Effects of dilute aqueous NaCl solution on caffeine aggregation

Area of Science:

• Physical Chemistry
• Computational Chemistry
• Biophysical Chemistry

Background:

• Caffeine is a widely consumed stimulant with complex solution behavior.
• Understanding caffeine's interactions in aqueous solutions is crucial for pharmacology and food science.
• The influence of salts on molecular association in biological systems is an active area of research.

Purpose of the Study:

• To investigate the impact of sodium chloride (NaCl) concentration on the self-association properties of caffeine molecules.
• To elucidate the structural and dynamic changes in caffeine-water-salt systems using molecular dynamics simulations.
• To quantify the effects of salt on caffeine clustering, hydrogen bonding, and water structure.

Main Methods:

• Molecular dynamics (MD) simulations were performed in the isothermal-isobaric (NPT) ensemble.
• Simulations included eight caffeine molecules in pure water and at three different NaCl concentrations.
• Analysis involved radial distribution functions, solvent accessible surface area, cluster analysis, and hydrogen bond analysis.

Main Results:

• Increasing NaCl concentration enhanced caffeine-caffeine association, indicated by changes in the radial distribution function.
• Salt addition promoted the formation of higher-order caffeine clusters and reduced solvent accessible surface area.
• A modest decrease in water-caffeine hydrogen bonds and alterations in water structure (second shell collapse) were observed.
• Salt ion pair formation decreased, and hydrophobic sites of caffeine experienced dehydration.

Conclusions:

• Salt concentration significantly influences caffeine's self-association in aqueous solutions.
• NaCl promotes caffeine clustering by altering solvent structure and reducing hydration of caffeine.
• These findings provide insights into the behavior of caffeine and other molecules in saline biological environments.