Small-molecule-induced folding of a synthetic polymer

Article abstract of DOI:10.1002/anie.200501448

(Chemical Equation Presented) Stack 'em high: A polyimide with pyromellitic diimide units linked by hexaoxy-ethylene segments can be made to fold by cooperative two-point interactions on addition of a folding agent (see scheme). The ammonium group of the folding agent forms complexes with the oxyethylene spacer which greatly facilitates the formation of charge-transfer complexes between the aromatic units of the two components.

Full text of DOI:10.1002/anie.200501448

Angewandte
Chemie
Donor–Acceptor Systems
DOI: 10.1002/anie.200501448
Small-Molecule-Induced Folding of a Synthetic
Polymer**
Suhrit Ghosh and S. Ramakrishnan*
The remarkable range of chemical functions that evolution
has elicited from biopolymers has inspired chemists to design
synthetic systems that can mimic both the structural and
functional features of these elegant long-chain molecules.
Although the efforts to mimic functions such as molecular
recognition, catalysis, and so forth has led to the development
of systems such as molecular-imprint polymers,[1] the attempts
to understand and emulate structural features has given rise
to the area of foldamers.[2] In most such systems, the core
design element utilizes multiple inter- or intramolecular
noncovalent interactions that can be stabilized/destabilized
by an external trigger. The cooperativity and reversibility of
these weak noncovalent interactions are, thus, of paramount
importance in the design of synthetic analogues that can
emulate biological systems.
Supramolecular science, which deals with the design and
utilization of noncovalent interactions to build superstruc-
tures with small molecular building blocks, has witnessed
intense activity over the past decade.[3] The extension of these
ideas has resulted in the generation of supramolecular
polymers in solution, formed through multiple hydrogen-
bonding interactions[4] or through metal–ion coordination
between monomeric building blocks.[5] In the context of
conventional polymer molecules, a similar approach in which
noncovalent interactions occur between neighboring (or equi-
spaced) segments within a single polymer chain, has been
explored to stabilize specific conformations (secondary
structures) in solution.[2] On the basis of these considerations,
several research groups have examined new types of oligom-
ers and polymers, which adopt well-defined conformations in
solution guided by hydrogen-bonding interactions along the
backbone,[6] steric and/or bond-angle constraints,[7] solvopho-
bic effects, and so forth.[8] Although the large majority of
foldamers are based on precisely defined oligomers with
relatively rigid backbones, far fewer are based on flexible
systems.[9]
Recently, we demonstrated that truly flexible synthetic
macromolecules can be designed to fold under the influence
[*] S. Ghosh, Prof. S. Ramakrishnan
Department of Inorganic and Physical Chemistry
Indian Institute of Science
Bangalore 560012 (India)
Fax: (+91)802-360-1552
E-mail: raman@ipc.iisc.ernet.in
[**] We would like to thank DST, New Delhi, and 3M India Ltd, for their
financial support.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2005, 44, 5441 –5447
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5441

Communications
of several relatively weak intrachain intersegment interac-
tions, such as formation of a charge-transfer (CT) complex,
solvophobic effects, and metal–ion complexation, working in
tandem.[10] Detailed spectroscopic studies of these (donor–
spacer–acceptor–spacer)n type polymers, in conjunction with
studies of model systems, have suggested the formation of
extended donor–acceptor stacks by suitable folding of single
polymer chains.[11] In a bid to develop simpler polymeric
systems that can fold under similar conditions, we present
herein a conceptually new approach for the folding of
synthetic polymers based on a polyimide that contains only
acceptor units linked by hexaoxyethylene (6OE) spacers of
the type (acceptor–spacer)n. In this design, we utilize an
external small-molecule folding agent (donor type) that is
designed to interact simultaneously with two adjacent seg-
ments along the polymer chain so that the polymer folds in a
predetermined manner. As depicted in Scheme 1, the design
specifically entails the formation of a CT complex between
the donors of the folding agent and the acceptors along the
polymer chain, in tandem with the complexation of the
ammonium group of the folding agent with the 6OE spacer.[12]
The latter interaction is expected to restrict the conformation
of the flexible OE spacer so that the two adjacent acceptor
units along the polymer chain can be brought close enough to
form an effective CT interaction with the donor unit in the
folding agent. Such a multiple-point interaction, which is key
to the development of supramolecular science, has been
extensively utilized to enhance associations between small
molecules, as well as between polymers and small mole-
cules.[13] An interesting example of the latter is the work of
Meijer and co-workers,[14] in which they describe anchoring
(clicking-in) small functional molecules onto the periphery of
dendrimers through the simultaneous use of electrostatic and
hydrogen-bonding interactions.
