3 7 0
H.
The large shielding effects can be rationalized by considering inclusion of the aromatic ring into the
internal cavity. This phenomenon is indeed expected to induce shielding ring currents and to enhance the
inequivalence due to substitution. This assumption is further supported by the chemical shifts of protons
the phenyl ring of the amino-acid. The corresponding signals are indeed deshielded relative to free
phenylalanine as encountered for the inclusion of the free amino-acid in
This deshielding
effect is due to a strong modification of the polarity experienced by the phenyl ring upon inclusion in the
relatively hydrophobic cavity of the cyclodexttin.
At this point, one must make a clear distinction between inter- and intramolecular complexes. NMR
provides evidences for the reality of the latter situation leading to a model where the modified
heptaose includes its own aromatic ring in the hydrophobic cavity. This is indeed supported by the fact that the
NMR spectra of both compounds in deuterium oxide are not affected by concentration in the l-20
range.
In the case of intermolecular inclusion complexes, a large concentration dependence is expected owing to the
generally weak association constants involved in these processes In the present case, additional interactions
have to be considered (i.e. intramolecular hydrogen bonds) to account for the unexpected stability of these
inclusion complexes. New ultra-high resolution bidimensional NMR experiments dedicated to an accurate
sequential determination of chemical shifts and coupling constants for all protons are currently being
undertaken and will be described elsewhere. Preliminary data has already shown that several torsional angles
derived from the coupling constants are unusual and fully support the presence of intramolecular complexes.
These molecules are hence of considerable interest as they provide pure inclusion complexes in solution. A
complete NMR analysis and the subsequent modelling of ring current effects and coupling constants is
expected to provide, in conjunction with molecular graphics analysis, the first example of three-dimensional
determination in these series and a better understanding of molecular adaptation phenomena involved
in inclusion processes.
References
1. (a) Armstrong, D.W. Liq. Chromarogr.
(b) Toda, F. Topics in Current
Springer Verlag, Berlin.
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A.D.
Res. Chem.
3. Tanaka, Y.; Sakuraba, H.; Nakanishi, H. J. Org. Chem.
4. Warsh, D.; Vbgtle, F. Topics in Current Chemistry
Springer Verlag, Berlin.
5. Boland, W.;
6. Murakama, T.; Harata, K.; Morimoto, S. Chem.
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W.A.; Krebber, R.;
D.G. Helv. Chim.
1979, 72, 1288-1292
H.; Miocque, M. Tetrahedron
8.
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Trans. II 1987, 1323-1336
in press.