Computed Crystal Energy Landscapes for Understanding and Predicting Organic Crystal Structures and Polymorphism

Abstract

The phenomenon of polymorphism, the ability of a molecule to adopt more than one crystal structure, is a well-established property of crystalline solids. The possible variations in physical properties between polymorphs make the reliable reproduction of a crystalline form essential for all research using organic materials, as well as quality control in manufacture. Thus, the last two decades have seen both an increase in interest in polymorphism and the availability of the computer power needed to make the computational prediction of organic crystal structures a practical possibility. In the past decade, researchers have made considerable improvements in the theoretical basis for calculating the sets of structures that are within the energy range of possible polymorphism, called crystal energy landscapes. It is common to find that a molecule has a wide variety of ways of packing with lattice energy within a few kilojoules per mole of the most stable structure. However, as we develop methods to search for and characterize "all" solid forms, it is also now usual for polymorphs and solvates to be found. Thus, the computed crystal energy landscape reflects and to an increasing extent "predicts" the emerging complexity of the solid state observed for many organic molecules. This Account will discuss the ways in which the calculation of the crystal energy landscape of a molecule can be used as a complementary technique to solid form screening for polymorphs. Current methods can predict the known crystal structure, even under "blind test" conditions, but such successes are generally restricted to those structures that are the most stable over a wide range of thermodynamic conditions. The other low-energy structures can be alternative polymorphs, which have sometimes been found in later experimental studies. Examining the computed structures reveals the various compromises between close packing, hydrogen bonding, and pi-pi stacking that can result in energetically feasible structures. Indeed, we have observed that systems with many almost equi-energetic structures that contain a common interchangeable motif correlate with a tendency to disorder and problems with control of the crystallization product. Thus, contrasting the computed crystal energy landscape with the known crystal structures of a given molecule provides a valuable complement to solid form screening, and the examination of the low-energy structures often leads to a rationalization of the forms found.

Modeling molecular crystals formed by spin-active metal complexes by atom–atom potentials

“…In this case the model includes the entropy factor implicitly, and the lattice parameters found by direct minimization of U should actually refer to the room temperature. The accuracy of the atom-atom approach is corroborated by extensive statistics obtained for organic molecular crystals [32,33,34]. Typically it provides the accuracy level of ca.…”

Rubrene: The Interplay between Intramolecular and Intermolecular Interactions Determines the Planarization of Its Tetracene Core in the Solid State

“…4,5 While the solid-state conformation and packing of organic molecules intimately depends on the growth conditions, the chemical structure plays an obvious, defining role. [6][7][8][9] A classic example is tetracene functionalized with phenyl rings at the 5-, 6-, 11-, and 12-positions, a compound referred to as rubrene, 1 (see Figure 1). The presence of these phenyl rings converts the typical herringbone structure found in oligoacenes to a slipped-cofacial packing of the π-conjugated tetracene backbones.…”

Hidden polymorphs drive vitrification in B2O3

“…This is the case for instance for Chlorothalonil or Aspirin. On the contrary, 2,3-dichloronitrobenzene shows a monomorphic behavior because of the large energy difference (> 7 kcal.mol −1 ) between the most stable form and its other polytypes [15].…”

“…This is the case for instance for Chlorothalonil or Aspirin. On the contrary, 2,3-dichloronitrobenzene shows a monomorphic behavior because of the large energy difference (> 7 kcal.mol −1 ) between the most stable form and its other polytypes [15].The existence of a correlation between a system's ability to amorphise and the presence of numerous crystal polymorphs with comparable energies is remarkable since it seemingly applies to a very broad range of materials, which includes organic, inorganic and metallic systems. In addition, several studies have pointed out a structural link between the glassy and the known crystalline phases [4,5].…”

“…3b). The enthalpy separation between B 2 O 3 -I and the second lowest polymorph rapidly increases with pressure (∼ 0.8 kcal/mol at 0.5 GPa and ∼ 1.3 kcal/mol at 1.0 GPa), gradually leading to a situation in which a monomorphic behavior is expected [15]. This is fully in line with the experimental observation that a threshold pressure (0.4-1.0 GPa) is required to observe B 2 O 3 -I crystallisation from the melt [7][8][9].…”