Solubility of N-(9-fluorenylmethoxycarbonyloxy)-succinimide in several aqueous co-solvent solutions revisited: Solvent effect, preferential solvation and dissolution and transfer properties

Abstract

Preferential solvation of N-(9-fluorenylmethoxycarbonyloxy)-succinimide (Fmoc-OSu) in mixtures of DMF (1) + water (2), ethanol (1) + water (2), ethylene glycol (EG, 1) + water (2) and DMSO (1) + water (2) was investigated by inverse Kirkwood–Buff integrals method. In ethanol-rich and intermediate contents, ethanol preferentially solvated Fmoc-OSu; and for the four aqueous co-solvent blends in water-rich composition regions, Fmoc-OSu was preferentially solvated by water. The solvent effect was described through modeling the Gibbs energy change of Fmoc-OSu solubility by linear solvation energy relationships. The main contribution to solubility variation of Fmoc-OSu was the solvent dipolarity-polarizability and solubility parameter. The dissolution and transfer enthalpy, entropy and Gibbs free energy were discussed in detail. Analysis outcomes of thermodynamic dissolution and enthalpy–entropy compensation demonstrated that two different mechanisms, enthalpy-driven and entropy-driven controlled the solubility variation of Fmoc-OSu in the DMF/EG/DMSO + water mixtures; and enthalpy-driven, in the ethanol + water mixture.