Aromatic Residues Regulating Electron Relay Ability of S-Containing

Aug 28, 2012 - ... Z.; Wishart, J. F.; Isied, S. S. J. Am. Chem. Soc. 2004, 126, 13888−13889. (22) Donoli, A.; Marcuzzo, V.; Moretto, A.; Toniolo, C...
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Aromatic Residues Regulating Electron Relay Ability of S‑Containing Amino Acids by Formations of S∴π Multicenter Three-Electron Bonds in Proteins Xiaohua Chen,†,* Ye Tao,† Jilai Li,‡ Hongjing Dai,† Weichao Sun,† Xuri Huang,‡ and Zidong Wei† †

School of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 400030, People's Republic of China State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, People's Republic of China

‡

S Supporting Information *

ABSTRACT: The ab initio calculations predict that the side chains of four aromatic amino acids (Phe, His, Tyr, and Trp residues) may promote methionine and cystine residues to participate in the protein electron hole transport by the formation of special multicenter, three-electron bonds (S∴π) between the Satoms and the aromatic rings. The formations of S∴π bonds can efficiently lower the local ionization energies, which drive the electron hole moving to the close side chains of S-containing and aromatic residues in proteins. Additionally, the proper binding energies for the S∴π bonds imply that the self-movement of proteins can dissociate these three-electron bonds and promote electron hole relay.

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INTRODUCTION In numerous biological processes, the protein-based electron transfer reactions play an elementary role.1−7 Therefore, the exact pathway of electron transfer within proteins has been a source of controversy,9 which has become the focus of extensive and intensive theoretical10−16 and experimental17−23 investigations in the past few decades. The two possible electron pathways, through bonds and through space, are generally accepted, supporting the one-step superexchange mechanisms.24−26 In addition, it has been reported that the side chains of tryptophan (Trp),3 tyrosine (Tyr),7,8,23 methionine (Met), and cystine (Cys)27 residues can act as the relay stations to speed up the rate of electron transfer in proteins, favoring the multistep hopping mechanism. Recently, it has been proposed that the secondary bonds and some weakly special interactions, including noncovalent and weak-covalent interactions, may play an essential role in electron transfer for the redox reactions in chemical and biological processes.16 These special structures have low redox potentials and may serve as the relay stations to facilitate protein electron transfer.1,2 There are two main reasons to favor the side chains of Tyr and Trp residues as relay stations to participate in protein longrange electron transfer.2,7−9 One is that their oxidation potentials are the lowest among the 20 natural amino acids. The other is that their side chains can release a proton to an adjacent functional group (such as the side chains of aspartic and glutamic acids, waters, and so on) when an electron moves out, and then the surrounding fragments deliver the proton back when the hopping continues. Obviously, these processes involve more complex proton-coupled electron transfer © 2012 American Chemical Society

reactions, and the function of electron relay for Tyr and Trp residues depends upon the possibility of reversible of proton transfer in proteins.8 In contrast, the redox potentials of Cys and Met are high, and especially Met cannot involve proton transfer to take part in the electron transport processes in proteins. However, Giese and co-worker have confirmed that these two residues are the efficient relay stations to facilitate the long-range electron transfer reactions.27 They have attributed this result to the influence of the neighboring functional group, which can form a two-center, three-electron (2c-3e) bond between the S-atom and the O-atom (or N-atom) in the neighboring group.28−32 The formation of a 2c-3e bond can reduce the redox potential of the S-containing group, supporting the S-containing residue's release of an electron. Then the dissociation of the 2c-3e bond promotes the hole hopping to another relay station. In addition, it has been proposed that the neighboring amide can lower the oxidation potential of S-containing groups by formation of S− O 2c-3e bonds, which indirectly proves that the formation of a S−O 2c-3e bond can participate in the long-range electron transfer in proteins.33−35 All these reports imply that the electron relay functionality of S-containing groups may be regulated by the local neighboring environment in proteins. A similar example is that the relay ability of tryptophan residues is controlled by the local microenvironment in proteins.36 Because of the complexity of proteins, however, the importance Received: June 22, 2012 Revised: July 24, 2012 Published: August 28, 2012 19682

