Phenanthrene co-guest lets crystalline sponge solve X-ray structures of 24 of 30 small molecules
Adding phenanthrene to palladium-based cages extended the 2G crystalline sponge method to low-polarity C15 molecules, which gave no guest-containing crystals without it.
Researchers have extended the second-generation crystalline sponge (2G-CS) method to small, low-polarity molecules by adding phenanthrene as a co-guest. The work was published on 20 October 2026 in Angewandte Chemie International Edition and announced by the National Institutes of Natural Sciences on 4 November. X-ray structures were obtained for 24 of 30 low-polarity C15 compounds, mostly sesquiterpenoids 
doi.orgAngewandte Chemie International Editiondoi.orgOpen source ↗. Under standard conditions, none of the 30 gave guest-containing crystals doi.orgAngewandte Chemie International Editiondoi.orgOpen source ↗.
Where the sponge method failed
The 2G-CS method determines a molecule's structure without crystallizing the molecule itself. The molecule is captured inside hollow palladium-based cages that assemble into a crystal doi.orgAngewandte Chemie International Editiondoi.orgOpen source ↗. The method works for guests with molecular weights of 300 to 1500 regardless of polarity, but often fails for low-polarity molecules of 200-300 doi.orgAngewandte Chemie International Editiondoi.orgOpen source ↗. The authors attribute this to a cage cavity that is too large for such molecules. The molecules likely have too much freedom of motion and interact only weakly with the host doi.orgAngewandte Chemie International Editiondoi.orgOpen source ↗.
The team used a size-compensation strategy. A flat aromatic modulator is encapsulated together with the target molecule, and the pair fills the cavity. The ternary complex forms preferentially when both guests are present doi.orgAngewandte Chemie International Editiondoi.orgOpen source ↗. The host requires no chemical modification doi.orgAngewandte Chemie International Editiondoi.orgOpen source ↗. Among six modulators tested, phenanthrene gave the highest inclusion level for (+)-longifolene, about 40% of cages by NMR. The same phenanthrene-based protocol was then applied to the other 29 compounds without further optimization.
Structures and absolute configurations
Phenanthrene enabled structure determination for 24 of the 30 compounds (80%) doi.orgAngewandte Chemie International Editiondoi.orgOpen source ↗. The successes spanned hydrocarbons, macrocycles, fused-ring compounds and linear molecules, and the arrangement of the modulator varied with the guest. Eleven of the 24 structures had not been reported before, including that of longifolene, a liquid first isolated in 1920 doi.orgAngewandte Chemie International Editiondoi.orgOpen source ↗. With the standard cage, the complexes crystallized under nearly uniform conditions with very similar lattice parameters. The guest electron density was nonetheless clear enough for assignment.
A chiral version of the cage gave the absolute configurations of five selected compounds, including four hydrocarbon natural products doi.orgAngewandte Chemie International Editiondoi.orgOpen source ↗. These included the assignment of (+)-longifolene as (1R,2S,7S,9S). The four hydrocarbons matched earlier assignments. The authors believe this is the first crystallographic characterization of these four unmodified parent hydrocarbons.
The approach keeps the method's operational simplicity, microscale sample use and rapid analysis. Because modulator uptake can be checked by NMR before crystallization, the authors propose that screening other modulators could adapt the same host to other classes of analytes.
