(−)-Huperzine A is found in the plant families of the Huperziaceae, Lycopodiaceae, and Selaginella. It is a highly potent, specific, and reversible inhibitor of acetylcholinesterase (AChEI) and has been extensively evaluated for bioactivity, especially for activity towards cholinesterases and for treatment of Alzheimer's disease (AD).

Huperzine A is a monohydrate form (H1) occurring in nature and is marked under the same solid-state form. In our previous study, three Huperzine A polymorphs in its pure form were reported.

During the process of crystal form screening, a remarkable property of Huperzine A was revealed: all crystals obtained from common solvents at room or lower temperatures were solvated forms and the anhydrous forms could only be prepared at 50 °C or higher temperatures.

In this study, researchers from Shanghai Institute of Materia Medica,CAS  report a new polymorphic monohydrate form (H2) and four solvates synthesized under different solvent systems and crystallization conditions.

All the crystal structures were elucidated by single crystal structure analysis. The crystal structures show that channels or void spaces can readily be formed in Huperzine A crystals, which entails the formation of versatile solvent inclusion in systematic, reoccurring packing patterns. The thermo properties and moisture dependent stabilities were studied by TGA, DSC and DVS, and the guest contents were examined by TGA.

The form transformation, packing efficiency of the anhydrous forms, hydrates and solvates of Huperzine A were also determined and the results were correlated with the differences in their thermodynamic stabilities.

This work has been published on the CrystEngComm.

Full text: http://pubs.rsc.org/en/content/articlehtml/2013/ce/c3ce41965g.

Three-dimensional packing (view down the a-axis) of Huperzine A solvates