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chains, and the corresponding interaction structures are named as M-Xxx_S∴π or C-Xxx_S∴π (Xxx denotes Phe, His, Tyr, and Trp, Scheme 1). The one-chain models represent that both the S-containing and aromatic cation residues lie close in the same peptide chain, which are named as MetXxx_S∴π and CysXxx_S∴π (Xxx denotes Phe, His, Tyr, and Trp). In addition, the S∴π bonds are further considered in the α-helical systems. These S∴π bonded complexes can serve as primary models for peptide molecules of biological importance where higher-order structures may bring aromatic functional groups into close proximity to the S-containing groups. All gas-phase calculations are carried out by using the Gaussian 03 suite of programs.37 The UB3LYP38 hybrid functional in conjunction with the 6-31+G(d,p) basis set39 is utilized to optimize all geometries fully and to perform the harmonic vibrational analyses for confirming minima (all real frequencies). A larger basis set, 6-311++G(d,p), is also used to verify the reliability of 6-31+G(d,p). For all the S∴π-bonded complexes considered here, B3LYP shows essentially no dependence on a change in the size and flexibility of the basis set. In addition, to further verify the applicability of the B3LYP/6-31+G(d,p) method, theBHandHLYP/6-31+G(d,p) and MP2/6-31+G(d) methods are also carried out to examine the simple models. The results are in agreement with those using the B3LYP/6-31+G(d,p) calculations. Therefore, the B3LYP method was mainly used to investigate the S∴π-bonded radical cations in this work. In an effort to explore the new functionality of the S∴π (assisting the S-containing amino acids to take part in electron hole migration in proteins), the interactions between the Scontaining residues (Met and Cys) and the corresponding surrounding fragments need to be detected with proper parameters, including ionization energy (IE), binding energy (BE), and ultraviolet (UV) spectrum, and so on. The adiabatic IE (IEa) is the difference in energy between a S∴π-bonded complex (cation) and its corresponding closed-shell complex in their fully optimized states. In contrast, the vertical electron affinity (EAv) is the difference in energy between a S∴π-bonded complex (cation) and its corresponding closed-shell complex without change in structure (the latter has one more electron than the former). There is a good line correlation between EAv's and IEa's, as shown in Table 1and Supporting Information Figure S2. Therefore, the trend of EAv's for all the S∴π-bonded complexes can replace that of IEa's for the corresponding neutral structures. EAv's instead of IEa's are used in the relevant analyses in this work. The BEs for the S∴π-bonded complexes are calculated by subtracting basis set superposition errors by means of the counterpoise approach.40,41 The time-dependent density functional response theory (TDDFT)42 calculations are performed to find out the excitation wavelength to excite an electron from a doubly occupied bonding orbital to the singly occupied antibonding orbital (σ/σ*) of S∴π-bonded complexes with the B3LYP/6-31+G(d,p)-optimized geometries. All these parameters are obtained by carrying out single-point calculations at the B3LYP/6-311++G(d,p)//B3LYP/6-31+G(d,p) 43 level of theory. The restricted molecular orbital contours are used to display the orbital character. Other data, including the shortest distances, BEs, EAv's, orbital characteristics, and correlations among several quantities for all structures, are listed in the Supporting Information.

of individual weak interactions in controlling the relay functionality of S-containing groups in proteins is not yet understood in detail. Motivated by these studies1−3,33,34 and with the aim of exploring all the possible electron transfer pathways in proteins, in this work, we mainly examine the relay ability of S-containing groups (the side chains of Cys and Met) modulated by the adjacent aromatic amino acids through ab initio calculations. Our investigation reveals that the neighboring aromatic rings can promote the S-containing groups' participation in the longrange electron transfer processes in proteins by forming special lone pair-π (lp-π), multicenter, three-electron bonds (S∴π) with lower redox potentials. These findings should be invaluable for further understanding how proteins regulate the microstructures to construct effective electron transfer channels, which is a general topic of substantial current interest.

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COMPUTATIONAL METHODS A number of high-resolution protein structures have been checked to reveal that there are close contacts between the side chain of Met (or Cys) and the aromatic rings (including the side chains of Phe, His, Tyr, and Trp). In this work, therefore, we mainly examine the effect of aromatic amino acids on the relay ability of the S-containing residues. An examination is needed of the interactions between the side chains of Scontaining and aromatic cation residues of two neighboring peptide units in the different peptide chains or the same peptide chain. To well address this issue, we investigate the interactions between the side chains of Met (or Cys) and the aromatic cation residue (Phe, His, Tyr, or Trp) from simple to complex models. The interactions are divided into three classes: simple models, two-chain models, and one-chain models. The simple models include only the side chains of Met (or Cys) and the aromatic rings of Phe (or His, Tyr, Trp), named as MΠ_S∴π or CΠ_S∴π (“M” and “C” denote the side chains of Met and Cys, respectively; Π indicates F, H, Y, and W for the side chains of Phe, His, Tyr, and Trp, respectively), as shown in Scheme 1. In the two-chain models, the aromatic amino acids include two peptide units, the S-containing residues only remain the side Scheme 1. Schematic Representation of the Considered S∴π-Bonded Radical Cations for Simple Models and TwoChain Models

