Evaluation of DFT Methods and Implicit Solvation Models for Anion‐Binding Host‐Guest Systems

Abstract

Although supramolecular chemistry is traditionally an experimental discipline, computations have emerged as important tools for the understanding of supramolecules. We have explored how well commonly used density functional theory quantum mechanics and polarizable continuum solvation models can calculate binding affinities of host‐guest systems. We report the calculation of binding affinities for eight host–guest complexes and compare our results to experimentally measured binding free energies that span the range from −2.3 to −6.1 kcal mol−1. These systems consist of four hosts (biotin[6]uril, triphenoxymethane, cryptand, and bis‐thiourea) with different halide ions (F−, Cl−, Br−) in various media including organic and aqueous. The mean average deviation (MAD) of calculated from measured ΔGa is 2.5 kcal mol−1 when using B3LYP‐D3 with either CPCM or PCM. This MAD value lowers even more by eliminating two outliers: 1.1 kcal mol−1 for CPCM and 1.2 kcal mol−1 for PCM. The best DFT and implicit solvation model combination that we have studied is B3LYP−D3 with either CPCM or PCM.

The Interplay of Weakly Coordinating Anions and the Mechanical Bond: A Systematic Study of the Explicit Influence of Counterions on the Properties of (Pseudo)rotaxanes

“…This notable difference underlines the importance of regarding explicit counterion effects in calculations. Larger uncertainties are frequently encountered for charged molecular systems in solution [ 54 , 59 , 60 ].…”

“…Results for the pseudorotaxane and (hypothetical) rotaxane formation without counterions and with Cl were compared to calculations, where was obtained in vacuo, and we additionally computed instead, using the COSMO-RS approach [ 58 ] with its fine parametrisation utilising the Cosmotherm programme [ 73 ]. Resulting Gibbs free association energies when no counterions were present are quite off, which is not surprising, as COSMO-RS may yield unreasonable results if charged species are evaluated [ 54 , 59 , 60 ]. On the other hand, results for the Cl complexes agreed very well, with deviations below 3 kJ/mol.…”

Better performance of Hartree–Fock over DFT: a quantum mechanical investigation on pyridinium benzimidazolate types of zwitterions in the light of localization/delocalization issues

“…Associated to delocalization problem, self-interaction error associated with DFT is discussed in a recent work of Lee et al [ 71 ]. They discussed about the difference in properties predicted by DFT and HF method for anions.…”

“…They discussed about the difference in properties predicted by DFT and HF method for anions. They even suggested that HF theory can be a naive solution to address the problem, shown by DFT methods in predicting the frontier molecular orbital energies and other related properties of anionic systems [ 71 ]. As the systems considered here are zwitterionic natures (with the donor part anionic in nature), hence underperformance of DFT compared to HF may also be addressed as explained by Lee et al [ 71 ].…”

Accurate Quantum Chemical Prediction of Gas-Phase Anion Binding Affinities and Their Structure-Binding Relationships

“…In this context, several groups have developed large datasets of benchmark ionic interaction energies and used these datasets to evaluate the performance of contemporary wavefunction, DFT, and semiempirical methods. , The Houk group has also evaluated DFT methods in conjunction with implicit solvation models to predict the anion binding free energies of eight host–guest complexes in aqueous and organic solvents. The mean absolute deviation in computed binding free energy is 10.5 kJ mol –1 when the B3LYP-D3 functional is used with the conductor-like polarizable continuum model or polarizable continuum model implicit solvent model . However, to evaluate a binding constant to within an order of magnitude of experiment, the error in the computed binding free energy must be smaller than 5.7 kJ mol –1 at 298 K. In quantum chemistry, this error margin is usually referred to as “chemical accuracy”.…”