title: Theoretical investigations of the hydrolysis pathway of verdoheme to biliverdin.
abstract: Conversion of iron(II) verdoheme to iron biliverdin in the presence of OH(-) was investigated using B3LYP method. Both 3-21G and 6-31G* basis sets were employed for geometry optimization calculation as well as energy stabilization estimation. Calculation at 6-31G* level was found necessary for a correct spin state estimation of the iron complexes. Two possible pathways for the conversion of iron verdoheme to iron biliverdin were considered. In one path the iron was six-coordinate while in the other it was considered to be five-coordinate. In the six-coordinated pathway, the ground state of bis imidazole iron verdoheme is singlet while that for open chain iron biliverdin it is triplet state with 4.86 kcal/mol more stable than the singlet state. The potential energy surface suggests that a spin inversion take place during the course of reaction after TS. The ring opening process in the six-coordinated pathway is in overall -2.26 kcal/mol exothermic with a kinetic barrier of 9.76 kcal/mol. In the five-coordinated pathway the reactant and product are in the ground triplet state. In this path, hydroxyl ion attacks the iron center to produce a complex, which is only 1.59 kcal/mol more stable than when OH(-) directly attacks the macrocycle. The activation barrier for the conversion of iron hydroxy species to the iron biliverdin complex by a rebound mechanism is estimated to be 32.68 kcal/mol. Large barrier for rebound mechanism, small barrier of 4.18 kcal/mol for ring opening process of the hydroxylated macrocycle, and relatively same stabilities for complexes resulted by the attack of nucleophile to the iron and macrocycle indicate that five-coordinated pathway with direct attack of nucleophile to the 5-oxo position of macrocycle might be the path for the conversion of verdoheme to biliverdin.
authors.affiliation: Department of Chemistry, Faculty of Sciences, Shahid Beheshti University, Evin 19839-63113, Tehran, Iran.
authors.forename: Mahin
authors.initials: M
authors.lastname: Gheidi
authors.forename: Nasser
authors.initials: N
authors.lastname: Safari
authors.forename: Homayoon
authors.initials: H
authors.lastname: Bahrami
authors.forename: Mansour
authors.initials: M
authors.lastname: Zahedi
mesh_terms: D001664:Biliverdine / Q000737:chemistry*; D003198:Computer Simulation; D006418:Heme / Q000031:analogs & derivatives* / Q000737:chemistry; D006868:Hydrolysis; D006878:Hydroxides / Q000737:chemistry*; D007501:Iron / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction
chemical_list: D006878:Hydroxides; C099547:verdoheme; D006418:Heme; D007501:Iron; D001664:Biliverdine