Density functional calculation of quinone electrode potentials

Here, we have applied density functional methods, in combination with free energy hydration calculations, to calculate two‐electron electrode potentials for quinones and naphthoquinones. While we find that the free‐energy perturbation method, implemented within a molecular dynamics framework, is superior to the PM 3— SM 3 continuum method for determining free energies of hydration, the computationally less expensive PM 3— SM 3 method does perform well when there is not an internal hydrogen bond. Generally, all the density functional approaches investigated gave good energetics when applied to this problem, but the Beck '88—Vosko—Wilk—Nusair combination of functionals for the exchange‐correlation energy gave the best results. The density functional results are marginally better than the Møller‐Plesset second‐order perturbation results. Moreover, because the results are obtained using a thermodynamic cycle which involves taking differences in total energies, the results are not too dependent on the quadrature scheme used to calculate the exchange‐correlation energy. By using semiempirically optimized geometries and the PM 3— SM 3 method for determining free energies of hydration, it has been possible to calculate electrode potentials for a series of large molecules (naphthoquinones) to within about 30 mV of experiment. This result is extremely encouraging and shows that density functional methods offer great promise in the design of redox‐active molecules such as bioreductive anticancer agents. © 1995 John Wiley & Sons, Inc.