Unveiling the thermal properties of l-Homophenylalanine by conventional and fast scanning calorimetry

Thermal properties of biomolecules are crucial for biopharmaceutical engineering. The direct determination of these properties by using conventional calorimeters is often impossible for biological compounds due to decomposition during slow heating. l -Homophenylalanine ( l -HPA), a chiral unnatural amino acid, is used as a pharmaceutical intermediate and a precursor for producing various pharmaceutical drugs, such as for treatment of hypertension or cardiovascular diseases. Classical Differential Scanning Calorimetry (DSC) failed to provide melting properties for this compound, which is a common limitation observed for other amino acids. In the current study, this limitation is overcome by using Fast Scanning Calorimetry (FSC). By applying FSC with different heating rates, we succeeded in avoiding decomposition and thus determined the sublimation and vapor pressure data of l -HPA. A reversible endothermal event occurs around 393 K, regardless of the heating rate, while it is absent in racemic dl -homophenylalanine ( dl -HPA). l -HPA displays a very low volatility at room temperature. The enthalpy of sublimation was assessed via the simplified Clausius–Clapeyron equation, the rigorous Clarke–Glew equation and machine learning (ML) prediction. The thermodynamic data and solid-state behavior studied may assist in developing effective computational protocols, such as prediction of solubility of l -HPA in different solvents and further distinguishing polymorphs.