Synthesis and guest inclusion for molecular catcher-based structure determination

Natural products and drugs containing long alkyl chains are difficult to grow in the form of single crystals. This makes it challenging, if not impossible, to determine their molecular structures through conventional single-crystal X-ray diffraction. We recently reported a 'molecular catcher' technique using a pillar[5]arene-incorporated metal-organic framework (MOF), namely a 'molecular catcher', that enables rapid and accurate determination of crystal structures for long-alkyl-chain compounds without a need to grow single crystals. In this approach, presynthesized pillar[5]arene-containing MOF crystals are soaked in a solution of the target compound. The compound is captured into the MOF crystals, which are then analyzed by X-ray diffraction, allowing the crystal structure of the guest to be determined. Here we describe detailed protocols for the synthesis of this pillar[5]arene-containing MOF and its further use in structure determinations. In brief, the MOF crystals required for this Protocol are prepared from an in-house synthesized pillar[5]arene derivative, a commercially available tetraphenyl ethylene derivative and zinc nitrate hexahydrate in N,N-dimethylformamide. The resulting crystals are washed with fresh N,N-dimethylformamide to remove unreacted starting materials and can be used directly for guest inclusion without further solvent exchange. The most critical step is selecting MOF crystals with suitable size and quality. We recommend using optical microscopy for preliminary screening to evaluate crystal size and quality as the selection criteria. By soaking the MOF crystals in a solution of the target compound, target-included MOF crystals suitable for X-ray diffraction analysis can be obtained. The entire process-from starting materials to determining the crystal structure-can be completed within 10 d.