The influence of the crystal sponge framework on guest molecule conformation

Abstract

The crystalline sponge (CS) method has become an important technique for structural elucidation of compounds that are challenging to crystallise. The impact of the CS environment on guest molecule conformations has not been systematically studied. We present a computational investigation of the conformations of organic molecules of varying flexibility in a set of experimentally determined CS structures, comparing them to gas phase conformers and, where available, pure and co-crystal structures. Via solid state and molecular density functional theory calculations, we quantify the total relative energy, conformational energy, and intramolecular strain of guest molecules, as well as framework strain. Our results show that while CS structures induce distortion in guest geometries (total relative energies up to 41 kJ mol⁻¹), they generally adopt low-energy conformations, often within 2 kJ mol⁻¹ of the global energy minimum. Intramolecular strain in CS structures is often lower than in conventional crystal structures, suggesting a more neutral packing environment where molecules are closer to their favoured isolated-molecule geometries. We also observe that multiple guests can influence each other's geometries, even in the absence of direct guest–guest interactions. These findings provide a quantification of conformational distortion that can form the basis for interpreting molecular geometries obtained from CS structures.