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The Flexibility of Carboxylate Ligands in Methane Monooxygenase and Ribonucleotide Reductase: A Density Functional Study Maricel Torrent, Djamaladdin G. Musaev,* and Keiji Morokuma* Cherry L. Emerson Center for Scientific Computation and Department of Chemistry, Emory UniVersity, Atlanta, Georgia 30322 ReceiVed: October 9, 2000
Available experimental data for the active sites of the hydroxylase component of methane monooxygenase (MMOH) and the R2 subunit of ribonucleotide reductase (R2) indicates high flexibility of the ligand environment of the iron centers in these two metalloproteins, suggesting that carboxylate ligands may play a special role for proper enzymatic functioning. By using quantum chemical methods, here we have investigated (1) the so-called 1,2-carboxylate shift (i.e., shift of a bridging carboxylate ligand from µ-1,1 to µ-1,2 between two metal centers), and (2) the monodentate T bidentate rearrangement of terminal carboxylate ligands (bound to only one metal center), in the reduced forms of MMOH and R2. Our results show that (i) MMOH-like and R2-like structures, with a µ-1,1 and µ-1,2 bridged carboxylate ligand, respectively, are energetically very close; (ii) complexes with lower coordination numbers in the Fe2 center are computed to be slightly more stable than those with higher coordination numbers, and (iii) the two studied carboxylate shifts are easy processes, not only thermodynamically but also kinetically, with activation barriers of only a few kcal/mol. Our conclusion that the carboxylate ligands of dinuclear complexes such as MMOHred and R2red are very flexible is in a good agreement with the available experimental data.
I. Introduction Methane monooxygenase (MMO) and ribonucleotide reductase (RNR) are two of the most extensively characterized members of the binuclear non-heme iron proteins.1 Several studies of MMOH and R2 show extensive homologies between these two enzymes (for example, both of them contain two similar E/D-X-X-H sequences), as well as flexibility of the ligand environment of the Fe centers.2-7 In the literature, this ligand flexibility has been postulated to be one of the most important factors for the proper functioning of the enzymes. Indeed, X-ray studies of the core structure of oxidized MMOH (MMOHox) isolated from Methylococcus capsulatus show that at 4 °C the two Fe atoms are triply bridged by one hydroxo, and two µ-1,2-carboxylate ligands with an Fe-Fe distance of ∼3.4 Å.2 Each Fe center has one histidine ligand. In addition, Fe1 has one terminal aquo and one carboxylate ligand, while Fe2 has two carboxylate ligands (see Scheme 1). On the other hand, the structure recorded at -160 °C shows an aquo bridge replacing one of the carboxylate bridges; the resulting structure has one µ-OH, one µ-H2O, and one carboxylate bridge with a shorter Fe-Fe distance (∼3.1 Å).3 The fact that crystallographic studies support diamond core structures with short Fe-Fe distances, as well as a structure with a longer Fe-Fe distance, dictated by the nature of one (or more) bridge(s), suggests that the core structure must be relatively flexible. Similarly, the oxidized binuclear active site of the R2 subunit of RNR from Escherichia coli (R2met) shows one µ-oxo and one 1,2carboxylate bridge with an Fe-Fe distance of ∼3.2 Å, and one histidine ligand for each Fe center.4 In addition, Fe1 has a terminal aquo and a chelating carboxylate ligand, whereas Fe2 has two monodentate terminal carboxylate ligands (like in MMOH), and one terminal aquo ligand. As shown in the literature, the oxidized forms of MMOH and R2 (MMOHox and R2met) including two ferric Fe atoms,
