Solvation and aggregation of heteroaromatic drugs in the Reline deep eutectic solvent - a combined molecular dynamics...

Area of Science:

• Physical Chemistry
• Computational Chemistry
• Materials Science

Background:

• Deep eutectic solvents (DES) are promising for drug delivery.
• Understanding drug-solvent and drug-drug interactions in DES is crucial for formulation.
• Heteroaromatic drugs like allopurinol, losartan, and omeprazole present unique interaction profiles.

Purpose of the Study:

• To investigate the molecular interactions and aggregation behavior of allopurinol, losartan, and omeprazole in a choline chloride/urea DES.
• To elucidate the roles of hydrogen bonding and π-stacking in drug aggregation within the DES.
• To provide insights for designing optimized DES formulations for drug delivery.

Main Methods:

• Molecular dynamics (MD) simulations were employed to study dynamic interactions.
• Density functional theory (DFT) analyses were used to evaluate drug-drug interactions and binding energies.
• Combined angular/radial distribution functions and natural bond orbital theory were utilized.

Main Results:

• Drug addition decreased DES conductivity and diffusion coefficients.
• Allopurinol, the smallest drug, had a more pronounced effect on DES structure and formed smaller aggregates compared to losartan and omeprazole.
• DFT revealed π-stacking interactions stabilize drug dimers, with varying energies and interplanar distances.

Conclusions:

• Drug aggregation in DES is influenced by drug size and intermolecular forces, particularly π-stacking.
• The study provides a molecular-level understanding of drug behavior in DES.
• Findings can guide the rational design of DES for enhanced drug delivery applications.