Salt Effects on Caffeine across Concentration Regimes.

Area of Science:

• Physical Chemistry
• Biophysical Chemistry

Background:

• Salts impact molecular solvation, as demonstrated by the Hofmeister series, influencing protein salting-in/salting-out.
• Solvation is linked to solvent accessible surface area (SASA), with proportionality constants varying by salt concentration and type.

Purpose of the Study:

• To investigate the molecular driving forces behind tertiary solutions with changing solute and osmolyte concentrations.
• To develop and validate a new theoretical framework for describing salt effects on molecular solvation.

Main Methods:

• Multiscale computer simulations (e.g., Monte Carlo) were employed.
• Vapor-pressure osmometry was used to study caffeine-salt solutions.
• A novel potential energy function dependent on instantaneous surface area, salt type, and concentration was developed.

Main Results:

• The solvent accessible surface area (SASA) description effectively captures molecular driving forces in complex solutions.
• The new potential energy function enables efficient exploration of many-body interactions.
• Thermodynamic properties at elevated solute and salt concentrations were accurately predicted.

Conclusions:

• The SASA model provides a robust framework for understanding salt effects on molecular solvation.
• The developed computational approach allows for accurate thermodynamic predictions in complex solutions.
• This work advances the understanding of solute-osmolyte interactions and their thermodynamic consequences.