pH control of the reaction mechanism: interactions of the Au(i)-NHC complex with thioredoxin reductase (modeled by cysteine and selenocysteine); ab initio and DFT calculations

Abstract

Interactions of Cys and Sec amino acids with a simple model of the Au(I)-NHC complex were explored using DFT functionals and post-HF methods. In addition to the conventional quantum chemical description with the NVT canonical ensemble, a transformation to the grand-canonical ensemble was performed. This approach allowed for the consideration of chemical species with different numbers of protons and the evaluation of reactions at constant pH. For this purpose, a new thermodynamic state function, the Gibbs-Alberty free energy (ΔGA⁰), was introduced, with the proton chemical potential as the natural variable, and applied to Cys/Sec-Au(I)NHC interactions. Having determined all the necessary pK_a values, the pH-dependent equilibrium constant was expressed for both Cys and Sec coordination to the gold(I) complex. The dependences of ΔGA⁰(Cys) and ΔGA⁰(Sec) as functions of varying pH demonstrated a clear preference for Sec coordination under acidic and neutral conditions, which shifted near pH ≈ 8, where Cys coordination became thermodynamically more stable.