Comprehensive understanding of oxidation properties of ferrocene- and cymantrene- tagged breast cancer prodrug, Tamoxifen

Abstract

A study of the redox properties of tamoxifen, one of the most common drug for treatment of breast cancer, with Density Functional Theory is presented here. Prediction of redox potential is exceedingly complicate and requires deeper understanding and careful consideration of factors which affect redox behavior of tamoxifen including the influence of ion paring and deprotonation. We carried out DFT calculations to gain oxidation potentials of each species. To consider ion pairing effect of tamoxifen derivatives in solvent, counterion, [$B(C_6F_5)_2F_2]^{-}$, is introduced. In the case of 2a and 2b, the computed reaction energy profiles are in fair agreement with experimental oxidation potentials. Otherwise we provide redox potentials of 2c which take into account the deprotonation reaction that occurs during the oxidation process because of the low pKa value of hydroxyl group of 2c structure. Meanwhile, oxidation property of tamoxifen can be improved by attaching cymantrene tag and electron donating group to the molecule, especially ethylene branch of the tamoxifen derivatives.