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Table 1. The Shortest Distances (RSXs) between the S-Atom and the Aromatic Rings, Vertical Electron Affinities (EAv's), Adiabatic Ionization Energies (IEa's), Binding Energies (BEs), and Spectroscopy of S∴π Bonds for the Simple Models species RSX (Å) EAv (eV/mol) IEa (eV/mol) BE (kcal/mol) λ (nm) f

RSX (Å) EAv (eV/mol) IEa (eV/mol) BE (kcal/mol) λ (nm) f

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MF1_S∴π

MF2_S∴π

MF3_S∴π

MH1_S∴π

2.91 7.18 7.65 25.7 610.4 0.1893

2.90 7.14 7.62 25.3 644.4 0.2210

2.90 7.12 7.63 24.6 673.9 0.2343

3.07 6.96 7.57 22.2 678.5 0.1773

CF1_S∴π

CF2_S∴π

CF3_S∴π

CH1_S∴π

2.89 7.38 7.92 18.4 624.1 0.1779

2.91 7.45 7.96 17.8 583.1 0.1888

2.89 7.50 8.01 18.3 617.6 0.2203

3.05 7.19 7.80 15.7 673.3 0.1571

MY1_S∴π

MW1_S∴π

MW2_S∴π

MW3_S∴π

M-Pep1_S∴π

3.19 6.58 7.07 9.0 854.9 0.1434

3.28 6.62 7.08 8.8 869.9 0.1236

3.46 6.79 7.14 7.6 1352.5 0.1220

2.47 6.36 7.39 32.8 439.1 0.2145

CY1_S∴π

CW1_S∴π

CW2_S∴π

CW3_S∴π

C-Pep1_S∴π

3.37 7.28 7.80 9.0 968.8 0.1035

3.30 6.75 7.23 5.8 828.0 0.1196

3.41 6.75 7.23 5.6 852.3 0.1190

3.52 6.94 7.29 4.5 1354.2 0.0871

2.44 6.66 7.81 41.9 421.0 0.2439

3.24 7.06 7.59 13.9 987.5 0.1250 species

RESULT AND DISCUSSION We first analyzed how the aromatic amino acids control the relay ability of Met and Cys in simple models. Figure 1 shows

Figure 2. Orbital interaction diagram showing S∴π bond formation between a sulfide radical cation and an aromatic ring. Figure 1. The structure of MF1_S∴π with the corresponding singly occupied molecular orbital (SOMO) and second highest doubly occupied molecular orbital (HDMO-1).

eV, which is much lower than that of dimethyl sulfide (8.64 eV/ mol) or that of methylbenzene (8.64 eV/mol). In addition, the EAv of MF1_S∴π is also lower than that of Trp (7.24 eV/mol), an effective relay station in proteins.2,3 This result implies that the formation of the S∴π bond can facilitate an electron hole's moving toward these two close side chains in proteins. Then the separating of these two close side chains induced by the protein movement may promote hole migration from this site to another relay station in proteins. In addition to the side chain of Phe, the side chains of other aromatic residues, including His, Tyr, and Trp, can also enhance the relay ability of the side chain of Met by the formation of S∴π bonds. The corresponding stable interaction structures between dimethyl sulfide and the side chains of His, Tyr, and Trp are named as MH1_S∴π, MY1_S∴π, and MW1_S∴π, respectively, as shown in Supporting Information Figures S5−S8. The nearest distances between the S-atom and the aromatic rings for MH1_S∴π, MY1_S∴π, and MW1_S∴π are 3.07, 3.24, and 3.19 Å, respectively (Table 1). Their corresponding EAv's are 6.96, 7.06, and 6.58 eV, which are all sharply lower than that of dimethyl sulfide (8.64 eV). In addition, their EAv's are all lower than that of the corresponding aromatic fragment (8.30 eV for 4-methylimidazole, 7.90 eV for 4-methylphenol, and 7.24 eV for 3-methylindole). All these results indicate that the formations of S∴π bonds between the S-atom and the neighboring aromatic rings can efficiently trap an electron hole in proteins. However, the BE values follow the decreasing order of MF1_S∴π > MH1_S∴π > MY1_S∴π > MW1_S∴π, as listed in Table 1. This may be

