How Do the Thiolate Ligand and Its Relative Position Control the

Article pubs.acs.org/JPCA

How Do the Thiolate Ligand and Its Relative Position Control the Oxygen Activation in the Cysteine Dioxygenase Model? Xin Che, Jun Gao,* Dongju Zhang, and Chengbu Liu* Key Laboratory of Colloid and Interface Chemistry, Ministry of Education, Institute of Theoretical Chemistry, School of Chemistry & Chemical Engineering, Shandong University, Jinan 250100, P. R. China S Supporting Information *

ABSTRACT: In the iron(II)-thiolate models of cysteine dioxygenase, the thiolate ligand is a key factor in the oxygen activation. In this contribution, four model compounds have been theoretically investigated. This comparative study reveals that the thiolate ligand itself and its relative position are both important for the activation of O2. Before the O2 binding, the thiolate ligand must transfer charge to Fe(II), and the effective nuclear charges of Fe(II) is decreased, which results in a lower redox potential of compounds. In other words, the thiolate ligand provides a prerequisite for the O2 activation. Furthermore, the relative position of the thiolate ligand is discovered to determine the reaction path of O2 activation. The amount of charge transfer is crucial for these reactions; the more charge it transfers, the lower the related redox potentials. This work really helps think deeper into the O2 activation process of mononuclear nonheme iron enzymes.

1. INTRODUCTION Dioxygen is an essential molecule in every living organism, whose activation is responsible for many metabolically important transformations in biology.1−5 It is catalyzed by the dioxygen-activating enzymes, which comprise some mononuclear nonheme iron enzymes.6−9 Cysteine dioxygenase (CDO) is such an iron-dependent metalloprotease, whose function is to catalyze the oxidation reaction of cysteine during the oxygen activation process. This reaction is the first step of the cysteine catabolic pathway and plays a crucial role in the metabolism and bioconversion.10,11 So, CDO is vital to maintain the health of the organism.12−19 The typical structure of the active site of nonheme iron(II) dioxygenases is a 2-His-1carboxylate facial triad;20−25 however, a third histidine imidazole group takes the place of the carboxylate ligand in CDO, forming a His3 facial triad. In order to explore the property and catalytic mechanism, some experimental26−30 and theoretical10,11,31 researches have been carried out. However, in contrast to its important role in health, little is known about its mechanism.31−33 Many small-molecule model complexes have been synthesized and characterized in mimicking the catalytic role via the biomimetic approaches, which provides better understanding of the reactivity properties and reaction mechanism for metalloproteases.34−37 Recently, Goldberg’s group has first reported structural and functional synthetic models of CDO.39,40 In their studies, bis(imino)pyridine ligand (BIP),38−45 thiolate ligand (SPh),46−51 and trifluoromethanesulfonic acid ligand (OTf−) have been employed to synthesize the iron(II)−thiolate complexes [(iPrBIP)FeII(SPh)(Cl)] (A) and [(iPrBIP)FeII(SPh)(OTf)] (B). Then, the computational study of Goldberg’s group and de Visser’s group has proved that the model complexes can closely mimic the enzymatic process of CDO.52 © 2012 American Chemical Society

To study the properties of the two structures, the noniron(II)− thiolate complexes [(iPrBIP)FeII (Cl)2] (C) and [(iPrBIP)FeII (OTf)2] (D) have been used in the comparative study, and the experiments show that the complexes (A) and (B) can activate O2 by the reaction of Fe-oxygenation and S-oxygenation, while the complexes (C) and (D) cannot activate O2 (Figure 1). It is

Figure 1. Different reactive modes with O2 for complexes (A)−(D).

found that the thiolate ligand is of importance to the O2 activation and the relative position of the thiolate ligand appears to play a critical role in determining the outcome of O2 activation. So, the question raised here is how the thiolate ligand and its relative position control the oxygen activation in the cysteine dioxygenase models. The research on it can give us further understanding of the O2 activation. This work is intended to compare four models based on theoretical calculation. These models have been selected from the works of Goldberg’s group: two of them represent Received: January 5, 2012 Revised: May 2, 2012 Published: May 15, 2012 5510

dx.doi.org/10.1021/jp3001515 | J. Phys. Chem. A 2012, 116, 5510−5517

The Journal of Physical Chemistry A

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Figure 2. UB3LYP/B1 optimized structures and the relative energies (UB3LYP/B2//B1+ZPE) of Models (A)−(D) (Ar, 2,6-iPr2−C6H3). Bond lengths are in Å and energies in kcal·mol−1, and they are listed in the order of the singlet, triplet, quintet, and septet state.

