Protonation of Enniatin B in Nitrobenzene: Experimental and Theoretical Study with Respect to Other Univalent Cations

Based on extraction experiments, the exchange extraction constant of the reaction H₃O⁺(aq) + <b>1·</b>Na⁺(nb) ⇄ <b>1·</b>H₃O⁺(nb) + Na⁺(aq) in the system water-nitrobenzene (<b>1</b> = enniatin B; aq = aqueous phase, nb = nitrobenzene phase) was evaluated to be log <i>K</i> _ex (H₃O⁺, <b>1·</b>Na⁺) = 0.9 ± 0.15. Furthermore, the stability constant of the <b>1·</b>H₃O⁺ complex in water-saturated nitrobenzene was calculated for a temperature of 25 °C as log <i>K</i> _nb (<b>1·</b>H₃O⁺) = 6.4 ± 0.2. Analogously, the stability constants of some other univalent metal cations have been determined by a similar method. Additionally, quantum mechanical calculations (M06-D3/DefSVPP in nitrobenzene) were used to determine the most probable structures of the cationic complexes <b>1·</b>H₃O⁺ and <b>1·</b>Na⁺. For comparison, three different conformers of <b>1·</b>H₃O⁺ (nb) were also investigated, considering the nesting H₃O⁺ ion into the enniatin B ring. In the most stable resulting complex, the H₃O⁺ cation is centrally positioned and stabilized by three relatively strong hydrogen bonds to the three carbonyl oxygen atoms of the parent enniatin B ligand. The interaction energies, <i>E</i>(int), of the <b>1·</b>H₃O⁺ and <b>1·</b>Na⁺ complexes in nitrobenzene were found to be 196.81 and 82.19 kJ/mol, respectively, confirming the formation of protonated complexes.