Scheme 1. Folding of a synthetic polymer aided by two-point
interactions with a folding agent.
pyromellitic anhydride under standard conditions for poly-
imide synthesis.[16] Two folding agents, namely, D2-NH3+ and
+
D3-NH3 , that contain a naphthalene donor linked to an
ammonium group through a two- or a three-carbon-atom
spacer, respectively, were prepared along with 1,5-dimethoxy-
naphthalene (D) that serves as a model donor which is devoid
of the ammonium group (see Scheme 2). The structures of the
various model compounds and polymer were confirmed by
standard spectroscopic techniques, and the molecular weight
Mn of PI-6OE was determined to be 20500 Da (polydispersity
index (PDI) = 1.7) by gel-permeation chromatography
(GPC).[17] PI-6OE forms a colorless solution, but an intense
yellow color develops in the presence of D2-NH3+ because of
the characteristic CT absorption band at 450 nm.
The polyimide PI-6OE was prepared from the appropri-
ate diamine (derived from hexaethylene glycol)[15] and
Scheme 2. Structures of the polymer, model compounds, and folding agents.
5442
www.angewandte.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2005, 44, 5441 –5447

Angewandte
Chemie
+
The interaction of PI-6OE with the folding agents was
investigated by monitoring the intensity of the CT band by
UV/Vis spectroscopic analysis and by following the chemical
shift of the aromatic protons of the pyromellitic diimide
acceptor unit by 1H NMR spectroscopic analysis. Figure 1
folding agents D2-NH3+ and D3-NH3 , along with the simple
model donor D as a control experiment, is shown in Figure 2.
It is evident that although both the folding agents that contain
an ammonium group cause a dramatic change in the d value,
the simple donor molecule that does not contain this group
Figure 2. Variation in the chemical shift of the acceptor ring protons da
+
in PI-6OE in the presence of D+NH4SCN, D2-NH3+, and D3-NH3
(top) and variation in the CT band intensity ACT in the presence of
D+NH4SCN, D2-NH3+, and D3-NH3+ (bottom). The solvent used is
CDCl3/CH3CN (1:1). The mole equivalents are calculated with respect
to the polymer repeating unit.
1
Figure 1. Variation in the aromatic region of the H NMR spectra of PI-
6OE (top) and AA-6OE (bottom) as a function of the addition of
increasing amounts of D2-NH3+. The signal that arises from the
pyromellitic diimide acceptor protons is indicated by an arrow. The
solvent used is a CDCl3/CH3CN mixture (1:1, v/v).
causes only a marginal variation. This upfield shift of the
acceptor proton suggests the formation of donor–acceptor CT
stacks, as was elaborated in our earlier report.[11] Similarly, a
significant increase in the intensity of the CT band in the UV/
Vis spectra of the polymer solution occurs in the presence of
the two donors that contain ammonium groups while only a
marginal increase is seen in the presence of the simple donor
(Figure 2), despite the fact that both the control experiments
were done in the presence of an equimolar quantity of
NH4SCN with respect to D. The independent complexation of
the ammonium ion with the OE loop would be expected to at
least partially aid the CT interaction with D. These compa-
1
depicts the variation in the H NMR spectra of PI-6OE with
+
increasing amounts of D2-NH3 . The signal marked by an
arrow, from the pyromellitic diimide unit in the polymer, is
seen to move continuously upfield on addition of increasing
amounts of the donor species. The remaining signals in the
aromatic region are from the naphthalene ring of the folding
agent, the intensities of which increase and are accompanied
by a small downfield shift.[18]
A plot of the variation in the chemical shift of the acceptor
proton as a function of the concentration of the two different
Angew. Chem. Int. Ed. 2005, 44, 5441 –5447
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5443

Communications
rative studies clearly demonstrate the importance of the
cooperative two-point interaction, namely, the coordination
of the ammonium group with the OE loop and the concom-
itant CT interaction between the donor and acceptor units, in
the generation of the postulated folded structure. Further-
more, as anticipated, the length of the spacer that connects
the ammonium group to the naphthalene donor also plays an
important role in governing the efficacy of the CT interac-
tions. It is apparent from the variations in the UV/Vis and
NMR spectra that D2-NH3+ is a more effective folding agent
+
than D3-NH3 (see Figure 2).[19] This dependence on the
spacer length reaffirms the importance of the crown ether
type complexation of the ammonium group with the OE
segment of the polymer in directing the formation of the
postulated folded structure.
