Noninnocent effect of axial ligand on the heme degradation process: a theoretical approach to hydrolysis pathway of verdoheme to biliverdin.

Conversion of iron(II) verdoheme to iron(II) biliverdin in the presence of hydroxyl ion as a nucleophile and imidazole, pyridine, water, hydroxyl, cyanide, phenolate, chloride, thiolate and imidazolate as axial ligands was investigated using the B3LYP method and the 6-31G basis set. In the five-coordinated pathway the reactants and products are in the ground triplet state. In this path, hydroxyl ion directly attacks the macrocycle. The exothermic energy for addition of hydroxyl ion to iron(II) verdoheme with various ligands is 169.55, 166.34 and 164 kcal mol(-1) for water, pyridine and imidazole, energies which are around 30-60 kcal mol(-1) more exothermic than those for the other axial ligands used in this study. Therefore, imidazole, water and pyridine axial ligands can facilitate hydrolytic cleavage of iron(II) verdoheme to form open-chained helical iron(II) biliverdin complexes. The activation barrier for the conversion of iron(II) verdoheme hydroxyl species to the iron(II) biliverdin complex is estimated to be 5.2, 4.2, 4.35, 13.76 and 14.05 kcal mol(-1) for imidazole, water, cyanide, thiolate and imidazolate, respectively.