2025-03-06 分子科学研究所
◆この新技術は、優れた分子捕捉力を持つかご型分子を結晶内に固定化することで、従来の結晶スポンジ法の欠点を克服し、高極性分子や分子量1,000を超える中分子の構造解析を可能にしました。特に、中分子医薬品やその候補化合物の構造解析に有効であり、次世代創薬への貢献が期待されています。既に100を超える解析例があり、適用範囲の広さと操作の簡便さが実証されています。
＜関連情報＞
対称性ミスマッチ戦略による結晶性スポンジとしての超分子配位ケージ Supramolecular coordination cages as crystalline sponges through a symmetry mismatch strategy
Wei He,Yikuan Yu,Kenta Iizuka,Hiroki Takezawa & Makoto Fujita
Nature Chemistry
Abstract
The crystalline sponge method enables single-crystal X-ray diffraction analysis of guests absorbed within single-crystalline porous materials. However, its application with large or highly polar guests remains challenging. In this study, we addressed some of these limitations using palladium-based octahedron-shaped M6L4 (Td) coordination cages as crystalline sponges. The key to facilitate the crystallization of the cage is the addition of large aromatic polysulfonates (‘sticker’ anions); the symmetry mismatch between the cage and the sticker (D2h) results in a low-symmetry space group (P1¯), preventing guest disorder and leading to the formation of guest-accessible channels in the crystal. Guests can be encapsulated either before or after cage crystallization. The size and host–guest properties of the cavity enable analysis of a broad range of compounds, including water-soluble molecules, large amphiphilic molecules (molecular weight of ~1,200) and molecular aggregates. We have demonstrated the versatility of the cage–sticker strategy through its application to a triaugmented triangular-prism-shaped M9L6 cage, extending the guest scope to medium-sized pharmaceutical molecules.