To probe the extent of the folding, model compound AA-
6OE (see Scheme 2) which contains two acceptor units linked
by a hexaoxyethylene spacer was synthesized[20] and its
interaction with the folding agents studied by both UV/Vis
and NMR spectroscopic analysis. The variation in the
1
aromatic region of the H NMR spectra of AA-6OE as a
function of increasing concentration of the folding agent D2-
+
NH3 is compared with that of the polymer in Figure 1. It is
apparent that a significant upfield shift of the acceptor
protons is seen in this case as well, although the extent of the
shift is clearly smaller in the model compound than in PI-
6OE. The variation of the chemical shift of the acceptor
proton upon interaction with the two folding agents in the
case of the polymer is compared with that of the model
compound AA-6OE in Figure 3. For both folding agents, it is
clear that the extent of the shift is significantly higher for the
polymer than for the model compound. This enhanced shift is
clearly a reflection of the fact that the acceptor units in the
model can never be sandwiched between two donors, unlike
in the case of the polymer in which extended stacking would
cause the acceptor units to be sandwiched between two
donors. Interestingly, the final chemical shifts of the donor
(naphthalene) protons are nearly identical for both the
polymer and the model compound (see Figure 1), as
expected, because in both cases the donor could become
sandwiched between the acceptor units. In addition, as
anticipated, the extent of folding exhibits strong temperature
dependence, as is evident from the significant upfield shift
upon cooling (see inset in Figure 3).[11] Again, it is seen that
the polymer exhibits much stronger temperature dependence
than the AA-6OE model, thus causing the difference in their
chemical shifts to become as large as 0.3 ppm at the lowest
temperature probed. We ascribe this difference to the
formation of extended stacks in the case of the polymer.[21]
To gain further insight into the extent of the stacking, a Job
plot was constructed from the absorbance of the CT band,
which suggested that the acceptor/donor ratio was 1:0.85 for
the polymer PI-6OE (the maximum value in the Job plot was
seen at approximately 0.46, see the Supporting Information).
Although, in a general sense a ratio of 1:1 need not imply the
formation of an extended stack, in our case, however, it can be
reasoned that it does confirm the formation of a stack. It is
apparent in the present system that the interaction of the
ammonium group with the OE spacer is essential for the
Figure 3. Variation in the chemical shift of the acceptor ring protons da
+
in PI-6OE and AA-6OE in the presence of D3-NH3+ (top) and D2-NH3
(bottom). Inset: Effect of temperature on the chemical shift of PA-6OE
+
+
and AA-6OE in presence of D3-NH3 (the ratio of D3-NH3 to polymer
repeating unit/model compound was 4:1).
formation of a CT complex and, more importantly, leads to
the sandwiching of the donor between two adjacent acceptors
to form an acceptor-donor-acceptor type unit. Evidence for
this sandwiching also comes from the Job plot of the model
compound AA-6OE, which suggests the formation of an
exact 1:1 complex (see the Supporting Information for
details). Thus, an acceptor/donor ratio of 2:1 in case of the
polymer would suggest the formation of only acceptor–
donor–acceptor-type interactions with no extended stacking.
On the other hand, if all the OE spacer sites form complexes
with the ammonium group of the folding agent, as expected
with an acceptor/donor ratio of 1:1, then the formation of an
infinitely extended stack is implied. Although the exact scale
of the stacking continues to be a challenging problem, a rough
estimate on the basis of the Job plot of our polymer suggests
the formation of stacks that consist of six donor–acceptor
pairs on average.
