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 Sr 2+ (aq) + 2A − (aq) +  1 (nb) ⇄  1 ·Sr 2+ (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 K ex ( 1 ·Sr 2+ ,2A − ) = 0.1 ± 0.1. Further, the stability constant of the 1 ·Sr 2+ complex in nitrobenzene saturated with water was calculated for a temperature of 25 °C: log β nb ( 1 ·Sr 2+ ) = 9.2 ± 0.1. Finally, applying quantum mechanical DFT calculations, the most probable structure of the proven 1 ·Sr 2+ cationic complex was derived. In the resulting complex, the “central” cation Sr 2+ 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 ·Sr 2+ complex, involving the 7-point correction for the basis set superposition error, was calculated as −894.5 kJ/mol.