2, 3) are shown in Figure 2, and the optimized parameters based on the Basis Set B1 and the energies (ΔE) from the Basis Set B2 with ZPE corrections at UB3LYP/B1 are also given. It is shown in Figure 2 that the Fe−S bond of Model (A) is almost perpendicular to the N(1)−N(2)−N(3) plane, whereas the S(1) of PhS− ligand of Model (B) is nearly located in the N(1)−N(2)−N(3) plane. Hence, compared with the open site, the PhS− ligand of Model (A) is at trans position, and the PhS− ligand of Model (B) is at cis position. In Models (C) and (D), Cl(1) atom and the OTf− ligand replace the PhS− ligand in Models (A) and (B), respectively. The relative energies given in Figure 2 tell us that the quintet state of four models all have the lowest energies, which are 31.0−38.6 kcal·mol−1 lower than the singlet states, 14.3−16.3 kcal·mol−1 lower than the triplet states, and 23.4−37.2 kcal·mol−1 lower than the septet states. It is clear that the high-spin quintet state is the ground state, which can also find supports in the experimental evidence for Models (A) and (C).39,40,61 Although the Pierce’s group recently showed that the substrate-bound form of FeIII−CDO with superoxide anion had a ground state with S = 3,62 the studies of many nonheme enzymes and its related biomimetic models indicated that the quintet state was more active.32,63−65 Considering the higher energy, the septet spin state is not further taken into consideration in the remainder of this article. In addition, Models (A) and (B) both have isomeric structures, e.g., Model (A) with Cl in axial and equatorial plane and Model (B) with OTf− in axial and equatorial plane. The energies of quintet state for these isomeric structures have been compared (see Figure S1, Supporting Information). It shows that the energies of Models (A) and (B) are slightly lower than their corresponding isomeric structures. In the experiment of Goldberg’s group, the synthesized complexes (A) and (B) with PhS− in axial and equatorial plane have taken place different oxidation reactions. To directly compare with the phenomena presented in the experiment, only the synthesized model complexes (A) and (B) been selected in this article. The shared structural units of four models are the BIP ligand and the Fe(II) center. In order to evaluate the optimized structures, the relevant bond lengths and bond angles, which are formed by the N atom in the BIP ligand and the Fe(II) center, are compared with the X-ray crystal structure (see Table 1). The data show that the quintet state is only in agreement with the experimental values. So, the model of the quintet state is used to analyze electronic structures, bonding descriptions, and frontier orbitals in this section. According to the frontier orbital theory of quantum chemistry, the frontier orbital and its nearby molecular orbital have the most important influence on the activity of the

structures that can activate O2, while the other two cannot activate O2. Additionally, two key points of the O2 activation process have been investigated: the first one in which O2 is not bound to the sixth open site of iron reflects the intrinsic properties of the activation of O2, whereas the second one in which O2 is bound to that site reflects the interactions between O2 and models. In the comparative study of these four models, the role of thiolate ligand and its relative position have been explored and electronic structures, bonding descriptions, and frontier orbitals have been analyzed.

