Linear free-energy relationships in binding of oxygen and carbon monoxide with heme model compounds and heme proteins

Abstract

For almost a decade heme model compounds were designed to test the influence of proximal base restraint or of distal steric hindrance on the ligand affinity. Despite the variety of molecular structures which were successively proposed, the evaluation of the reported data is rendered difficult because of the small number of examples available within each series. In this paper the kinetics of binding of O2 and CO is reported with a series of 9 closely related heme models is reported. The ''basket-handle porphyrins'' allow one to modify the constraints exerted on a chelated proximal base as well as the chemical environment of the distal side of the heme. One salient feature of these models is the possibility of introducing a H-bond stabilization of the oxygen by incorporating an amide group in the vicinity of the Fe center. The structural changes among models are sufficiently ''soft'' to cause an almost continuous variation of the binding constants and rate parameters. The latter are found to obey a definite linear free energy relationship which proves that the series is homogeneous from a thermodynamic viewpoint. This suggests an alternative way for comparing the trends in ligand binding in different heme model families with those of heme proteins, which is developed in the discussion using literature data.