Haemoglobin and Myoglobin: Coordination Chemistry Doing a Job

The haem group

Both proteins are built around the same prosthetic group: an iron ion held in a porphyrin ring, a planar tetradentate macrocycle that supplies four nitrogen donors. That accounts for four of the six coordination positions of an octahedral iron centre.

The fifth position is occupied by a histidine residue from the protein — the proximal histidine — which anchors the haem to the protein. The sixth is left open, and that is the site where oxygen binds. Everything functionally interesting happens at that one position.

The spin-state change, which is the whole mechanism

In deoxygenated haem the iron is high-spin iron(II). A high-spin d⁶ ion is relatively large, too large to sit inside the porphyrin cavity, so it lies slightly out of the ring plane, pulled toward the proximal histidine.

When oxygen binds at the sixth site, the iron becomes low spin. A low-spin d⁶ ion is smaller, and it now fits into the cavity, moving into the plane of the ring.

Myoglobin versus haemoglobin

The functional logic follows from the shapes of the curves. A transport protein must both pick oxygen up efficiently where it is abundant and release it where it is scarce. A sigmoidal curve is steep in the middle, so a modest fall in oxygen pressure produces a large release. A hyperbolic curve is not, which is why myoglobin holds oxygen rather than delivering it — and why the storage protein must have the higher affinity, or the transfer would run the wrong way.

The Bohr effect

Haemoglobin's affinity for oxygen falls as pH falls and as carbon dioxide concentration rises. Actively respiring tissue produces both, so haemoglobin releases more oxygen precisely where it is most needed. In the lungs the reverse conditions restore high affinity for loading.

This is an example of allosteric regulation: a molecule binding at one site changes the affinity at another. Questions often ask for the direction of the effect and the reason, and the answer should connect the chemistry to the physiological requirement rather than stating one alone.

Carbon monoxide

Carbon monoxide binds at the same sixth coordination site but far more strongly than oxygen, so it blocks the site effectively irreversibly on physiological timescales. Two points are commonly examined:

• CO is a strong-field π-acceptor ligand, high in the spectrochemical series, which is why it binds so tightly to iron(II).
• Free haem binds CO even more strongly than the protein-bound form does. The protein pocket sterically discourages the linear Fe–C–O geometry CO prefers, while accommodating the bent geometry oxygen adopts. The protein therefore reduces CO affinity relative to oxygen — a genuine piece of structural discrimination, and a good higher-order question.

Other bioinorganic systems worth knowing

Note the pattern examiners look for: chlorophyll and haem share the same macrocyclic framework with a different metal, and cytochromes use the same haem group for electron transfer rather than oxygen binding. The chemistry is reused; the function changes with the metal and the protein environment.

Frequently asked questions

Why is oxygenated haemoglobin diamagnetic?

Because the iron becomes low-spin d⁶ on binding, with all six electrons paired in the t_2g set. Deoxyhaemoglobin, being high spin, is paramagnetic. Magnetic measurements were historically what established the spin-state change.

Why does the iron not simply oxidise to iron(III)?

In free solution it would. The protein prevents two haem groups from meeting and forming the bridged species that leads to oxidation, so the hydrophobic pocket is what keeps the iron in the functional oxidation state.

Is oxygen bound end-on or side-on?

End-on and bent in haemoglobin and myoglobin. The bent geometry is part of why the protein can discriminate against carbon monoxide, which prefers a linear arrangement.

How much bioinorganic detail is needed?

For IIT-JAM, generally the haem structure, the two curves and cooperativity. CSIR-NET goes further into the spin-state argument, the Bohr effect and comparisons across metalloprotein classes.