2. COMPUTATIONAL METHODS Four models have been selected: two of them are thiolateligated complexes (A) and (B), and the other two are nonthiolate-ligated complexes [(iPrBIP)FeII(Cl)2] (C) and [(iPrBIP)FeII(OTf)2] (D) (Figure 1). In Model (C), the atom Cl replaces the PhS− ligand in Model (A). In Model (D), the OTf − ligand replaces the PhS− ligand in Model (B). The initial structures of computational models used in this article are all based on X-ray crystal structures. All calculations were performed on the Gaussian0953 package. The geometries were optimized through using the UB3LYP54 hybrid density functional available in the package, which was known to predict properties of CDO-like compounds with good reproducibility,10,31,55 and the polarizable continuum model PCM56 with dichloromethane solvent parameters was applied to consider the influence of the solvent effects. The effective core potential with the double-ξ quality basis sets (LanL2DZ)57 was used to describe Fe and S atoms, and the calculations of the other atoms were carried out with the 6-31G(d) basis set (Basis Set B1). The frequency calculations were performed on the optimized geometries to ensure that they had no imaginary mode, and the zero-point energy (ZPE) corrections were then made. Subsequent singlepoint calculations with a triple-ξ quality basis sets (TZVP)58 on all atoms were done to correct the energies (Basis Set B2). All energies reported in this work were obtained with UB3LYP/B2 with ZPE corrections at UB3LYP/B1. In addition, the theoretical natural bond orbital (NBO)59 analysis was also performed to obtain the natural charges and Wiberg bond indices, and the molecular orbitals were plotted by way of using the program Molekel.60 3. RESULTS AND DISCUSSION 3.1. Electronic Structures, Bonding Descriptions, and Frontier Orbitals for Models (A)−(D). The optimized structures of Models (A)−(D) in four spin states (S = 0, 1, 5511



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relevant spin-down MOs. The compositions of the relevant spin-down frontier molecular orbitals for Models (A)−(D) are listed in Table 2. The energy-level diagrams (relative to the highest occupied MO) and the charge transitions of the four models are shown in Figure 4, and the primary interactions of the molecular orbitals are given in Figure S2, Supporting Information. In Model (A), as shown in Figure 4, the S π-based MOs are the two highest-energy double-occupied MOs, and the Fe dz2based MO is located at the lower part next to the S π-based MO. The other four Fe d-based MOs are half-occupied MOs. The composition analysis of Fe d-based MOs and S π-based MOs are listed in Table 2, which indicates that there are two types of interactions between Fe(II) and S. The first one is the Fe−S σ-interaction, which includes interactions of the dz2−pz orbital and the dyz−py orbital. The dz2 and dyz atomic orbitals are mixed up, and the combination of these orbitals develops the σ-interaction with πop orbitals. The second one is the Fe−S π-interaction, which includes dxy and px orbitals (see Figure S2, Supporting Information). Because the occupation of the spinup MO is prior in the calculation, the Fe dxy- and dyz-based MOs are half-occupied and the dz2-based MO is doubleoccupied in Model (A). The PhS− ligand prefers to transfer charge from Sπip- and Sπop-based MOs to Fe dxy- and dyz-based MOs, respectively. So the PhS− ligand is both the π-donor and the σ-donor of Fe(II), and the charge transition paths are marked with arrows in Figure 4. The amount of charge transfer of PhS− ligand to Fe(II) is 0.451e (Table S2, Supporting Information). In Model (B), the two S π-based MOs and the Fe dz2-based MO are the three highest-energy double-occupied MOs, and the other four Fe d-based MOs are half-occupied. The composition analysis reveals that the π-interaction and the σinteraction can be found between Fe(II) and S(1) of the PhS− ligand. The dx2−y2 orbital and the px orbital develop the Fe− S(1) π-interaction, while the dz2 orbital and the pz orbital engage in the Fe−S(1) σ-interaction (see Table 2 and Figure S2, Supporting Information). In a similar way to Model (A), the Fe−S(1) interactions make the PhS− ligand transfer charge to Fe(II) mainly via the S(1)πip-based MO → Fe dx2−y2-based MO as a π-donor, which is marked with arrows in Figure 4, and the charge transferred is 0.440e (Table S2, Supporting Information). With the analysis of the thiolate-ligated Models (A) and (B), the PhS− ligand functions as the π-donor and the σ-donor to transfer charge to Fe(II). To effectively transfer charge, the PhS− ligand based MOs should be as close as possible to the highest-energy double-occupied MO, and at the same time, there should be effective interactions between Fe(II) and S. In Model (C), the replacement of the PhS− ligand by the Cl(1) atom weakens the bond strength, and the Wiberg bond indices reduce from 0.65 to 0.55 (Table S1, Supporting Information). According to Table 2, the Fe−Cl(1) πinteraction includes dxy and px orbitals, and the primary interaction works in the antibonding state (see Figure S2, Supporting Information). Meanwhile, the highest occupied molecular orbital is the Fe dxy-based rather than the Cl(1)3pbased MO. It suggests that the Cl(1) atom should not be an efficient electron-donor. There is only 0.339e charge transferred from Cl(1) to Fe(II) (Table S2, Supporting Information). It makes sense that the electronegativity of Cl is larger than S, so its valence electrons are more shackled by the atomic nucleus, resulting in the weak electron-donating ability. For Model (D),

