Quantum Chemistry serving biotechnologies: the interesting case of metalloenzyme active sites

Chemistry of life involves a huge number of reactions that needs bioinorganic catalysts, such as metalloenzymes. 1 Thanks to these proteins, Nature can accomplish some of the most thermodynamically and kinetically challenging chemical tasks, at outstanding rates, at room pressure and temperature, and by means of only cheap and bioavailable metal ions. Since a longstanding goal in chemistry is the replacement of noble metal-based catalysts with the use of first row (relatively earth-abundant) transition metals, scientists have devoted intensive efforts in the study of these natural machineries. Their final aim is to uncover the basic principles of metalloenzymes reactivity, and to transfer them into the design of noblemetal-free synthetic devices, such as homogeneous biomimetic catalysts, able to carry out the same transformations of the natural systems.2 Such so-called biomimetic approach is sometimes inescapable, since the direct utilization of metalloenzymes, for the development of inexpensive and efficient technological systems, is often prohibitive. 3 Because of the elusive and intrinsically complicated chemistry of transition metals, experimental investigations generally need to be complemented by the use of computational tools (especially Quantum-Mechanical ones), which are becoming more and more popular in this research area. The main focus of our research is the QM investigation, in the Density Functional Theory (DFT) framework, of two specific iron-sulfur metalloenzymes and their related biomimetic catalysts. Both systems under study, namely [FeFe]-hydrogenases and [Mo (or V)]-nitrogenases enzymes, are intriguing for their potential application in the biofuel production and energy storage fields.4,5 Indeed, [FeFe]-hydrogenases can reversibly store energy in the form of molecular hydrogen (starting from protons and electrons), which can be used as green and powerful fuel.4 Nitrogenases, instead, are incredibly efficient in reducing highly inert substrates into value-added chemical. Remarkably, they can also activate CO2 and recycle it by its direct conversion into hydrocarbons.6 These two cases study will be taken into account to illustrate the role and the predictive power of DFT tools in the rational design of biomimetic catalysts and in the development/tuning of their reactivity and molecular properties.