Synthetic Heme-Dioxygen Complexes

Momenteau, M.; Reed, Christopher A.

doi:10.1021/cr00027a006

Cited by 624 publications

(626 citation statements)

References 83 publications

(105 reference statements)

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“…The ground state is an open-shell singlet, in accordance with the experimental observation that the O 2 adduct is silent in electron paramagnetic resonance experiments (38). However, the spin is unevenly distributed in the complex with a surplus of ␣ spin on O 2 (0.75 electrons) and a surplus of ␤ spin on iron (-0.79e), as is quantified in Table III and illustrated in Fig.…”

Section: Resultssupporting

confidence: 84%

“…The Dissociated States-Isolated deoxyheme is experimentally a high-spin quintet (38). The optimized structure of this complex (Table II) agrees well (within 0.02 Å) with the crystal structure of deoxymyoglobin at 1.15 Å resolution (36).…”

Section: Resultssupporting

confidence: 62%

“…1, bottom. The literature is rich in discussions about the nature of the Fe-O bond (38,39). In particular, it has been argued whether the electronic structure of oxyheme is better described as singlet oxygen bound to low-spin Fe II (2) or as a superoxide radical antiferromagnetically coupled to low-spin Fe III (40).…”

Section: Resultsmentioning

confidence: 99%

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How O2 Binds to Heme

Jensen

Ryde

2004

Journal of Biological Chemistry

185

189

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We have used density functional methods to calculate fully relaxed potential energy curves of the seven lowest electronic states during the binding of O 2 to a realistic model of ferrous deoxyheme. Beyond a Fe-O distance of ϳ2.5 Å, we find a broad crossing region with five electronic states within 15 kJ/mol. The almost parallel surfaces strongly facilitate spin inversion, which is necessary in the reaction of O 2 with heme (deoxyheme is a quintet and O 2 a triplet, whereas oxyheme is a singlet). Thus, despite a small spin-orbit coupling in heme, the transition probability approaches unity. Using reasonable parameters, we estimate a transition probability of 0.06 -1, which is at least 15 times larger than for the nonbiological Fe-O ؉ system. Spin crossing is anticipated between the singlet ground state of bound oxyheme, the triplet and septet dissociation states, and a quintet intermediate state. The fact that the quintet state is close in energy to the dissociation couple is of biological importance, because it explains how both spin states of O 2 may bind to heme, thereby increasing the overall efficiency of oxygen binding. The activation barrier is estimated to be <15 kJ/mol based on our results and Mö ssbauer experiments. Our results indicate that both the activation energy and the spin-transition probability are tuned by the porphyrin as well as by the choice of the proximal heme ligand, which is a histidine in the globins. Together, they may accelerate O 2 binding to iron by ϳ10 11 compared with the Fe-O ؉ system. A similar near degeneracy between spin states is observed in a ferric deoxyheme model with the histidine ligand hydrogen bonded to a carboxylate group, i.e. a model of heme peroxidases, which bind H 2 O 2 in this oxidation state.All electrons have a spin, which is an intrinsic quantum chemical property that can take only two possible values, normally called ␣ and ␤ (or spin up and down). Almost all normal organic molecules contain an even number of electrons and also an equal number of ␣ and ␤ electrons. They are then said to have paired spin or to be singlets. Molecular oxygen (O 2 ) is a famous exception to this rule. In its ground state, it has two more electrons of one spin state than the other. Thus, it is said to have two unpaired electrons or to be a triplet. The singlet state of O 2 , with all electron spins paired, is ϳ90 kJ/mol higher in energy than the triplet ground state (1).A chemical reaction can normally not change the spin state of an electron. Therefore, reactions between singlet and triplet states are formally spin-forbidden, which means that they are slow. This is the reason why organic matter may exist in an atmosphere containing much O 2 . There is a strong thermodynamic drive of O 2 to oxidize organic matter to H 2 O and CO, but because these products (as well as the organic molecules) are singlets (whereas O 2 is a triplet), this reaction is spin-forbidden and therefore very slow at ambient temperatures. On the other hand, this is a problem when living organisms want to emp...

