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

• DOI: 10.1021/acs.jpcb.5b12333
• Publication Date: 2016-02-04T12:59:58Z
• Authors: Brian P. Mayer; Daniel J. Kennedy; Edmond Y. Lau; Carlos A. Valdez
• Keywords: Moiety; Amide; Affinities; Molecular model; Chemical shift

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