An atomic surface site interaction point description of non-covalent interactions

Area of Science:

• Computational chemistry
• Molecular modeling
• Physical organic chemistry

Background:

• Molecular electrostatic potential surfaces (MEPS) offer insights into non-covalent interactions.
• Previous models like SSIP provided a foundation for representing molecular interactions.
• Accurate parameterization of interaction sites is crucial for predictive molecular modeling.

Purpose of the Study:

• To introduce and validate the Atomic Interaction Point (AIP) model for describing non-covalent interactions in organic molecules.
• To develop a simplified yet accurate method for calculating molecular interaction properties.
• To enable direct implementation of interaction parameters in solvation free energy calculations.

Main Methods:

• Utilized density functional theory (DFT) to calculate MEPS.
• Defined interaction sites (AIPs) based on MEPS extrema and molecular orbitals.
• Employed high and low electron density MEPS to characterize polar and non-polar sites, respectively.
• Validated the AIP model by predicting solvation free energies using the SSIMPLE model.

Main Results:

• The AIP model accurately identifies polar (s-holes, H-bond donors/acceptors) and non-polar (π-systems, halogens) interaction sites.
• Predicted free energy of transfer for 1504 compounds from n-hexadecane to water with a root mean square error of 5 kJ mol⁻¹.
• Demonstrated the utility of AIPs in mapping and quantifying non-covalent interactions in intermolecular complexes using X-ray crystal structures.

Conclusions:

• The AIP model provides a robust and simplified representation of molecular non-covalent interactions.
• AIPs facilitate accurate prediction of solvation free energies and analysis of complex stability.
• This approach enhances the understanding and quantification of intermolecular forces in chemical systems.