Crystal or Glass? Chemical and Crystallographic Factors in the Amorphization of Molecular Materials

The creation of long-lived amorphous phases has potential applications in numerous fields; for example, the instability of the amorphous phase leads to higher solubility of pharmaceutical phases, often leading to higher bioavailability. The rate of recrystallization of an amorphous phase poses a significant limitation to the application of many such phases; however, understanding the energetic and structural factors that control the stability of molecular amorphous phases is limited by empirical classifications based on thermal analysis used to identify materials. From a set of molecularly related benzanilides, examples of all three classes have been identified, allowing use of crystal structural analysis, Raman spectroscopy, and energetic calculations to determine the structural factors playing a role in the different stabilities. While the behavior of most systems reflects the relative energy of the crystalline phase to the amorphous phase, kinetic factors based on whether a NH···OC hydrogen bond is present in the crystalline phase play a key role in stabilizing the amorphous phase as the loss of this bond reduces the conversion rate. In contrast, systems without this bond display fast recrystallization due to the greater structural similarity between the amorphous and crystalline phases.