an interaction conformation between the side chains of Met and Phe (named as MF1_S∴π) with the plots of the corresponding singly occupied molecular orbital (SOMO) and second-highest doubly occupied MO (HDMO-1). The nearest distance between the S-atom of dimethyl sulfide and the C2-atom of toluene is 2.91 Å, indicating a strong interaction between these two fragments. It is clearly shown that its SOMO is an antibonding orbital and delocalizes over the two molecular fragments with an electron. On the contrary, HDMO-1 is a bonding orbital with two electrons and also delocalizes over the two molecular fragments. Therefore, the interaction of SOMO and HDMO-1 produces a special multicenter, three-electron bond (S∴π bond, a new semibond) between the singly occupied 3p lone pair of the S-atom and doubly occupied πorbital of benzene. Figure 2 describes the formation of the S∴π bond. The SOMO of the dimethyl sulfide radical and the highest occupied MO (HOMO) of methylbenzene interact to form two new MO's: one is a bonding orbital, HDMO-1 of MF1_S∴π, and the other is an antibonding orbital, SOMO of MF1_S∴π, as mentioned above. The BE of this S∴π bond is 25.7 kcal/mol, which demonstrates the strong interaction between the two fragments. More importantly, the formation of S∴π bond can lower the oxidation potential of Met. The value of EAv indirectly indicates the magnitude of the oxidation potential, as mentioned above. The predicting EAv of MF1_S∴π is 7.18 19684

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The formation of the S∴π bond can be confirmed by the corresponding absorption spectrum through the TD-DFT calculations. The spectral characteristics indicate an electron transition from the doubly occupied lp-π bonding orbital (σ) to the singly occupied lp-π antibonding orbital (σ*) as shown in Figure 2. However, the discrepancies for the S∴π bonds between the side chain of Met and the four aromatic side chains are reflected in a change of the absorption λmax for the lowestenergy optical band. The λmax for MF1_S∴π, MH1_S∴π, MW1_S∴π, and MY1_S∴π are 610.4, 678.5, 854.9, and 987.5 nm, respectively, as displayed in Table 1. The notable increase in the λmax from MF1_S∴π to MY1_S∴π is attributed to the nature of S∴π bonds between the S-atom of Met and the four aromatic side chains. The λmax of a S∴π bond depends upon the relative position of the σ and σ* levels, which involves the overlap between the 3p orbital of the S-atom and the highest occupied π orbital of aromatic rings. An increase of 3p-π overlap causes a drop in the σ level and a rise in the σ* level, leading to an increasing σ/σ* separation. Consequently, the increasing overlap results in a blue shift, which also can be reflected by the high binding energy as above analysis, while the a decreasing overlap causes a red shift with a lower binding energy. The minimum distance between the S-atom and the aromatic ring is an important factor to determine the extent of 3p-π overlap. The longer distance indicates a smaller overlap, and conversely, the shorter distance means a larger overlap. Therefore, the increasing order of the minimum distances, 2.91 Å for MF1_S∴π < 3.07 Å for MH1_S∴π < 3.19 Å for MW1_S∴π < 3.24 Å for MY1_S∴π, is in full agreement with the increasing absorption λmax order of MΠ1_S∴π as mentioned above. In addition, the geometries of S∴π bonds between the CH3SCH3 and the same aromatic side chain vary on the basis of the local microsurroundings in proteins, resulting in the variation of absorption λmax. For example, the λmax's for MF1_S∴π, MF2_S∴π, and MF3_S∴π are 610.4, 644.4, and 673.9 nm, respectively. This change in the λmax's indicates the diversification of the coupling modes between the side chains of Met and Phe cation residues in proteins, which leads to the different extent of overlap between the 3p orbital of the S-atom and the π-orbital of methylbenzene. The minimum distances for the three structures are almost equal, ∼2.90 Å, as shown in Table 1; however, the S-atom of Met faces nearly the center of the aromatic ring in MF1_S∴π, the about half ring in MF2_S∴π, and the edge of the ring at the C4-atom in MF3_S∴π. Therefore, these relative spatial positions cause the lp-π overlap to decrease from MF1_S∴π to MF2_S∴π to MF3_S∴π, which leads to the decreasing σ/σ* separation in the same order. Consequently, this results in the increase in the absorption λmax in the order of MF1_S∴π < MF2_S∴π
MH1_S∴π > MY1_S∴π > MW1_S∴π. Furthermore, the decreasing values of EAv with respect to the lower EAv's of two monomers (ΔEAv) for them are in full agreement with the decreasing order of BEs as shown in Figure 3, indicating a good correlation between the binding strengths of S∴π bonds and the ΔEAv values.

Figure 3. The linear correlation of the binding energies and the decreasing values of vertical electron affinities (which are the differences between the vertical electron affinities of the simple S∴πbonded complexes and the lower vertical electron affinities of the two monomers, ΔEAv) for all the simple S∴π-bonded complexes. It is clear that the higher the binding strengths of the S∴π bonds are, the higher the values of ΔEAv are.

