Solution-State Structure and Affinities of Cyclodextrin: Fentanyl Complexes by Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Simulation

Brian P. Mayer, Daniel J. Kennedy, Edmond Y Lau, Carlos A. Valdez

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Cyclodextrins (CDs) are investigated for their ability to form inclusion complexes with the analgesic fentanyl and three similar molecules: acetylfentanyl, thiofentanyl, and acetylthiofentanyl. Stoichiometry, binding strength, and complex structure are revealed through nuclear magnetic resonance (NMR) techniques and discussed in terms of molecular dynamics (MD) simulations. It was found that β-cyclodextrin is generally capable of forming the strongest complexes with the fentanyl panel. Two-dimensional NMR data and computational chemical calculations are used to derive solution-state structures of the complexes. Binding of the fentanyls to the CDs occurs at the amide phenyl ring, leaving the majority of the molecule solvated by water, an observation common to all four fentanyls. This finding suggests a universal binding behavior, as the vast majority of previously synthesized fentanyl analogues contain this structural moiety. This baseline study serves as the most complete work on CD:fentanyl complexes to date and provides the insights into strategies for producing future generations of designer cyclodextrins capable of stronger and more selective complexation of fentanyl and its analogues.

Original languageEnglish (US)
Pages (from-to)2423-2433
Number of pages11
JournalJournal of Physical Chemistry B
Volume120
Issue number9
DOIs
StatePublished - Mar 17 2016
Externally publishedYes

Fingerprint

Cyclodextrins
magnetic resonance spectroscopy
Fentanyl
Nuclear magnetic resonance spectroscopy
affinity
Molecular dynamics
molecular dynamics
nuclear magnetic resonance
Computer simulation
analogs
simulation
amides
Nuclear magnetic resonance
molecules
stoichiometry
Molecules
inclusions
Complexation
Amides
Stoichiometry

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Surfaces, Coatings and Films

Cite this

Solution-State Structure and Affinities of Cyclodextrin : Fentanyl Complexes by Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Simulation. / Mayer, Brian P.; Kennedy, Daniel J.; Lau, Edmond Y; Valdez, Carlos A.

In: Journal of Physical Chemistry B, Vol. 120, No. 9, 17.03.2016, p. 2423-2433.

Research output: Contribution to journalArticle

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