FeIII, are the resting state of these enzymes. Only their twoelectron reduced forms, MMOHred and R2red, with two ferrous, FeII, iron centers are capable of reacting with O2, the reaction that initiates both the catalytic cycle of MMO and the formation of a stable tyrosyl radical in R2 of RNR. Structural studies demonstrated2-4,6 that two-electron reduction of MMOHox and R2met dramatically changes the ligand environment of the Fe centers. Indeed, for MMOH, during reduction two hydroxo/aquo bridging ligands move out and one of the carboxylate ligands of Fe2, Glu243, shifts to form a monodentate bridge between the two metals as well as coordinating to Fe2 center in a bidentate manner.3 Therefore, the two Fe atoms are changed from six-coordinate (6C) to five-coordinate (5C), with one vacant site for each Fe. Spectroscopic studies are in accord with such a (5C, 5C) assignment for the reduced state of MMOH.5 Similarly, in R2met the two-electron reduction leads to dissociation of two oxo/aquo bridging ligands.6 However, upon reduction of R2met the terminal ligand Asp84 shifts from chelating to monodentate terminal position to Fe1, a shift which has no analogue in the counterpart reduction of MMOH. Carboxylate ligand Glu238 in R2, which moves from terminal monodentate in Fe2 to a bridging position, also gives a bidentate bridge rather than monodentate as in MMOH. Thus, according to crystallographic studies,6 R2red has two approximately equivalent 4C Fe centers. Spectroscopic data,7 on the contrary, indicate that Fe1 and Fe2 atoms in R2red are 5C and 4C, respectively. The challenge comes in reconciling the CD/MCD studies with the structural data. Here, we have preferred to chose a starting structural model for R2 with inequivalent sites (Scheme 1). So far, the asymmetric view seems to have a larger acceptance. This view has been supported by a very recent study8 proposing that Glu204 is actually bidentate to Fe2 in solution, and therefore, suggesting that Fe2 is a 5C site. Further support to the asymmetric view comes from the reduced binuclear active site
10.1021/jp003692m CCC: $20.00 © 2001 American Chemical Society Published on Web 12/07/2000
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SCHEME 1
of manganese-substituted E. coli which has been found to have a water ligand bound to Mn1.9 The data presented above are indicative of (i) a high flexibility of the ligand environment in MMOH and R2, and (ii) a substantial difference in the most active forms of MMOH and R2 (MMOHred and R2red). In other words, these data clearly demonstrate that the carboxylate ligands may play a special role for proper functioning of these enzymes. Indeed, the flexibility of these ligands allows them to coordinate the Fe centers as a function of enzymatic needs: as bidentate ligands (bridging or chelating) when saturation of the first coordination sphere of Fe centers is required, and as monodentate (terminal) ligands when one (or more) vacant coordination site(s) in the Fe centers are needed (for example upon dioxygen or substrate coordination) to enable a certain reaction step to take place. Extensive studies of carboxylate coordination modes in diiron complexes, which are believed to be biomimetic analogues of the MMOHred and R2red,10 as well as substrate (O2 molecule) coordination to these complexes by Lippard and co-workers11,12 show that (1) having bulky steric ligands [such as XDK, m-xylylenediamine bis(propyl Kemp’s triacid)imide, derivatives] in the bridging carboxylate ligands could facilitate a µ-1,1 T µ-1,2-carboxylate shift, and (2) the 1,2-carboxylate shift could be a rate-determining step of the entire substrate (O2) coordination and ligand rearrangement process.12 Recently, Nordlund and co-workers13 using mutation experiments demonstrated that substrate (azide) coordination to R2red subunit of RNR could cause 1,2-carboxylate shift of one of the bridging carboxylate ligands, Glu238. The authors believe that such a carboxylate shift (of Glu238) could be a key feature for understanding the dioxygen activation mechanism at the Fe centers.13 They have outlined a detailed reaction mechanism for dioxygen activation adopting the following three assumptions: (1) one of the carboxylate ligands retains its µ-1,1-bridging conformation throughout the dioxygen activation reaction, (2) no protein- or dioxygen-derived ligands leave the coordination sphere during the reaction, and (3) the Fe ions will never have a coordination number higher than 6.13 Despite the progress presented above, still both the mechanism and the factors affecting the flexibility of the carboxylate ligands in MMOHred and R2red, together with the energetics associated with these processes, remain unknown and need additional and comprehensive studies.
