Extended Hartree–Fock theory of chemical reactions. VIII. Hydroxylation reactions by P450

Abstract

ABSTRACT:We have investigated the reaction pathways for the primary hydroxylation reaction of trimethylmethane by a high-valent Fe(IV)AO porphyrincation radical species known as compound I at the B3LYP/CEP-31G level. The isoelectronic analogy of the Fe(IV)AO core of compound I to a molecular oxygen (O 2 ) has been successfully used to clarify the important roles of the singlet excited state of the Fe(IV)AO core in the alkane hydroxylation, which has hitherto been neglected. The reaction is initiated by the rate-determining hydrogen-atom abstraction from the substrate to give a discrete radical intermediate complex, in accordance with the conventional radical rebound mechanism. Similar to the chemistry of O 2 , however, one of the singlet excited states, i.e., the diradical component of the 1 ⌬ state of the Fe(IV)AO core intercepts the triplet ground state (the 3 ⌺ state) in the region of the transition state for the hydrogen abstraction. Our findings strongly indicate that the exchange polarization or intersystem crossing for the nonradiative transition to the locally singlet state is highly important to enhance the reactivity of compound I.

Extended Hartree–Fock theory of chemical reactions. IX. Diradical and perepoxide mechanisms for oxygenations of ethylene with molecular oxygen and iron‐oxo species are revisited

“…The spin coupling between the triplet ground state of the iron‐oxo core and doublet ligand radical provides the quartet 4 [ 3 (↑Fe(IV)O↑) 2 (·L↑)] ( 4 1 ) and doublet 2 [ 3 (↑Fe(IV)O↑) 2 (·L)] ( 2 1 ↓), leading to the so‐called two‐state reactivity (TSR) model 12, 13. On the other hand, our isolobal analogy in Scheme lends support previous four configurations model 26 since another two doublet excited configurations 2 [ 1 (↑Fe(IV)O↓) 2 (·L↑)] ( 2 1 ′) and 2 [ 1 (↓Fe(IV)O↑) 2 (·L↑)] ( 2 1 ″) are resulted fro m the excited singlet states of 1 (Fe(IV)O) in analogy with atomic oxygen (O) and molecular oxygen (O 2 ). We have already elucidated the electronic structures and geometries of the four configurations of compound I (CpI) 26 with BS MO calculation with and without spin projection.…”

“…The isolobal analogy in Scheme provides possible mechanisms of epoxidation reactions of alkenes with the compound I, which is constructed of the Fe(IV)O core and ligand radical (·L). As shown previously 25, 26, the spin density on the ligand part (·L) is more or less populated over the porphyrine (Por) and sulfur atom (SR) of cysteine group (L = (Por)(SR)). The spin coupling between the triplet ground state of the iron‐oxo core and doublet ligand radical provides the quartet 4 [ 3 (↑Fe(IV)O↑) 2 (·L↑)] ( 4 1 ) and doublet 2 [ 3 (↑Fe(IV)O↑) 2 (·L)] ( 2 1 ↓), leading to the so‐called two‐state reactivity (TSR) model 12, 13.…”

“…For example, metal perepoxide intermediate may be formed in polar environments as in the case of singlet oxygen reaction investigated in Section 3.5: note that MPE formation is indeed compatible with ionic reactions such as NIH shift 16, 18–21. Thus, the isolobal analogy in Scheme is useful for qualitative understanding of both singlet ( 1 Δ xy ) and triplet ( 3 Σ xy ) metal DR mechanisms as well as singlet ( 1 Δ xx ) metal PE mechanism proposed previously 16, 18, 26. Further quantitative discussions require several BS calculations such as HDFT (B2LYP, B3LYP, MPW1K) and CCSD(T), together with the symmetry‐adapted (SA) CASPT2 calculation, including with solvation effects as shown in Section 3.…”

“…Judging from the computational results in Section 3, 2 SP2 for the MPE pathway seems less stable than the metal DR (MDR) pathways in gas phase as shown in Figure 11. The relative stability between them may be dependent on solvation energies and other factors such as polar substituents and participation of bound waters 26. The four configurations model along MDR pathway, together with the MPE pathway, based on Scheme is useful for qualitative understanding of both singlet ( 1 Δ xy ) and triplet ( 3 Σ xy ) metal DR mechanisms as well as singlet ( 1 Δ xx ) metal PE mechanism since the d yz spin on Fe ion remains intact for the bond exchange process though it plays an important role for the exchange stabilization 26.…”

“…The concept of orbital‐symmetry breaking and resulting diradical molecular orbitals (DODS) 16, 18–21 has been applied to elucidate orbital interaction schemes in epoxidation reactions with compound I (CpdI) as shown in Figures 9–11. Since CpdI can be regarded as a three spin system, four configurations model 26 including one quartet and three doublet configurations: 4 [ 3 (↑Fe(IV)O↑) 2 (·L↑)] ( 4 1 ), 2 [ 3 (↑Fe(IV)O↑) 2 (·L↓)] ( 2 1 ), 2 [ 1 (↑Fe(IV)O↓) 2 (·L↑)] ( 2 1 ′), and 2 [ 1 (↓Fe(IV)O↑) 2 (·L↑)] ( 2 1 ″), are inevitable for theoretical explanation of the diradical (DR) mechanisms for epoxidation of alkenes with CpdI. The local singlet diradical mechanism is concluded for 2 TS1( 2 1 ) and 2 TS1′ ( 2 1 ′) of CpdI on the basis of BS MO interaction schemes, whereas the local triplet diradical mechanism is resulted for 4 TS1 ( 4 1 ) and 2 TS1″ ( 2 1 ″).…”