A similar tendency can be found for the S∴π interactions between the side chains of Cys and Phe (or His, Tyr, and Trp) cation residues, as shown in the Supporting Information (Figures S9−S12). However, the BE of the CΠ_S∴π complex is lower than that of the corresponding MΠ_S∴π complex, as shown in Table 1. In addition, the EAv of the CΠ_S∴π complex is higher than that of the corresponding MΠ_S∴π complex. Both may be attributed to the different bonding groups for the S-atom in these two cases. The S-atom of CH3SCH3 has a greater capability to denote an electron than that of CH3SH.

Figure 4. The structure of M-Phe1_S∴π with the corresponding singly occupied molecular orbital and highest doubly occupied molecular orbital. 19685

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peptide backbone reduces the overlap of the 3p orbital of the Satom of dimethyl sulfide and the π-orbital of the benzene fragment, leading to a decreasing σ/σ* separation and a reducing of absorption intension (f); however, the EAv of MPhe1_S∴π is 6.79 eV/mol, which is lower than that of MF_S∴π (∼7.63 eV/mol) and that of Phe (7.98 eV/mol). This result indicates that the close contacts between the two side chains of Met and Phe residues in proteins can efficiently lower the local ionization potential to trap an electron hole by forming a S∴π bond. In addition, the moderate binding energy (11.2 kcal/ mol) implies a good conductivity of this S∴π relay station. The self-movement of proteins may cause the separation of the side chains of these two residues and promote the electron hole's moving from this site to another relay station. A similar analysis can be made for the other M-Xxxn_S∴π and C-Xxx_S∴π systems (Xxx = Phe, His, Tyr, and Trp; the details are in the Supporting Information). In fact, as shown in Table 2, the BEs of M-Phe2_S∴π (28.2 kcal/mol), M-His_S∴π (23.4 kcal/mol), and M-Tyr_S∴π (14.6 kcal/mol) are greater than those of the corresponding only side-chain models listed in Table 1. The presence of a peptide framework results in new interactions between the side chain of Met and the peptide framework by the formation of one or two intermolecular hydrogen bonds (H-bonds). There are two intermolecular H-bonds for M-Phe2_S∴π and M-His_S∴π and a H-bond for M-Tyr_S∴π (Supporting Information Figure S13), which play an important role in enhancing the BEs for these complexes. Therefore, the contribution of S∴π bonds to the BEs is lower than those of the corresponding simple models; however, the EAv's of M-Phe2_S∴π (6.78 eV/mol), MHis_S∴π (6.53 eV/mol), and M-Tyr_S∴π (7.00 eV/mol) are all lower than those of the corresponding simple models (∼7.63 eV/mol for MF_S∴π, 7.57 eV/mol for MH_S∴π, and 7.59 eV/ mol for MY_S∴π), respectively. The decreases in the BEs and EAv's indicates that the formations of these S∴π-bonded complexes may be good relay stations to facilitate hole migration in proteins. In addition, the cases that the Met (or Cys) and the aromatic cation residues (including Phe, His, Tyr, and Trp) are in the same peptide chain were carefully examined. Our calculations reveal that S∴π bonds can also be formed in these cases, and their EAv's are sharply lower than those with only one residue (Supporting Information Table S4). However, it is particularly worth noting that the contribution of MO's to S∴π bonds in these cases may be different from the above analyzing scenarios. Figure 5 depicts the structure of MetPhe1_S∴π with the interesting front MO's (SOMO, HDMO-4, and HDMO-5). The shortest distance between the two side chains of Met and Phe cation residues is only 3.10 Å, which is the structural base for the formation of the S∴π bond. It is clear that the SOMO is antibonding and mainly delocalized over the two side chains of Met and Phe, consistent with the MF1_S∴π complex. However, the bonding orbitals between the S-atom of Met and the

MF3_S∴π. A similar analysis can be made for the other isomers of MΠ_S∴π and CΠn_S∴π (Π = F, W, n = 1, 2, 3; the details are in the Supporting Information). We second examined the effect of the peptide framework on the stabilities of S∴π bonds through adding the two peptide units to the aromatic rings. Practically, our calculations reveal that the side chains of Met (or Cys) residues can form S∴π bonds with all four aromatic amino acids, as displayed in Figure 4 and Supporting Information Figures S13−S14. Compared with the only side-chain structures of MΠn_S∴π, the shortest distances between the S-atoms and the aromatic rings in MXxxn_S∴π are lengthened, as listed in Table 2. This originates Table 2. The Shortest Distances (RSX) between the S-Atom and the Aromatic Rings, Vertical Electron Affinities (EAv's), Binding Energies (BEs), and Spectroscopy of S∴π Bonds for the Two-Chain Models species MPhe1_S∴π RSX (Å) EAv (eV/mol) BE (kcal/mol) λ (nm) f

