On pH controlling of the reaction mechanism: Interactions of 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 Au(I)-NHC complex are explored using DFT functionals and post-HF methods. Besides the conventional quantum chemical description with NVT canonical ensemble, transformation to the grand-canonical ensemble is performed. In this way, chemical species with different number of protons can be considered and reactions at constant pH evaluated. For this purpose, a new thermodynamic state function is introduced with proton chemical potential as natural variable - Gibbs-Alberty free energy (ΔGA0) and applied to Cys/Sec - Au(I)NHC interactions. Having determined all the necessary pKa values, the pH dependent equilibrium constant can be expressed for both Cys and Sec coordination to the gold(I) complex. Dependences of ΔGA0(Cys) and ΔGA0(Sec) as functions of varying pH demonstrates visible preference for Sec coordination in acidic and neutral conditions, which is changed in the vicinity of pH ≈ 8 where Cys coordination becomes thermodynamically more stable.