Kinetic parameters and linear free energy relationships of O2 and CO binding with closely related heme models of hemoglobins and cytochromes P-450

Abstract

The binding of O₂ and CO with various derivatives of two recently synthesized encumbered porphyrins (1 and 2) has been investigated using laser flash photolysis. These compounds bear an aliphatic chain directly anchored on the pyrrole positions of the macrocycle. With either a nitrogenous base or a thiolate group as a fifth axial ligand of the Fe^II atom, they model the active site of hemoglobins or cytochromes P-450 respectively and are able to bind O₂ and CO as a sixth ligand. Compared to analogous complexes of slightly encumbered porphyrins, we observed a reduction of O₂ and CO affinities by several orders of magnitude, mainly reflected in decreased association rates. These effects are attributed to the strong central steric hindrance due to the presence of the aliphatic chain. The results also provide evidence for steric discrimination against CO binding. Linear free energy relationships show that all derivatives of 2, including the thiolate-ligated complex in spite of its very different kinetic and equilibrium parameters, behave as only one homogenous family and reasonably model the reactivity of mammalian hemoproteins for both CO and O₂ binding. On the contrary, compound 1 belongs to the class of severely encumbered porphyrins.