RSX (Å) EAv (eV/mol) BE (kcal/mol) λ (nm) f

MPhe2_S∴π

MHis_S∴π

MTyr_S∴π

MTrp1_S∴π

3.10 6.79

3.33 6.78

3.08 6.53

3.27 7.06

3.42 6.38

11.2

28.2

23.4

14.6

8.1

690.4 0.0173

712.9 0.0812

771.6 0.0607 species

801.33 0.0418

1491.4 0.0592

CPhe_S∴π

CHis_S∴π

CTyr_S∴π

CTrp1_S∴π

CTrp2_S∴π

3.10 7.40

3.04 6.65

3.15 6.70

3.33 6.38

3.44 6.52

10.1

11.3

12.0

7.3

5.5

755.58 0.1112

743.4 0.1271

866.55 0.1042

1136.26 0.0525

1478.9 0.0582

in the presence of peptide units, which enlarges the delocalization of SOMO and HDMO (or HDMO-1). Figure 4 displays the structure of M-Phe1_S∴π and the corresponding plots of SOMO and HDMO. Evidently, SOMO and HDMO are delocalized over the peptide fragment as well as the aromatic ring and dimethyl sulfide. Therefore, the binding strength between the S-atom of the dimethyl sulfide and benzene ring reduces as compared with the only side-chain model of MF_S∴π. The predicting BE of M-Phe1_S∴π is 11.2 kcal/mol, which is significantly lower than that of MF_S∴π (∼25.0 kcal/mol). This results in the increase in the distance between the S-atom and aromatic ring. Moreover, the presence of a peptide framework also induces the red shift of absorption spectra of the S∴π bond. The delocalization of SOMO and HDMO to the

Figure 5. The structure of MetPhe1_S∴π with the plots of SOMO, HDMO-4, and HDMO-5. 19686

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all presently underway using quantum mechanics/molecular mechanics simulation.

benzene moiety of Phe are HDMO-4 and HDMO-5, not a MO, as it is with the simple models. Both HDMO-4 and HDMO-5 partly reside at the two side chains. Then the association of HDMO-4 and HDMO-5 produces a two-electron bonding between the two side chains as well as the MF1_S∴π complex with HDMO as the two-electron bonding. According the topologies of SOMO, HDMO-4, and HDMO-5, therefore, it may be concluded that the joining of these three MO's produces a S∴π bond between the S-atom and the aromatic ring. A similar analysis is made for the other same-chain models (MetXxx_S∴π and CysXxx_S∴π), as shown in Supporting Information Figures S15−S16, which are not discussed here for simplicity. In addition, the examination of the close Met and Tyr lying in the same α-helix confirms that the S∴π bond can also be formed in the same α-helix (the details are in Supporting Information Figure S16). Overall, all these imply that the neighboring aromatic rings in the same main chain (or α-helix) can facilitate participation of the S-containing residues in hole migration by forming the S∴π bonds. Similar analyses have reported that the neighboring oxygen atom can modulate the oxidation of S-containing groups by the formation of a S∴O 2c−-3e bond.10,30,34 We also examined the formation of a S∴O bond between the side chain of Met (Cys) and the O-atom of a peptide unit, named as M-pep_S∴O (or C-pep_S∴O), as shown in the Supporting Information. The EAv's for the M-pep_S∴O and C-pep_S∴O bonded complexes are 6.36 and 6.66 eV/mol, respectively, which are sharply lower than those of their corresponding isomers. More importantly, the BEs are very strong: 32.8 kcal/mol for M-pep_S∴O and 41.9 kcal/mol for C-pep_S∴O. The low EAv and the high BE imply that the formation of the S∴O bond can efficiently trap an electron hole. Therefore, the formation of the S∴O bond in the Met-containing systems can accelerate the oxidation of thioethers to sulfoxides, in excellent agreement with previous reports.10,30,34 In contrast, the EAv's for all the S∴π-bonded complexes are in the range of 6.38−7.50 eV, and their BEs vary from 5.5 to 25.7 kcal/mol. These proper EAv and BE values support the S∴π bonds' taking part in the hole migration in proteins as the relay stations. Therefore, the neighboring aromatic rings can regulate the relay abilities of the S-containing side chains by the formation of S∴π bonds in proteins. In summary, these studies are of relevance to interactions between the close side chains of S-containing and aromatic cation residues, which may participate in electron hole transport in proteins. The ab initio calculations reveal the possibility for the formation of the S∴π bonds between these close cation residues, which can facilitate electron hole migration in proteins as efficient relay stations. This indicates that the aromatic rings may regulate the relay abilities of Scontaining residues by lowering the local redox potentials. The modulation ability of aromatic rings mainly reflects the redox potentials and the binding extent of the S∴π bonds, which varies with the different aromatic amino acids and the arrangements of the same aromatic ring according to the local microsurroundings in proteins. Evidently, the proper values of the EAv and BE for the S∴π bonds can efficiently promote the S-containing residues' participation in the hole migration in proteins. We hope that future experiments will verify some of our predictions. The next objective is the prediction of rates for electron transfer through the S∴π bonds in proteins, which requires estimates of Gibbs free energies, reorganization free energies, and electronic coupling elements,

