Solute polarization and the design of cobalt complexes as redox-active therapeutic agents

A combination of quantum mechanical density functional calculations and the Poisson-Boltzmann continuum method has been used to calculate the electrode potential of [Co(en)], [Co(NH)], and [Co(CO)] relative to that of [Co(dien)]. Excellent results (to within ∼ 100 mV) were obtained for [Co(en)] but not for the other complexes (errors 300 mV +). Based on hydration energies calculated using the polarized continuum method, a significant proportion of the error has been attributed to the solute polarization energy. Explicit inclusion of the solute polarization energy reduces the errors by up to 200 mV. The solute polarization energy is generally only treated in an average way in the Poisson-Boltzmann method. Consequently, a novel approach to the explicit determination of the solute polarization energy within a Poisson-Boltzmann framework is described. This approach is based on the effective multipoles of Ferenczy et al. [J. Phys. Chem. A 101, 5446 (1997)] and uses the mulfit code to describe an induced dipole as a set of equivalent distributed monopoles. In addition, pseudopotentials were useful for speeding up the geometry optimizations and for rapidly assessing basis set trends but were not useful for obtaining accurate energy differences.