Anion Complexes with Tetrazine-Based Ligands: Formation of Strong Anion−π Interactions in Solution and in the Solid State

Ligands <b>L1</b> and <b>L2</b>, consisting of a tetrazine ring decorated with two morpholine pendants of different lengths, show peculiar anion-binding behaviors. In several cases, even the neutral ligands, in addition to their protonated HL⁺ and H₂L²⁺ (L = <b>L1</b> and <b>L2</b>) forms, bind anions such as F^–, NO₃^–, PF₆^–, ClO₄^–, and SO₄^2– to form stable complexes in water. The crystal structures of H₂<b>L1</b>(PF₆)₂·2H₂O, H₂<b>L1</b>(ClO₄)₂·2H₂O, H₂<b>L2</b>(NO₃)₂, H₂<b>L2</b>(PF₆)₂·H₂O, and H₂<b>L2</b>(ClO₄)₂·H₂O show that anion−π interactions are pivotal for the formation of these complexes, although other weak forces may contribute to their stability. Complex stability constants were determined by means of potentiometric titration in aqueous solution at 298.1 K, while dissection of the free-energy change of association (Δ<i>G</i>°) into its enthalpic (Δ<i>H</i>°) and entropic (TΔ<i>S</i>°) components was accomplished by means of isothermal titration calorimetry measurements. Stability constants are poorly regulated by anion–ligand charge–charge attraction. Thermodynamic data show that the formation of complexes with neutral ligands, which are principally stabilized by anion−π interactions, is enthalpically favorable (−Δ<i>G</i>°, 11.1–17.5 kJ/mol; Δ<i>H</i>°, −2.3 to −0.5 kJ/mol; <i>T</i>Δ<i>S</i>°, 9.0–17.0 kJ/mol), while for charged ligands, enthalpy changes are mostly unfavorable. Complexation reactions are invariably promoted by large and favorable entropic contributions. The importance of desolvation phenomena manifested by such thermodynamic data was confirmed by the hydrodynamic results obtained by means of diffusion NMR spectroscopy. In the case of <b>L2</b>, complexation equilibria were also studied in a 80:20 (v/v) water/ethanol mixture. In this mixed solvent of lower dielectric constant than water, the stability of anion complexes decreases, relative to water. Solvation effects, mostly involving the ligand, are thought to be responsible for this peculiar behavior