Anion and radical anion products of flutamide studied by IR spectra and density functional calculations

Abstract

Flutamide, antiandrogen drugs for prostate cancer, was studied by spectroscopic and DFT methods to estimate its ability to form anion and radical anion products. The azanion was generated in DMSO‑d6 solution by treatment with sodium methoxide and the resulting spectral changes were followed by IR spectroscopy. IR measurements in electrochemical solution cell were performed to characterize the reductive behavior of flutamide. The different conformers of flutamide, its anion and radical anions, the spectral changes expected related to the conversion into anionic species and several molecular parameters were computationally estimated based on DFT. The structure, electronic charge and spin density distribution of azanion and protonated/deprotonated radical anion species were assessed by correlating the observed IR changes to the predicted vibrational frequencies and based on calculated structural parameters. The obtained information may enhance the understanding of the possible routes for metabolizing and interaction of flutamide with biomolecules relevant to its therapeutic action.