Development of Monopole Interaction Models for Ionic Compounds. Part I: Estimation of Aqueous Henry’s Law Constants for Ions and Gas Phase p K a Values for Acidic Compounds

• Published in: Molecular informatics 2014-02, Vol.33 (2), p.92-103
• Main Authors: Hilal, S. H., Saravanaraj, A. N., Carreira, L. A.
• Format: Article
• Language: English
• ISSN: 1868-1743; 1868-1751
• DOI: 10.1002/minf.201300092

The SPARC (SPARC Performs Automated Reasoning in Chemistry) physicochemical mechanistic models for neutral compounds have been extended to estimate Henry’s Law Constant ( HLC ) for charged species by incorporating ionic electrostatic interaction models. Combinations of absolute aqueous p K a values, relative p K a values in the gas phase, and aqueous HLC for neutral compounds have been used to develop monopole interaction models that quantify the energy differences upon moving an ionic solute molecule from the gas phase to the liquid phase. Inter‐molecular interaction energies were factored into mechanistic contributions of monopoles with polarizability, dipole, H‐bonding, and resonance. The monopole ionic models were validated by a wide range of measured gas phase p K a data for 450 acidic compounds. The RMS deviation error and R 2 for the OH, SH, CO 2 H, CH 3 and NR 2 acidic reaction centers (C) were 16.9 kcal/mol and 0.87, respectively. The calculated HLCs of ions were compared to the HLCs of 142 ions calculated by quantum mechanics. Effects of inter‐molecular interaction of the monopoles with polarizability, dipole, H‐bonding, and resonance on acidity of the solutes in the gas phase are discussed.