Accurate theoretical prediction of electrode potentials would be of great benefit in many areas of medicinal chemistry. In particular, the efficacy of many bioreductively activated chemo therapeutic agents can frequently be related to their redox behaviour. Nitroarenes are a typical example. These compounds have shown considerable promise in the treatment of many cancers.
In the present study we have used a quasi-quantum mechanical/classical mechanics (QM/CM) approach to calculate the relative one-electron reduction potentials for a set of 8 nitroarenes. Gas phase electron affinities were calculated using GAMESS-UK. The solvation terms were then calculated using the Free Energy Perturbation (FEP) method implemented in AMBER.
The results were very promising; in general, the agreement between theory and experiment was better than 1 kcal/mol.
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