Reversible polymerization driven by folding

Article abstract of DOI:10.1021/ja026957e

Bisfunctionalized m-phenylene ethynylene imine oligomers were polymerized in the polar solvent acetonitrile, resulting in high-molecular weight poly(m-phenylene ethynylene imine)s. It is hypothesized that this polymerization, which proceeds through the re

Full text of DOI:10.1021/ja026957e

Published on Web 08/03/2002
Reversible Polymerization Driven by Folding
Dahui Zhao and Jeffrey S. Moore*
Departments of Chemistry and Material Science and Engineering, UniVersity of Illinois, Urbana, Illinois 61801
Received May 17, 2002
The design and synthesis of nonnatural, hetero-sequenced
copolymers having well-defined folded structures (tyligomers)1 and
capabilities of performing functions that rival those of natural
biopolymers such as proteins remains an important, unsolved
challenge for chemists. The magnitude of possible sequences, even
for a binary monomer pool, makes the search for tyligomers a
daunting problem. The majority of random sequences from an
irreversible copolymerization of an amphiphilic pair of monomers
will likely either be insoluble in the reaction medium or adopt
noncompact, disordered conformations in solution.2 We hypothesize
that a reversible polymerization in which chain folding or collapsing
drives high-polymer formation will yield a much smaller subset of
all possible sequences and therefore greatly streamline the search
for tyligomers. As a first step to test this hypothesis, it is essential
to show that in a closed system, energy gained by folding can drive
a reversible polymerization toward the formation of high polymers.
Here we report a polymerization that implements the concept of
supramolecular-assisted, dynamic-covalent polymerization.3,4
Previously, our laboratory has shown that the equilibrium
distribution of monoimine-functionalized m-phenylene ethynylene
oligomers can be shifted in polar solvents to selectively favor
oligomers that adopt a stable helical conformation.5,6 On the basis
of these observations, we predicted that bisimine functionalized
m-phenylene ethynylene oligomers could be driven to high polymer
under similar conditions (Figure 1). Since the equilibrium constant
of imine metathesis is close to unity,5,7 only low-molecular weight
oligomers are expected for a closed system at equilibrium in the
absence of a driving force such as folding.8 In polar media, the
collapse of long chains into compact conformations should increase
stability as a result of intramolecular, solvophobic, and aromatic
stacking interactions, consequently shifting the equilibrium in favor
of longer chains. As the reaction proceeds, monomer units will
continuously add onto the existing ordered structures. A distinctive
characteristic of this polymerization is that a high degree of
polymerization follows from noncovalent interactions, rather than
from the free energy gained in covalent bond formation or the
removal of byproducts, as in most step-growth polymerizations.8,9
To demonstrate that folding can drive a reversible polymerization,
tetrameric oligomers 1 and 2, both having bis-imino end groups,
were synthesized and used as monomers for imine metathesis
polymerization.10 The reaction between 1 and 2 (1:1 equiv at 5
mM) was first carried out in two different solvents (acetonitrile
and chloroform) in the presence of 0.5 mM oxalic acid as a catalyst.
These two solvents were chosen because m-phenylene ethynylene
oligomers have previously been shown to adopt an ordered helical
conformation in acetonitrile and a random conformational state in
chloroform.11 The reactions were conducted in dry solvents at room
temperature for 6 d to ensure that equilibrium had been achieved.12
After the reactions were quenched with triethylamine, the product
mixtures were analyzed by size-exclusion chromatography (SEC)
in THF.13 The SEC traces of the products from reactions conducted
in the two solvents are shown in Figure 2. In chloroform (trace b),
the major components of the reaction mixture were the starting
materials (Mn ) 1.8 kDa), their dimers (Mn ) 3.6 kDa), and trimers,
along with a small amount of higher oligomers. Such a molecular-
weight distribution is in good agreement with the theoretically
calculated statistical distribution of a closed-system metathesis
polymerization in which the equilibrium constant is near unity.8 In
contrast, a high-molecular weight product was obtained when the
equilibrium took place in acetonitrile (trace j).14,15 These results
support the hypothesis that the stabilizing energy derived from
intrachain noncovalent interactions can drive the metathesis equi-
librium toward high polymers.
If indeed the folding energy is the driving force for the
equilibrium shifting and consequently elongation of the polymer
chains, the molecular weight of the resulting poly(m-phenylene
ethynylene imine)s should correlate with conformational stability.
Our previous studies on m-phenylene ethynylene oligomers have
illustrated a nearly linear relationship between helix stability and
chloroform composition in chloroform/acetonitrile binary mixtures.11b
The folding propensity of the oligomers diminishes as the m-
phenylene ethynylene backbone becomes better solvated from the
