Solubility of Fmoc- l -Leucine in 12 Monosolvents: Solvent Effects Analysis, Molecular Simulation, Model Correlation, and Comparison with Structurally Similar Substances

Fmoc- l -leucine shows significant application potential in fields such as self-assembled materials, nanotechnology, biomaterials, and drug delivery; however, there has been no report on its solubility until now. This study not only fills the gap in Fmoc- l -leucine solubility data but also provides important support for its industrial applications, functional material design, and fundamental research on amino acid derivatives through multidimensional methods and structure–property correlation analysis (qualitative analysis, quantitative analysis, and model correlation). This study used the static weighing method to determine the solubility of Fmoc- l -leucine in the temperature range of 283.15 to 323.15 K, with results showing that solubility increases with rising temperature. Additionally, binding energy, MEPs, and HS analyses were conducted, indicating that the dissolution process is primarily influenced by hydrogen bonding. Furthermore, the relationships between solubility and molecular structure were explored for Fmoc- l -leucine, l -leucine, and N -acetyl- l -leucine, revealing that the Fmoc group significantly influences solubility. In summary, the data were correlated using four thermodynamic models (modified Apelblat model, NRTL model, Margules model, and UNIQUAC model). The results indicated that the modified Apelblat model provided the best fit.