Core electronic structure of pharmacophores via in silico X-ray photoelectron spectroscopy: Artemisinin derivatives

The aim of the work was to elucidate the relationship between core electronic structure of oxygen functional groups and measured biological activity of artemisinin derivatives. The electronic structures of artemisinin and its derivatives have been studied via calculated K-shell (O1s and N1s) vertical, ionization energies. The calculations were performed using GW method implemented in NWChem software. We have also tried to use IP-EOM-DLPNO-CCSD method for the same purpose, but have found that this method overestimates the absolute core electron binding energies (CEBE) by approximately 2 eV vs. experimental values in relevant reference molecules. On the other hand, the GW underestimates CEBE by approximately 0.1 eV. We discuss possible reaction mechanisms which underlie biological activities of artemisinins on the basis of correlation between O1s ionization energies and quantitative biological activity reported in the literature. We suggest that two mechanisms: reductive scission and open peroxide model are operational in different artemisinin derivatives.