Quantum chemical analysis of alternative pathways for iron activation step for artemisinin, a new antimalarial drug

SummaryMalaria is a mosquito-borne parasitic infection. It can be said that malaria is a very important tropical mosquito-borne infectious disease. The selection of antimalarial drugs depends on the species and the reported resistance pattern in each setting. Artemisinins are a new group of antimalarial drugs against the drug-resistant strains of malarial parasites. The mechanism of action of artemisinin compounds consists of two important steps: (a) activation and (b) alkylation. In the activation step by iron, there are two possible pathways for developing C-4 free radical: (a) 1.5 H-shift and (b) C–C cleavage. Here, the author performs a quantum chemical analysis of the activation reaction of artemisinin by the two alternative pathways. According to this study, the required energy for compound formation in C–C cleavage is more than that for C–O cleavage. It can be noted that the C–C cleavage pathway is less preferable, implying that the 1.5 H-shift should be the more common phenomenon.