@article{10.1021/acs.jpcb.6c02825,
    author = {Sha, Bowen and Soodan, Akhilesh and Lompe, Kim Maren and Barin, Gokhan and Vlugt, Thijs J. H. and Peristeras, Loukas D. and Moultos, Othonas A.},
    title = {Inclusion Complexation
of Native and Functionalized
α-, β-, and γ-Cyclodextrins
with PFAS: An Experimental and Molecular Simulation Study},
    journal = {The Journal of Physical Chemistry B},
    volume = {130},
    number = {30},
    pages = {7718-7737},
    year = {2026},
    month = {07},
    abstract = {β-Cyclodextrin (β-CD)-based polymers have
shown high
adsorption capacities for removing per- and polyfluoroalkyl substances
(PFAS) from drinking water. PFAS capture by these materials involves
many physical and chemical processes, such as adsorption and inclusion
complexation. Quantifying the underlying host–guest binding
between CDs and PFAS nevertheless remains essential because it governs
the primary inclusion step. Here, we investigated native and linker-modified
CD–PFAS inclusion complexes in aqueous solution using isothermal
titration calorimetry (ITC) and molecular dynamics (MD) simulations
with the attach–pull–release (APR) method. We computed
the Gibbs free energies of binding for α-, β-, and γ-CDs
with seven linear PFAS, including perfluorocarboxylic acids and perfluorosulfonic
acids, and found reasonable agreement with our experimental measurements
and previously reported data. Comparison between implicit and explicit
solvent calculations suggests that the apparently better agreement
of the implicit solvent model for some native monomer complexes is
likely due to error cancellation rather than a more transferable physical
description, whereas explicit solvent is required to capture solvent-related
salt and linker effects. Overall, β-CD exhibited the strongest
binding affinities, whereas α-CD showed negligible affinities
and γ-CD bound PFAS more weakly than β-CD. Hydrogen bonding,
interaction-energy decomposition, and solvent-accessible surface area
showed that host–guest hydrogen bonding cannot uniquely predict
affinities, and that hydrophobic dehydration plays a dominant role
in binding. We further examined how background ion concentration affects
β-CD–PFAS binding and found that explicit solvent simulations
capture a clear salt dependence, with Li/Merz ion parameters describing
the high-salinity trend more reasonably than the Joung–Cheatham
model. To mimic the local microenvironment surrounding CD units in
polymers, we also examined three linker-modified β-CD models
containing phenyl groups. Bind3P water correctly reproduced the experimentally
reported enhancement of PFAS adsorption with increasing linker number,
and energy decomposition showed that linker groups strengthen PFAS
binding by enhancing local hydrophobic confinement and specific linker–guest
interactions. Overall, this combined experimental and computational
study provides molecular-level insight into the building blocks of
cyclodextrin polymers and lays the groundwork for future in silico
construction of CD polymer models for PFAS adsorption under diverse
water-matrix conditions.},
    issn = {1520-6106},
    doi = {10.1021/acs.jpcb.6c02825},
    url = {https://doi.org/10.1021/acs.jpcb.6c02825},
    eprint = {https://pubs.acs.org/jpcbfk/article-pdf/130/30/7718/66021067/acs.jpcb.6c02825.pdf},
}