Interaction of the divalent lead cation with cyclosporin A: an experimental and theoretical study

On the basis of extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium Pb²⁺(aq) + 1·Sr²⁺(nb) ? 1·Pb²⁺(nb) + Sr²⁺(aq) occurring in the two-phase water–nitrobenzene system (1 = cyclosporin A; aq = aqueous phase, nb = nitrobenzene phase) was evaluated as log K _ex (Pb²⁺, 1·Sr²⁺) = 0.1 ± 0.1. Further, the stability constant of the 1·Pb²⁺ complex in nitrobenzene saturated with water was calculated for a temperature of 25 °C: log β _nb (1·Pb²⁺) = 9.2 ± 0.2. Finally, applying quantum chemical DFT calculations, the most probable structure of the proven 1·Pb²⁺ cationic complex species was derived. In the resulting complex, the “central” cation Pb²⁺ is bound by four bonding interactions to the corresponding four oxygen atoms of the parent cyclosporin A ligand. The interaction energy, E(int), of the considered 1·Pb²⁺ complex was found to be ?1016.3 kJ/mol, confirming also the formation of this complex.