Quantitative approaches to understanding conformational flexibility in crystalline sponges

The crystalline sponge (CS) method has expanded the capabilities of single crystal X-ray diffraction (SCXRD) chemical structure determination and analysis to liquid or oily compounds. Guest molecules encapsulated within the porous metal-organic framework (MOF) have variable intermolecular interaction strengths, both with the pore and other guest molecules, and often exhibit multiple molecular conformations. Quantification and understanding of these features has previously proved challenging and thus limited the insights available from structural models. Through combination of the CS method, conventional SCXRD, Nuclear Magnetic Resonance spectroscopy, single-molecule and periodic DFT, and energy calculations based on electron density, we determine intra- and intermolecular energy changes across a spectrum of physical environments. We explore the MOF pore environment experienced by a systematic family of small organic molecules and showcase the tools available for quantification of these complex systems.