Abstract
Redox processes are an important step in many chemical and biochemical reactions. One simple approach to calculate the free energy change of a redox process is linear response approximation (LRA). However, variability in conformational and energy-gap sampling poses a challenge in balancing computational cost and accuracy. Herein, we calculate the redox properties of the one-electron oxidation processes for small, biologically relevant redox-active molecules (e.g., phenol, phenolate, benzene, indole, lumiflavin) in aqueous solution using two conformational sampling strategies. We sampled the conformations using molecular mechanics (MM) and hybrid quantum mechanics/molecular mechanics (QM/MM) simulations to investigate how these techniques affect redox properties. We also performed QM/MM energy-gap sampling while varying the QM region to investigate its impact on overall redox behavior. We observed free energy of oxidation, and consequently, oxidation potential differs consistently by ∼0.2-0.4 V between QM/MM and MM sampling for the molecules under investigation. Overall, we infer that computationally cheaper MM sampling would be adequate for computing the redox properties of small molecules when corrected by a system-specific correction factor.