Cytochrome P450s are a ubiquitous class of heme proteins which utilize a proximal thiolate ligand to catalyze challenging and complex chemical transformations. A unique class of the P450 superfamily, cytochrome P450 nitric oxide reductases (Cyt P450nor), catalyze the reduction of nitric oxide (NO) to nitrous oxide (N<sub>2</sub>O) and as a result prevent the accumulation of this toxic metabolite during anaerobic respiration in soil dwelling fungi and yeast. In the proposed mechanism of Cyt P450nor, a ferric heme binds NO to form a ferric heme-nitrosyl complex, which subsequently reacts with NADH and another equivalent of NO to close the catalytic cycle. These ferric heme-nitrosyls with thiolate coordination are stable in a protein environment, but the generation of a stable model complex remains highly elusive. This is challenging due to reductive nitrosylation of the ferric heme in the presence of excess NO and the decomposition of the complex by nitrosylation of the thiolate ligand resulting in a ferrous heme-nitrosyl complex. This work focuses on the use of a doubly hydrogen-bonded thiolate ligand, S-2,6-di(trifluoracetylamino) thiophenol and other unique thiolate ligands, to prevent these undesirable side reactions. Here, preparation and characterization of these ferric complexes and their reactivity with NO at low temperatures is presented with the use of an <i>in situ</i> UV-Vis spectroscopy immersion probe. The corresponding ferric heme-nitrosyls with thiolate coordination are characterized using a range of different spectroscopic methods to further understand the effect of the thiolates donor strength on the Fe-NO unit in relation to their enzymatic function in Cyt P45nor.

Synthesis and spectroscopic characterization of ferric heme-thiolate complexes as models for cytochrome P450nor

254th National Meeting (2017)

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