Peptidic Scaffolds Enable Rapid and Multivariate Secondary Sphere Evolution for an Abiotic Metallocatalyst.

Area of Science:

• Bioinorganic Chemistry
• Catalysis
• Peptide Chemistry

Background:

• Metalloenzymes utilize secondary sphere interactions for efficient catalysis.
• Synthesizing complex abiotic scaffolds for these interactions is challenging.

Purpose of the Study:

• To develop a modular and rapid synthetic strategy for creating peptide-based ligand platforms.
• To enhance the catalytic activity of metalloenzymes by engineering the secondary coordination sphere.

Main Methods:

• Utilized solid-phase peptide synthesis and non-canonical amino acids.
• Constructed a ligand platform with up to four unique residues in the secondary coordination sphere.
• Applied the scaffold to an iron-based C-H oxidation catalyst.

Main Results:

• Achieved more than a twofold increase in catalytic activity for the iron catalyst.
• Identified a correlation between higher activity and a hydrophobic pocket above the iron center.
• Demonstrated that peptides provide a versatile platform for diverse secondary coordination spheres.

Conclusions:

• Peptide-based ligand platforms offer a modular and efficient approach to engineer metalloenzyme catalysis.
• Engineered secondary sphere interactions can significantly enhance catalyst performance.
• This strategy overcomes synthetic bottlenecks in creating complex catalytic systems.