title: Theoretical evaluation of adiabatic and vertical electron affinity of some radiosensitizers in solution using FEP, ab initio and DFT methods.
abstract: The biological activity of radiosensitizers is associated to their electron affinity (EA), which can be divided in two main processes: vertical and adiabatic. In this work, we calculated the EAs of nitrofurans and nitroimidazoles (Fig. 2) using Hartree-Fock (HF) and density functional theory (DFT) methods and evaluated solvent effects (water and carbon tetrachloride) on EAs. For water, we combined the polarized continuum model (PCM) and free energy perturbation (FEP) (finite difference thermodynamic integration, FDTI) methods. For carbon tetrachloride, we used the FDTI method. The values of adiabatic EA obtained are in agreement with experimental data (deviations of 0.013 eV). The vertical EAs were calculated according to Cederbaum's outer valence Green function (OVGF) method. This methodology, which relies on theoretical aspects of free energy calculations on charged molecules in solution, was used to select potential selective radiosensitizers from recently reported compounds and could be helpful in the rational design of new and more selective bioreductive anticancer drugs.
authors.affiliation: Departamento de Química, Instituto Militar de Engenharia, Praça General Tibúrcio 80, 22290-270 Rio de Janeiro-RJ, Brazil.
authors.forename: Teodorico C
authors.initials: TC
authors.lastname: Ramalho
authors.forename: Ricardo Bicca
authors.initials: RB
authors.lastname: de Alencastro
authors.forename: Mauro Aquiles
authors.initials: MA
authors.lastname: La-Scalea
authors.forename: José Daniel
authors.initials: JD
authors.lastname: Figueroa-Villar
mesh_terms: D002251:Carbon Tetrachloride / Q000737:chemistry; D004563:Electrochemistry; D004583:Electrons; D008956:Models, Chemical; D015394:Molecular Structure; D009581:Nitrofurans / Q000737:chemistry; D009593:Nitroimidazoles / Q000737:chemistry; D011838:Radiation-Sensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D015203:Reproducibility of Results; D012996:Solutions / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D009581:Nitrofurans; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D012996:Solutions; D014867:Water; D002251:Carbon Tetrachloride