J . Org. Chem. 1999, 64, 6217-6226
6217
NMR Detection of Sim u lta n eou s F or m a tion of [2]-
a n d [3]P seu d or ota xa n es in Aqu eou s Solu tion betw een
r-Cyclod extr in a n d Lin ea r Alip h a tic r,ω-Am in o a cid s,
a n r,ω-Dia m in e a n d a n r,ω-Dia cid of Sim ila r Len gth , a n d
Com p a r ison w ith th e Solid -Sta te Str u ctu r es
Kyriaki Eliadou, Konstantina Yannakopoulou,* Aliki Rontoyianni, and Irene M. Mavridis
Institute of Physical Chemistry, National Center for Scientific Research “Demokritos”,
Ag. Paraskevi 15310, Athens, Greece
Received J anuary 4, 1999
The interactions of 11-aminoundecanoic acid (1), 12-aminododecanoic acid (2), 1,12-diaminododecane
(3), and 1,13-tridecanoic diacid (4) with R-cyclodextrin (RCD) were studied in aqueous solution by
NMR spectroscopy. The association modes were established with titration and continuous variation
plots, variable temperature NMR spectra, and dipolar interactions as recorded in 2D ROESY spectra.
The studies were carried out at pH 7.3 and 13.6. These long, linear bifunctional molecules were
found to form simultaneously [2]- and [3]pseudorotaxanes with RCD in the aqueous solution. At
the higher pH the 1:1 adducts were present at concentrations higher than at the neutral pH. The
longer guests formed complexes enriched in the 2:1 constituent at both pH values. There were
clear indications that the [2]pseudorotaxanes are present in two isomeric forms. The presence of
isomers also in the [3]pseudorotaxanes was not ruled out. Various exchange rate regimes were
observed; clearly in neutral solutions the formation of the 1:1 complexes was fast in the NMR time
scale, whereas the threading of a second RCD ring was a slower process. In the solid state, the
adduct of RCD/2 had the structure of a [3]pseudorotaxane, in accordance with previously solved
crystal structures of RCD/3 and âCD/4. The species in solution, in contrast with those present in
the solid state, are therefore of varying nature, and thus the frequently and conveniently assumed
1:1 stoichiometry in similar systems is an oversimplification of the real situation.
The introduction of linear molecules inside cyclodex-
trins (CDs) has been the subject of investigation in
several laboratories.1-5 Part of the interest arises from
the foreseeable possibility of inducing the arrangement
of the macrocyclic molecules into larger arrays, by either
covalently bonding the guest molecules1 or by utilizing
their known modes of association to achieve further
organization into higher order supramolecular systems2
that could be termed as pseudopolyrotaxanes.3 Guest
molecules with end-functional groups capable of either
reacting or associating are therefore desired. Linear long-
chain molecules bearing terminal amino or carboxylic
functionalities have been popular inserts of mostly RCD,4
to form the corresponding pseudorotaxanes,3 whereupon
suitable stoppering has afforded various cyclodextrin [2]-
rotaxanes, molecules assembled like a wheel and its
axle.2a,b,5 Although solid-state studies have been carried
out regarding polycondensation,1b,c rotaxane isolation,5
and crystal structure characterization,2c little attention
has been paid to the true nature of the species in aqueous
solution prior to crystallization, precipitation, or reaction
to rotaxane products. In this work we investigate in detail
by NMR spectroscopy the interaction of bifunctional
aliphatic molecules, 11-aminoundecanoic acid (1), 12-
aminododecanoic acid (2), 1,12-diaminododecane (3), and
1,13-tridecanoic diacid (4), with RCD (Scheme 1) in
aqueous solution. These are all bifunctional molecules,
bearing end groups capable of hydrogen bonding, and of
length capable of threading in sequence two cyclodextrin
rings. Several reports have appeared in the literature.
The interaction of 1 with RCD has been studied by
microcalorimetry;6 however, structural information could
not be easily extracted from thermodynamic data alone
and therefore 1:1 stoichiometry was assumed for the
system. Polycondensation of RCD/1 as the 2:1 complex
to form a water-soluble pseudorotaxane polyamide1b was
an intriguing result, but the work focused on the solid-
state process, bypassing the behavior of the species in
solution. The threading of diamine 3 into RCD has been
a rather popular project.5a,5c The corresponding [2]rotax-
ane, bearing metalloorganic stoppers, was the first cy-
* Tel: 301-6503962. Fax: 301-6511766. E-mail: dyanna@mail.
demokritos.gr.
(1) (a) Harada, A.; Kamachi, M. Macromolecules 1990, 23, 2821-
2823. (b) Steinbrunn, M. B.; Wenz, G. Angew. Chem., Int. Ed. Engl.
1996, 35, 2139-2141. (c) Wenz, G.; Keller, B. Angew. Chem., Int. Ed.
Engl. 1992, 31, 197-199.
(2) For the general idea, see (a) Amabilino, D. B.; Stoddart, J . F.
Chem. Rev. 1995, 95, 2725-2824. (b) Fyfe, M. C. T.; Stoddart, J . F.
Acc. Chem. Res. 1997, 30, 393-401. (c) Makedonopoulou, S.; Mavridis,
I. M.; Yannakopoulou, K.; Papaioanou, I. J . Chem. Soc., Chem.
Commun. 1998, 2133-2134. (d) Harada, A.; Nishiyama, T.; Kawaguchi,
Y.; Okada, M.; Kamachi, M. Macromolecules 1997, 30, 7115-7118.
(3) (a) Raymo, F. M.; Stoddart, J . F. Trends Polym. Sci. 1996, 4,
208-211. (b) Ashton, P. R.; Philp, D.; Spencer, N.; Stoddart, J . F. J .
Chem. Soc., Chem. Commun. 1991, 1677-1679.
(4) (a) Isnin, R.; Salam, C.; Kaifer, A. E. J . Org. Chem. 1991, 56,
35-41. (b) Harada, A.; Li, J .; Kamachi, M. Macromolecules 1994, 27,
4538-4543. (c) Toki, A.; Yonemura, H.; Matsuo, T. Bull. Chem. Soc.
J pn. 1993, 66, 3382-3386.
(5) (a) Nepogodiev, S. A.; Stoddart, J . F. Chem. Rev. 1998, 98, 1959-
1976. (b) Harada, A.; Li, J .; Kamachi, M. J . Am. Chem. Soc. 1994, 116,
3192-3196. (c) Ogino, H. New J . Chem. 1993, 17, 683-688. (d) Isnin,
R.; Kaifer, A. E. J . Am. Chem. Soc. 1991, 113, 8188-8190. (e) Isnin,
R.; Kaifer, A. E. Pure Appl. Chem. 1993, 65, 495-497. (f) Horsky, J .
Eur. Polym. J . 1998, 34, 591-596.
(6) Castronuovo, G.; Elia, V.; Fessas, D.; Giordano, A.; Velleca, F.
Carbohydr. Res. 1995, 272, 31-39.
10.1021/jo990021f CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/27/1999