Solv-ccCA: Implicit Solvation and the Correlation Consistent Composite Approach for the Determination of pKa

Area of Science:

• Computational chemistry
• Physical chemistry

Background:

• Direct theoretical methods offer advantages over relative methods for pKa prediction.
• Relative methods are limited by the need for experimental values of reference acid molecules.

Purpose of the Study:

• To introduce a direct theoretical route for pKa prediction.
• To incorporate the SMD universal solvation model within the correlation consistent Composite Approach (ccCA).

Main Methods:

• The developed Solv-ccCA methodology was employed.
• A thermodynamic cycle combining gas-phase and solution-phase calculations was utilized.
• Several density functionals were evaluated for use with the SMD model.

Main Results:

• The Solv-ccCA methodology achieved a mean absolute deviation (MAD) of 1.0 pKa unit for nitrogen-containing species.
• Accurate theoretical pKa values were predicted.
• The performance of various density functionals with the SMD model was assessed.

Conclusions:

• The Solv-ccCA method provides a reliable and direct route for theoretical pKa prediction.
• This methodology expands the applicability of theoretical calculations to diverse chemical systems.
• The study validates the effectiveness of combining solvation models with composite approaches for accurate pKa determination.