In this paper we aimed to investigate using quantum chemical methods: (i) the carboxylate shift that involves two metal centers (called “1,2-carboxylate shift”)14 and explore whether structures such as MMOHred and R2red in Scheme 1 can be exchanged through this bimetallic shift, and (ii) the bidentate T monodentate carboxylate rearrangement within one metal center. Since only the reduced forms of these enzymes are capable for substrate oxidation, below we will study only MMOHred and R2red. Our studies of the roles of substrate (O2) coordination and electronic and steric effects from the ligands (R) associated with bridging carboxylates to the 1,2-carboxylate shift between two metal centers, and the bidentate T monodentate carboxylate rearrangement within one metal center are in progress. These results will be reported separately. II. Computational Procedure and Choice of Model/Spin State To be able to conduct the extensive studies we have to choose a reasonable model for the MMOHred and R2red. According to the above presented experimental data and our15 and others16 experience, the reasonable model of MMOHred and R2red should include two imidazole rings modeling the histidines, four C1 carboxylates modeling glutamate and aspartate residues, and one water molecule. As important as the model is the choice of the correct spin state for our calculations. According to spectroscopic studies,17 MMOHred includes two ferromagnetically coupled FeII centers, and has a total spin S ) 4 at the ground state. The spectroscopic picture for R2red is slightly more complex; based on Mo¨ssbauer studies, the two Fe centers in R2red are high-spin ferrous ions.18 EPR studies of R2red show a very weak integer spin signal, considered to derive from a small fraction of molecules having ferromagnetically coupled sites.19 Magnetic circular dichroism studies show a paramagnetic center with a saturation behavior indicating two Fe centers with Ms ) (2 at the ground state. However, a spin Hamiltonian analysis of the saturation magnetization behavior indicates that the two Fe atoms are weakly (J ) ∼0.5 cm-1) antiferromagnetically coupled.7,20 Since the exchange coupling constant of R2red is extremely small, we have considered both MMOHred and R2red as ferromagnetically coupled high-spin species, and we have studied them at their 2Ms + 1 ) 9 spin states. (Test calculations
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Figure 1. Optimized geometries of the equilibrium structures (Nimag ) 0) (distances in Å).
Figure 2. Optimized geometries of the transition states (distances in Å).
with multiplicity 2Ms + 1 ) 7 have been also done for MMOHred and R2red; our results indicate that the latter multiplicity is not the ground-spin state for these systems, in good agreement with the above assumption). In these calculations one can use with confidence a spin-unrestricted open-shell single-determinant method like B3LYP21 with a double-ζ quality basis set lanl2dz and Hay-Wadt pseudopotential for the Fe centers.22 Full geometry optimizations have been carried out for all stationary points. The nature of these structures has been confirmed by performing vibrational frequency calculations, i.e., the transition states (TSs) with one imaginary frequency (Nimag ) 1) and the equilibrium structures with none (Nimag ) 0). All calculations have been performed by using Gaussian 98.23
III. Results and Discussions Geometries of the calculated equilibrium structures and TSs are shown in Figures1 and 2, respectively. In Figure 3, we schematically present the obtained mechanisms of the µ-1,1 T µ-1,2 carboxylate shift, and the bidentate T monodetate carboxylate rearrangement in MMOHred and R2red, together with their corresponding relative energies. As seen from Figure 1, we have found two sets of minima: (a) structures 1 and 3, with one monodentate (µ-1,1) and one bidentate (µ-1,2) Fe-Fe bridging carboxylate ligands (hereafter we call these structures MMOH-like structures), and (b) structures 2 and 4 with two bidentate (µ-1,2) Fe-Fe bridging carboxylate ligands (which we call R2-like structures). Structures
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Figure 3. Schematic representation of the reaction mechanism and the energetics of 1,2-carboxylate shift (horizontal) and monodentateTbidentate rearrangement (vertical) in MMOH-like and R2-like systems. For clarity, ligands not directly involved have been omitted.
