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We have performed hybrid density functional theory (DFT)calculationson the reactivities of low-lying doublet and quartet ferryl–oxo[Fe(IV)O] oxidants and a doublet perferryl–oxo [Fe(V)O]oxidant as a new key active species in cytochrome P450. Several aspectsof the mechanism of hydrogen-atom abstraction from propane by theabove active species of compound I models have been addressed in detail.The results, based on fully optimized structures, demonstrate thatthe perferryl–oxo oxidant can contribute to the reactivityof compound I owing to the presence of a highly reactive pπatomic radical character of the oxo ligand. The perferryl–oxospecies can abstract a hydrogen atom from propane with an activationbarrier of only 0.6–2.5 kcal mol–1, whichis substantially smaller than that for the ferryl–oxo species(13.4–17.8 kcal mol–1). The role of the doubletperferryl species in the heterolytic and homolytic O–O bondcleavage in precursor (protonated) compound 0 coupled with the subsequentC–H bond activation has also been explored by grid search offerryl and perferryl potential surfaces using two parameters. Ourcalculations suggest that the perferryl–oxo oxidant is catalyticallycompetent, if the O–O bond cleaves heterolytically. The interplaybetween the accessible ferryl and perferryl states of compound I withquite different reactivities could be a possible reason for elusivenessof compound I in native P450 catalysis on the one hand and variousdegrees of detection in shunt reactions using peroxy acids on theother hand. [ABSTRACT FROM AUTHOR]

We have performed hybrid density functional theory (DFT) calculations on the geometric and electronic structures of low-lying doublet and quartet ferryl–oxo [Fe(IV)O] oxidants and a doublet perferryl–oxo [Fe(V)O] oxidant in Cytochrome P450. Fully optimized structures of compound I models have been determined, and the proper symmetry of wave functions has been restored by the spin-projection technique. The results show that the perferryl–oxo species is relatively low lying, as compared with the excited state of the ferryl–oxo species, if the iron–oxo bond is properly described as the mixing of several appropriate excited electronic configurations to minimize electron repulsion. This means that the perferryl–oxo species is virtually in a mixed-valent resonance state, ↑Fe(V)O ↔ ↑Fe(IV)•↑–↓•O, containing a highly reactive pπ atomic oxygen radical. The anionic thiolate ligand acts as a Lewis σ base and functions to achieve the stability of the perferryl–oxo complex and to activate the oxo ligand trans to it by asymmetric bond distortion along the O–Fe–S axis by lengthening the Fe–O bond and shortening the Fe–S bond, prior to the hydrogen-atom abstraction from the substrate. [ABSTRACT FROM AUTHOR]

The primary coordination sphere of the multinuclear cofactor (Mn 4 CaO x ) in the oxygen-evolving complex (OEC) of photosystem II is absolutely conserved to maintain its structure and function. Recent time-resolved serial femtosecond crystallography identified large reorganization of the primary coordination sphere in the S 2 to S 3 transition, which elicits a cascade of events involving Mn oxidation and water molecule binding to a putative catalytic Mn site. We examined how the crystallographic fields, created by transient conformational states of the OEC at various time points, affect the thermodynamics of various isomers of the Mn cluster using DFT calculations, with an aim of comprehending the functional roles of the flexible primary coordination sphere in the S 2 to S 3 transition and in the recovery of the S 2 state. The results show that the relative movements of surrounding residues change the size and shape of the cavity of the cluster and thereby affect the thermodynamics of various catalytic intermediates as well as the ability to capture a new water molecule at a coordinatively unsaturated site. The implication of these findings is that the protein dynamics may serve to gate the catalytic reaction efficiently by controlling the sequence of Mn oxidation/reduction and water binding/release. This interpretation is consistent with EPR experiments; g ∼ 5 and g ∼ 3 signals obtained after near-infrared (NIR) excitation of the S 3 state at 4 K and a g ∼ 5 only signal produced after prolonged incubation of the S 3 state at 77 K can be best explained as originating from water-bound S 2 clusters ( S total = 7/2) under a S 3 ligand field, i.e., the immediate one-electron reduction products of the oxyl-oxo ( S total = 6) and hydroxo-oxo ( S total = 3) species in the S 3 state.

The O 2 release of the oxygen-evolving complex of the photosystem II (PSII) is one of the essential processes responsible for the highly efficient O 2 production. Despite its importance, the detailed molecular mechanism is still unsolved. In the present study, we show that the O 2 release is directly coupled with water insertion into the Mn cluster based on the quantum mechanics/molecular mechanics (QM/MM) calculations. In this mechanism, the O 2 molecule first dissociates from the Mn sites in order, that is, the O atom coordinating to the Mn3 (O5a) first dissociates, then the other O atom coordinating to the Mn1 (O5d) dissociates in the next step in the late S 4 state (1 → 2). Next, the O 2 migrates to a space surrounded by the Val185 and His332 side chains as one water molecule coordinating to the Ca 2+ ion (W3) comes into the O 2 bonded site (2 → 3). Finally, a pre-S 0 state (4) is formed after a proton transfer from the inserted water to the other proton acceptor site (W2) (3 → 4). The highest activation barrier during these reactions was found at the O 2 release step (2 → 3) that only requires E ⧧ = 12.7 kcal mol -1 ( G ⧧ = 10.4 kcal mol -1 ). A series of the reactions (2 → 3) look like a chain crash of billiard balls because the W3 is inserted into the catalytic center from the water-abundant side (Ca 2+ ion side), and then the O 2 moiety is pushed out to the opposite side (Val185 side). The hydrophobic residue of Val185 covers the active O5 site and forms an O 2 -specific permeation tunnel. The present sequential reactions clearly demonstrate the efficient removal of the toxic O 2 from the catalytic center and implications of the essential roles of Val185, Ca 2+ ions and water molecules, which are all present in the active site of PSII as the indispensable constituents.

We have studied the early phase of the S2 → S3 transition in the oxygen-evolving complex (OEC) of photosystem II using the hybrid density functional theory with a quantum mechanical model composed of 338-341 atoms. Special attention is given to the vital role of water molecules in the vicinity of the Mn4CaO5 core. Our results demonstrate how important the dynamic behavior of surrounding water molecules is in mediating critical chemical transformations such as binding and deprotonation of substrates and hydration of the catalytic site and identify a strong coupling of water-chain relocation near the redox-active tyrosine residue Tyr161 (TyrZ) with oxidation of the Mn4CaO5 cluster by TyrZ(•+). The oxidation reaction is further promoted when the catalytic site is more solvated by water. These results indicate the importance of surrounding water molecules in biological catalysts as they ultimately lead to effective catalytic function and/or favorable electron-transfer dynamics.