5444
www.angewandte.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2005, 44, 5441 –5447

Angewandte
Chemie
To test the reversibility of such an interaction-induced
folding, an experiment to extricate the folding agent with a
crown ether was carried out. Thus, PI-6OE in the folded state
to nearly colorless at the end of the titration with the crown
ether, which is consistent with the complete disappearance of
the CT band in the UV/Vis spectra (Figure 4). These experi-
ments clearly confirm that the folding is completely reversible
and also suggest that the folding/unfolding equilibrium can be
controlled by an appropriate external agent.
+
(in the presence of 8 equiv of D2-NH3 ) was titrated with
[18]crown-6, which is known to bind very strongly with
ammonium ions.[22] In Figure 4, the variation of the chemical
In conclusion, we have demonstrated a new approach to
folding a flexible synthetic polymer in solution by utilizing a
small molecule as a folding agent. The folding agent was
designed to interact cooperatively with two adjacent segments
of the polymer chain, such that one interaction facilitates the
other, thus leading to the formation of a stacked structure. An
ammonium cation in the folding agent forms a complex with a
hexaoxyethylene spacer thereby aiding the CT interaction
between a naphthalene donor and a pyromellitic diimide
acceptor in the polymer. Control experiments with a model
naphthalene donor, along with an equimolar amount of an
ammonium salt, clearly helped delineate the importance of
linking the two interacting subunits in the folding agent, and
thereby confirmed the importance of cooperativity in such a
folding process. Importantly, the folding was also shown to be
completely reversible and the polymer unfolds when the
folding agent is extricated by formation of a stronger complex
with [18]crown-6. Further work to explore the generality and
utility of such a small-molecule-induced folding of synthetic
polymers would be of great interest and is currently being
studied.
Experimental Section
Pyromellitic dianhydride and 1,5-dihydroxynaphthalene were pur-
chased from the Aldrich Chemical Co. and were purified by
sublimation and recrystallization (from nitromethane), respectively.
Dry and purified solvents were used in all the syntheses and
spectroscopic studies. All the solvents and common synthetic reagents
were purified according to standard procedures.[23] The NMR experi-
ments were performed using a Bruker 400 MHzspectrometer and
UV/Vis spectra were measured using a Ocean Optics spectrometer.
The molecular weights were determined by GPC with chloroform as
the eluent at 358C, two PL-gel mixed-bed columns were used for
separation, and a Viscotek TDA Model 300 was used as the detector.
The universal calibration method based on a polystyrene standard
was used to estimate the molecular weights. Isothermal titration
calorimetry (ITC) experiments were performed with a VP-ITC
Microcal LLC instrument in a CHCl3/CH3CN solvent mixture (1:1).
Mass-spectrometric data were obtained on a Q-TOP Micromass
spectrometer. Elemental analysis was performed with a Carlo Erba
1106 CHN analyzer.
Folding studies: In a typical NMR titration experiment, a
polymer solution (1.5 mL, 1.92 mm) was prepared in CDCl3/CH3CN
(1:1 v/v; solution A). An aliquot of this solution (0.6 mL) was placed
in the NMR tube and a large excess ( ꢀ 10–15 equiv) of donor
molecule was dissolved in the remaining solution (solution B).
Solution A was then titrated with solution B (20–150-mL steps), which
resulted in a series of solutions of fixed polymer concentration but
with various amounts of donor. Similarly, the UV/Vis experiments
were performed in CHCl3/CH3CN (1:1).
Figure 4. Reversal of the chemical shifts of the acceptor protons da of
PI-6OE (top) and the disappearance of CT absorption band (bottom)
in the presence [18]crown-6. The mole equivalents were calculated with
respect to the polymer repeating unit.
shift is plotted, first for the addition of increasing amounts of
the folding agent to the polymer and subsequently for the
addition of increasing amounts of [18]crown-6. It is clear from
the plot that there is a complete reversal of the chemical shift,
as a signal with nearly the same value as that for the unfolded
polymer is observed, although slightly more than one
equivalent of [18]crown-6 was required to effect this complete
reversal. The color of the solution changes from deep yellow
In the experiment with the crown ether, a solution containing a
polymer/donor mixture in a 1:7 ratio in CHCl3/CH3CN (1:1) was
titrated with a solution of [18]crown-6 in CHCl3/CH3CN (1:1) that
also contained a polymer/donor mixture in a 1:7 ratio. Therefore, the
concentration and relative molar ratios of the polymer and donor
molecules were kept constant, and the only variable was the
Angew. Chem. Int. Ed. 2005, 44, 5441 –5447
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5445

Communications
concentration of [18]crown-6. The Job plot experiment based on UV/
U. S. Schubert, Adv. Mater. 2004, 16, 1043; e) B. J. Benjamin,
J. J. R. Stuart, J. Am. Chem. Soc. 2003, 125, 13922.
Vis spectroscopic analysis was performed in CHCl3/CH3CN (1:1), and
the total concentration (polymer+ folding agent) was maintained at
12 mm for the polymer and 6 mm for the model compound.
