Margareta R. A. Blomberg

Singlet and triplet energy surfaces of NiH2

Contracted CI calculations have been performed for the concerted dissociation of NiH2 into Ni and H2. All low‐lying states have been considered. The most important result of the calculations is that the 1A1 state is much lower in energy than the other states for bent geometries. This state even forms a slightly stable complex with an H–Ni–H angle of 49°. The binding is between Ni sd‐hybridized orbitals and a weakened H2 molecule. The ground state of NiH2 is, however, found to be a linear 3Δg state, with the lowest singlet almost 1.5 eV higher in energy at this geometry. The forbidden dissociation reactions for the triplets and singlets with the lowest barriers proceed in steps with the occupation of each symmetry changing by only one unit in each step. The lowest triplet barrier is 1.8 eV, and for this state a concerted dissociation is slightly preferred over a stepwise loss of a hydrogen at a time. The mechanism for the concerted triplet dissociation may also be through spin‐orbit coupling to the 1A1 sta...

Quantum Chemical Studies of Mechanisms for Metalloenzymes

ing a hydrogen atom from substrates with relatively weak X−H bonds (Figure 56). Such a situation was found in the catalytic cycle of ACCO, where cleavage of the N−H bond is facilitated by the ferrous ion capable of (partly) reducing the resulting N-based radical to an anion. In the catalytic cycle of HEPD and in the reaction of HppE with an enantiomer of the native substrate, a C−H bond at the carbon hosting a deprotonated alcohol group is severed by the superoxide. In these cases transfer of a hydrogen atom to the superoxide is coupled to one-electron reduction of Fe(III) to Fe(II), which yields aldehyde or ketone products. In a similar way a thioaldehyde is produced during the initial steps of the IPNS catalytic cycle. Figure 53. Reaction catalyzed by NDO. Figure 54. X-ray structure of the non-heme iron cofactor in the NDO active site (PDB 1O7G). Figure 55. Reaction mechanism for the dihydroxylation reaction catalyzed by NDO suggested on the basis of the results of a DFT study. Relative energy values in kilocalories per mole are given beneath the structures shown and above the arrows for the transition states connecting them. Chemical Reviews Review dx.doi.org/10.1021/cr400388t | Chem. Rev. 2014, 114, 3601−3658 3636 The most often encountered reaction of the Fe(III)−O2 species is an electrophilic attack on an electron-rich (co)substrate that yields an Fe(II) intermediate with a peroxide bridge between the ferrous ion and an organic molecule (Figure 57). In all examples shown in the figure the reactive spin state is a quintet with high-spin Fe(III) antiferromagnetically coupled to the superoxide radical. This particular electronic structure allows for a smooth two-electron reaction, leading to a ferrous intermediate featuring a high-spin Fe(II) ion, i.e., also lying on a quintet PES. When the substrates are easily one-electron-oxidized, as, for example, carotenoids or catecholates, already the ternary enzyme−dioxygen−organic substrate complex may contain an organic radical along with the superoxide anion stabilized by coordination to the metal (Figure 58). With proper (antiferromagnetic) alignment of the spins of the unpaired electrons on the two radicals, direct coupling between them proceeds with a straightforward formation of a new C−O bond. With the O2 ligand already protonated, several different reaction scenarios are usually plausible, and one of them, arguably the simplest, involves a transfer of the HOO group from the metal ion to the organic substrate (Figure 59). In the reaction of HEPD, it is the distal, i.e., originally protonated, oxygen atom that attacks the aldehyde group and the proton is transferred to the second (proximal) oxygen atom with the help of a phosphonic group of the substrate. In this reaction HOO acts as a nucleophile. In the case of HGD, the HOO ligand has a partial radical character, and hence, in its attack on the aromatic ring, it behaves as an electrophilic reagent. Moreover, in the HGD and ACO cases, it is the proximal oxygen atom that is directly transferred from the metal ion to the organic radical, i.e., the proton remains on the same oxygen atom throughout the reaction. When a catalytic reaction involves a homolytic O−O bond cleavage, one end of the peroxo group is in contact with the metal ion, and it is reduced to HO− or RO− when the O−O bond breaks (Figure 60). The electron required for the reduction is provided usually by the ferrous ion; in intradiol dioxygenases, which host Fe(III) in the active site, a tyrosinate ligand can serve as a reductant. Heterolytic cleavage of the O−O bond typically yields highvalent iron(IV)−oxo species, and such a reaction requires Fe(II), a deprotonated proximal oxygen atom, and usually also that the distal oxygen atom has a chance to develop a second covalent bond when the O−O gets broken (Figure 61). The bonding partner for the distal oxygen can be a hydrogen (PDHs, IPNS, ACCO) or a (co)substrate’s carbon (αKAOs, ACO, Dke1) atom. Heterolysis to Fe(IV)O usually proceeds on the quintet PES. Finally, heterolytic O−O bond cleavage may proceed without changing the oxidation state of the metal but instead with coupled two-electron oxidation of an organic substrate (Figure Figure 56. Examples of Fe(II)/Fe(III)−O2 reactions involving hydrogen atom abstraction. Only the most relevant fragment of the substrate is shown. Figure 57. Examples of Fe(III)−O2 reactions involving electrophilic attack and two-electron oxidation of an organic (co)substrate. Figure 58. Examples of Fe(II)/Fe(III)−O2 reactions involving radical coupling between the superoxide and an organic radical. Only the most relevant fragment of the substrate is shown. Chemical Reviews Review dx.doi.org/10.1021/cr400388t | Chem. Rev. 2014, 114, 3601−3658 3637 62). In both cases depicted in the figure, a hydroperoxo group is bound to high-spin Fe(III), and when theO−Obond cleaves, the OH group remains on iron and the other oxygen atom forms two covalent bonds with the organic substrate. This kind of heterolytic O−O cleavage requires that the donor orbital of the organic substrate, i.e., the one that provides two electrons for reduction of the peroxo group, has a good overlap with the O−O σ* orbital. 