How tin metal prevents verdoheme ring opening? Comparative study of various nucleophiles

Abstract

The inhibitory role of tin metal in the verdoheme ring opening mechanism has been investigated using B3LYP method. Nucleophilic additions of OH −, NH 2 −, and CN − to three possibly six, five, and four coordinate verdoheme complexes of tin(IV) have been employed as model reactions. The results of calculations suggest that nucleophilic attacks to tin(IV) verdohemes does not result in the opening of the macrocycle, being in excellent agreement with experimental reports. In six coordinate tin(IV) verdoheme complex the formation of open ring helical complexes is favorable thermodynamically but not kinetically. In this coordination state, tin has no coordination role. Thus, direct addition of nucleophiles to the positive oxo-carbon centers and formation of a closed ring hydroxy compound is proposed for blocking the conversion of verdoheme to biliverdin. Contrary to zinc and iron analogues, in five and four coordinate pathways, such addition to oxo-carbons does not proceed toward stable open chain helical products. This is because formation of these complexes is unfavorable both thermodynamically and kinetically. It has been determined that in the latter pathways a closed ring compound is formed as final product by adding nucleophiles to tin atoms. It has been thus shown that high affinity of ligands for binding to both the fifth and sixth coordination sites of the highly charged Sn(IV) center is responsible for inhibiting the conversion of verdoheme complexes to biliverdin compounds. Results indicate that high tendency of tin(IV) metal to increase coordination state plays a crucial role in preventing verdoheme ring opening. These key points have been corroborated with the results obtained from molecular orbital calculations.