Table 1. Comparison of Experimental and Calculated Bond Lengths and Bond Angles for Models (A)−(D)a Model(A)X‑ray 1 Model(A) 3 Model(A) 5 Model(A) Model(B)X‑ray 1 Model(B) 3 Model(B) 5 Model(B) Model(C)X‑ray 1 Model(C) 3 Model(C) 5 Model(C) Model(D)X‑ray 1 Model(D) 3 Model(D) 5 Model(D)

Fe−N(1)

Fe−N(2)

Fe−N(3)

∠N(1)−Fe−N(3)

2.212 2.080 2.108 2.293 2.238 2.110 2.119 2.283 2.219 2.071 2.104 2.318 2.219 2.097 2.129 2.316

2.053 1.876 1.885 2.122 2.091 1.921 1.932 2.157 2.086 1.890 1.898 2.161 2.086 1.891 1.908 2.150

2.192 2.074 2.107 2.309 2.208 2.103 2.121 2.352 2.240 2.071 2.104 2.306 2.240 2.074 2.099 2.331

141.2 157.3 146.2 139.8 139.0 155.9 148.7 140.4 142.7 158.0 149.6 140.6 142.7 158.1 149.7 140.6

a

Lengths are in Å and angles in degree, and the left-hand superscript number indicates the spin state.

compounds.66 In this study, the frontier orbital has been analyzed, and the sum of squares of atomic orbital coefficients, which are normalized, is used to represent their contributions to the molecular orbital. To identify the role of PhS− ligand, DFT calculations are first performed on the free ligand. As is shown in Figure 3, the

Figure 3. Sπip and Sπop MO of free thiolate ligand.

dominant components of the two highest-energy occupied MOs are sulfur 3p orbitals,67 which are labeled as Sπip and Sπop based on the established nomenclature.68 The πip orbital lies in the plane of the aromatic ring, whereas the πop orbital is perpendicular to the plane. For the Fe(II)−thiolate complexes, the bonding interactions between the πip and πop orbitals and the Fe d orbital depend on two structural parameters: the Fe− S−C(1) bond angle and the Fe−S−C(1)−C(2) dihedral angle. In Models (A) and (B), the Fe−S−C(1) bond angles are 112.8° and 116.5°, and the Fe−S−C(1)−C(2) dihedral angles are, respectively, 92.8° and 92.8°. This reveals that the πip orbital is mainly perpendicular to the Fe−S bond and develops the π-interaction with the Fe d orbital, while the πop orbital is primarily oriented along the Fe−S bond and engages in the σinteraction with the Fe d orbital. On the basis of the above analysis, the quintet state, i.e., the ground state, is analyzed. For half-occupied MOs, the electron is occupied in the spin-up MOs. Hence, electronic structures, bonding descriptions, and frontier orbitals are inferred from the 5512



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Table 2. Compositions (%) of the Fe d-Based MOs and S-, Cl-, and O-Based MOs for Models (A)−(D) Based on Spin-down MOsa Model (A) Fe 3d orbitals (%)

SPhS (%)

MO label

occ

yz

xz

x2 − y2

xy

z2

px

py

pz

Fe dyz Fe dxz Fe dx2−y2 Fe dxy Sπip Sπop Fe dz2

1 1 1 1 2 2 2

25.3 3.0 2.1 2.7 1.8 0.0 30.6

5.9 36.9 19.2 6.5 1.6 0.0 0.0

0.0 20.9 44.4 0.0 0.0 3.4 0.0

0.0 3.3 1.2 58.4 1.7 2.8 7.3

16.8 4.0 0.0 7.5 4.2 11.1 30.7

0.0 0.0 0.0 2.3 63.3 4.0 0.0

2.3 0.0 1.8 0.0 0.0 8.3 0.0

0.0 0.0 1.9 0.0 2.2 20.6 6.0

Model (B) Fe 3d orbitals (%)