Synthesis of the polymer: Hexaethylene glycol diamine[15]
(0.494 g, 1.76 mmol) was placed in the reaction vessel and dissolved
in freshly distilled m-cresol (3 mL). The purified pyromellitic
dianhydride (0.384 g, 1.76 mmol) was added to this solution in one
portion, and the reaction mixture was stirred at 858C for 2 h under a
continuous flow of N2 gas. The reaction mixture was cooled to room
temperature, and m-cresol (2 mL), dry toluene (5 mL), and isoquino-
line (8 drops) were added. The reaction mixture was stirred at 1858C
for another 6 h in an inert atmosphere with continuous azeotropic
removal of water. The reaction mixture was cooled to room temper-
ature, and the viscous liquid was poured into methanol (50 mL). The
fine powdery precipitate was centrifuged, redissolved in a minimum
volume of chloroform, and reprecipitated from methanol to obtain
the desired polymer as a white fibrous material. The product was
dried under vacuum at 1008C for 3 h. Yield: 62%.
For fractionation, methanol was added dropwise to a solution of
the polymer (150 mg) in chloroform (10 mL) until the solution
became cloudy. The mixture was stirred for another 15 min as a
colorless oil separated and stuck to the walls of the vessel. The
supernatant was decanted, and the oil was dissolved in chloroform
(1 mL) and reprecipitated from methanol to form the fibrous
colorless polymer. The product was dried under vacuum for 3 h at
1008C, and the recovery was found to be approximately 30%.
1H NMR (400 MHz, CDCl3): d = 8.257 (s, 2H, Ar-H), 3.950 (t,
4H, N-CH2), 3.768 (t, 4H, N-CH2-CH2-), 3.658–3.581 ppm (m, 16H,
rest of the oligoethylene protons); 13C NMR: d = 166.17, 137.26,
118.27, 70.59, 70.53, 70.03, 67.68, 37.93 ppm. Elemental analysis (%)
calcd for C22H26N2O9: C 57.14, H 5.66, N 6.06; found: C 56.82, H 5.51,
N 5.93.
[6] a) Y. Hamuro, S. J. Geib, A. D. J. Hamilton, J. Am. Chem. Soc.
1997, 119, 10587; b) Y. Hamuro, S. J. Geib, A. D. J. Hamilton, J.
Am. Chem. Soc. 1996, 118, 7529; c) J. Zhu, R. D. Parra, H. Zeng,
E. Skrzypczak-Jankun, X. C. Zeng, B. Gong, J. Am. Chem. Soc.
2000, 122, 4219; d) L. Yuan, H. Zeng, K. Yamato, A. R. Sanford,
W. Feng, H. S. Atreya, D. K. Sukumaran, T. Szyperski, B. Gong,
J. Am. Chem. Soc. 2004, 126, 16528.
[7] a) V. Berl, I. Huc, R. G. Khoury, J. M. Lehn, Nature 2000, 407,
720; b) A. Petitjean, L. A. Cuccia. J. M. Lehn, H. Nierengarten,
M. Schmutz, Angew. Chem. 2002, 114, 1243; Angew. Chem. Int.
Ed. 2002, 41, 1195.
[8] a) A. Tanatani, M. J. Mio. , J. S. Moore, J. Am. Chem. Soc. 2001,
123, 1792; b) R. B. Prince, L. Brunsveld, E. W. Meijer, J. S.
Moore, Angew. Chem. 2000, 112, 234; Angew. Chem. Int. Ed.
2000, 39, 228; c) J. C. Nelson, J. G. Saven, J. S. Moore, P. G.
