Axial-equatorial equilibrium in substituted cyclohexanes: a DFT perspective on a small but complex problem.

Area of Science:

• Chemistry
• Computational Chemistry
• Quantum Chemistry

Background:

• Modeling chemical systems requires accurately capturing complex interactions.
• Axial-equatorial equilibrium in substituted cyclohexanes exemplifies a simple yet challenging system.
• This equilibrium depends on the balance between London dispersion and steric repulsion.

Purpose of the Study:

• To systematically evaluate the performance of various density-functional approximations (DFAs) for modeling steric interactions.
• To assess the accuracy of 48 exchange-correlation functionals in predicting axial-equatorial equilibrium in 20 mono-substituted cyclohexanes.
• To introduce the SAV20 dataset for benchmarking DFAs on challenging noncovalent interactions.

Main Methods:

• High-accuracy coupled cluster calculations [CCSD(T)] were used as a reference.
• A comprehensive set of 48 DFAs, including semilocal, hybrid, and double hybrid functionals, were tested.
• The SAV20 dataset, comprising 20 mono-substituted cyclohexanes, was utilized for evaluation.

Main Results:

• Common and advanced DFT approaches, including dispersion-corrected methods, showed difficulties in accurately modeling the steric balance.
• The PBE-QIDH/DH-SVPD protocol was identified as a cost-effective option.
• Performance on the SAV20 dataset did not correlate with results from other standard noncovalent interaction benchmarks (S66, IDISP, NC15).

Conclusions:

• The SAV20 dataset presents unique physicochemical challenges not covered by existing benchmarks.
• Accurate modeling of steric interactions in simple systems remains a significant challenge for current DFT functionals.
• Further development of DFAs is needed to reliably predict conformational equilibria governed by subtle energetic balances.