Mechanosynthesis of Higher‐Order Cocrystals: Tuning Order, Functionality and Size in Cocrystal Design**

Abstract

The ability to rationally design and predictably construct crystalline solids has been the hallmark of crystal engineering research. To date,n umerous examples of multicomponent crystals comprising organic molecules have been reported. However,t he crystal engineering of cocrystals comprising both organic and inorganic chemical units is still poorly understood and mostly unexplored. Here,w er eport anew diverse set of higher-order cocrystals (HOCs) based on the structurally versatile-yet largely unexplored-phosph(V/ V)azane heterosynthon building block. The novel ternary and quaternary cocrystals reported are held together by synergistic and orthogonal intermolecular interactions.N otably,t he HOCs can be readily obtained either via sequential or onepot mechanochemical methods.C omputational modelling methods reveal that the HOCs are thermodynamically driven to form and that their mechanical properties strongly depend on the composition and intermolecular forces in the crystal, offering untapped potential for optimizing material properties.

Harnessing Noncovalent Interactions for a Directed Evolution of a Six-Component Molecular Crystal

“…25 Garcia and coworkers have attained the mechanochemical synthesis of an organic−inorganic hybrid ternary and quaternary crystal. 26 A six component cocrystal has been reported by Desiraju et al which remains a record in the chemical literature. 27 The concept has been further generalized into a robust strategy for the synthesis of multicomponent molecular solids by Desiraju and co-workers.…”

“…Jones and co-workers reported the formation of multicomponent crystal forms of the biologically active hydrazone (BZH) with four dicarboxylic acids, malonic, succinic, glutaric, and mesaconic acids . Garcia and co-workers have attained the mechanochemical synthesis of an organic–inorganic hybrid ternary and quaternary crystal . A six component cocrystal has been reported by Desiraju et al which remains a record in the chemical literature .…”

Synthesis of Ternary Cocrystals, Salts, and Hydrates of Acefylline with Enhanced Dissolution and High Permeability

“…The PXRD plots of preparation via Method 1, Method 2, and overlay of calculated and experimental line patterns for ACF-INA-3,5-DHBA (1:1:1) and ACF-PIP-3,5-DHBA (1:0.5:1) are displayed in Figure4. A sequential method for the synthesis of HOCs was recently reported86 during the period of this manuscript revision and repetition of our experiments. Our results add to the sequential supramolecular synthesis of HOCs (ternary and quaternary) from lower-component binary systems51,86 for the category of pharmaceutical cocrystals and salts.…”

The unique opportunities of mechanosynthesis in green and scalable fabrication of metal–organic frameworks

“…Nowadays, mechanosynthesis is validated as an effective versatile synthetic method for the fabrication of a wide variety of high-value products such as organic, inorganic, or hybrid organic-inorganic materials. 20,21,30 This synthesis process has appeared to provide an effective and amenable route for selfassembly processes of MOF materials as well as their commercialization purposes. Mechanosynthesis refers to the chemical reactions that are usually caused by a mechanical force through grinding or milling without the need for using high temperatures or bulk solvents to dissolve the reagents.…”