A Molecular Orbital Study on Tetranactin-NH₄+ Complex

Abstract

The inclusion complex of NH₄+ with tetranactin increases the fluxes of ions across thin lipid membranes. When NH₄+ is inserted into the ionophore of tetranactin, the conformation changes greatly ; this structural change is called an "induced fit." When the conformation change of tetranactin is induced by the approach of NH₄+, the four ether oxygens of the tetrahydrofuran rings and the four carbonyl oxygens of the ester groups function to include NH₄+ in the molecule. The ether oxygens rotate inwards to hold NH₄+ inside tetranactin, and the carbonyl oxygens rotate inwards to prevent NH₄+ from escaping. The four ether oxygens form linear hydrogen bonds with NH₄+. Although the four carbonyl oxygens approach NH₄+ at distances similar to those of the four ether oxygens, the carbonyl oxygens do not form linear hydrogen bonds with NH₄+. In order to clarify the induced fit mechanism of the ionophore, in this paper, the inclusion complex of NH₄+ with tetranactin was studied with regard to the arrangement of NH₄+ in the tetranactin molecule from a quantum-chemical point of view. Since tetranactin is too large for double zeta ab initio SCF calculations, functional groups which have large contributions to the insertion of NH₄+ were selected as a model for the tetranactin ; the model consisted of four HCHO molecules and four H₂O molecules. The model was in good accord with the actual result, and thus appears to be appropriate. Tetranactin is composed of four homonactinic acid moieties, and the interaction energy between each of them and NH₄+ is significant for the arrangement of NH₄+. The interaction energy between NH₄+ and the four ether groups was -73.2 kcal/mol, and the interaction energy between NH₄+ and the four carbonyl groups was -39.4 kcal/mol. The interaction energy between NH₄+ and the ether groups was thus about 1.9 times larger than that between NH₄+ and the ester groups. The interaction energy between NH₄+ and the eight ether and ester groups was -109.0 kcal/mol. From the results of geometry optimizations, the interaction energy between NH₄+ and CH₃OCH₃ was larger than that between NH₄+ and HCOOH by 5.8 kcal/mol due to the electrostatic interaction energy. Therefore, even though the four carbonyl groups may move to accommodate NH₄+ in tetranactin, the four ether groups of tetranactin will interact more strongly with NH₄+ than the four carbonyl groups, and NH₄+ will orient to the ether groups. Moreover, when perturbation of the ionophore by the rotation of NH₄+ is neglected, the rotational inhibition energy of NH₄+ in tetranactin was calculated to be 9.8 kcal/mol ; thus, NH₄+ is expected to orient to the four ether oxygens.