1 and 3, as well as 2 and 4, are different from each other only by the coordination mode of the terminal carboxylate ligand (which models Glu114 in MMOHred and Asp84 in R2red) located on Fe1; the terminal carboxylate ligand binds to the Fe center monodentately in structures 1 and 2, but bidentately in structures 3 and 4. Thus, horizontally (in Figure 3), processes 1 T 2 and 3 T 4 involve migration of one of the carboxylate ligands between the two Fe centers, from being monodentate bridge, µ-1,1, between the two metals (as well as coordinating to Fe2 center in a bidentate manner, left) to form a bidentate, µ-1,2, bridge between the two irons (right). This is the so-called 1,2carboxylate shift. During the first process, 1 T 2, the terminal carboxylate of Fe1 is monodentately coordinated to the metal center, while during the second process, 3 T 4, this carboxylate coordinates bidentately (chelating) to the Fe1 center. In other words, during the first process, 1 T 2, the coordination numbers of the Fe centers change from (5C, 5C) in 1 to (5C, 4C) in 2, while during the second process, 3 T 4, the coordination numbers of the Fe centers change from (6C, 5C) in 3 to (6C, 4C) in 4. Meantime, vertically in Figure 3, the processes 1 T 3 and 2 T 4 correspond to a monodentate (top) T bidentate (bottom) rearrangement of the terminal carboxylate ligand of the Fe1 center. During these processes, the coordination number of Fe1 increases by one, from 5C in 1 (and 2) to 6C in 3 (and 4). First, let us discuss processes 1 T 2 and 3 T 4, corresponding to the 1,2-carboxylate shift. Comparison of the energies of 1 and 2 pairs, as well as 3 and 4 pairs shows (see Figure 3) that R2-like structures, 2 and 4, with lower coordination numbers, are energetically preferred over their MMOH-like analogues, 1 and 3; structure 2 is calculated to be 7.9 kcal/mol more stable than structure 1. Similarly, structure 4 is 4.9 kcal/mol more stable than 3. The obtained difference in the energetics of the processes 1 T 2 vs 3 T 4 can be also due to the ligand environment of the Fe centers; indeed, in the first process we
go from (5C, 5C) in 1 to (5C, 4C) in 2, while in the second process we go from (6C, 5C) in 3 to (6C, 4C) in 4. Starting from the most stable 2 with the lowest (5C, 4C) coordination, one extra coordination on Fe1 gives 1.2 kcal/mol of destabilization for 4 with (6C, 4C), one extra coordination on Fe2 gives 7.9 kcal/mol of destabilization for 1 with (5C, 5C), and two simultaneous extra coordinations give 6.1 kcal/mol for 3 with (6C, 5C), which is lower than the sum of the two single coordinations (1.2 + 7.9) by 3.0 kcal/mol due to a cooperative effect. These changes in the ligand environment do also have an effect on the metal-metal distance. From MMOH-like structures, 1 and 3, (left) to R2-like structures, 2 and 4, (right) the Fe1-Fe2 distance increases by ∼0.5 Å due to the loss of one (carboxylate) bridge. This is in excellent agreement with the difference in the Fe-Fe distance for the crystallographically determined structures of MMOHred and R2red,3,6 and also with recent mutagenic studies involving µ-1,1 T µ-1,2 carboxylate shifts.13,24 Thus, studies of the azide-bound reduced form of the R2-Phe208Ala/Tyr122Phe mutant of E. coli have shown13 that Glu238 coordinates the Fe1 center in a novel µ-1,1 bridging mode with one of the carboxylate O atoms, forming a bridge between the two Fe ions and the other O being coordinated to Fe2. Through this new bridging (µ-1,1) the Fe-Fe distance is shortened to ∼3.4 Å as compared to ∼3.9 Å for the structure of the reduced wild-type protein (where Glu238 has a µ-1,2 bridging mode). Also, in the structure of the R2-Asp84Glu mutant,24 Glu238 has been found to adopt a µ-1,1 configuration as well, with its second O atom also bound to Fe1; such a bridging decreases again the distance between the two Fe atoms, from 3.9 to 3.5 Å. Our results above are in accord with the assumption that the core structure of these enzymes must be relatively flexible. The energy minima 1 and 2, as well as 3 and 4, are separated from each other with small energetic barriers, 0.7 and 1.6 kcal/
