The antimalarial activity of a series of synthetic 1,2,4-trioxanes is correlated with molecular structure by using a pharmacophore search method (CATALYST). The technique is shown to have predictive accuracy and confirms that docking between an active trioxane and the receptor, heme, is the crucial step for drug action.

Artemisinin and related molecules are potential antimalarials that contain the 1,2,4-lrioxane ring system. Several new derivatives have been synthesized and tested in Geneva, and this article presents the results of a systematic study of the structure of these molecules, both by the semiempirical PM3 method and using ab initio SCF methods. The results highlight the feasibility of full optimizations with 3-2 1G and 6-3 1G* basis sets for these large molecules. Molecular electrostatic potential (MEP) maps are evaluated and used in an attempt to identify the key features of the molecules that are necessary for their activity. There is good agreement between the PM3 and ab initio maps as to the qualitative predictions.

The relative stabilities of hydrogen at (or near) the tetrahedral interstitial and bond-centered sites as well as that of hydrogen dimers in the molecular and bond-centeredantibonding configurations are calculated at the ab initio level in molecular clusters for c-C, Si, Ge, and o.-Sn. The trends show that the lowest-energy configurations change as one goes down the Periodic Table. The relative stability of the possible equilibrium sites aKects which charge states of H are likely to be realized in a given host. This in turn a8'ects the di8'usion properties of H and its interactions with dopants and other defect centers. The trends in equilibrium geometries and relative stabilities show that silicon is a particular case among group IV hosts in which both isolated interstitials and both dimer states are close to each other in energy. We also examine some properties of two charge states of molecular hydrogen in Si in order to determine the key features of their electron paramagnetic resonance spectra.

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