Synthesis and oxygenation studies of monomolecular hemoprotein models

Abstract

The preparation and properties of molecules modeling the active site of natural oxygen carriers have received considerable attention in recent years for the elucidation of the factors that control the binding reactions of molecular oxygen and carbon monoxide in some hemoproteins. Such compounds have been synthesized following three requirements which seem necessary in the biological functions of natural systems: 1. pentacoordination of the iron(II) ion by a nitrogenous base on the proximal site; 2. steric protection of the heme in order to prevent it from irreversible oxidation into μ-oxo iron(III) dimers; 3. control of the dioxygen environment on the distal site. Several groups have investigated these three problems separately [1]. As part of our studies of the stereochemical influences on the formation and stability of oxygenated model compounds, we have prepared two series of porphyrin derivatives which correspond to the three structural conditions mentioned above. ▪ ▪ All the compounds were synthesized following the concept of both face hindered tetraphenylporphyrins (‘basket handle’ porphyrins) in which two opposite mesophenyl rings are bridged by a convenient chain [2,3]. The proximal base (pyridine or imidazole) was inserted into one of the handles. The size and polarity of the cage on the distal side can be modified to some extent by suitable chemical changes of the second handle. The newly ‘hanging base’ porphyrins were prepared either from 5,10,15,20-tetrakis( o-hydroxyphenyl)porphyrin (series A, compounds 1–4) or from 5,10,15,20-tetrakis( o-aminophenyl)porphyrin (series B, compounds 5–8). Thus the main structural difference between the two series lies in the presence of non polar ether groups in the former and of polar amide linkage in the latter [4]. Their iron(II) complexes have a magnetic high spin state (S = 2) characteristic of deoxymyoglobins and hemoglobins. Addition of O 2 and CO to these complexes results in the formation of hexacoordinated diamagnetic species (S = O), as in oxy and carbooxyhemoproteins, without any paramagnetic perturbations by low lying thermally excited states. A systematic study of the O 2 and CO rates and equilibrium binding constants has been carried out in toluene by laser flash photolysis using a modified exchange rate law [5]. This clearly establishes the important role of factors such as the distal steric hindrance, the proximal base constraint and the polarity of the dioxygen environment in the control of the O 2 binding and the stability of oxygenated complexes. The association rate constants of O 2 and CO are of the same order of magnitude in the two series, but a large variation in the dissociation rate constants is observed. The smaller dissociation rate constants are observed for the compounds having amide linkages as compared with their analogous ether bearings linkages. This results in an increase of the intrinsic stability of the oxygenated derivatives up to the values observed in the natural compounds. The proton magnetic resonance spectra of the oxygenated complexes indicate that the bound dioxygen molecule lies preferentially in a plane oriented toward the distal amide groups in the B series, in contrast with series A in which four nearly equivalent orientations are observed. This preferential orientation of the oxygen molecule results from an hydrogen bonding interaction with the amide groups as shown by the chemical shift of the corresponding protons. The role of this bond in the stability and the bent geometry of the oxygenated complex is of the same type as those proposed for hemoproteins involving distal histidine [6, 7].