Wolynes, Science 1997, 277, 1793; d) J. M. Heemstra, J. S. Moore,
J. Am. Chem. Soc. 2004, 126, 1648; for related polymeric systems,
see; e) R. S. Hecht, A. Khan, Angew. Chem. 2003, 115, 6203;
Angew. Chem. Int. Ed. 2003, 42, 6021; f) L. Arnt, G. N. Tew,
Macromolecules 2004, 37, 1283.
[9] a) W. Wang, L.-S. Li, G. Helms, H.-H. Zhou, A. D. Q. Li, J. Am.
Chem. Soc. 2003, 125, 1120; b) A. D. Q. Li, W. Wang, L.-Q.
Wang, Chem. Eur. J. 2003, 9, 4594; c) E. E. Neuteboom, S. C. J.
Maskers, E. W. Meijer, R. A. J. Janssen, Macromol. Chem. Phys.
2004, 205, 217; d) R. S. Lokey, B. L. Iverson, Nature 1995, 375,
303; e) J. Q. Nguyen, B. L. Iverson, J. Am. Chem. Soc. 1999, 121,
2639; f) A. J. Zych, B. L. Iverson, J. Am. Chem. Soc. 2000, 122,
8898; g) G. J. Gabriel, B. L. Iverson, J. Am. Chem. Soc. 2002, 124,
15174; h) M. A. Balbo Block, S. Hecht, Macromolecules 2004,
37, 4761.
[10] S. Ghosh, S. Ramakrishnan, Angew. Chem. 2004, 116, 3326;
Angew. Chem. Int. Ed. 2004, 43, 3264.
Received: April 27, 2005
[11] S. Ghosh, S. Ramakrishnan, Macromolecules 2005, 38, 676.
[12] K+ and NH4+ ions are known to have similar size-selective
preferences on complexation with crown ethers. We have shown
that a donor–acceptor polymer that contains a 6OE spacer forms
complexes most strongly with K+ ions.[10,11] Therefore, a poly-
imide that contains 6OE spacers was chosen in the present study.
For reviews of the complexation of crown ethers and podands
with cations, see: a) G. K. Gokel, W. M. Leevy, M. E. Weber,
Chem. Rev. 2004, 104, 2723; b) H. G. Lohr, L. F. Vogtle, Acc.
Chem. Res. 1985, 18, 65, and references therein; c) Comprehen-
sive Supramolecular Chemistry, Vol. 1 (Ed.: G. W. Gokel),
Pergamon/Elsevier, Oxford, 1996; d) R. M. Izatt, J. S. Brad-
Shaw, S. A. Nielsen, J. D. Lamb, J. J. Christensen, Chem. Rev.
1985, 85, 271.
[13] a) G. Kaiser, T. Jarrosson, S. Otto, Y.-F. Ng, A. D. Bond, J. K. M.
Sanders, Angew. Chem. 2004, 116, 1993; Angew. Chem. Int. Ed.
2004, 43, 1959; b) L. Kovbasyuk, R. Kramer, Chem. Rev. 2004,
104, 3161; c) F. Ithan, G. K. Blanchette, V. Rotello, Macro-
molecules 1999, 32, 6159; d) V. Berl, M. J. Krische, I. Huc, J. M.
Lehn, R. Schmutz, Chem. Eur. J. 2000, 6, 1938.
Published online: July 29, 2005
Keywords: charge transfer · crown compounds ·
.
donor–acceptor systems · polymer folding
[1] a) G. Wulff, Chem. Rev. 2002, 102, 1; b) K. Haupt, K. Mosbach,
Chem. Rev. 2000, 100, 2495; c) Molecularly Imprinted Polymers,
Man-Made mimics of Antibodies and their Application in
Analytical Chemistry (Ed.: B. Sellergren), Elsevier, New York,
2001; d) S. C. Zimmerman, N. G. Lemcoff, Chem. Commun.
2004, 5.
[2] a) S. H. Gellman, Acc. Chem. Res. 1998, 31, 173; b) D. J. Hill,
M. J. Mio, R. B. Prince, T. S. Huges, J. S. Moore, Chem. Rev.
2001, 101, 3893; c) C. Schmuck, Angew. Chem. 2003, 115, 2552;
Angew. Chem. Int. Ed. 2003, 42, 2448.
[3] a) J. M. Lehn, Supramolecular Chemistry—Concepts and Per-
spectives, Wiley-VCH, Weinheim, 1995; b) C. A. Schalley, A.
