Solvation Free Energies of Ion Dissociations in Dichloromethane: En Route to Accurate Computations.

Area of Science:

• Computational Chemistry
• Physical Chemistry
• Supramolecular Chemistry

Background:

• Implicit solvent models fail to accurately predict dissociation free energies of proton-bound pyridine dimers in organic solvents.
• Previous studies highlighted significant discrepancies between quantum mechanical calculations and experimental trends.

Purpose of the Study:

• To investigate computational methods for accurately calculating dissociation free energies (ΔGdiss) of proton-bound pyridine dimers.
• To determine the necessary computational approaches for reproducing experimental trends and magnitudes in solvent.

Main Methods:

• Computational study of proton-bound pyridine dimer dissociation in gas phase and dichloromethane (DCM).
• Investigated ensemble free energy, umbrella sampling, thermodynamic integration, and explicit solvation.
• Employed semiempirical quantum mechanics (SE) for conformational free energy and molecular dynamics (MD) with molecular mechanics (MM) for explicit solvation and solvent configurational entropy.

Main Results:

• Explicit solvation using molecular mechanics (MM) successfully reproduced experimental dissociation free energies in DCM within an acceptable error margin.
• The study identified prerequisites for accurate free energy calculations in solution.
• Analysis of solvation free energy calculation limitations was performed.

Conclusions:

• Explicit solvation with MM is a viable method for accurately calculating dissociation free energies of proton-bound pyridine dimers in DCM.
• This approach overcomes the limitations of implicit solvent models for this class of compounds.
• Further analysis and discussion on the limitations of the solvation free energy calculation approach are provided.