Lewis, J.C.

ChemBioChem 2014, 15, 223-227, 10.1002/cbic.201300661

Strain‐promoted azide–alkyne cycloaddition (SPAAC) can be used to generate artificial metalloenzymes (ArMs) from scaffold proteins containing a p‐azido‐L‐phenylalanine (Az) residue and catalytically active bicyclononyne‐substituted metal complexes. The high efficiency of this reaction allows rapid ArM formation when using Az residues within the scaffold protein in the presence of cysteine residues or various reactive components of cellular lysate. In general, cofactor‐based ArM formation allows the use of any desired metal complex to build unique inorganic protein materials. SPAAC covalent linkage further decouples the native function of the scaffold from the installation process because it is not affected by native amino acid residues; as long as an Az residue can be incorporated, an ArM can be generated. We have demonstrated the scope of this method with respect to both the scaffold and cofactor components and established that the dirhodium ArMs generated can catalyze the decomposition of diazo compounds and both SiH and olefin insertion reactions involving these carbene precursors.

Jarvis, A.G.; Kamer, P.C.J.

Bioorg. Med. Chem. 2014, 22, 5657-5677, 10.1016/j.bmc.2014.07.002

Oxidation reactions are an important part of the synthetic organic chemist’s toolkit and continued advancements have, in many cases, resulted in high yields and selectivities. This review aims to give an overview of the current state-of-the-art in oxygenation reactions using both chemical and enzymatic processes, the design principles applied to date and a possible future in the direction of hybrid catalysts combining the best of chemical and natural design.

Lewis, J.C.

Tetrahedron 2014, 70, 4245-4249, 10.1016/j.tet.2014.03.008

New catalysts for non-directed hydrocarbon functionalization have great potential in organic synthesis. We hypothesized that incorporating a Mn-terpyridine cofactor into a protein scaffold would lead to artificial metalloenzymes (ArMs) in which the selectivity of the Mn cofactor could be controlled by the protein scaffold. We designed and synthesized a maleimide-substituted Mn-terpyridine cofactor and demonstrated that this cofactor could be incorporated into two different scaffold proteins to generate the desired ArMs. The structure and reactivity of one of these ArMs was explored, and the broad oxygenation capability of the Mn-terpyridine catalyst was maintained, providing a robust platform for optimization of ArMs for selective hydrocarbon functionalization.