Developing Biomolecular Hydrogen Evolution Catalysts Using De Novo Designed Self-Assembling Metallopeptides and Metallothionein Scaffolds

The imbalance between the consumption and production of energy is one of the global issues of the century. At present, the most used source of energy is fossil fuel. Even though these are non-renewable source of energy that depletes over time, burning fossil fuel can cause several environmental problems, which include significant issues such as global warming; ocean acidification; and the issues such as water pollution from coal mining. Thus, it is important to find a renewable and environmentally friendly source of energy to meet the increasing demands of the rapidly growing global population. Hydrogen is considered a secure and non-polluting energy source. This can be used as an alternative source of energy to the existing commonly used fossil fuel. This can thus contribute to a low-carbon future and bring down the global CO2 emission from fossil fuel combustion to a significant extent. [NiFe] hydrogenases are one type of metalloenzymes that can produce dihydrogen reversibly from protons and electrons. Even though these hydrogenases can offer a green source of H2; poor production yield, complexity, and O2 reactivity prevent the use of these hydrogenases for large-scale purposes. We employed a method known as the de novo design for the first time to design artificial hydrogenases (ArH) by mimicking the active site of these hydrogenases. This serves as a simpler, structural, and functional analog of complex metalloenzymes. The multi-metallic site is a characteristic of several enzymes including NiFe hydrogenase, FeFe hydrogenase, and acetyl-CoA synthase. Inspired by these enzymes, we explored the possibility of Metallothionein (MT) protein to use as a potential scaffold for ArH. MTs are Cys-rich metal-binding proteins found in a wide range of organisms ranging from bacteria to humans. These proteins have the affinity to bind to both essential and non-essential metals. The high metal affinity of these proteins is explored for the possibility of MT protein to use as an ArH. To summarise, this dissertation focuses on the construction of functional ArH using the de novo peptide design approach and using MT protein scaffold. Chapter 2 discusses a de novo-designed artificial metallopeptide hydrogenase and insights into photochemical processes. It also explains the role of protonates Cys in hydrogen production. This work has been published under the citation “ChemSusChem 2021, 14, 2237–2246”. Chapter 3 discusses the approach of exploring a thiol-rich metallothionein-2 protein towards HER. This chapter outlines the strategy of using a thiol-rich protein with a multi-metallic site for improving H2 production. This manuscript is under preparation and would be published. Chapter 4 discusses Ruthenium (Ru) conjugated Nickel- tetramer peptide using orthogonal protection of Cys, with the assumption of improved photocatalytic hydrogen production from the proximity of Ru and the Nickel center. This work will not be published now as it needs further investigation