Chemists have long relied on X-ray crystallography to unambiguously determine a molecule’s structure. But in some cases, it can be devilishly difficult to grow the crystals required for this technique. A few years ago, chemists introduced the crystalline sponge method, in which a metal-organic framework, or MOF, is soaked like a sponge with a solution of a compound. Weak interactions between the MOF and the compound hold it inside the MOF, allowing the compound’s structure to be determined by X-ray diffraction. But the method is not perfect and is often used as a last resort. Omar M. Yaghi, Seungkyu Lee, and Eugene A. Kapustin of the University of California, Berkeley, have now devised a way to make this kind of structure determination more reliable. The UC Berkeley chemists lock the molecules they are studying in place by covalently linking them to the aluminum atoms of a chiral framework known as MOF-520 (Science 2016, DOI: 10.1126/science.aaf9135). This ensures the molecules align within the MOF, making it easier to solve structures via X-ray analysis. The team demonstrated the technique works with primary alcohols, phenols, vicinal diols, and carboxylic acids. Using the chiral MOF makes it possible to determine absolute stereochemistry, as the researchers demonstrate with jasmonate, a compound for which no crystal structure had been reported previously.