Can We Predict the Isosymmetric Phase Transition? Application of DFT Calculations to Study the Pressure Induced Transformation of Chlorothiazide

Abstract

Isosymmetric structural phase transition (IPT, type 0), in which there are no changes in the occupation of Wyckoff positions, the number of atoms in the unit cell, and the space group symmetry, is relatively uncommon. Chlorothiazide, a diuretic agent with a secondary function as an antihypertensive, has been proven to undergo pressure-induced IPT of Form I to Form II at 4.2 GPa. For that reason, it has been chosen as a model compound in this study to determine if IPT can be predicted in silico using periodic DFT calculations. The transformation of Form II into Form I, occurring under decompression, was observed in geometry optimization calculations. However, the reverse transition was not detected, although the calculated differences in the DFT energies and thermodynamic parameters indicated that Form II should be more stable at increased pressure. Finally, the IPT was successfully simulated using ab initio molecular dynamics calculations.

Keywords: CASTEP; DFT; ab initio molecular dynamics; aiMD; phase transition; polymorphism.

Figure 1

Chemical structure of chlorothiazide (CT).

Figure 2

The change of unit cell edge “a” length with respect to pressure. Green circles—Form I, Red circles—Form II.

Figure 3

The change of unit cell edge “a” length with respect to pressure. Green circles—experimental Form I; red circles—experimental Form II; blue circles—calculated ones. Top left—using PBE TS and starting from Form I; top right—using PBESOL and starting from Form I; bottom left—using PBE TS and starting from Form II; top right—using PBESOL and starting from Form II.

Figure 4

(A): Differences between the energies (Form I—Form II) of the structures modeled using PBE TS functional, with respect to pressure. (B): The change of unit cell edge “a” length obtained from calculations using PBE TS functional, with respect to pressure. Yellow circles—using Form I as initial; violet circles—using Form II as initial.

Figure 5

(A): Differences between the energies (Form I—Form II) of the structures modeled using PBESOL functional, with respect to pressure. (B): The change of unit cell edge “a” length obtained from calculations using PBE TS functional, with respect to pressure. Yellow circles—using Form I as initial; violet circles—using Form II as initial.

Figure 6

Differences between the thermodynamic parameters: free energy (ΔG, black dots) enthalpy (ΔH, green dots), temperature times entropy (TΔS, blue dots); Form I—Form II; of the structures modelled using PBE TS functional at 293 K, with respect to pressure.

Figure 7

Running average of the unit cell edge length “a” obtained from aiMD simulation at T = 293 K and p = 6.2 GPa using PBE TS functional. Horizontal lines represent the experimental values.

Figure 8

Running average of the unit cell angle “α” obtained from aiMD simulation at T = 293 K and p = 6.2 GPa using PBE TS functional. Horizontal lines represent the experimental values.