Two Crystalline Forms of Sesquiterpene Lactone Helenalin - X-Ray and NMR Study

Abstract

Helenalin, a naturally occurring sesquiterpene lactone of the pseudoguaianolide type, has been reported to exist in two polymorphic forms, both crystallizing in the monoclinic space group P21. In this paper we report the X-ray structure of the third room temperature polymorph, crystallizing in the orthorhombic space group P212121. The isolated molecules in all three polymorphs exhibit nearly the same molecular conformation, so the three crystalline modifications differ mainly in the mode the molecules pack in the solid state. Two main hydrogen bond acceptors, the oxygen atom of the cyclopentenone ring and the oxygen atom of the lactone carbonyl group, are competing in the hydrogen bond formation with the secondary hydroxyl group. Having an access to two polymorphs which differ in the hydrogen bond acceptors, we have performed the solid state 13C NMR measurements using a cross-polarization magic angle spinning technique. By comparison of the spectra taken in non-polar solvent with the spectra taken in the solid state we were able to demonstrate the shielding effects resulting from the intermolecular hydrogen bonding in crystals. The fast conformational equilibrium between two conformers TC(10) and TC(7) was suggested from NMR study of helenalin in solution.