Bioinspired Tungsten Model Complexes for Acetylene Hydratase

For most of us, acetylene (C2H2) in known as a welding gas as its combustion produces a very hot flame. However, for the anaerobic bacterium Pelobacter acetylenicus acetylene is a source of food and the sole source of carbon. Acetylene is converted to ATP which provides the energy for the organism to live. In the first step, acetylene and one molecule of water react to acetaldehyde enabled by the enzyme Acetylene hydratase (AH), which is in many ways unique. It contains a tungsten atom at its core which is vital for its biological function. Tungsten represents the heaviest metal within the periodic table know to play a role in living organisms. Furthermore, AH is the only known enzyme that uses C2H2 as its natural substrate. Although it share structural features with other tungsten and molybdenum enzymes, it enables a completely other reaction type. How the enzyme performs this unusual reaction is largely unknown. This research proposal aims at the elucidation of factors that allow the enzyme to work. Enzymes are very large molecules which complicates their investigation. One of the possibilities to obtain information is the preparation of small chemical compounds that imitate the inner core of the enzyme which simplifies the investigation. The thus obtained knowledge will deliver detailed understanding on how the acetylene reacts and is converted to aldehyde. For this purpose tungsten compounds with a surrounding similar to that found in AH will be synthesized. In a stepwise way they will be exposed to acetylene and to water. The binding of acetylene to tungsten and water will be investigated by state-of-the-art chemical and analytical methods. The outcome of the research will not only increase the knowledge specifically on the enzyme, but also on the potential use acetylene in other chemical reactions.

Although very small, the acetylene molecule contains a significant amount of energy. Depending on how this energy is utilized, acetylene can serve as a welding gas for joining metal pieces or as a food source for the bacterium Pelobacter acetylenicus. This bacterium employs the enzyme acetylene hydratase (AH), which contains the bulky element tungsten (W) in a high oxidation state, to facilitate the reaction between water and acetylene. During this reaction, acetaldehyde is formed, which can then enter the metabolic cycle to produce ATP, the molecular unit of currency in life. However, the precise interaction between the enzyme, water, and acetylene remains unclear, necessitating modeling studies to elucidate this reaction. Moreover, acetylene derivatives are a versatile starting material for the development of new pharmaceuticals. Thus, research in this field not only benefits health care but also has the potential to reduce health costs. Inspired by nature's elegance, we aimed to create a tungsten compound that could facilitate the reaction between acetylene and water. We prepared various biomimetic tungsten compounds decorated with sulfur-rich ligands and reacted them with acetylene. This part of the study is significant because it enhances our understanding of tungsten-acetylene adducts, which are rare and not well understood. Depending on the strength of the acetylene binding to the tungsten center, reactions with nucleophiles can yield a variety of products. For example, in a basic aqueous solution, the acetylene ligand reduces to ethylene, accompanied by the oxidation of the metal center. Surprisingly, the W-acetylene adducts we prepared were unreactive toward acetylene hydration. Although they did not react with water, acetylene did react with other molecules (nucleophiles) in the presence of the tungsten center. This suggested that the desired acetylene hydration might occur as a two-step process. Indeed, when reacting a nitrogen-rich W complex with acetylene, we observed an intermediate vinyl species, which is a more reactive acetylene surrogate. This species readily reacts with water to yield acetaldehyde. For the first time, a model complex was found to facilitate the challenging reaction between acetylene and water. This discovery delivers an important biological insight: amino acid residues near the W center in the active site of AH could be crucial for reacting with acetylene before reacting with water. This idea could shift the course of research for enzyme modeling and for sustainable reactions involving alkynes.