CONICET | Buscador de Institutos y Recursos Humanos

Malaria remains one of the most devastating endemic diseases in the world[1]. Drugs continue to be the only treatment option, despite the fact that most antimalarials available are old, frequently limited in efficacy and with severe side effects. It is estimated that, in the absence of adequate solutions, the number of victims will increase dramatically, due to the proliferation of multi-drug resistant Plasmodium falciparum parasites[1]. Artemisinin (1), a sesquiterpene lactone 1,2,4-trioxane extracted from Artemisia annua, and its oil- and water-soluble derivatives, artemether, artether and sodium artesunate, are widely used in the treatment of Malaria. It is accepted that the mode of action of artemisinins is mediated by the endoperoxide bridge, which upon Fe(II)-induced homolytic cleavage generates oxy radicals that rearrange to carbon-centered radicals capable of damaging parasitic biomolecules[2]. In addition to some toxicity, low solubility and low yield of artemisinins extraction, there is a standing fear that artemisinin derivatives might become ineffective through development of resistance. Accordingly, successful efforts have been made towards the design and preparation of synthetic endoperoxides with improved pharmacological properties[3]. However, in spite of the huge importance of these compounds, the information concerning their detailed structural analysis and reactivity is very scarce. Accordingly, a systematic investigation of the structure, photochemistry and thermal stability of selected trioxanes, trioxolanes and tetroxanes is being undertaken in our labs. In this presentation, the structure and photochemistry of trioxolane 2, isolated in a cryogenic argon matrix, will be presented and discussed. Results are based on FTIR spectroscopy assisted by extensive molecular orbital calculations.