326 J. Phys. Chem. B, Vol. 105, No. 1, 2001 mol, respectively. The TSs corresponding to these barrier heights, TS12 and TS34 (see Figure 2) have only one imaginary frequency, 88i and 84i cm-1, respectively, which, according to our normal-mode analysis, mainly correspond to 1,2-carboxylate shift. Geometries of these TSs are quite self-explanatory. The distance between Fe2 and the bridging oxygen, Ob, increases from 2.098 Å in 1, to 2.498 Å in TS12 and to 3.547 Å in 2. Likewise, the bond length between Fe2 and the O atom axially bound to this iron, Oax, decreases from 2.650 Å in 1, to 2.168 Å in TS12 and to 2.018 Å in 2. Similar changes are found for the 3 f 4 conversion via TS34: Fe2-Ob ) 2.093 Å in 3, 2.497 Å in TS34, and 3.514 Å in 4, whereas Fe-Oax ) 2.543 Å in 3, 2.140 Å in TS34, and 1.978 Å in 4. It should be also noted that the Fe1-Fe2 distance in these TSs (3.805 Å in TS12 and 3.800 Å in TS34) is approximately halfway between the computed Fe-Fe distance in MMOH-like structures (3.5 Å) and in R2like structures (4.0 Å). The first process, 1 f 2, during which Fe1 remains 5C, while Fe2 changes its ligand environment from 5C to 4C, is kinetically and thermodynamically more favorable than the second process, 3 f 4, where Fe1 remains 6C, but Fe2 changes its ligand environment again from 5C to 4C during the process. Our calculations clearly show that rearrangements 1 f 2 and 3 f 4 are exothermic processes and could take place with very small energetic barriers. The key point from the presented data is that the 1,2-carboxylate shift involved in MMOHred and R2red structures is an easy process both thermodynamically and kinetically, which is consistent with the above presented experimental observations.2-7 Next, let us discuss the monodentate T bidentate rearrangement of the terminal carboxylate ligand in Fe1, i.e., processes 1 T 3 and 2 T 4 for MMOH-like (left) and R2-like (right), respectively. As one can see from Figure 3, for an MMOH-like structure, the carboxylate ligand modeling Glu114 in the real system prefers to be chelating (structure 3) rather than monodentate terminal (structure 1); the process 1 f 3 is calculated to be slightly exothermic by 1.8 kcal/mol and occurs with a small, 1.0 kcal/mol, energetic barrier calculated from 1. The TS corresponding to this barrier, TS13, is characterized to be a real TS with one imaginary frequency of 64i cm-1 (Figure 2). Normal-mode analysis shows that this imaginary frequency mainly corresponds to the motion of the Fe1-Od bond (Od ) “dangling” oxygen). During this process the Fe1-Od bond distance reduces from 3.415 Å in 1, to 2.750 Å in TS13 and to 2.304 Å in 3, accompanied with the changes in bond angles in Fe1-O-C-Od moiety. As mentioned above, crystallographic3 and spectroscopic5 studies of MMOH suggest that the reduced form of this metalloenzyme contains two 5C ferrous centers, which implies a monodentate terminal Glu114 ligand in Fe1. This small discrepancy between experiment and calculated data can be ascribed to the fact that the present calculations do not take into account, for instance, possible effects of the protein surroundings (thus, the terminal Od atom in 1 might be better stabilized by solvent or by second-sphere ligands in the real metalloenzyme). Within the expected accuracy of calculations, however, there is a fair agreement with experimental results. Also, it may well be that small variations in the reaction conditions (pH, temperature) easily reverse the preference observed so far. The key point here is that, regardless of the sign of the enthalpy of reaction, the computed energy difference is rather small (1 kcal/mol). What really counts is that the interconversion is predicted to be nearly thermoneutral and kinetically very easy as suggested by the small barrier. On the contrary, in the case of R2-like structures, the carboxylate ligand modeling Asp84 prefers to be monodentate
Torrent et al. terminal (2) rather than chelating (4) to the Fe1 center. The process 2 f 4 is found to be slightly endothermic by 1.2 kcal/ mol, and takes place with a 1.4 kcal/mol barrier at the transition state, TS24 (Figure 3). During this process, the distance between Fe1 and Od reduces from 3.655 Å in 2, to 2.601 Å in TS24 and 2.391 Å in 4. The performed normal-mode analysis is consistent with these geometry changes, and confirms that TS24 is a real TS with one, 60i cm-1, imaginary frequency. Changes in other geometry parameters of complex 2 during the process are insignificant and will not be discussed. The present result agrees well with experimental observations6 showing that in the reduced form of R2 the terminal ligand Asp84 prefers to be monodentately coordinated to the Fe1 center. Finally, it should be noted that, with the current model, a H-bond interaction between H2O and one carboxylate ligand in Fe2 is present in both MMOH- and R2-like forms. This interaction is preserved in all rearrangements in Figure 3 and does not affect the studied “shift” reaction. IV. Conclusions From the results and discussions presented above, one may conclude the following. (1) The MMOH-like, 1 and 3, and R2-like, 2 and 4, structures are energetically very close to each other and separated