CALCULATION OF ONE-ELECTRON REDUCTION POTENTIALS FOR NITROHETEROCYCLIC HYPOXIA-SELECTIVE AGENTS

Theoretical one-electron reduction potentials, E(1), have been determi ned for a set of eight nitroarene hypoxic cell radiosensitisers using a combination of classical statistical mechanics and quantum mechanica l methods. Gas-phase electron affinities were calculated using ab init io Hartree-Fock calculations and relative hydration energies were comp uted using the free energy perturbation (FEP) method. The results were used to estimate the relative one-electron reduction potentials for t hese molecules in solution. In general, the computed results are in go od agreement with experiment although further work is required to dete rmine the limitations of the method. Nevertheless, the method shows su fficient promise to be of value in the rational design of improved oxi dative agents for use as hypoxia-selective radiosensitisers and biored uctivity activated cytotoxins.