S(1)PhS (%) x −y 2

MO label

occ

yz

xz

xy

Fe dyz Fe dxz Fe dxy Fe dx2−y2 S(1)πop S(1)πip Fe dz2

1 1 1 1 2 2 2

24.7 8.9 6.6 0.0 0.0 0.0 9.6

1.3 14.9 12.3 26.8 5.3 2.6 14.5

0.0 14.1 48.5 2.6 0.0 0.0 0.0

MO label

occ

x2 − y2

z2

Fe dx2−y2 Fe dz2 Fe dxz Fe dyz Fe dxy Cl(1)3p

1 1 1 1 2 2

24.1 10.6 1.4 0.0 0.0 0.0

1.5 29.4 0.0 35.7 0.0 0.0

2

0.0 11.0 1.1 47.2 1.6 3.2 14.1 Model (C)

z

2

8.6 14.0 1.0 1.1 17.0 1.5 33.6

px

py

pz

0.0 0.0 0.0 3.9 3.7 41.0 0.0

0.0 0.0 0.0 2.7 29.0 19.4 0.0

0.0 0.0 0.0 0.0 2.6 2.5 2.0

Fe 3d orbitals (%)

Cl(1) (%)

xz 0.0 3.5 62.0 3.0 5.9 0.0 Model (D)

yz

xy

px

py

pz

2.8 17.6 6.5 37.7 0.0 0.0

0.0 0.0 5.5 1.8 63.7 7.6

0.0 0.0 0.0 0.0 14.3 61.5

0.0 5.8 0.0 0.0 0.0 0.0

0.0 0.0 0.0 1.9 0.0 0.0

Fe 3d orbitals (%)

a

MO label

occ

x −y

yz

z

Fe dx2−y2 Fe dyz Fe dz2 Fe dxz Fe dxy O(2)Otf 2p

1 1 1 1 2 2

19.7 0.0 0.0 1.4 7.4 0.0

0.0 47.1 0.0 0.0 5.8 0.0

0.0 0.0 47.0 24.1 0.0 0.0

2

2

2

O(2)otf (%) xz

xy

px

py

pz

0.0 0.0 25.8 40.1 1.7 0.0

1.8 3.7 0.0 2.0 70.3 0.0

0.0 0.0 0.0 0.0 1.6 21.7

0.0 1.1 0.0 0.0 0.0 8.9

0.0 0.0 0.0 0.0 0.0 0.0

The atomic orbital coefficients, which are less than 1%, are ignored. The occupation number is counted based on spin-up and spin-down MOs.

when the OTf− ligand replaces the PhS− ligand in Model (B), the little π-interaction between Fe and O(2)otf can be ignored. The Fe dxy-based MO also occupies the highest-energy doubleoccupied MO, but the energy differences between doubleoccupied MOs and half-occupied MOs become larger. The Fe− O(2)otf bond strength is the weakest among four models (0.33 in Table S1, Supporting Information). It is because the electronegativity of atom O is larger than that of S and Cl that the charge transferred to Fe(II) is only 0.239e (Table S2, Supporting Information). 3.2. Activation Process of O2 for Models (A1)−(D1). The optimized structures of Models (A1)−(D1) in three spin states (S = 0, 1, 2) are shown in Figure 5. They are generated by way of attacking the sixth open coordination of iron for the oxygen molecule. The UB3LYP/B1 optimized parameters and the relative energies computed at the UB3LYP/B2//B1+ZPE level are also described in this figure. It is worthwhile to note

that, in Models (A1)−(D1), when the oxygen molecule attacks the open coordination, the potential O2 binding site has two different directions resulting from the asymmetry of the structure. All of them have been calculated, and the more stable structures have been selected for the analyses of Models (A1)−(D1) (see Figure S3, Supporting Information). The orientations of oxygen molecules in these four models are different: only the oxygen molecule of Model (A1) is oriented along the direction of N(2)−Fe, and oxygen modules in the other three models are oriented in the opposite direction, as shown in Figure 5. The high-spin quintet state is the ground state with the energies of about 10.0 kcal·mol−1 and 25.0 kcal·mol−1 lower than the triplet and singlet states, respectively. The compositions of the relevant spin-down frontier molecular orbital for Models (A1)−(D1) in the quintet state are listed in Table S3, Supporting Information, to save space. The primary interactions of the molecular orbitals are given in Figure S4, 5513



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Figure 6. Energy-level diagrams of the molecular orbitals for Models (A1)−(D1) based on the spin-down MOs. The charge transitions are indicated by arrows.