with small energetic barriers. Structures 2 and 4 (which correspond to R2red) with lower coordination numbers in the Fe2 center are found to be a few kcal/mol more stable than those with higher coordination numbers (1 and 3, respectively). Thus, both the 1,2-carboxylate shift, i.e., the shift of one of the bridging carboxylate ligands from µ-1,1 to µ-1,2 bridging mode between the two Fe centers, as well as monodentate T bidentate rearrangement of terminal carboxylate ligand take place very easily in these systems. (2) These reactions can take place reVersibly, under proper experimental conditions. Our results indicate that, at least in the first steps of the dioxygen activation reaction, the two enzymes can access common intermediates, the fate of which may be selectively regulated after the initial steps (in fulfillment of the different oxidative functions of each metalloenzyme). (3) The present calculations are also consistent with the available experimental data showing high flexibility of the carboxylate ligands, as well as a nonrigid core structure, in MMOHred and R2red. The major conclusions of this study rationalize the experimental observations that multiple isomers may be found in a single protein depending on the conditions of crystallization and other subtleties (e.g., substitutions remote from the diiron center, binding of small molecules). These conclusions are especially important to those studying the diiron-carboxylate proteins, because it would indicate that interconversion of the various forms should be facile.25 This indication would, in turn, allow for the possibilities that the subtle differences in coordination among the various proteins are of little or no functional significance and that these two O2-activating diiron proteins may utilize a common initial pathway for oxygen activation. An alternative hypothesis, of course, would be that the subtle differences are functionally important and serve to dictate that different initial diiron(II)-O2 adducts with different reactivities form in the proteins. Distinguishing which of these hypotheses is correct is currently one of the most important objectives of research on these non-heme metalloproteins, both experimentally and theoretically. Calculations that take into account the effects of the protein environment using the ONIOM scheme26 are in progress in our lab.
DFT Study of Flexible Carboxylate Ligands Our studies of the roles of substrate (dioxygen) coordination to the Fe centers, together with electronic and steric effects of R-ligands of the carboxylates in the mechanism (and relative energies) of the 1,2-carboxylate shift, and monodentate T bidentate rearrangement are also in progress. Acknowledgment. The author is grateful to Prof. Harold Basch of Bar-Ilan University for stimulating discussions. The present research is in part supported by a grant (CHE96-27775) from the National Science Foundation. M.T. acknowledges a Postdoctoral Fellowship from the Spanish Ministerio de Educacio´n y Cultura. Computer time allocated at the Emerson Center for Scientific Computation of Emory University, the Center for Supercomputing Applications (NCSA), and Maui High Performance Computer Center (MHPCC) is acknowledged. Supporting Information Available: Cartesian coordinates of intermediates 1-4 and TSs TS12, TS34, TS13, TS24. This material is available free of charge via the Internet at http:// pubs.acs.org. References and Notes (1) Solomon, E. I.; Brunold, T. C.; Davis, M. I.; Kemsley, J. N.; Lee, S.-K.; Lehnert, N.; Neese, F.; Skulan, A. J.; Yang, Y.-S.; Zhou, J. Chem. ReV. 2000, 100, 235-349. (2) Rosenzweig, A. C.; Frederick, C. A.; Lippard, S. J.; Nordlund, P. Nature 1993, 366, 537-543. (3) Rosenzweig, A. C.; Nordlund, P.; Takahara, P. M.; Frederick, C. A.; Lippard, S. J. Chem. Biol. 1995, 2, 409-418. (4) Nordlund, P.; Eklund, H. J. Mol. Biol. 1993, 232, 123-164. (5) Pulver, S. C.; Froland, W. A.; Lipscomb, J. D.; Solomon, E. I. J. Am. Chem. Soc. 1997, 119, 387-395. (6) Logan, D. T.; Su, X.-D.; Åberg, A.; Regnstro¨m, K.; Hajdu, J.; Eklund, H.; Nordlund, P. Structure 1996, 4, 1053-1064. (7) Pulver, S. C.; Tong, W. H.; Bollinger, M. J., Jr.; Stubbe, J.; Solomon, E. I. J. Am. Chem. Soc. 1995, 117, 12664-12678. (8) Yang, Y.-S.; Baldwin, J.; Ley, B. A.; Bollinger, J. M., Jr.; Solomon, E. I. J. Am. Chem. Soc. 2000, 122, 8495-8510. (9) Atta, M.; Nordlund, P.; Åberg, A.; Eklund, H.; Fontecve, M. J. Biol. Chem. 1992, 267, 20682-20688. (10) (a) Que, L., Jr. J. Chem. Soc., Dalton Trans. 1997, 3933-3940. (b) Suzuki, M. Pure Appl. Chem. 1998, 70, 955-960. (c) Reynolds, R. A., III.; Dunham, W. R.; Coucouvanis, D. Inorg. Chem. 1998, 37, 1232-1241.
