Multi and Single-Reference Methods for the Analysis of Multi-State Peroxidation of Enolates

In spite of being spin-forbidden, some enzymes are capable of catalyzing the incorporation of O 2 ( 3 Σ − g ) toorganic substrates without needing any cofactor. It has been established that the process followed by theseenzymes starts with the deprotonation of the substrate forming an enolate. In a second stage, the peroxidationof the enolate formation occurs, a process in which the system changes its spin multiplicity from a triplet stateto a singlet state. In this article, we study the addition of O 2 to enolates using state-of-the-art multi-referenceand single-reference methods. Our results confirm that intersystem crossing is promoted by stabilization ofthe singlet state along the reaction path. When multi-reference methods are used, large active spaces arerequired, and in this situation, Semistochastic Heat-Bath Configuration Interaction (SHCI) emerges as apowerful method to study these multi-configurational systems and is in good agreement with LCCSD(T)when the system is well-represented by a single-configuration.