Book chapters

Artificial metalloenzymes (ArMs) are an emerging class of biocatalysts that aim to merge the attractive features of homogeneous catalysis and biocatalysis. While mainly studied in vitro, recently there has been a growing interest in the application of artificial metalloenzymes in vivo. Reviewed herein are the different approaches to assemble artificial metalloenzymes in vivo and the main areas of application: for biocatalytic synthesis and for in vivo activation of anti-tumor drugs in or near cancer cells.

Supramolecular assembly has proven a powerful method for the creation of artificial metalloenzymes. Here we describe our work on DNA- and protein-based artificial metalloenzymes. These artificial metalloenzymes have proven potent catalysts in Lewis acid catalysis in many archetypal C-C bond forming reactions. Additionally, iron-porphyrin-based artificial metalloenzymes for cyclopropanation reactions were developed. It was shown that in most designs, structural dynamics, both conformational dynamics and cofactor-binding dynamics are very important for catalysis. Finally, new developments such as artificial enzyme containing two abiological catalytic groups for synergistic catalysis, as well as supramolecular assembly of artificial metalloenzymes in vivo and their application in catalysis are discussed.

Lewis acid catalysis is undisputedly of great significance for synthetic chemistry. Hence, many hybrid catalysts have been designed that can function as Lewis acid. These hybrid catalysts are based on DNA, protein, or peptide scaffolds. In this chapter an overview of the hybrid catalysts reported for three important classes of Lewis acid-catalyzed reactions is given: C-C bond-forming reactions, C-X bond-forming reactions, and hydrolysis reactions.

This chapter describes the use of DNA as chiral bio-scaffold in the design of hybrid catalysts and their application in asymmetric catalysis. Some current and relevant examples are discussed, followed by an overview of mechanistic studies. DNA-based asymmetric catalysis is an exponent of the general concept of hybrid catalysts, which aims to merge the attractive properties of homogeneous and bio-catalysis. There are two main approaches to the anchoring of a transition metal complex to DNA. In covalent anchoring, the ligand for the metal is attached to the DNA via a chemical bond. A particularly attractive aspect of supramolecular anchoring is the easy formation of the catalyst since it involves spontaneous self-assembly of the transition metal complex with DNA. Moreover, in this approach it is usually DNA from natural sources, such as calf thymus or salmon testes DNA, that is used.

The DNA molecule, which contains the blueprint of life, has played a pivotal role in the biological revolution. In recent years, many non-biological applications of this remarkable molecule have been explored. In this chapter we will review the use of DNA in metal catalysis. Three general approaches will be discussed: metal-dependent DNAzymes, DNA-templated catalysis, and the recently introduced concept of DNA-based asymmetric catalysis.