Interplay between salt bridge, hydrogen bond and anion-π 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-π 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 π-π stacking binding mode. Density Functional Theory (DFT) calculations performed on the interaction of SCN⁻ with the plain tetrazine ring showed that the anion-π 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-π interactions are of major importance in the interplay of weak forces contributing to the formation of similar anion complexes.