Acidity constants from vertical energy gaps: density functional theory based molecular dynamics implementation.

Area of Science:

• Computational Chemistry
• Physical Chemistry
• Chemical Thermodynamics

Background:

• Accurate computation of acidity constants (pKa) requires treating solvent and solute at the same theoretical level.
• Existing methods face challenges, particularly under extreme pH conditions.

Purpose of the Study:

• To develop and validate a novel computational method for calculating pKa values.
• To enable accurate pKa predictions by integrating solvent and solute treatment within a unified theoretical framework.

Main Methods:

• Implementation of a density functional theory (DFT) based molecular dynamics approach.
• Utilizing a half-reaction scheme to compute free energies of dissociation via vertical energy gaps.
• Accounting for and mitigating finite system size effects through combined half-reactions.

Main Results:

• The developed method accurately predicts pKa values for a diverse set of organic and inorganic acids and bases.
• Observed asymmetric solvent response to protonation/deprotonation, correlated with hydrogen bonding strength.
• Validation across a broad spectrum of pKa values (20 units).

Conclusions:

• The new DFT-based molecular dynamics method provides a robust tool for pKa calculations.
• The findings offer insights into solvent behavior during proton transfer processes.
• The method is applicable to various chemical systems, including those at high or low pH.