Enzymatic Methane Hydroxylation: sMMO and pMMO
53
bonding and the energy barrier for the activation of a methane C–H bond, to compare
them with corresponding experimental values.
A further improvement in studying the reactivity of MMOH Q toward methane is
to incorporate entire protein of sMMO. In this direction, Noodlemann et al. investigated at 2001 the structure of active site in sMMO by considering electrostatic
interactions between the active site and the protein environment, and found that the
protein plays an influential role in determining the structure and the energetics of
the active site [90–93]. After the development in the computation of the enzymatic
reactions, Morokuma et al. [73] directly incorporated protein environments by using
mixed quantum mechanics/molecular mechanics (QM/MM) ONIOM approaches
[108, 109]. ONIOM calculations found that the protein environments control local
structures of the active sites of MMOH ox and MMOH red . After that, Friesner group
also performed QM/MM calculations containing ~7200 atoms to investigate the
potential energy surface of the methane to methanol conversion by MMOH Q [87, 88].
3 Key Factors in Determining Reactivity of MMOH Q
Toward Methane
First, let us discuss key factors in determining the reactivity of MMOH Q , summarized
in Table 1. One is the coordination number of iron cations in the active site of
MMOH Q , and the other is its spin state. Although EXAFS studies [30] suggested that
MMOH Q has an iron cation whose coordination number is no greater than 5, its exact
structure has not been clear. Because of the uncertainty in the coordination number
of iron cations in MMOH Q , different computational models have been proposed.
Models that contain octahedrally-coordinated diiron species were used by many
research groups (e.g. Siegbahn [59, 63], Morokuma [66, 68, 74], and Friesner [77,
83] groups). In contrast, Yoshizawa group used a different model containing 4- or
5-coordinated diiron species [44, 46, 52, 53, 56], putting considerable emphasis on
the EXAFS findings.
As is well known, the coordination number of iron cations determines their
d-orbital splitting. When an iron atom is octahedrally coordinated, the relevant d
orbitals are splitting into three low-lying t 2g orbitals and two highly-lying e g orbitals
[110]. If MMOH Q involves a kind of edge-shared six-coordinate diiron(IV) complex
where iron–iron interaction is weak, energy levels of their d-based frontier orbitals are
basically described in Fig. 5a. Since formal charge of each iron cation in MMOH Q
is +4, each iron cation has four d-electrons. Accordingly MMOH Q has eight delectrons that are housed on the split d orbitals. Depending on how eight electrons
are housed on the split d orbitals, there are at least four types of spin states in MMOH Q ,
as depicted in Fig. 5b–e. In
9 A or
5 A, four parallel spins (high-spin (HS)) or two
parallel spins (intermediate-spin (IS)) on both iron cations are ferromagnetically
coupled, respectively. On the other hand, antiferromagnetically coupled diiron(IV)
53
bonding and the energy barrier for the activation of a methane C–H bond, to compare
them with corresponding experimental values.
A further improvement in studying the reactivity of MMOH Q toward methane is
to incorporate entire protein of sMMO. In this direction, Noodlemann et al. investigated at 2001 the structure of active site in sMMO by considering electrostatic
interactions between the active site and the protein environment, and found that the
protein plays an influential role in determining the structure and the energetics of
the active site [90–93]. After the development in the computation of the enzymatic
reactions, Morokuma et al. [73] directly incorporated protein environments by using
mixed quantum mechanics/molecular mechanics (QM/MM) ONIOM approaches
[108, 109]. ONIOM calculations found that the protein environments control local
structures of the active sites of MMOH ox and MMOH red . After that, Friesner group
also performed QM/MM calculations containing ~7200 atoms to investigate the
potential energy surface of the methane to methanol conversion by MMOH Q [87, 88].
3 Key Factors in Determining Reactivity of MMOH Q
Toward Methane
First, let us discuss key factors in determining the reactivity of MMOH Q , summarized
in Table 1. One is the coordination number of iron cations in the active site of
MMOH Q , and the other is its spin state. Although EXAFS studies [30] suggested that
MMOH Q has an iron cation whose coordination number is no greater than 5, its exact
structure has not been clear. Because of the uncertainty in the coordination number
of iron cations in MMOH Q , different computational models have been proposed.
Models that contain octahedrally-coordinated diiron species were used by many
research groups (e.g. Siegbahn [59, 63], Morokuma [66, 68, 74], and Friesner [77,
83] groups). In contrast, Yoshizawa group used a different model containing 4- or
5-coordinated diiron species [44, 46, 52, 53, 56], putting considerable emphasis on
the EXAFS findings.
As is well known, the coordination number of iron cations determines their
d-orbital splitting. When an iron atom is octahedrally coordinated, the relevant d
orbitals are splitting into three low-lying t 2g orbitals and two highly-lying e g orbitals
[110]. If MMOH Q involves a kind of edge-shared six-coordinate diiron(IV) complex
where iron–iron interaction is weak, energy levels of their d-based frontier orbitals are
basically described in Fig. 5a. Since formal charge of each iron cation in MMOH Q
is +4, each iron cation has four d-electrons. Accordingly MMOH Q has eight delectrons that are housed on the split d orbitals. Depending on how eight electrons
are housed on the split d orbitals, there are at least four types of spin states in MMOH Q ,
as depicted in Fig. 5b–e. In
9 A or
5 A, four parallel spins (high-spin (HS)) or two
parallel spins (intermediate-spin (IS)) on both iron cations are ferromagnetically
coupled, respectively. On the other hand, antiferromagnetically coupled diiron(IV)