Cocrystals: Synthesis, Structure, and Applications

Abstract

The crystal structure of a compound, the 3D orientation and organization of molecules in a highly regular manner, ultimately determines most of the fundamental physical properties of that particular material, for example, thermal stability, hygroscopicity, conductivity, and mechanical strength. Consequently, an ability to control and change the crystalline environment of a material without altering the molecular properties would be of enormous significance to both manufacturers and consumers of solid specialty chemicals such as pharmaceuticals, pigments, energetic materials, toxins, foodstuff, and detergents. Preparation of cocrystals—homogeneous crystalline solids composed of different molecular building blocks—offers an additional path for incorporating functional molecules, active ingredients, within a crystalline casing, but the synthetic challenges associated with supramolecular synthesis are numerous and nontrivial. This chapter describes several strategies for the assembly of cocrystals using hydrogen bonds and halogen bonds and provides a more in‐depth examination of how the electrostatic charge on individual attempts can be used to control efficiency and selectivity of supramolecular synthesis. Finally, a few examples of applications of cocrystals in pharmaceutical sciences are discussed.

The structure of the melamine–cyanuric acid co-crystal

“…The original report has been very highly cited and the structure used to illustrate the concept of crystal engineering. [20][21][22] The complementarity of the melamine and cyanuric acid units has been used to rationalise the stability and relatively poor aqueous solubility of the co-crystal. This model has been used as the basis of elegant studies of CA.M crystal growth 23 and studies of CA.M under pressure.…”

Mechanochemistry for Organic Chemists: An Update

“…This section highlights the use of mechanochemistry for the assembly of complex structures, including supramolecular complexes, covalent organic frameworks (COFs), rings, and cages. An early report of mechanochemical functionalization of complex molecules was provided by Aakeröy et al, who modified cavitands by mechanochemical transformation of peripheral aldehyde groups into oximes. Reaction was complete within 5 min, in excellent yields and without any by‐products, avoiding tedious purification procedures required for solution‐made products.…”

Detonation Velocity Assessment of Energetic Cocrystals Using QSPR Approach

“…The properties of a cocrystal is typically varied from its pure components, in terms of morphology, thermal behavior, sensitivity, detonation performance and so forth. [4][5][6] According to the literature, some energetic cocrystals have been reported. For instance, Bolton et.al reported the CL-20:HMX cocrystal in a 2:1 molar ratio and the results indicated that the sensitivity of CL-20 was 30 n O /n H .…”