On the atomic structure of cocaine in solution

Area of Science:

• Neuroscience
• Physical Chemistry
• Pharmacology

Background:

• Cocaine is an amphiphilic drug known for its ability to cross the blood-brain barrier (BBB).
• Understanding the molecular interactions of cocaine at the BBB is crucial for explaining its neurological effects.

Purpose of the Study:

• To investigate the atomic-scale structure and hydration of cocaine in aqueous solutions.
• To elucidate the mechanism by which cocaine crosses the hydrophobic blood-brain barrier.

Main Methods:

• Neutron diffraction was employed to study cocaine's structure in solution.
• Computational methods were used in conjunction with experimental data.

Main Results:

• Cocaine's conformation and hydration facilitate BBB crossing by shielding hydrophilic regions.
• Cocaine forms approximately 5 bonds with water molecules, with localized water in internal cavities.
• Water-mediated internal hydrogen bonding suggests a novel interaction mechanism with the BBB.

Conclusions:

• Cocaine's structure and hydration enable it to interact with the BBB without prior deprotonation.
• Solution-state structural studies are vital for understanding the biological functions of neurologically active molecules.