Multi- and single-reference methods for the analysis of multi-state peroxidation of enolates

Abstract

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

Spin-Forbidden Addition of Molecular Oxygen to Stable Enol Intermediates—Decarboxylation of 2-Methyl-1-tetralone-2-carboxylic Acid

“…At the reactants asymptote, is 1.83, which is very close to the value obtained for isolated O (1.84), which indicates that the O=O bond is not perturbed by the substrate. This is different from what was observed for the interactions between O and the negatively charged enolates, for which was somewhat smaller, even at large internuclear distances [ 36 ]. Also at the reactants asymptote, is compatible with a double bond, while and are close to the expected values for single bonds ( ∼1).…”

“…For the CO-pathway, the system first has to overcome a barrier of around 22–29 kcal/mol (depending on the level of theory, see Table 1 ) on the triplet state. As commented above, the singlet state was significantly higher in energy, but contrary to what was observed for spin-forbidden reactions between a negatively charged enolate and molecular oxygen [ 36 ], the energy of the singlet state does not decrease with the approach of molecular oxygen and the substrate, and we observe either an energy plateau or even a barrier. For those systems, it was proposed that the reaction could also proceed via direct electron transfer, after which the reaction proceeds barrierless [ 30 ].…”

“…At this point, it is possible to compare the results obtained for this reaction with those obtained for the enzymatic cofactorless of O to organic substrates, for which the deprotonation of the substrate is a common preactivation step. When the substrate is deprotonated, there is no barrier on the triplet potential energy surface, and the rate constant of the process depends on the energy of the MECP and the hopping probability, the latter being increased by the negative charge of the system [ 27 , 36 ]. If O is added to a neutral substrate, there is a higher barrier on the triplet state, similar to or even higher than that associated with ISC.…”

“…[ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]), but there is no consensus mechanism. For example, the reaction catalyzed by glucose oxidase needs a proton donor (His516) [ 31 ], whereas for the DpgC-catalyzed reaction, peroxidation occurs without charged residues or water molecules that could act as a base [ 27 , 36 ].…”

Revisiting photocyclization of the donor–acceptor stenhouse adduct: missing pieces in the mechanistic jigsaw discovered

“…Multi-reference methods such as multistate complete active space second-order perturbation (MS-CASPT2), 30 multi-reference configuration interaction (MRCI) 31 and Semistochastic Heat-Bath Configuration Interaction (SHCI) 32 also show good performance in describing photoisomerizations including nonadiabatic processes. In this work, we carried out high-level MS-CASPT2 and state-average complete active space self-consistent field (SA-CASSCF) calculations using an (14 e , 11 o ) active space (active orbitals are shown in Fig.…”