Three polytypes of lapachol, a natural pigment with promising pharmacological properties.

The crystal structures of two polymorphs of lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthalenedione, C15H14O3] - a natural pigment relevant in traditional medicine and of considerable scientific interest due to its broad spectrum of biological and pharmacological activities - one with triclinic (P1)and the other with monoclinic (P21/c) space-group symmetries have been redetermined and are compared with a newly identified form, also monoclinic. The three crystal structures are polytypes since they share dimeric layers of hydrogen-bonded lapachol molecules, which connect through π-stacking within a layer. Adjacent layers in the three compounds are held together by weak van der Waals forces between allylic side chains. However, they adopt distinct stacking modes: successive layers are translated along the c axis in the triclinic form, translated and rotated 90° along the b axis in the first monoclinic form and translated and rotated 90° along the a axis in the new monoclinic form. These variations in interlayer arrangement, arising from different relative orientations of interacting allylic moieties, result in subtle differences in the density of the three forms.