J. Phys. Chem. B, Vol. 105, No. 1, 2001 327 (d) Moe¨nne-Loccoz, P.; Baldwin, J.; Ley, B. A.; Loehr, T. M.; Bollinger, J. M., Jr. Biochemistry 1998, 37, 14659-14663. (11) (a) Zhang, X.-X.; Fuhrmann, P.; Lippard, S. J. J. Am. Chem. Soc. 1998, 120, 10260-10261. (b) Lee, D.; Lippard, S. J. J. Am. Chem. Soc. 1998, 120, 12153-12154. (12) (a) Herold, S.; Lippard, S. J. J. Am. Chem. Soc. 1997, 119, 145156. (b) LeCloux, D. D.; Barrios, A. M.; Mizoguchi, T. J.; Lippard, S. J. J. Am. Chem. Soc. 1998, 120, 9001-9014. (13) Andersson, M. E.; Ho¨gbom, M.; Rinaldo-Matthis, A.; Andersson, K. K.; Sjo¨berg, B.-M.; Nordlund, P. J. Am. Chem. Soc. 1999, 121, 23462352. (14) Rardin, R. L.; Tolman, W. B.; Lippard, S. J. New J. Chem. 1991, 15, 417-430. (15) Basch, H.; Mogi, K.; Musaev, D. G.; Morokuma, K. J. Am. Chem. Soc. 1999, 121, 7249-7256. (16) Siegbahn, P. E. M. Inorg. Chem. 1999, 38, 2880-2889. (17) (a) Pulver, S.; Froland, W. A.; Fox, B. G.; Lipscomb, J. D.; Solomon, E. I. J. Am. Chem. Soc. 1993, 115, 12409-12422. (b) Wallar, B. J.; Lispcomb, J. D. Chem. ReV. 1996, 96, 2625-2657 and references therein. (18) Lynch, J. B.; Juarez-Garcia, C.; Mu¨nck, E.; Que, L., Jr. J. Biol. Chem. 1989, 264, 8091-8096. (19) Elgren, T. E.; Hendrich,, M. P.; Que, L., Jr. J. Am. Chem. Soc. 1993, 115, 9291-9292. (20) (a) Pulver, S. C.; Tong, W. H.; Bollinger, J. M.; Stubbe, J.; Solomon, E. I. J. Am. Chem. Soc. 1995, 117, 12664-12678. (b) Yang, Y.-S.; Broadwater, J. A.; Pulver, S. C.; Fox, B. G.; Solomon, E. I. J. Am. Chem. Soc. 1999, 121, 2770-2783. (21) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (b) Becke, A. D. Phys. ReV. A 1988, 38, 3098-3100. (c) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785-789. (22) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299-310. (23) Gaussian 98, ReVision A.1; Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A. Jr.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A.; Gaussian, Inc.: Pittsburgh, PA, 1998. (24) Voegtli, W. C.; Khidekel, N.; Baldwin, J.; Ley, B. A.; Bollinger, J. M., Jr.; Rosenzweig, A. C. J. Am. Chem. Soc. 2000, 122, 3255-3261. (25) While this work was in the process of review, a experimental study came out suggesting that different isomers might have similar energies, which makes our theoretical predictions very valuable: ref 24. (26) Dapprich, S.; Komaromi, I.; Byun, K. S.; Morokuma, K.; Frisch, M. J. J. Mol. Struct. (THEOCHEM), 1999, 461-462, 1-21.
