The surface site interaction point approach to non-covalent interactions

Area of Science:

• Chemistry
• Biochemistry
• Materials Science

Background:

• Molecular system properties depend on numerous weak non-covalent interactions.
• Predicting these interactions is crucial for understanding structure-function relationships.

Purpose of the Study:

• To review the Surface Site Interaction Point (SSIP) approach for modeling non-covalent interactions.
• To highlight both empirical and computational methods for deriving SSIP parameters.
• To demonstrate the application of SSIPs in predicting thermodynamic properties of molecular ensembles.

Main Methods:

• Utilizes empirical non-covalent interaction parameters (α and β) for functional group interactions.
• Employs ab initio calculation of the Molecular Electrostatic Potential (MEP) surface to derive SSIPs.
• Applies the SSIMPLE algorithm to calculate intermolecular interaction speciation and predict thermodynamic properties.

Main Results:

• SSIPs provide a quantitative understanding of solvent effects in solution-phase equilibria.
• The approach accurately describes non-covalent interactions at macroscopic interfaces and in the solid state.
• SSIPs enable accurate predictions of partition coefficients, association constants, and cocrystal formation probability.

Conclusions:

• The SSIP approach offers a simple, intuitive, and accurate method for predicting molecular system properties.
• It effectively links chemical structure to non-covalent interactions without requiring computationally intensive simulations.
• SSIPs are valuable for understanding and predicting the behavior of complex molecular ensembles.