162
Y. Hori and T. Abe
5 Theoretical Predictions for a Methane Hydroxylation
Catalyst
pMMO has monocopper and dicopper sites, which is reported to play an essential role
in methane hydroxylation. The knowledge of the reaction mechanism of methane
hydroxylation by pMMO provides strategies for the catalytic design of methane
hydroxylation. The reaction mechanism by pMMO was explored by Yoshizawa and
Shiota, combining DFT and QM/MM methods [32]. They considered the monocopper and dicopper active sites of the enzyme as Cu
III –oxo (or Cu
II –O · ) and bis(μoxo)Cu
II Cu
III , respectively. The formation of the Cu
III –oxo species by reaction with
Cu
I species and O 2 is calculated to be endothermic by 17.8 kcal mol
−1 , while the
formation of the bis(μ-oxo)Cu
II Cu
III species by reaction with the dicopper site and
O 2 is exothermic by 59.3 kcal mol
−1 . QM/MM calculations show that the Cu
III –oxo
species is coordinated by His48, His72, and Glu75, and bis(μ-oxo)Cu
II Cu
III species
is coordinated by His33, His137, His139, and Glu35. In the dinuclear copper site, the
formal charge of the copper ion coordinated by Glu35 is assigned to be +3 and that of
the other copper ion is +2. Yoshizawa and Shiota alleged that the glutamate residues
play an important role in the compensation of electronic charges after the formation
of the copper–oxo species [32]. Both active species promote methane hydroxylation
under physiological conditions. The reaction mechanism involves H-abstraction of
methane by the oxygen atom in a mononuclear or dinuclear site, yielding a methyl
intermediate that is stabilized by coordination to copper. The intermediate then undergoes methyl migration from the metal to the hydroxo group, giving rise to methanol.
The transition energy of the C–H bond cleavage of methane and the formation energy
of the methanol complex are computed to be 16.6 and −52.9 kcal mol
−1 relative to
the Cu
III –oxo species and methane, respectively, in monocopper-oxo species, and
17.6 and −49.2 kcal mol
−1 relative to the bis(μ-oxo)Cu
II Cu
III species and methane,
respectively, in dicopper-oxo species. These mechanistic results using DFT calculations demonstrate that mono- or dicopper-oxo species as an active site has enough
potential for the methane activation, and the complex with a dicopper site is a
candidate for generating the active species for the methane activation.
According to the above knowledge, DFT was used to numerically assess the
catalytic performance of a dicopper complex, which used H 2 O 2 to catalyze the
selective hydroxylation of benzene to phenol, for the hydroxylation of methane to
methanol [33]. The focus was on the dicopper complex [Cu 2 (μ-OH)(6-hpa)](ClO 4 ) 3
(A) with a dinucleating ligand 1,2-bis[2-[bis(2-pyridylmethyl)aminomethyl]-6pyridyl]ethane (6-hpa), as shown in Fig. 10.
Complex A forms Cu
II O · and Cu
II O 2
· species as active species, using H 2 O 2
through three steps via intermediates with Cu 2 O 2 and (CuO 2 H) 2 cores [34]. DFT
calculations showed that the Cu
II O · and Cu
II O 2
· moieties in complex 1 are stably
separate owing to the long Cu–Cu distance of 6.06 Å. The computed potential energy
diagram of methane hydroxylation by complex 1 demonstrated that the reaction is
initiated by the C–H bond cleavage of methane by the Cu
II O · core rather than Cu
II O 2
·
core, because the activation energies are 10.2 and 34.0 kcal mol
−1 , respectively. The
Y. Hori and T. Abe
5 Theoretical Predictions for a Methane Hydroxylation
Catalyst
pMMO has monocopper and dicopper sites, which is reported to play an essential role
in methane hydroxylation. The knowledge of the reaction mechanism of methane
hydroxylation by pMMO provides strategies for the catalytic design of methane
hydroxylation. The reaction mechanism by pMMO was explored by Yoshizawa and
Shiota, combining DFT and QM/MM methods [32]. They considered the monocopper and dicopper active sites of the enzyme as Cu
III –oxo (or Cu
II –O · ) and bis(μoxo)Cu
II Cu
III , respectively. The formation of the Cu
III –oxo species by reaction with
Cu
I species and O 2 is calculated to be endothermic by 17.8 kcal mol
−1 , while the
formation of the bis(μ-oxo)Cu
II Cu
III species by reaction with the dicopper site and
O 2 is exothermic by 59.3 kcal mol
−1 . QM/MM calculations show that the Cu
III –oxo
species is coordinated by His48, His72, and Glu75, and bis(μ-oxo)Cu
II Cu
III species
is coordinated by His33, His137, His139, and Glu35. In the dinuclear copper site, the
formal charge of the copper ion coordinated by Glu35 is assigned to be +3 and that of
the other copper ion is +2. Yoshizawa and Shiota alleged that the glutamate residues
play an important role in the compensation of electronic charges after the formation
of the copper–oxo species [32]. Both active species promote methane hydroxylation
under physiological conditions. The reaction mechanism involves H-abstraction of
methane by the oxygen atom in a mononuclear or dinuclear site, yielding a methyl
intermediate that is stabilized by coordination to copper. The intermediate then undergoes methyl migration from the metal to the hydroxo group, giving rise to methanol.
The transition energy of the C–H bond cleavage of methane and the formation energy
of the methanol complex are computed to be 16.6 and −52.9 kcal mol
−1 relative to
the Cu
III –oxo species and methane, respectively, in monocopper-oxo species, and
17.6 and −49.2 kcal mol
−1 relative to the bis(μ-oxo)Cu
II Cu
III species and methane,
respectively, in dicopper-oxo species. These mechanistic results using DFT calculations demonstrate that mono- or dicopper-oxo species as an active site has enough
potential for the methane activation, and the complex with a dicopper site is a
candidate for generating the active species for the methane activation.
According to the above knowledge, DFT was used to numerically assess the
catalytic performance of a dicopper complex, which used H 2 O 2 to catalyze the
selective hydroxylation of benzene to phenol, for the hydroxylation of methane to
methanol [33]. The focus was on the dicopper complex [Cu 2 (μ-OH)(6-hpa)](ClO 4 ) 3
(A) with a dinucleating ligand 1,2-bis[2-[bis(2-pyridylmethyl)aminomethyl]-6pyridyl]ethane (6-hpa), as shown in Fig. 10.
Complex A forms Cu
II O · and Cu
II O 2
· species as active species, using H 2 O 2
through three steps via intermediates with Cu 2 O 2 and (CuO 2 H) 2 cores [34]. DFT
calculations showed that the Cu
II O · and Cu
II O 2
· moieties in complex 1 are stably
separate owing to the long Cu–Cu distance of 6.06 Å. The computed potential energy
diagram of methane hydroxylation by complex 1 demonstrated that the reaction is
initiated by the C–H bond cleavage of methane by the Cu
II O · core rather than Cu
II O 2
·
core, because the activation energies are 10.2 and 34.0 kcal mol
−1 , respectively. The