One- and two- electron reductions in miniSOG and their implication in catalysis

In the last years, the unconventional bioorthogonal catalytic activation of anticancer metal complexes by flavin and flavoproteins photocatalysis has been described [Alonso-de Castro et al., Angew. Chem.,Int. Ed., 2018, 57, 3143]. The reactivity is based on a two-electron redox reaction of the photoactivated flavin. Furthermore, when it comes to flavoproteins, we recently reported that site mutagenesis can modulate and improve this catalytic activity in miniSOG [Gurruchaga-Pereda et al., J. Phys. Chem. Lett., 2021, 12, 19, 4504]. In this paper, we analyze the reductive half-reaction in the different miniSOG environments by means of density functional theory. We observe that the redox properties of the flavin, and consequently, the reactivity of miniSOG changes upon selected mutations, unveiling the physico- chemical fundamentals of this modulation: the competition between the single and double reduction of the flavin, and the electron transfer probability from the protein to the flavin, which are both ultimately related to the stability of the electron accepting orbitals of the flavin in the different coordination modes. Both factors alter the reactivity of miniSOG, in line with the experimental results in the literature.