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ASSOCIATED CONTENT

S Supporting Information *

The complete citation for ref 37 as well as the atom in molecule (AIM) calculations, calculated molecular geometries, orbital characters, vertical electron affinities (EAv's), binding energies (BEs), and ultraviolet spectra for all S∴π-bonded complexes and correlations among several quantities. This information is available free of charge via the Internet at http://pubs.acs.org/

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was financially supported by NSFC of China (21003162), by the Science Foundation for The Excellent Youth Scholars of the Ministry of Education of China, by a Project Sponsored by the Scientific Research Foundation of Chongqing University.

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REFERENCES

(1) Giese, B.; Eckhardt, S.; Lauz, M. Electron Transfer in Peptides and Proteins. Encyclopedia of Radicals in Chemistry, Biology and Materials; Wiley: New York, 2012, DOI: 10.1002/ 9781119953678.rad046. (2) Bollinger, J. M., Jr. Science 2008, 320, 1730−1731. (3) Shih, C.; Museth, A. K.; Abrahamsson, M.; Blanco-Rodriguez, A. M.; Bilio, A. J. D.; Sudhamsu, J.; Crane, B. R.; Ronayne, K. L.; Towrie, M.; Vlček, A., Jr.; Richards, J. H.; Winkler, J. R.; Gray, H. B. Science 2008, 320, 1760−1762. (4) Prytkova, T. R.; Kurnikov, I. V.; Beratan, D. N. Science 2007, 315, 622−625. (5) Yang, H.; Luo, G. B.; Karnchanaphanurach, P.; Louie, T. M.; Rech, I.; Cova, S.; Xun, L. Y.; Xie, X. S. Science 2003, 302, 262−266. (6) Page, C. C.; Moser, C. C.; Chen, X.; Dutton, P. L. Nature 1999, 402, 47−52. (7) Cordes, M.; Giese, B. Chem. Soc. Rev. 2009, 38, 892−901. (8) Stubbe, J.; Nocera, D. G.; Yee, C. S.; Chang, C. Y. Chem. Rev. 2003, 103, 2167−2202. (9) Long, Y.; Abu-Irhayem, E.; Kraatz, H. Chem.Eur. J. 2005, 11, 5186−5194. (10) Beratan, D. N.; Skourtis, S. S.; Balabin, I. A.; Balaeff, A.; Keinan, S.; Venkatramani, R.; Xiao, D. Acc. Chem. Res. 2009, 42, 1669−1678. (11) Voityuk, A. A. J. Phys. Chem. B 2011, 115, 12202−12207. (12) Migliore, A. J. Chem. Theory Comput. 2011, 7, 1712−1725. (13) Issa, J. B.; Krogh-Jespersen, K.; Isied, S. S. J. Phys. Chem. C 2010, 114, 20809−20812. (14) Jones, M. L.; Kurnikov, I. V.; Beratan, D. N. J. Phys. Chem. A 2002, 106, 2002−2006. (15) Chen, X.; Zhang, L.; Zhang, L.; Sun, W.; Zhang, Z.; Liu, H.; Bu, Y.; Cukier, R. I. J. Phys. Chem. Lett. 2010, 1, 1637−1641. (16) Chen, X.; Zhang, L.; Wang, Z.; Li, J.; Wang, W.; Bu, Y. J. Phys. Chem. B 2008, 112, 14302−14311. (17) Ron, I.; Pecht, I.; Sheves, M.; Cahen, D. Acc. Chem. Res. 2010, 43, 945−953. (18) Lloveras, V.; Vidal-Gancedo, J.; Figueira-Duarte, T. M.; Nierengarten, J.; Novoa, J. J.; Mota, F.; Ventosa, N.; Rovira, C.; Veciana, J. J. Am. Chem. Soc. 2011, 133, 5818−5833. (19) Wierzbinski, E.; de Leon, A.; Yin, X.; Balaeff, A.; Davis, K. L.; Reppireddy, S.; Venkatramani, R.; Keinan, S.; Ly, D. H.; Madrid, M.; 19687