5.2. Dinuclear Non-Heme Iron Enzymes 5.2.1. Methane Monooxygenase. MMO is an enzyme which inserts one oxygen from O2 into methane to form methanol. The active site of the soluble form of MMO is shown in Figure 63. It contains an iron dimer complex linked by oxygen-derived ligands and has four glutamates and two histidines. Due to the presence of a well-resolved X-ray structure, and the technical importance of the reaction catalyzed, this was actually the first redox-active enzymemechanism that was treated with the cluster model using modern DFT functionals in 1997. Several groups were active at an early stage, and the most essential parts of the reaction mechanism were determined more than a decade ago. A comprehensive review of this development was written by Friesner et al. In short, the active species (compound Q) has a diamond core structure with two bridging oxo groups and is in an Fe2(IV,IV) state, one of themost oxidized species in nature. One of the oxo groups of compound Q activates nethane by an abstraction of one hydrogen atom. The TS is linear in C···H···O to form an Fe2(III,IV) state and amethyl radical. The loss of entropy at the TS is a large part of the barrier. In the second step, the methyl radical recombines with the bridging hydroxide formed in the first step. The TS for this step was first located by Basch et al. This rebound mechanism was criticized by interpretations of radical clock experiments, which appeared to show that there could not be a sufficiently long-lived alkyl radical to be consistent with a two-step mechanism. A concerted mechanism with simultaneous cleavage of the C−H bond and formation of the C−O bond was therefore suggested. Several explanations were suggested to resolve this apparent discrepancy between experiment and theory. In one of them, it was concluded that the radical clock probe molecules Figure 59. Examples of HOO transfer reactions. Only the most relevant fragment of the substrate is shown. Figure 60. Examples of O−O bond homolysis facilitated by oneelectron reduction of the proximal oxygen atom. Only the most relevant fragment of the substrate is shown. Figure 61. Examples of heterolytic O−O bond cleavage yielding iron(IV)−oxo species. Figure 62. Examples of heterolytic O−Obond cleavage proceeding with direct two-electron oxidation of the organic molecule. Chemical Reviews Review dx.doi.org/10.1021/cr400388t | Chem. Rev. 2014, 114, 3601−3658 3638 were chemically so different from methane that different mechanisms were likely. The probes are much easier to ionize and could form cations instead of radicals. Another suggestion was a so-called two-channel mechanism of the dynamics involving a bound radical intermediate. A third possibility could be something analogous to the two-state reactivity mechanism suggested for P450 to explain similar discrepancies in that case, but this has not been tested. In summary, a concerted mechanism, as suggested by the experiments, has never been found in DFT modeling calculations for methane hydroxylation by MMO, at least when reasonable models have been tried, and the suggestion has therefore not survived. In the initial phase of the MMO studies, there were problems converging to proper electronic states. These problems were solved by Friesner et al., who were able to obtain the correct antiferromagnetic coupling of compound Q with two high-spin irons. A state of key importance is also the first intermediate after Q, with an electronic structure characterized as Fe2(III,IV)− O•, discussed further below in connection with mixedMn−Fe dimers. It was found that already at the TS for hydrogen abstraction the iron dimer is in an Fe2(III,IV) state as it is in the product of this step. The bridging oxygen radical would then act as a hydrogen atom abstractor. At the TS, the spins are divided between a bridging oxo ligand and the methyl, while the iron spins stay essentially constant from the Fe2(III,IV)−O state to the product. The O−O bond cleavage to reach compound Q is also a significant step in the catalytic cycle. Again, several groups were involved in studying this step at an early stage. There was essential agreement among these studies on the mechanism. First, a peroxide (compound P) is formed between the two irons in an Fe2(III,III) state. Several different structures of P are nearly degenerate. In the TS for the O−O cleavage, the oxygens are symmetric, but only one of the irons is redox-active. In the final Figure 63. Active site of methane monooxygenase. Figure 64. R1 and R2 proteins in RNR. Chemical Reviews Review dx.doi.org/10.1021/cr400388t | Chem. Rev. 2014, 114, 3601−3658 3639 stage, the other iron also changes its oxidation state to IV, and compound Q is formed. In the study by Friesner et al.,

