Experimental and DFT study on complexation of the strontium cation with cyclosporin A

Abstract

By using extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium Sr2+(aq) + 2A−(aq) + 1(nb) ⇄ 1·Sr2+(nb) + 2A−(nb) occurring in the two-phase water-nitrobenzene system (A− = picrate, 1 = cyclosporin A; aq = aqueous phase, nb = nitrobenzene phase) was evaluated as log Kex (1·Sr2+,2A−) = 0.1 ± 0.1. Further, the stability constant of the 1·Sr2+ complex in nitrobenzene saturated with water was calculated for a temperature of 25 °C: log βnb (1·Sr2+) = 9.2 ± 0.1. Finally, applying quantum mechanical DFT calculations, the most probable structure of the proven 1·Sr2+ cationic complex was derived. In the resulting complex, the “central” cation Sr2+ is bound by five bonds to the corresponding five oxygen atoms of the parent cyclosporin A ligand. The interaction energy, E(int), of the investigated 1·Sr2+ complex, involving the 7-point correction for the basis set superposition error, was calculated as −894.5 kJ/mol.