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Section: Resultssupporting

confidence: 84%

Section: Resultssupporting

confidence: 62%

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How O2 Binds to Heme

Jensen

Ryde

2004

Journal of Biological Chemistry

185

189

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“…The Soret of the spectral intermediate is more like that of a p-type hyper spectrum than oxy-P450 and is similar to that of the ferrous carbon monoxide P450 cam complex (Gouterman, 1978;Hanson et al, 1976). Correlations among a wide range of metalloporphyrin spectra (Momenteau & Reed, 1994;Wang & Brinigar, 1979) suggest that red-shifting of both the Soret and visible bands is consistent with an increased electron density on the ligands of the spectral intermediate, compared to oxy-P450.…”

Section: Resultsmentioning

confidence: 78%

Reduced Oxy Intermediate Observed in D251N Cytochrome P450_cam

1997

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Cytochrome P450s are ubiquitous heme proteins responsible for various oxidative metabolic processes. The overall rate-determining step in the catalytic cycle of native cytochrome P450 cam is the reduction of the dioxygen complex, which has made detection of catalytic intermediates after this reduction impossible. However, for the site-specific mutant D251N cytochrome P450 cam (which affects proton transfer near the catalytic center), the overall rate-determining step occurs after the reduction of oxy-P450. As a consequence, we have observed in the UV-visible spectrum during catalytic turnover a new intermediate that is one electron reduced from oxy-P450 with an intact dioxygen bond.

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“…29 This is because of the hydrolysis of the oxygen complex which is promoted by electrophiles such as protons. 37 …”

Section: ■■ 2 Synthesis Of the Cco Modelmentioning

confidence: 99%

Using Functional Models to Understand the Four-Electron Reduction of Dioxygen by Cytochrome c Oxidase Under Steady State Conditions

Collman

Decréau

2009

Bull. Jpn. Soc. Coord. Chem.

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A new functional biomimetic model of cytochrome c oxidase is reported. It is synthesized in 32 steps. Single turnover reaction with oxygen leads to the same intermediates as the ones reported in the enzyme: Fe(III)O 2˙-/Cu(I)/PhOH (oxygen complex), and Fe(IV)=O/Cu(II)/PhO˙ (PM). A sister model derivatized with an alkyne was immobilized on azide-functionnalized self-assembled monolayer (SAM) coated gold electrodes by Cu(I)-catalyzed click chemistry. The rate of electron transfer from the electrode to the model was controlled by the length of the linker in the SAM. Steadystate turnover was achieved at biologically relevant electron transfer, where CuB and Tyr244 mimics rapidly deliver their electrons, hence minimizing the release of partially reduced oxygen species (PROS). Using Functional Models to Understand the Four-Electron Reduction of Dioxygen by Cytochrome c Oxidase Under Steady State ConditionsBull. Jpn. Soc. Coord. Chem. Vol.54 (2009) 4 a partially-reduced enzyme (mixed valence) where heme a and CuA are oxidized and the active site is reduced (4 available electrons). The rate at which electrons are transferred one-at-atime by cyt. c to CcO is much slower than the rates of internal electron transfer between the various redox sites in CcO (Fig. 1). Hence, during steady-state turnover (when the enzyme continuously reduces dioxygen), CcO is always starved for electrons which suggests that the mixed valence state must be involved.2 As a result, a supply of electrons from a nearby organic redox-active center becomes important for partially reduced CcO to reduce dioxygen without leaking PROS.Several studies suggested Tyr244 to be the likely source of the fourth electron 9-11 and a proton in the mixed valence enzyme. 12Mimicking the active site of cytochrome c oxidase may be important for two reasons: 1) a model is well defined, hence it could help understand the mechanism of oxygen reduction by CcO, and hence is relevant to health-related matters; 2)CcO is at the heart of the mammalian energy machinery and

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Synthetic Heme-Dioxygen Complexes

Cited by 624 publications

References 83 publications

How O2 Binds to Heme

How O2 Binds to Heme

Reduced Oxy Intermediate Observed in D251N Cytochrome P450_cam

Using Functional Models to Understand the Four-Electron Reduction of Dioxygen by Cytochrome c Oxidase Under Steady State Conditions

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Synthetic Heme-Dioxygen Complexes

Cited by 624 publications

References 83 publications

How O2 Binds to Heme

How O2 Binds to Heme

Reduced Oxy Intermediate Observed in D251N Cytochrome P450cam

Using Functional Models to Understand the Four-Electron Reduction of Dioxygen by Cytochrome c Oxidase Under Steady State Conditions

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Reduced Oxy Intermediate Observed in D251N Cytochrome P450_cam