respect, we synthesize model systems using Schlenk techniques and determine their spectroscopic and electrochemical properties. This information is then correlated to the experimentally known reactivities of these systems and the postulated mechanisms of the enzymatic reactions using quantum-chemical calculations. The synthetic work mainly focuses on various porphyrin ligands, their transition metal complexes and corresponding NO adducts as well as studies of their reactivity.

We are especially interested in the nitric oxide reductases (NORs), which allow to study the reactivity of coordinated NO as a function of active site variations in different 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 as shown in Scheme 1 . 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 systematic 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 Research home) in correlation with density functional theory (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 as described above.