Does DFT-D estimate accurate energies for the binding of ligands to metal complexes?

Abstract

We have studied the homolytic dissociation of a methyl radical from a model of methyl cobalamin. For this reaction, density functional theory with an atom-pairwise dispersion correction (DFT-D) gives a dispersion contribution to the bond dissociation energy (BDE) of 22-51 kJ/mol depending on the functional, i.e. much more than common estimates for the total dispersion interaction energy of the methyl group in typical solvents. We show that this large energy correction results from many rather small (0-2 kJ/mol) interactions that arise between the ligand and the metal and the other ligands when a short metal-ligand bond is formed. The energy terms result mostly from atom pairs connected by two or three bonds, i.e. terms that normally are ignored or scaled down at the molecular mechanics level, and have large contributions from r -8terms. The added dispersion energy diminishes the variation in the calculated BDE observed among various generalised-gradient approximation functionals, whereas a gap still persists to the results of hybrid functionals. Model calculations at the local MP2 and CCSD (second-order perturbation theory and coupled cluster theory with single and double excitations) levels are in agreement with the dispersion interactions estimated by DFT-D (23-29 kJ/mol). However, both the DFT-D and the wavefunction-based results include middle-range correlation effects that vary much among different DFT methods owing to their different density-based description also in the short-range regime. Therefore, it is not meaningful to discuss which DFT method gives the most accurate estimate of the dispersion contribution to the BDE. Moreover, for a balanced treatment of dispersion during the binding reaction in solution, the dispersion energy of the ligand and the unbound complex with the surroundings needs also to be considered, which decreases the net dispersion contribution to binding by ~20 kJ/mol.

Free-energy perturbation and quantum mechanical study of SAMPL4 octa-acid host–guest binding energies

“…Figure S2. Apparently, DFT-D2 overestimates dispersion effects, as has also been observed before [93].…”

Large Density-Functional and Basis-Set Effects for the DMSO Reductase Catalyzed Oxo-Transfer Reaction

“…that the enzyme active-site cavity does not change during the reaction and is not solvated before the substrate binds. 36 This seems to be a reasonable assumption, considering that the crystal structures of DMSOR show that the active site is buried in the enzyme. 5 From Table 2, it can be seen that the presence of a pre-formed cavity in the enzyme is predicted to give non-polar energies that favor the TS1, IM and TS2 states by 38 kJ/mol.…”

“…35 These calculations used the UAKS radii (united atom topological model for Kohn-Sham theory) 34 and they are needed to obtain valid solvation energies for all reactants, as well as a balance in the dispersion energy terms for reactions in which a ligand from solution binds to or dissociates from a metal complex. 36 Single-point energy calculations were also performed with the def2-QZVPP (QZP) basis set. 44 In order to further refine the energetics of the reaction pathway, single-point calculations with local correlation methods were performed on the optimized structures.…”

Perspective: Found in translation: Quantum chemical tools for grasping non-covalent interactions

“…Thus, the "correction term" may not only comprise the actual dispersion contribution but also include a portion of the correlation energy that was not captured by the original functional. 54 In fact, the energetic contribution to the "dispersion correction" is better used to gauge the inadequacy of the original functional than to measure any physical interaction (see Box 2). This is because such corrections were originally developed to cure the inability of DFT to describe long-range interactions that, in regions of overlapping electron density, are generally treated directly by the exchange-correlation functional.…”