Axial Imidazole Distorsion Effects on the Catalytic and Binding Properties of Chelated Deuterohemin Complexes

The effect of strain in the axial coordination of imidazole to the heme has been studied in the chelate complexes
deuterohemin-histidine (DH-His) and deuterohemin-alanylhistidine (DH-AlaHis). Molecular mechanics calculations
indicate that three types of distortion of the axial ligand occur in DH-His, due to the relatively short length
of the arm carrying the donor group: tilting off-axis, tipping, and inclination of the imidazole plane with respect
to the axial Fe-N bond. The effects of tilting (¢ç 10°) and inclination of the imidazole ring (¢ä 17°) are
dominant, while tipping is small and is probably of little importance here. By contrast, the axial imidazole
coordination is normal in DH-AlaHis and other computed deuterohemin-dipeptide or -tripeptide complexes
where histidine is the terminal residue, the only exception being DH-ProHis, where the rigidity of the proline
ring reduces the flexibility of the chelating arm. The distortion in the axial iron-imidazole bond in DH-His has
profound and negative influence on the binding and catalytic properties of this complex compared to DH-AlaHis.
The former complex binds more weakly carbon monoxide, in its reduced form, and imidazole, in its oxidized
form, than the latter. The catalytic efficiency in peroxidative oxidations is also reduced in DH-His with respect
to DH-AlaHis. The activity of the latter complex is similar to that of microperoxidase-11, the peptide fragment
incorporating the heme that results from hydrolytic cleavage of cytochrome c