Effect of High Pressure on the Crystal Structures of Polymorphs of l‑Histidine

The effect of pressure on the crystal structures of the two ambient-pressure polymorphs of the amino acid l-histidine has been investigated. Single-crystal diffraction measurements, up to 6.60 GPa for the orthorhombic form I (P2₁2₁2₁) and 6.85 GPa for the monoclinic form II (P2₁), show their crystal structures undergo isosymmetric single-crystal-to-single-crystal first-order phase transitions at 4.5 and 3.1 GPa to forms I′ and II′, respectively. Although the similarity in crystal packing and intermolecular interaction energies between the polymorphs is remarkable at ambient conditions, the manner in which each polymorph responds to pressure is different. Form II is found to be more compressible than form I, with bulk moduli of 11.6(6) GPa and 14.0(5) GPa, respectively. The order of compressibility follows the densities of the polymorphs at ambient conditions (1.450 and 1.439 g cm^–3 for phases I and II, respectively). The difference is also related to the space-group symmetry, the softer monoclinic form having more degrees of freedom available to accommodate the change in pressure. In the orthorhombic form, the imidazole-based hydrogen atom involved in the H-bond along the c-direction swaps the acceptor oxygen atom at the transition to phase I′; the same swap occurs just after the phase transition in the monoclinic form and is also preceded by a bifurcation. Concurrently, the H-bond and the long-range electrostatic interaction along the b-direction form a three-centered H-bond at the I to I′ transition, while they swap their character during the II to II′ transition. The structural data were interpreted using periodic-density-functional theory, symmetry-adapted perturbation theory, and semiempirical Pixel calculations, which indicate that the transition is driven by minimization of volume, the intermolecular interactions generally being destabilized by the phase transitions. Nevertheless, volume calculations are used to show that networks of intermolecular contacts in both phases are very much less compressible than the interstitial void spaces, having bulk moduli similar to moderately hard metals. The volumes of the networks actually expand over the course of both phase transitions, with the overall unit-cell-volume decrease occurring through larger compression of interstitial void space.