Evaluating interaction energy versus electron density relationships to estimate inter and intramolecular H-bonding

We investigate the computational effects on the relationships between interaction energy (ΔE) and electron density (ρ), at the critical point obtained from 19 intermolecular H-bonded dimers, to estimate inter and intramolecular interactions of larger H-bonded systems. Our analysis examines basis set superposition error (BSSE) effects, dispersion energy corrections, and the exchange-correlation energy model on the ΔE vs. ρ linear regressions. The calculations were carried out within density functional theory (DFT) combined with the 6-31+G(d,p) and def2-TZVPP basis sets. This procedure quantifies the average effects of BSSE for different levels of approximation, and underscore the sensitivity of the ΔE estimation together with dispersion corrections. This is valuable for the development of DFT-based estimators of multiple interaction energies of large H-bonded systems with low computational cost. We have applied this procedure by analyzing H-bonded biological molecules, such as DNA base pairs, an asparagine side chain, and an AZT molecule. Our estimated H-bond interaction energies are in agreement with previous studies, and emphasize the importance of methodological considerations for accurately predicting interaction energies using DFT combined with topological parameters. [Display omitted] •Dispersion correction improves accuracy in H-bond energy estimations.•B3LYP-D3(BJ) is less affected by BSSE than BP86-D3(BJ).•ΔE vs. ρ H-bond correlations models validated for DNA and biological H-bonded systems.