A new grand-canonical potential for the thermodynamic description of the reactions in solutions with constant pH

This review emphasizes the necessity to perform additional Legendre transformation of the free energy for a correct thermodynamic description of reactions in the environment with constant pH. The power of this new thermodynamic potential (Gibbs-Alberty free energy Delta GA(0)) is demonstrated on three examples. First example, a DFT-based study of interaction of cisplatin with glycine, demonstrates the grand canonical character of the potential, which is manifested by the fact that Delta GA(0) energy is not dependent on a concrete form of molecules (protonated or deprotonated) used for energy evaluation. This independence on concrete molecular form strongly contradicts to the standard quantum-mechanical approach where only a single protonation state is used to represent each molecule. Second example, the reaction of hydroxo form of cisplatin with methionine which exhibits quite interesting pH dependency, demonstrates that it is possible to predict metal coordination sites of the amino acid based on proton (hydronium) concentration in solution: in neutral environment the metal binds to thio-group, in basic solutions to amino-group of the amino acid, and in acidic solutions to carboxyl group. This prediction is in the remarkable agreement with the pH-dependent migration of the coordination site observed experimentally in Reedijk laboratory. The final example is the combination of the approach with QM/MM MD simulations of the interaction of (hydrated) mercury cation with thymine. In this reaction, Delta GA(0) changes from endergonic to exergonic when the pH passes from acidic to basic values. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

This article highlights the importance of performing additional Legendre transformations in a constant pH environment for a correct thermodynamic description of reactions. The power of the new thermodynamic potential (ΔGA(0)) is demonstrated through three examples, showing its grand canonical character and pH dependency. The combination of this approach with QM/MM MD simulations also reveals interesting changes in energy values based on pH shifts.