Study of the single-crystal X-ray diffuse scattering in paracetamol polymorphs.

Area of Science:

• Crystallography
• Materials Science
• Solid-state Chemistry

Background:

• Paracetamol exhibits polymorphism, with distinct crystalline forms (I and II).
• The metastability of paracetamol form II and its transition to form I are not fully understood.
• Diffuse X-ray scattering can provide insights into crystal dynamics and phase transitions.

Purpose of the Study:

• To calculate single-crystal diffuse X-ray scattering for paracetamol polymorphs using Monte Carlo simulations.
• To investigate the origin of diffuse scattering and its potential to explain the metastability of paracetamol form II.
• To determine if diffuse scattering offers insights into the form II → I phase transition.

Main Methods:

• Monte Carlo (MC) simulations were employed to model paracetamol crystals.
• Force constants, derived from Buckingham-type potentials, were refined using the least-squares method.
• Analysis of correlation space and librational disorder was performed.

Main Results:

• MC models successfully reproduced single-crystal diffuse X-ray scattering patterns for paracetamol polymorphs.
• Strong displacive correlations were observed within hydrogen-bonded layers.
• Form II exhibited greater inter-layer disorder compared to form I.
• Librational disorder analysis was inconclusive due to small correlation values.
• The diffuse scattering was adequately modeled using harmonic potentials, suggesting a thermal origin.

Conclusions:

• Diffuse X-ray scattering in paracetamol polymorphs is primarily of thermal origin.
• The observed diffuse scattering does not provide additional information regarding the form II → I phase transition.
• The metastability of paracetamol form II cannot be explained by the analyzed diffuse scattering features.