A DFT study of the G3-Factor and derivatives

We present theoretical studies of the G3-Factor and two derivatives, the methylated (G3Me) and the fluorinated (G3F) endoperoxides. These endoperoxides were previously tested as alternative drugs against the parasite causing malaria. They showed promising activity. The geometry of each compound was optimized in its lowest singlet and triplet spin states at the B3LYP/6-311G∗ level of theory. It was followed by a NBO analysis. The ground state of the G-Factors is a singlet. The geometric parameters found by the DFT calculations are in agreement with available experimental results. The spin density distribution for the triplet state shows a biradical [] molecule. The singlet-triplet splitting is of 36.60, 33.96 and 34.09 kcal/mol (B3LYP/6-311G∗) and of 36.07, 33.51 and 33.60 kcal/mol (B3LYP/6-311++G∗∗) for the G3-Factor and the G3Me and G3F derivatives, respectively.