What is the difference in bond strength when comparing carbon monoxide (CO) bonded to heme and oxygen bonded to the heme?

• A. CO binds more weakly than O2
• B. CO does not bind heme
• C. CO binds to heme much more strongly than oxygen does
• D. CO binds about equally as O2

Answer: (C)

Binding to the heme iron involves a coordinate covalent bond between ferrous iron and the ligand. Carbon monoxide is a highly effective ligand: its lone pair donates strongly to the iron, and there is favorable π-backbonding from iron into the CO π* orbitals. This combination creates a very stable Fe–CO bond. Oxygen binding to heme, while possible, forms a weaker Fe–O2 interaction because it involves different orbital interactions and less effective backbonding, plus partial reduction steps that are less favorable for forming a strong, long-lasting bond. Because of these orbital and electronic factors, CO binds to heme much more strongly than O2, often outcompeting oxygen and preventing its release. This is why CO is such a potent inhibitor of oxygen delivery to tissues.