Rational design provides an attractive strategy to tune and control the reactivity of bioinspired catalysts. Although there has been considerable progress in the design of heme oxidase mimetics with active-site environments of ever-growing complexity and catalytic efficiency, their stability during turnover is still an open challenge. Herein, we show that the simple incorporation of two 2-aminoisobutyric acids into an artificial peptide-based peroxidase results in a new catalyst (Fe -MC6*a) with higher resistance against oxidative damage and higher catalytic efficiency. The turnover number of this catalyst is twice as high as that of its predecessor. These results point out the protective role exerted by the peptide matrix and pave the way to the synthesis of robust bioinspired catalysts.

The folding of a synthetic mini-hydrogenase is shown to enhance catalyst efficiency and longevity.

Inspired by natural heme-proteins, scientists have attempted for decades to design efficient and selective metalloporphyrin-based oxidation catalysts. Starting from the pioneering work on small molecule mimics in the late 1970s, we have assisted to a tremendous progress in designing cages of different nature and complexity, able to accommodate metalloporphyrins. With the intent of tuning and controlling their reactivity, more and more sophisticated and diverse environments are continuously exploited. In this review, we will survey the current state of art in oxidation catalysis using iron- and manganese-porphyrins housed within designed or engineered protein cages. We will also examine the innovative metal-organic framework (MOF) systems, exploited to achieving an enzyme-like environment around the metalloporphyrin cofactor.

The cover feature picture shows balls enclosing two artificial heme peroxidases. The cracked crystal ball and the steel ball symbolize the different features of the two molecules. A previous catalyst (FeMC6*), which suffered from bleaching during catalysis, was made more robust and active by inserting 2‐aminoisobutyric acid residues (Aib), thus giving rise to a new molecule (FeMC6*a) with improved catalytic behavior. The Aib residues are painted inside a set of gear wheels to signify their importance for catalyst function and stability. More information can be found in the communication by A. Lombardi et al. on page 1823 in Issue 17, 2018 (DOI: 10.1002/cbic.201800200).