Why don't we find more polymorphs?

Area of Science:

• Solid-state chemistry
• Materials science
• Computational chemistry

Background:

• Crystal structure prediction (CSP) is crucial for understanding polymorphism.
• CSP studies explore the crystal energy landscape computationally and experimentally.
• Predicted crystal structures often surpass known polymorphs in thermodynamic plausibility.

Purpose of the Study:

• To elucidate reasons why CSP typically yields more thermodynamically plausible structures than observed polymorphs.
• To highlight the complexities and limitations in current CSP methodologies and experimental observations.
• To discuss the potential for a general predictive theory of polymorphism.

Main Methods:

• Review and analysis of factors influencing CSP outcomes.
• Examination of approximations in computational calculations, including thermal effects.
• Consideration of molecular rearrangement during nucleation and growth.
• Analysis of experimental limitations and detection challenges for polymorphs.

Main Results:

• Approximations in calculations (e.g., neglecting thermal effects) contribute to discrepancies.
• Molecular rearrangement, structural defects, and experimental constraints limit direct comparison between predicted and observed structures.
• Metastable structures, unperformed/undetected experiments, and dynamic disorder further complicate CSP findings.

Conclusions:

• A comprehensive predictive theory for polymorphism requires understanding kinetic factors in multi-component crystallization.
• The crystal energy landscape reveals the inherent complexity of crystallization behavior for specific molecules.
• Bridging computational predictions with experimental realities remains a key challenge in polymorphism research.