Gold(I)–N–heterocyclic carbene hydration process; <i>ab initio</i>, DFT, and QM/MM molecular dynamics study

This study investigates the hydration reaction of a gold(I)-N-heterocyclic carbene [Au(I)-NHC] complex at both the quantum mechanical (QM) level and combined Quantum Mechanics/Molecular Mechanics (QM/MM) MD simulations. The main goals are to analyze the differences between implicit (PCM) and explicit solvation models and to compare the advantages and disadvantages of both approaches. Regarding the QM part, the B97D3 and B3PW91 functionals are combined with double-zeta basis sets and the C-PCM/UFF implicit solvation model and compared with the CCSD(T)/TZP computational level supplemented with the C-PCM (COSMO/Klamt radii) or D-PCM/scaled-UAKS solvation model. In addition, reaction force and reaction electronic flux (REF) analyses are performed along the intrinsic reaction coordinate (IRC) determined at the B3PW91/6-31+G(d)/SDD/C-PCM/UFF computational model for deeper insights into the reaction mechanism. Despite relatively high endergonicity, the TS structure is quite close to the center of the reaction coordinate, contrary to the Hammond principle. In the QM/MM MD part of the study, the B97D3 computational setting from the previous part is used as a QM core, and several different explicit water solvation models are explored in the MM environment. The TIP3P water model is compared with the OPC, POL3, TIP4P, and SPCE ones. Nevertheless, they all lead to very low activation barriers and mild endergonicity. Both ΔGr and ΔGa energies are visibly reduced compared to QM values when PCM models are applied. Since partial charges of water atoms within the QM calculations are visibly smaller than point charges in all the explored force-field water models, a modified TIP3P (with partial charges close to DFT RESP values and a LJ parameter conserving the correct water density) is used. In this manner, the energy profile is closer to QM results (with ΔGa = 8.2 and ΔGr = 6.4 kcal mol-1)-especially to the CCSD(T)/TZP/D-PCM/scaled-UAKS model (ΔGa = 14.6 and ΔGr = 9.1). Nevertheless, the hydration process is predicted to be endoergic in all explored models.