H-Bonded anion-anion complexes in fentanyl citrate polymorphs and solvates

Area of Science:

• Supramolecular Chemistry
• Computational Chemistry
• Crystallography

Background:

• Anion-anion interactions are crucial in crystal engineering and drug design.
• Fentanyl citrate is a widely used pharmaceutical agent.

Purpose of the Study:

• To experimentally and computationally investigate the binding modes of citrate anions in fentanyl citrate.
• To understand the thermodynamic and kinetic stability of these H-bonded anion-anion complexes.

Main Methods:

• X-ray characterization to determine experimental binding modes.
• High-level Density Functional Theory (DFT) calculations to assess stability and energy barriers.

Main Results:

• Observed two distinct H-bonded anion-anion complex structures involving citrate anions.
• DFT calculations revealed thermodynamic instability but kinetic stability for these complexes.
• Identified activation barriers up to 14 kcal mol⁻¹ for the complexes.

Conclusions:

• Fentanyl citrate forms complex H-bonded networks with citrate anions.
• The kinetic stability of these complexes is significant, despite their thermodynamic instability.
• Understanding these interactions is vital for pharmaceutical formulation and drug delivery.