We propose that due to the smaller cavity of 3a, none of the
fluorinated substituents reaches into the cavity. Accordingly,
Hm shows only a small upfield shift.
Finally, we measured the interaction of the fluorinated anti-
inflammatory drug diflunisal (20,40-difluoro-4-hydroxy-
biphenyl-3-carboxylic acid) with cyclodextrins 3b and 3c. It
was found by ITC that diflunisal binds to 3b in a 1 : 1 complex
with Ka = 2.15 ꢂ 103 Mꢁ1 and DH = ꢁ10.7 kJ molꢁ1 and
to 3c in a 2 : 1 complex with Ka = 1.46 ꢂ 103 Mꢁ1 and
DH = ꢁ8.5 kJ molꢁ1
.
We conclude that the fluorophobic effect can contribute
significantly to the stability of cyclodextrin host–guest
complexes in water and we anticipate that the water-soluble
fluorinated cyclodextrins described in this communication
may be of particular use for the selective solubilization of
fluorinated compounds.
Fig. 3 Job’s plot based on the 19F-NMR titration of cyclodextrin 3b
with p-trifluoromethylphenol.
Notes and references
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4
1H-NMR titration of cyclodextrin 3b with p-trifluoro-
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in Table 1. According to a 1 : 1 fit, the binding constant
Ka = 2.06 ꢂ 103 Mꢁ1, which is also consistent with the ITC data.
1H-NMR spectra for the complexation of cyclodextrin 3b
and p-trifluoromethylphenol (Fig. 4) show the expected down-
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hydroxyl group. Just like the trifluoromethyl group, Ho is
deshielded by the less polar surrounding of the cyclodextrin
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proximity to the trifluoroethyl group of the host.
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ꢀc
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 4369–4371 | 4371