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

Herein we report the experimental observation (X-ray characterization) of two different binding modes in H-bonded anion-anion complexes (anion = citrate) in N-(1-(2-phenylethyl)-4-piperidinylium)-N-phenyl-propanamide-citrate (fentanyl citrate). High level DFT calculations indicate that both types of anion-anion complexes (one with two and the other with four H-bonds) are thermodynamically unstable but kinetically stable with respect to the isolated anions with activation barriers as high as 14 kcal mol(-1).