Efficient Calculation of Microscopic Dissolution Rate Constants: The Aspirin-Water Interface

Area of Science:

• Computational chemistry
• Materials science
• Chemical physics

Background:

• Crystal dissolution is crucial in many chemical and pharmaceutical processes.
• Determining dissolution rates at the molecular level is computationally challenging.
• Understanding dissolution mechanisms requires advanced simulation techniques.

Purpose of the Study:

• To present an efficient molecular simulation approach for quantifying rare dissolution events from organic crystals.
• To utilize advanced simulation methods to overcome computational barriers in studying dissolution.
• To elucidate the atomic-scale mechanisms governing crystal dissolution.

Main Methods:

• Employing molecular dynamics simulations.
• Utilizing metadynamics to generate a bias potential for accelerating rare events.
• Implementing hyperdynamics simulations to enhance sampling of dissolution events.
• Applying the method to kink site dissolution at the aspirin(001)/water interface.

Main Results:

• Demonstrated an efficient method for calculating quantitative rate constants of rare dissolution events.
• Successfully accelerated the escape from bound states using a tailored bias potential.
• Validated the technique's robustness and acceleration capabilities through application to aspirin crystal dissolution.
• Provided insights into the atomic-scale mechanisms of crystal dissolution at an interface.

Conclusions:

• The presented molecular simulation approach is effective for studying rare dissolution events.
• Metadynamics combined with hyperdynamics offers a powerful tool for investigating crystal dissolution mechanisms.
• This technique can be broadly applied to understand dissolution processes in various organic crystalline systems.