A simple method for the evaluation of the second-order-perturbation energy from external double-excitations with a CASSCF reference wavefunction

Abstract A simple method is proposed for the evaluation of the second order perturbation energy associated with double replacements of inactive and active molecular orbitals by secondary orbitals in a CASSCF wavefunction. The formulas for the first order CI wavefunction and the second order energy are expressed in terms of the first and second order reduced density matrices over the active orbitals. The computational effort is essentially that required for one additional CASSCF iteration. Results are presented for a number of molecules, including N2, O2, CN+ and C2H6. The method gives in most cases improved results for properties related to near-equilibrium energies, while the results for e.g. dissociation energies are more ambiguous.

Significant van der Waals Effects in Transition Metal Complexes

There is, in general, very good experience using hybrid DFT to study mechanisms of enzyme reactions containing transition metals. For redox reactions, the B3LYP* functional, which has 15% exact exchange, has been shown to be particularly accurate. Still, there are some cases which have turned out to be quite difficult with large errors. In the present study, the effects of van der Waals interaction have been investigated for these cases, using the empirical formula of Grimme. The results are encouraging.

Quantum chemical studies of proton-coupled electron transfer in metalloenzymes.

Proton-coupled electron transfer (PCET) is a general name for a group of rather different reactions occurring in most redox-active enzymes. They all involve electron transfer from a donor to an acceptor, but the degree and character of proton coupling varies strongly from case to case. In the present text, the conventional use of the term PCET will be adopted, in which PCET stresses the fact that connected with an electron transfer (ET) there is a significant proton motion. PCET could be either a concerted one-step process or a twostep process in which there is a first step of ET followed by a second step of proton transfer. A different use of the term PCET exists, where it only stands for the concerted onestep process, but that definition will not be used here. For experimentally observed PCET reactions, the reader is referred to the comprehensive review by Huynh and Meyer.1 It is common to separate PCET reactions into different groups. The purpose of making a classification of the PCET reactions is to emphasize that enzymes have been adapted in quite different ways to the different types of these reactions. In one extreme, a proton and an electron are both transferred between the same donor and acceptor, more or less simultaneously. This type of reaction is here termed hydrogen-atom transfer (HAT). In the other extreme, the electron transfer occurs between one donor and one acceptor,

The dissociation of H2 on the Ni(100) surface

The dissociation of H2 on the (100) surface of Ni is investigated using a cluster model. The mechanism for dissociation of H2 directly above a Ni atom has little to no barrier and involves the Ni 3d electrons; elimination of the Ni 3d interaction with the H2 increases the barrier to more than 50 kcal/mol. The dissociation at the bridge site, treated without the Ni 3d interaction, leads to a barrier of about 30 kcal/mol, leading to the conclusion that the dissociation of H2 at any site on a Ni(100) surface requires strong 3d participation. The results are quantitatively different if the Ni 4p orbitals are not included. The effects of cluster size on the results are also discussed.