Figure 4. Energy-level diagrams of the molecular orbitals for Models (A)−(D) based on the spin-down MOs. The charge transition paths are indicated by arrows.

For Model (B1), the two S π-based MOs are the highestenergy double-occupied MO, the O(2)2p-based MO of O2 is the lowest-energy half-occupied MO, and the S(1)−O(2) σinteraction involves S(1) pz and O(2) pz orbitals (Figure S4, Supporting Information). These interactions may provide advantageous conditions for the charge to be transferred from S(1) to O(2), while it is unfavorable to transfer charge between Fe(II) and O(1). Furthermore, the Fe−S(1) π-interactions are still relatively strong, and the PhS− ligand can continue to transfer charge to Fe(II). In this model, on the one hand, the PhS− ligand can persist in transferring charge to Fe(II); on the other hand, it can also transfer charge to the O(2) atom of O2. The charge transfer number of the PhS− ligand is 0.254e in this step (Table S2, Supporting Information). The analysis of Model (B1) is also in agreement with the experiment in which the S of PhS− ligand is oxidized.61 On the basis of the analysis of Models (A1) and (B1), it is noticed that the modes for O2 activation are different. In Model (A1), the PhS− ligand only transfers a small amount of charge to Fe(II), and the dominant charge transfer is processed from Fe(II) to O(1). The O2 is activated and the Fe(II) is oxidized, but in Model (B1), Fe(II) transfers less charge to O(1), the

Supporting Information, and the energy-level diagrams and the charge transitions of the four models are shown in Figure 6. In Model (A1), the Fe dxy-based MO is the highest-energy double-occupied MO, the dyz-based MO is the lowest-energy half-occupied MO, and the two S π-based MOs are located at the lower part that is next to the Fe dxy-based MO, as shown in Figure 6. The composition analysis of Model (A1) in Table S3, Supporting Information, indicates that the Fe−O(1) σinteraction involves dyz and py orbitals. The bonding interaction between Fe(II) and S in Model (A1) is weaker than that in Model (A), which is proven by the bond length change (Fe− SModel(A1), 2.595 Å; Fe−SModel(A), 2.474 Å) and the Wiberg bond indices (0.65 to 0.52 in Table S1, Supporting Information). So, the PhS− ligand is no longer an efficient electron-donor, and the number of charge transfer is only 0.0981e (Table S2, Supporting Information). In this reaction step, Fe(II) mainly serves as a σ-donor to transfer charge to O(1) of the oxygen molecule, which is marked with the arrow in Figure 6, and therefore, the oxidation of Fe(II) occurs. The analysis of Model (A1) is just in agreement with the experiment in which Fe(II) is oxidized and the Fe−S bond is broken.61

Figure 5. UB3LYP/B1 optimized structures and the relative energies (UB3LYP/B2//B1+ZPE) of Models (A1)−(D1) (Ar, 2,6-iPr2−C6H3). Bond lengths are in Å and energies in kcal·mol−1, and they are listed in the order of the singlet, triplet, and quintet state. 5514



