Book chapter on sulfur oxygenation and functional models of NHase

Chapter 12 in the book “Bioinspired Catalysis”

Authors: Davinder Kumar and Craig A. Grapperhaus

This chapter highlights selected complexes with tetra- and penta-dentate chelates that provide key insights into the oxidized sulfur environment at the enzyme active site. Small-molecule mimics with variable S-oxidation levels provide an attractive method to address these interactions. It discusses a brief history of metal-thiolate sulfur-oxygenation is provided, followed by selected S-oxygenation studies relevant to nitrile hydratase (NHase). The NHase are divided by metal type and organized according to the donor atoms of the chelates. Several ruthenium catalysts have been reported as nitrile hydration catalysts. Ruthenium is also a logical choice for oxidation studies as the second-row transition metal maintains a consistent low spin, which was found to promote S-oxygenation.

The Importance of Oxidation in VCTLCSC

Just before my sabbatical on this blog, I was looking at the length of bonds which linked the metal to the sulphurs of the cysteine residues to test the state of evidence in the small molecule cystallographic record on how oxidation might change such bond lengths. There wasn't much data around for Co and Fe based systems to draw many inferences from. However, a new paper is just out looking at a model system based around Ru which has been synthesized in the various oxidation states of sulphur with the hope of giving some clues on what sulphur oxidation might offer to NHases.

Influence of Sequential Thiolate Oxidation on a Nitrile Hydratase Mimic Probed by Multiedge X-ray Absorption Spectroscopy by Jason Shearer, Paige E. Callan, César A. Masitas, and Craig A. Grapperhaus in Inorganic Chemistry (DOI: 10.1021/ic202453c).

They use a range of techniques including multiedge X-ray absorption spectroscopy and some serious hardcore DFT calculations to look at/predict how ionic and how Lewis acidic the complexed metal becomes as the sulphur ligands are sequentially oxygenated. Basically you get a harder Lewis acid as you move from naked sulphur through to a mixed sulfenato/sulfinato species. As the abstract graphic shows....

In the final few paragraphs, they speculate what this means for the mechanism of nitrile hydratase hydration (they say "hydrolysis" but that means the complete breaking up the whole bond to acid and ammonia in my book, not just breaking a couple of pi bonds with a molecule of water.). They show versions of the two most commonly proposed models- metal-bound hydroxide attacking a free floating nitrile, and metal-bound nitrile getting walloped by a hydroxide. They suggest that increasing hardness of the metal centre should favour the attachment of an oxygen based ligand over the nitrogen of a nitrile, and hence favour the metal bound hydroxide model. They end with the comment that harder Lewis acidity would actually aid NHase catalysis whatever was bound to the metal.