dx.doi.org/10.1021/jp306154x | J. Phys. Chem. C 2012, 116, 19682−19688

The Journal of Physical Chemistry C

Article

Beratan, D. N.; Achim, C.; Waldeck, D. H. J. Am. Chem. Soc. 2012, 134, 9335−9342. (20) Mandal, H. S.; Kraatz, H. J. Phys. Chem. Lett. 2012, 3, 709−713. (21) Malak, R. A.; Gao, Z.; Wishart, J. F.; Isied, S. S. J. Am. Chem. Soc. 2004, 126, 13888−13889. (22) Donoli, A.; Marcuzzo, V.; Moretto, A.; Toniolo, C.; Cardena, R.; Bisello, A.; Santi, S. Org. Lett. 2011, 13, 1282−1285. (23) Wittekindt, C.; Schwarz, M.; Friedrich, T.; Koslowski, T. J. Am. Chem. Soc. 2009, 131, 8134−8140. (24) Arimura, T.; Ide, S.; Suga, Y.; Nishioka, T.; Murata, S.; Tachiya, M.; Nagamura, T.; Inoue, H. J. Am. Chem. Soc. 2001, 123, 10744− 10745. (25) Sun, D.-L.; Rosokha, S. V.; Lindeman, S. V.; Kochi, J. K. J. Am. Chem. Soc. 2003, 125, 15950−15963. (26) Wells, M. C.; Lucchese, R. R. J. Phys. Chem. A 1999, 103, 7345− 7356. (27) Wang, M.; Gao, J.; Müller, P.; Giese, B. Angew. Chem., Int. Ed. 2009, 48, 4232−4234. (28) Champagne, M. H.; Mullins, M. W.; Colson, A. O.; Sevilla, M. D. J. Phys. Chem. 1991, 95, 6487−6493. (29) Fourré, I.; Bergès, J. J. Phys. Chem. A 2004, 108, 898−906. (30) Brunelle, P.; Rauk, A. J. Phys. Chem. A 2004, 108, 11032−11041. (31) Schöneich, C.; Pogocki, D.; Hug, G. L.; Bobrowski, K J. Am. Chem. Soc. 2003, 125, 13700−13713. (32) Giese, B.; Wang, M.; Gao, J.; Stoltz, M.; Müller, P.; Graber, M. J. Org. Chem. 2009, 74, 3621−3625. (33) Glass, R. S.; Schöneich, C.; Wilson, G. S.; Nauser, T.; Yamamoto, T.; Lorance, E.; Nichol, G. S.; Ammam, M. Org. Lett. 2011, 13, 2837−2839. (34) Glass, R. S.; Hug, G. L.; Schöneich, C.; Wilson, G. S.; Kuznetsova, L.; Lee, T.; Ammam, M.; Lorance, E.; Nauser, T.; Nichol, G. S.; Yamamoto, T. J. Am. Chem. Soc. 2009, 131, 13791−13805. (35) Fourré, I.; Bergès, J.; Houée-Levin,, C. J. Phys. Chem. A 2010, 114, 7359−7368. (36) Chen, X.; Dai, H.; Li, J.; Huang, X.; Wei, Z. ChemPhysChem 2012, 13, 183−192. (37) Frisch, M. J. et al. Gaussian 03, revision C.02; Gaussian, Inc.: Wallingford, CT, 2004. (38) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648−5652. (b) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785−789. (39) (a) McLean, A. D.; Chandler, G. S. J. Chem. Phys. 1980, 72, 5639−5648. (b) Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys. 1980, 72, 650−654. (c) Clark, T.; Chandrasekhar, J.; Spitznagel, G. W.; Schleyer, P. v. R. J. Comput. Chem. 1983, 4, 294− 301. (d) Frisch, M. J.; Pople, J. A.; Binkley, J. S. J. Chem. Phys. 1984, 80, 3265−3269. (40) Boys, S. F.; Bernardi, R. Mol. Phys. 1970, 19, 553−559. (41) van Duijneveldt, F. B.; van Duijneveldt-van de Rijdt, J. G. C. M.; van Lenthe, J. H. Chem. Rev. 1994, 94, 1873−1885. (42) Casida, M. E.; Jamorski, C.; Casida, K. C.; Salahub, D. R. J. Chem. Phys. 1998, 108, 4439−4449. (43) Kendall, R. A.; Dunning, T. H.; Harrison, R. J. J. Chem. Phys. 1992, 96, 6796−6806.

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