Chemical reaction mechanisms in solution from brute force computational Arrhenius plots

Area of Science:

• Computational chemistry
• Chemical kinetics
• Biochemical reaction mechanisms

Background:

• Decomposing activation free energies into enthalpic and entropic components reveals reaction mechanisms.
• Estimating entropy for condensed-phase reactions is computationally challenging due to numerous degrees of freedom.

Purpose of the Study:

• To demonstrate direct computer simulations of temperature-dependent free energy profiles for accurate thermodynamic activation parameter extraction.
• To validate the use of empirical valence bond (EVB) models for chemical reaction simulations.
• To analyze the hydrolytic deamination of cytidine and dihydrocytidine in water.

Main Methods:

• Utilizing empirical valence bond (EVB) models for computer simulations.
• Simulating the temperature dependence of free energy profiles.
• Extracting thermodynamic activation parameters (enthalpy and entropy).

Main Results:

• Direct computer simulations accurately yielded thermodynamic activation parameters for hydrolytic deamination reactions.
• The simulation energetics were insensitive to calibration by quantum mechanics or experimental data.
• Results agreed remarkably well with experimental data.

Conclusions:

• Computer simulations provide accurate thermodynamic activation parameters, aiding in mechanistic pathway elucidation.
• The method allows discrimination between alternative reaction mechanisms.
• It rationalizes differences in activation enthalpies and entropies for various pathways.