Molecular orbital studies of the mast cell zinc-histamine storage complex

Abstract

A zinc-histamine-heparin complex is proposed as a storage form of histamine in rat mast cells. A ring nitrogen and the ethylamine nitrogen of two histamine molecules in a square planar arrangement about one divalent zinc ion may intercalate with a portion of the heparin molecule such that two sulfonic acid or carboxylate residues provide the fifth and sixth coordinating ligands above and below the plane of the zinc histamine complex. Semiempirical molecular orbital calculations employing an iterative extended Huckel method, Cusach's modification, indicate that there is little or no covalent bonding between the Zn atom and the donor nitrogen atoms. Thus the stability of the complex would appear to be owing to electrostatic interactions. These data correlate well with the demonstrated case of liberation of histamine from mast cell granules.