Lutzen, M. Albrecht, Chem. Eur. J. 2004, 10, 1072.
[14] M. W. P. L. Baars, A. J. Karlsson, V. Sorokin, B. F. W. Waal,
E. W. de Meijer, Angew. Chem. 2000, 112, 4432; Angew. Chem.
Int. Ed. 2000, 39, 4262.
[15] For synthetic details, see the Supporting Information.
[16] J. G. Liu, M. H. He, Z. X. Li, Z. G. Qian, F. S. Wang, S. Y. J. J.
Yang, J. Polym. Sci. A 2002, 40, 1572.
[4] a) J.-M. Lehn, Supramolecular Polymers (Ed.: A. Cifferi),
Marcel Dekker, New York, 2000, p. 615; b) S. C. Zimmerman,
P. S. Corbin, Struct. Bonding (Berlin) 2000, 96, 63; c) L.
Brunsveld, J. A. J. M. Vekemans, J. H. K. K. Hirschberg, R. P.
Sijbesma, E. W. Meijer, Proc. Natl. Acad. Sci. USA 2002, 99,
4977; d) R. P. Sijbesma, E. W. Meijer, Chem. Commun. 2003, 5;
e) L. Brunsveld, B. J. B. Folmer, E. W. Meijer, R. P. Sijbesma,
Chem. Rev. 2001, 101, 4071; f) V. Berl, M. Schmutz, M. J.
Krische, R. G. Khoury, J.-M. Lehn, Chem. Eur. J. 2002, 8, 1227.
[5] a) D. Yu-Bin, W. Peng, H. Ru-Qi, D. S. Mark, Inorg. Chem. 2004,
43, 4727; b) U. S. Schubert, C. Eschbaumer, Angew. Chem. 2002,
114, 3016; Angew. Chem. Int. Ed. 2002, 41, 2892; c) H. Hofmeier,
U. S. Schubert, Chem. Soc. Rev. 2004, 33, 373; d) P. R. Andres,
[17] All spectral data and gel-permeation chromatograms are
available in the Supporting Information.
[18] The increase in intensity is simply a reflection of the increase in
the concentration of the donor species, whereas the downfield
shift arises from the mole-fraction weighted average of the free
and complexed naphthalene units. It may be recalled that
formation of a CT complex generally causes an upfield shift of
5446 www.angewandte.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2005, 44, 5441 –5447

Angewandte
Chemie
both the donor and acceptor units,[11] however, the downfield
shift of the donor protons in this case arises from the over-
whelming presence of free donor species.
[19] The association constants of the two folding agents with AA-
6OE were determined from the variation in the chemical shift of
the acceptor ring protons as a function of the folding-agent
concentration by using computer program EQNMR ver-
sion 2.10. (Freeware, M. J. Hynes, Chemistry Department, Uni-
versity College Galway, Ireland). The K values were found to be
850 and 600mÀ1 for D2-NH3+ and D3-NH3+, respectively, but
only 30mÀ1 for D + NH4+, thus confirming the cooperativity of
the interaction, as well as the importance of the spacer length for
effective binding and folding. The association constant for D2-
+
NH3 was also determined from ITC and was found to be
1050mÀ1, which is comparable to that obtained with NMR
spectroscopic analysis. Similar attempts to determine the
association constant for the polymer with ITC was difficult as
a simple plot that assumed a single association constant failed to
give a good fit. A probable reason for this failure is that several
different values of association constants could, in principle, be
required in the case of the polymer. Nevertheless, it is clear from
the values of K obtained for the model AA-6OE that linking the
two interacting segments in the folding agent is critical for the
generation of a folded structure in the polymer.
[20] For synthetic details, see the Supporting Information.
[21] The variable temperature experiment was done using D3-NH3
+
as the folding agent at a ratio of 4:1 molar equivalents with
respect to the polymer repeating unit to ensure that the
ammonium salt did not precipitate on cooling.
[22] [18]Crown-6 is known to form a very strong complex with
ammonium ions with an association constant K in the order of
106 mÀ1; see reference [12a].
[23] D. D. Perrin, W. L. F. Armarego, D. R. Perrin, Purification of
Laboratory Chemicals, 2nd ed., Pergamon, Oxford, 1980.
Angew. Chem. Int. Ed. 2005, 44, 5441 –5447
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5447