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PhS− ligand is the main electron-donor to O(2), O2 is activated by PhS− ligand, and the S of PhS− ligand will be oxidized. However, these two processes still share some similarities. The orbital involved in charge transfer should be located around the highest-energy double-occupied and lowest-energy half-occupied MOs. As shown in Model (C1), the Fe dxy-based MO is the highest-energy double-occupied MO, and the O(2)2p-based MO of O2 is the lowest-energy half-occupied MO. One little Fe−O(1) π-interaction between the dxy orbital and the px orbital is in the antibonding state, and the Fe−Cl(1) πinteraction is found similar to that in Model (C). In this model, the Fe−O(1) bond strength is very weak (Table S1, Supporting Information). Therefore, Fe(II) is not favorable to transfer charge to O2, and the O2 cannot be activated. It is also been proved by the experiment that O2 is not activated in the model.61 In Model (D1), the Fe dxy-based MO is near the highest-energy double-occupied MO, and the O(2)2p-based MO of O2 is the lowest-energy half-occupied MO. The composition analysis reveals that no effective Fe−O(1) interaction is found, and this model cannot also activate O2, which is supported by the experiment.61 3.3. Charge Transfer and Activation of O2. The comparison of four models indicates that the charge transfer process plays an important role during the activation of O2. In Models (A) and (B), the PhS− ligand functions as the π-donor and the σ-donor to transfer charge to Fe(II) via the effective Fe−S π-interaction and σ-interaction. This decreases the effective nuclear charges of Fe(II) and makes the energy gap narrowed between Fe d-based MOs and S π-based MOs.69 When O2 is coordinated with the open site, the PhS− ligand transfers a small amount of charge to Fe(II), and Fe(II) mainly transfers charge to O(1) of O2 in Model (A1), and in Model (B1), the PhS− ligand transfers charge to both Fe(II) and O(2) of O2. For the nonthiolate-ligated complexes, the weak electron-donating ability increases the structure Lewis acidity and results in an increased binding energy,70 so it is difficult to activate O2, and there is no oxidation reaction in them. In order to further understand the importance of charge transfer, the redox potentials for the (iPrBIP)FeII complexes61 and the amount of charge transfer are correlated (Figure 7).

Interestingly, the amount of charge transfer of PhS− ligand is closely correlated with the related redox potentials. The more charge it transfers, the lower the related redox potentials. It indicates that we may improve the model through adjustment of charge transfer ability of the ligand. PhSe− has a better charge transfer ability and provides lower redox potentials, but the mutation of S to Se in CDO makes CDO lose the ability of the O2 activation.11 It seems that not only is the charge transfer itself important for the O2 activation but also some other conditions are not discovered. Further theoretical studies on more models of CDO are still in need, and we are now working on it.

4. CONCLUSIONS In conclusion, the thiolate ligand is essential for the activation of O2, and its relative position plays a critical role in determining the oxidation reaction path. In the thiolate-ligated models, the PhS− ligand can simultaneously function as the πdonor and the σ-donor to transfer charge to Fe(II) via an operative interaction (shown in Scheme 1). On the one hand, Scheme 1. Charge Transfer Pathway and the Mode of O2 Activation

this decreases the effective nuclear charges of Fe(II) and lowers the redox potentials; on the other hand, the good electrondonating ability reduces the sixth ligand binding energy of the oxygen molecule by decreasing the structure Lewis acidity. The PhS− ligand provides a prerequisite for the activation of O2. The relative position of the PhS− ligand also plays an important role in the O2 activation process. In Scheme 1, when the PhS− ligand coordinates at the trans position, the Fe dbased MO will be the highest-occupied molecular orbital and transfers charge to the O(1)2p-based MO as the σ-donor. It will lead to the oxidization of Fe(II), and the Fe−S bond will break. When the PhS− ligand coordinates at the cis position, the S πbased MO are the highest-energy double-occupied molecular orbitals, and S transfers charge to the O(2) as the σ-donor. It will lead to the oxidization of S in PhS− ligand.

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ASSOCIATED CONTENT

S Supporting Information *

Primary interaction of molecular orbitals for Models (A)−(D) and (A1)−(D1), related NBO Wiberg bond indices and natural atomic charges, the compositions of atomic orbital for Models (A1)−(D1), and two configurations of Models (A1)−(D1). This material is available free of charge via the Internet at http://pubs.acs.org.

Figure 7. Linear relationship between the charge transfer number of the PhS− ligand and the related redox potentials for (iPrBIP)FeII complexes. 5515



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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (J.G.); [email protected] (C.L.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work is supported by the National Natural Science Foundation of China (No. 91127014), Natural Science Foundation of Shandong Province of China (No. ZR2010BZ005), and Independent Innovation Foundation of Shandong University (2009JC018 and 2010TS015). It is also supported by Virtual Laboratory for Computational Chemistry, Supercomputing Center of Chinese Academy of Science and High Performance Computing Center of Shandong University.

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