Mining Predicted Crystal Structure Landscapes with High Throughput Crystallization: Old Molecules, New Insights

Organic molecules tend to close pack to form dense structures when they are crystallized from organic solvents. Porous molecular crystals defy this rule: they typically crystallize with lattice solvent in the interconnected pores. However, the design and discovery of such structures is often challenging and time consuming, in part because it is difficult to predict solvent effects on crystallization. Here, we combine crystal structure prediction (CSP) with a high-throughput crystallization screening method to accelerate the discovery of stable hydrogen-bonded frameworks. We exemplify this strategy by finding new phases of two well-studied molecules in a computationally targeted way. Specifically, we find a new porous polymorph of trimesic acid, δ- TMA , that has a guest free hexagonal pore structure, as well as three new solvent-stabilized diamondoid frameworks of adamantane-1,3,5,7-tetracarboxylic acid ( ADTA ).