Interplay between salt bridge, hydrogen bond and anion-pi interactions in thiocyanate binding

The L2 ligand (3,6-bis(morpholin-4-ylethyl)-1,2,4,5-tetrazine) is constituted by a tetrazine ring decorated with two morpholine pendants. The crystal structure of the H2L2(SCN)2 anion complex shows the thiocyanate anion interacting with the ligand, protonated on the morpholine groups, through the formation of salt-bridge, anion-p and hydrogen bond interactions. The SCN anion lies over the tetrazine ring, with the nitrogen atom in proximity to the ring centroid, in a sort of p-p stacking binding mode. Density Functional Theory (DFT) calculations performed on the interaction of SCN with the plain tetrazine ring showed that the anion-p attraction alone is sufficient to form the complex, even in a simulated implicit water environment. The arrangement of the interacting partners in the DFT-optimized geometry of the most stable complex is very similar to the one actually assumed in the crystal structure. Potentiometric titrations performed in water (0.1 M Me4NCl, 298.1 ± 0.1 K) revealed that not only the protonated ligand forms, but even the neutral L2 molecule is able to bind SCN in solution. The stability of the complexes formed is almost insensitive to ligand charge, revealing that, even in water, anion-pi interactions are of major importance in the interplay of weak forces contributing to the formation of similar anion complexes.