Aqueous solution and solid-state behaviour of l-homophenylalanine: experiment, modelling, and DFT calculations

Area of Science:

• Physical Chemistry
• Chemical Engineering
• Materials Science

Background:

• Understanding amino acid solubility is crucial for pharmaceutical and chemical applications.
• L-homophenylalanine (l-Hpa) is a non-proteinogenic amino acid with limited solubility data available.
• Solid-state properties and aqueous behavior influence formulation and processing.

Purpose of the Study:

• To characterize the solid-state properties and aqueous solubility of l-homophenylalanine (l-Hpa).
• To determine the influence of temperature and pH on l-Hpa solubility.
• To model the solubility behavior using thermodynamic and computational methods.

Main Methods:

• Thermal analysis (TG, DSC, hot-stage microscopy) and temperature-resolved PXRD for solid-state characterization.
• Solubility measurements in water as a function of temperature and pH.
• Density functional theory (DFT) for pKa calculations.
• Perturbation theory (PC-SAFT) for thermodynamic modeling of solubility and density.

Main Results:

• L-homophenylalanine (l-Hpa) decomposes above 520 K, exhibiting no simple melting point.
• Observed solubilities for l-Hpa are exceptionally low for an amino acid.
• Solubility remains constant around the isoelectric point but increases sharply below pH 2.5 and above pH 9.5.
• PC-SAFT model accurately predicted solubility and density data.

Conclusions:

• L-homophenylalanine (l-Hpa) exhibits unusual thermal and solubility characteristics.
• Its solubility is highly pH-dependent, increasing significantly only in highly acidic or basic conditions.
• The PC-SAFT model provides a reliable framework for predicting l-Hpa's aqueous behavior.