How O2 Binds to Heme

Abstract

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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