Single crystal X-ray analysis using the crystalline sponge method for direct structure determination of new and earlier synthetic cannabinoids including OXIZIDs, AKB48, and JWH-424 from a trace sample

Synthetic cannabinoids are one of the most popular classes of recreational drugs and following China's class-wide ban on the existing synthetic cannabinoids, a new series of synthetic cannabinoids, known as "OXIZID", with major structural modifications to circumvent the law have started to be found on the drug market. Although the structures of newly emerging drugs of abuse need to be characterized for forensic (and subsequently even clinical testing) purposes, these characterizations are often impeded by the fact that synthesizing reference standards can be demanding and/or nuclear magnetic resonance spectroscopy requires a relatively large amount of sample (i. e., milligrams). Here, we report the structure determination of six synthetic cannabinoids, OXIZIDs (BZO-POXIZID, 5F-BZO-POXIZID, BZO-4en-POXIZID, and BZO-HEXOXIZID), AKB48, and JWH-424, using the crystalline sponge method via single crystal X-ray diffraction (SC-XRD). The crystal structures for all but BZO-HEXOXIZID are reported for the first time. The crystalline sponge method successfully revealed the structures of the six cannabinoids by soaking only 1-5 mu L solution containing 1-5 mu g drug into a porous crystal and subjecting the soaked crystal to SC-XRD. Among them, the structure determination of JWH-424 (an oily and non-crystalline compound) demonstrated the ability of the method to allow not only the visualization of three-dimensional structures but also the structure determination of non-crystalline compound. Therefore, the crystalline sponge method has great potential for an effective structural determination of synthetic cannabinoids, especially when the cannabinoids cannot readily be crystallized.