Entropy-Driven Isosymmetric Phase Transition in L-Serine Under Pressure: A Periodic DFT Study

Understanding pressure-induced isosymmetric phase transitions in molecular crystals requires consideration of both structural and thermodynamic factors, particularly in hydrogen-bonded systems. In this work, periodic density functional theory (DFT) calculations were employed to investigate the pressure-dependent behavior of L-serine and to elucidate the origin of its experimentally observed phase transition between Phase I and Phase IV. Geometry optimizations performed at ambient pressure and 8.8 GPa reproduce the compression of the crystal lattice and the pressure-driven stabilization of Phase IV. However, no spontaneous reorientation of the hydroxyl groups is observed, indicating that the transition is not accessible within a purely static framework. To further explore the stability of the system, a series of modified crystal structures with different hydroxyl group orientations was generated and analyzed, revealing a complex energy landscape at ambient conditions that becomes significantly simplified under compression. Phonon calculations within the quasi-harmonic approximation demonstrate that the experimentally observed Phase I structure is not stabilized by enthalpy but by vibrational entropy, whose contribution increases with temperature. These results show that the phase transition in L-serine is governed by an interplay between lattice energy, hydrogen-bond rearrangement, and vibrational effects, and highlight that an accurate description of polymorphic stability in such systems requires inclusion of both static and dynamic contributions.