Potential energy surfaces of MH2 (M = Co, Fe, and Cu)

The lowest low spin and high spin potential surfaces of MH2, where M is one of the metals Co, Fe, and Cu, have been investigated at the CI level. The results show that CoH2 and FeH2 are very similar to NiH2, which was investigated in an earlier study. On the low spin surface, which is chemically most interesting, H2 dissociates with little or no barrier and forms weakly bound bent complexes. The bonds are formed from sd hybrids. These results are in line with experimental findings for dissociative chemisorption of H2 on metal surfaces, where Fe, Co, and Ni are known to behave very similarly. Since sd hybrids for Cu can not be easily formed the addition of H2 to Cu leads to a high barrier, which means that on‐top dissociation of H2 on a copper surface is unlikely. This is a plausible explanation of why H2 dissociates with higher barriers on copper surfaces than on iron, cobalt and nickel surfaces. In gas phase, the ground states of MH2 are linear with high spin. The ordering of these linear states is expla...

PCI-X, a parametrized correlation method containing a single adjustable parameter X

Abstract A new method intended for the calculation of bond strengths is suggested and tested on a large variety of systems. The method is based on the simple fact that in a balanced treatment about the same percentage X of the correlation effects is obtained for every system. The total energy is then obtained by a simple extrapolation to 100 percent. Using a double zeta plus polarization basis set in a coupled cluster type calculation it is found that the percentage X is about 80. Small changes of the basis sets or methods do not change this percentage significantly. Since the method is parametrized and the underlying method is some type of configuration interaction the method is termed PCI- X . For a selection of 13 representative simple first-row molecules the present version of the PCI-80 method gives an average absolute deviation from experiment of 1.8 kcal/mol compared to 10.3 kcal/mol for the unparametrized calculations. For some of these bond strengths a Hartree-Fock limit correction is required. For transition metal complexes, for which the method is primarily aimed, the improvement can be quite dramatic compared to a normal standard treatment. The method is tested on essentially all small second-row transition metal systems studied experimentally, for 38 systems, and the average absolute deviation from these sometimes rather uncertain experiments is 5.1 kcal/mol (0.22 eV).

A theoretical study of the cis-dihydroxylation mechanism in naphthalene 1,2-dioxygenase

The catalytic mechanism of naphthalene 1,2-dioxygenase has been investigated by means of hybrid density functional theory. This Rieske-type enzyme, which contains an active site hosting a mononuclear non-heme iron(II) complex, uses dioxygen and two electrons provided by NADH to carry out the cis-dihydroxylation of naphthalene. Since a (hydro)peroxo-iron(III) moiety has been proposed to be involved in the catalytic cycle, it was probed whether and how this species is capable of cis-dihydroxylation of the aromatic substrate. Different oxidation and protonation states of the Fe–O2 complex were studied on the basis of the crystal structure of the enzyme with oxygen bound side-on to iron. It was found that feasible reaction pathways require a protonated peroxo ligand, FeIII–OOH; the deprotonated species, the peroxo-iron(III) complex, was found to be inert toward naphthalene. Among the different chemical patterns which have been explored, the most accessible one involves an epoxide intermediate, which may subsequently evolve toward an arene cation, and finally to the cis-diol. The possibility that an iron(V)-oxo species is formed prior to substrate hydroxylation was also examined, but found to implicate a rather high energy barrier. In contrast, a reasonably low barrier might lead to a high-valent iron-oxo species [i.e. iron(IV)-oxo] if a second external electron is supplied to the mononuclear iron center before dioxygenation.

Comparisons of results from parametrized configuration interaction (PCI‐80) and from hybrid density functional theory with experiments for first row transition metal compounds

Different methods and schemes have been tested for the difficult class of first row transition metal complexes. The systems investigated are the M+, MH+, MCH+3, and MCH+2 systems for the entire row and the Ni(CO)x systems with x=1–4. In general quite satisfactory results are obtained both at the PCI‐80 and hybrid density functional levels. In particular, for the MH+ and MCH+3 systems the PCI‐80 average deviation to experiments is of the same size as the uncertainty in the experiments. The MCH+2 systems are somewhat more difficult to describe and a rather large error is found for chromium at the PCI‐80 level, due to a large coupling of exchange energy loss and change of correlation energy resulting from the formation of two covalent d‐bonds. Scaling at the modified coupled pair functional (MCPF) level is also compared to scaling at the coupled cluster singles and doubles (CCSD) level. In most cases very similar results are obtained, but classes of systems can be identified where scaling works better at the...