(Salen)Mn(III) compound as a nonpeptidyl mimic of catalase: DFT study of the metal oxidation by a peroxide molecule

Catalase mimics can be used as therapeutic agents against oxidative stress in treatment of many diseases, including Alzheimer's disease, stroke, heart disease, aging, and cancer. (Salen)Mn(III) compounds have been proven to be promising as synthetic antioxidants that, in particular, dismutate H2O2, resulting in two water molecules and oxygen. An understanding of the mechanism of the dismutation process is an important basis for rational design and tuning these analogues to yield better therapeutic properties. In addition, the study of the catalytic mechanism of the functional biomimetics of enzymes might contribute to a better understanding of the complex enzymatic activities for the corresponding biological compounds. For the first time, using the density functional theory method, we have performed a quantum chemical investigation of the catalase activity of the (salen)Mn(III) compound. The real compound reacting with a peroxide molecule has been utilized in the calculations to avoid uncertainties connected with using incomplete models. The reaction has been studied on three different spin potential energy surfaces: the singlet, the triplet, and the quintet. The same H2O2 dismutation process has been also calculated with participation of an additional water molecule to check the possible explicit involvement of the solvent molecules in the proton-transfer process in the course of the reaction. Our findings suggest that the first part of the dismutation reaction-the metal oxidation by a peroxide molecule-is a one-step process. The concerted breaking of the O-O peroxide bond, oxidation of the Mn, and a water molecule formation occur on the triplet state potential energy surface. This process can be done effectively at the Mn catalytic center with only 3.6 kcal/mol of activation energy needed. No energetic advantages were found for the assisted proton-transfer mechanism with participation of an ancillary water molecule. Although the singlet state is not accessible on the reactant and TS parts of the reaction potential surface, it becomes the ground state in the vicinity of the final geometry and can play an important role in the second part of the dismutation process.