Beilstein J. Org. Chem. 2017, 13, 2509–2520.
least for the 2-O- and 3-O-regioisomers, identifies the 1:1 com- ed regioisomers. The difference is easier to explain considering
plexation as the probably dominant associative process.
inclusion complexation of NA-γ-CD rather than interaction of
NA groups only. Consequently, even though no direct evidence
The presence of unimers and/or short oligomers was confirmed for inclusion complexation of NA-γ-CD was obtained it should
by DLS even though objects with corresponding hydrodynamic not be omitted from considerations, especially because the
diameters of a few nm were observed only in solutions of the inclusion complexation of naphthalene derivatives with CDs
2
0
-O- and 3-O-regioisomers after filtration through a filter with (including γ-CD) is so well established [42].
.22 μm pores. Indeed, larger particles with diameter in the
range of tens and hundreds nm dominate the scattering, and The experiments performed clearly demonstrate the supramo-
such large objects of various morphologies were also detected lecular behavior of newly synthesized NA-γ-CDs in solution; at
by cryo-TEM. In this respect, the behavior of NA-γ-CD regio- the same time, the experiments showed the anticipated forma-
objects are also observed [22]. Thus, the supramolecular behav- plexation as a somewhat naive concept – other interactions, e.g.,
ior of NA-γ-CD seems to be determined not only by the interac- naphthalene stacking may occur between two NA-γ-CD mole-
the same type, i.e., NA/NA and γ-CD/γ-CD. In Figure 10 NA-γ-CD molecules may occur, leading to branched supramo-
various putative interactions of NA-γ-CD are schematically lecular structures or aggregation. It is to be hoped that the future
depicted indicating how small supramolecular structures such as research not only reveals details of NA-γ-CD interactions but
supramolecular oligomers or micelles as well as large one such also show how to utilize them in construction of functional
as aggregates can originate.
supramolecular assemblies.
Conclusion
New methods for highly regioselective mononaphthylallylation
of γ-CD to positions 2-O-, 3-O-, and 6-O- were developed. The
alkylation reagent 2-(3-chloroprop-1-enyl)naphthalene, used for
the reactions, can be easily prepared in large quantities without
the need for chromatographic separation. The method origi-
nally expected to be used for the preparation of the regio-
isomers based on the metathesis of allyl-γ-CD derivatives
proved to be inferior, giving about a 6 times lower overall yield
than the mononaphthylallylation procedure. Compared to allyl
derivatives, the NA-γ-CD derivatives are easy to prepare and
purify. Due to the presence of the double bond in the NA group,
they can be used as starting compounds for preparation of other
monosubstituted γ-CD derivatives.
Figure 10: Putative objects and interactions in naphthylallyl-γ-CD solu-
tion, depicted schematically for 6I-O-naphthylallyl-γ-CD (2c). (a) Cyclic
supramolecular dimer based on inclusion complexation. (b) Interac-
tions between naphthyl groups (stacking) leading to micellization or
aggregation. (c) Inclusion complexation of naphthyl into the CD cavity
leading to supramolecular polymerization. (d) Free 2c. (e) Interaction
between CD moieties leading to aggregation or precipitation.
We demonstrated that the supramolecular properties of indi-
vidual NA-γ-CD regioisomers substantially differ. The largest
difference is being observed between 2-O- and 3-O-isomers on
one hand and the 6-O- on the other. To explain the differences
As all three NA-γ-CD regioisomers were prepared, the effect of in the size of objects observed by different methods, various
the substituent position could be assessed. Particularly, differ- types of interactions have to be taken into account.
ent behavior was observed especially between the 2-O-, 3-O-
regioisomers on the one hand and the 6-O-one on the other.
Supporting Information
There are two underlying structural differences: (i) NA groups
face the wider CD side in the head-tail arrangement of 6-O-
Supporting Information File 1
isomers, (ii) the spacer of the 6-O-isomer is elongated by a CH2
group of glucose unit. The details of differences in behavior in
water could not be fully assessed due to the low solubility of the
Experimental part and data for compounds 2a, 2b, and 2c:
6
-O-regioisomer. In fact, the low solubility of the 6-O-regio-
isomer is the most striking difference in behavior of investigat-
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