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well-resolved, the aromatic protons of 7 shifted strongly and
became poorly resolved in comparison to 9. The overall much
larger upfield shifts in 7 are consistent with the off-stacked
configuration of the aromatics. Note that intermolecular
aggregation was already ruled out at much higher concen-
trations by the UV−vis spectroscopy (Figure 1b).
When more than one hydrophobe exists within the guest
molecule, the intraguest hydrophobic interactions could have a
strong impact on how the guest is bound by its host. Even
when the host−guest interaction is largely hydrophobic in
nature, our work shows that the intraguest interactions could
change the hydrophobic driving force strongly to override the
effect of intrinsic hydrophobicity. As a result, the most
hydrophobic guest may not bind most strongly in water and
could even become the weakest binder as shown by our binding
data. For the same reason, the binding affinity of multi-
hydrophobed compounds could not simply be extrapolated
from that of the single-hydrophobed ones, as the intraguest
interactions may differ from case to case. These phenomena are
not expected to be limited to aromatic hydrophobes whose
interactions have strong geometrical preferences. It is possible
that, when the hydrophobes are scattered on a semirigid
backbone (e.g., peptide), the intraguest interactions face
constraints set by the covalent framework and could also
influence their hydrophobic binding.
ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge on the
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(16) If this indeed were the case, the repulsion between the two
aromatic rings in compound 5 might not be enough to overcome the
hydrophobic interactions, as compound 5 displayed a different
energetic profile.
Experimental details, ITC titration curves, and NMR data
AUTHOR INFORMATION
■
Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the NSF (CHE-1708526 and DMR-1464927) for
financial support of this research.
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