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A molecular description of oxygen binding to hemoglobin


Olafson, Barry Duane (1979) A molecular description of oxygen binding to hemoglobin. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/7fss-rj50.


We discuss the bonding of O_2 to hemoglobin (Hb) at the molecular level. The ideas presented here are the results of ab initio calculations on idealized portions of the Hb molecule. The bond between Fe and O_2 is formed by coupling a triplet state of Fe to the triplet ground state of O_2. The electronic structure of the FeO_2 moiety is analogous to that of ozone. We show how the ozone model is in agreement with the EPR data for MnO_2 and CoO_2, predicting unpaired spin density on the Mn for the former molecule, and unpaired spin density on the O_2 ligand in CoO_2. Our calculations lead to a bound molecule with very little transfer of electron density onto the O_2 ligand. Valence bond ideas also indicate the similarity between HbO_2 and the formal Fe(III) complexes of HbOH and HbCN. The heme plane and axial imidazole ligand are seen to play a key role in promoting reversible O_2 binding. The effective size of high- spin Fe is not found to play a major role in the O_2 binding process. The Fe remains in the heme plane for four-coordinate molecules, regardless of the local spin state about the Fe. The Fe moves out of the heme plane for five-coordinate complexes in order to keep a strong dative bond to the axial ligand while reducing the nonbonded repulsions between the heme plane and the axial ligand. The spin state change on Fe is found to occur, not because the Fe moves into the plane of the porphyrin, but because the formation of the FeO_2 bond reduces the number of local exchange interactions that stabilize the high-spin state. The role of the coordination sphere of Fe pertaining to the chemistry of the Hb molecule is to reduce the energy separation between the atomic states. It makes an intermediate-spin state accessible for bond formation and thereby provides a mechanism by which an O_2 molecule can easily and reversibly bind to Hb. Neither the diamagnetic (t_(2g))^6 excited state of Fe nor the excited singlet state of O_2 play a role in the formation of the FeO_2 bond. We show how movement of the proximal imidazole, long thought to initiate the change in quaternary structure of Hb, is also responsible for the reduced O_2 affinity in the T quaternary form of Hb. Assuming that protein forces hinder the movement of the axial ligand leads to the calculation of protein forces in the T and R quaternary forms, and a prediction of the movement of Fe upon a change in the quaternary structure. This movement of the Fe center is found to be on the order of 0.05 Å. Based upon the structural studies of Perutz and co-workers we show how the different protein forces in the T and R quaternary forms can be traced to a small number of hydrogen bonds and salt bridges. This allows us to present a model that displays the molecular origin for the cooperative binding effect. Transferring these protein forces to the coboglobin molecule allows us to calculate the magnitude of the cooperative effect in this metal-substituted Hb. The predicted cooperative effect is found to be in excellent agreement with the experimentally determined value. The ozone model of transition metal-O_2 binding leads to the prediction of a second metal-O_2 stretching band between 1000-1200 cm^(-1). It has also been used to tentatively assign the near-infrared and z- polarized ultraviolet-visible spectra of HbO_2, HbCN, and HbCO.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Chemistry
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Goddard, William A., III
Thesis Committee:
  • Unknown, Unknown
Defense Date:14 July 1978
Record Number:CaltechTHESIS:11192009-093719542
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5388
Deposited By: Tony Diaz
Deposited On:01 Dec 2009 18:41
Last Modified:16 Apr 2021 23:18

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