DpgC‐Catalyzed Peroxidation of 3,5‐Dihydroxyphenylacetyl‐CoA (DPA‐CoA): Insights into the Spin‐Forbidden Transition and Charge Transfer Mechanisms**

Abstract

Despite being a very strong oxidizing agent, most organic molecules are not oxidized in the presence of O2 at room temperature because O2 is a diradical whereas most organic molecules are closed‐shell. Oxidation then requires a change in the spin state of the system, which is forbidden according to non‐relativistic quantum theory. To overcome this limitation, oxygenases usually rely on metal or redox cofactors to catalyze the incorporation of, at least, one oxygen atom into an organic substrate. However, some oxygenases do not require any cofactor, and the detailed mechanism followed by these enzymes remains elusive. To fill this gap, here the mechanism for the enzymatic cofactor‐independent oxidation of 3,5‐dihydroxyphenylacetyl‐CoA (DPA‐CoA) is studied by combining multireference calculations on a model system with QM/MM calculations. Our results reveal that intersystem crossing takes place without requiring the previous protonation of molecular oxygen. The characterization of the electronic states reveals that electron transfer is concomitant with the triplet–singlet transition. The enzyme plays a passive role in promoting the intersystem crossing, although spontaneous reorganization of the water wire connecting the active site with the bulk presets the substrate for subsequent chemical transformations. The results show that the stabilization of the singlet radical‐pair between dioxygen and enolate is enough to promote spin‐forbidden reaction without the need for neither metal cofactors nor basic residues in the active site.

Nonadiabatic Effects in the Molecular Oxidation of Subnanometric Cu5 Clusters

“…The region of electron transfer corresponds to the crossing between ionic and neutral states. 3,28 It can be observed in Figure 1 that the chemisorption well of the Cu 5 (O 2 ) 3 complex correlates directly with the ionic O 2 − + (Cu 5 (O 2 ) 2 ) + interacting pair. This implies that the incoming oxygen molecule captures an electron from the Cu 5 (O 2 ) 2 complex, becoming chemisorbed as a superoxo ion O 2 − .…”

“…The region of electron transfer corresponds to the crossing between ionic and neutral states. 3 , 28 …”

“… 1 , 2 The latter are correlated to excited ionic states of the M–O 2 pair, where the character of the O 2 molecule is either of singlet or doublet spin multiplicity. 3 For a better understanding of O 2 reactivity, it is therefore necessary to calculate the transition along the reaction pathway between the triplet O 2 molecule in the gas phase and its associated singlet/doublet peroxo/superoxo form when engaging in chemical bonding.…”

“…In section 2 we provide a detailed description of the computational methods. Results are presented in section 3, which includes an extended analysis of the electronic structure of the Cu 5 (O 2 ) 3 2. COMPUTATIONAL METHODS 2.1.…”

“…In the gas phase, the ground state of O 2 is a triplet as the molecule holds two unpaired electrons. However, when reacting with another species M such as a molecule, a metal cluster, or an extended metal-oxide surface, the bonding is generally associated with peroxo (O 2 2– ) or superoxo (O 2 – ) forms of molecular oxygen. , The latter are correlated to excited ionic states of the M–O 2 pair, where the character of the O 2 molecule is either of singlet or doublet spin multiplicity . For a better understanding of O 2 reactivity, it is therefore necessary to calculate the transition along the reaction pathway between the triplet O 2 molecule in the gas phase and its associated singlet/doublet peroxo/superoxo form when engaging in chemical bonding.…”