increase in the amount of chloroform in the solvent mixture. Hence,
increasing the chloroform composition in the cosolvent should
correspondingly lead to a lower degree of polymerization. Imine
metathesis between 1 and 2 was then conducted in a series of
acetonitrile/chloroform solvent mixtures (Figure 2). SEC analyses
of the polymerization products equilibrated in these solvents
revealed a good correlation between the molecular weight of the
products and the solvent composition (Figure 3). Taking into
account the nonlinear relationship between the degree of polym-
erization and the reaction conversion,8 the molecular weight
corresponds well with the folding energy. This correlation between
molecular weight and conformational stability was also manifested
by examining reactions conducted in a series of solvents in which
the m-phenylene ethynylene oligomers exhibited intermediate helix
stabilities between chloroform and acetonitrile.16 Varied molecular
weight was obtained from these solutions, consistent with the
expected conformational stability. These results further support the
conclusion that folding energy is the driving force for the equilib-
rium shifting and polymerization.
If the metathesis of the imine bonds is truly reversible, polymer
formation should be dynamic, and the molecular weight of the
products should respond to environmental changes that perturb the
folded structure. The reversibility of the polymerization was tested
by monitoring changes in the product’s molecular weight following
both solvent and temperature changes (Figure 4). Increasing the
reaction temperature, or adding the denaturing solvent chloroform,
displaced the equilibrium from a high-molecular weight position
* To whom correspondence should be addressed. E-mail: moore@scs.uiuc.edu.
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J. AM. CHEM. SOC. 2002, 124, 9996-9997
10.1021/ja026957e CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Figure 1. Imine metathesis polymerization between bis-imino m-phenylene ethynylene oligomers 1 and 2 (metathesis conditions: 1:1 equiv of the reactants
equilibrated in dry solvent at 5 mM in the presence of 0.1 equiv of oxalic acid for 6 d).
In conclusion, high-molecular weight poly(m-phenylene ethynyl-
ene imine)s were synthesized via a reversible metathesis reaction.
The data support the postulate that the folding energy is the driving
force for shifting the equilibrium to generate high polymers. The
degree of polymerization has been shown to correlate to the stability
of the corresponding oligomers in their helical conformation and
may be controlled by tuning the reaction conditions that determine
folding stability. Furthermore, the system exhibited adaptability
toward solvent and temperature changes by reversibly adjusting
the product’s molecular weight. Extension of these studies to hetero-
sequenced copolymers will be carried out soon.
Acknowledgment. This material is based upon work supported
Figure 2. SEC traces of metathesis reactants 1 and 2 (a) and products
by the National Science Foundation (Grant No. 0117792) and the
U.S. Department of Energy, Division of Material Science (Grant
No. DEFG02-96ER45439), through the Frederick Seitz Materials
Research Laboratory at the University of Illinois at Urbana-
Champaign.
equilibrated for 6 d at 5 mM rt in CHCl3 (b), CHCl3/CH3CN (vol % of
CHCl3: (c) 75%; (d) 50%; (e) 25%; (f) 20%; (g) 15%; (h) 10%; (i) 5%);
and CH3CN (j) solutions (the traces eluted at ca. 30 min are from the
byproduct 4).
Supporting Information Available: Molecular weight data and
syntheses of 1 and 2 (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
References
(1) Hill, D. J.; Mio, M. J.; Prince, R. B.; Hughes, T. S.; Moore, J. S. Chem.
ReV. 2001, 101, 3893-4012.
(2) (a) Dill, K. A. Biochemistry 1985, 24, 1501-1509. (b) Rao, S. P.;
Carlstrom, D. E.; Miller, W. G. Biochemistry 1974, 13, 943-952.
(3) Rowan, S. J.; Cantrill, S. J.; Cousins, G. R. L.; Sanders, J. K. M.; Stoddart,
J. F. Angew. Chem., Int. Ed. 2002, 41, 898-952.
(4) (a) Lehn, J.-M. Science 2002, 295, 2400-2403. (b) Reinhoudt, D. N.;
Crego-Calama, M. Science 2002, 295, 2403-2407.
Figure 3. Molecular weight Mw of the products from metatheses between
1 and 2 in CHCl3/CH3CN under the same condition as in Figure 2.
(5) Oh, K.; Jeong, K.-S.; Moore, J. S. Nature 2001, 414, 889-893.
(6) (a) Nishinaga, T.; Tanatani, A.; Oh, K.; Moore, J. S. J. Am. Chem. Soc.
2002, 124, 5934-5935. (b) Zhao, D.; Moore, J. S. J. Org. Chem. 2002,
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(7) To´th, G.; Pinte´r, I.; Messmer, A. Tetrahedron Lett. 1974, 735-738.
(8) Odian, G. Principles of Polymerization, 2nd ed.; John Wiley & Sons:
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(9) Tindall, D.; Pawlow J. H.; Wagener, K. B. Alkene Metathesis in Organic
Synthesis; Springer: New York, 1998; pp 183-198.
(10) Besides 1 and 2, a pair of trimeric bisimino-monomers having three
m-phenylene units were also synthesized and studied under the same
metathesis conditions. Interestingly, cyclization as opposed to polymer-
ization occurred in acetonitrile, giving rise to a macrocycle containing
six m-phenylene moieties and two imino units in nearly quantitative yield.
(11) (a) Nelson, J. C.; Saven, J. G.; Moore, J. S.; Wolynes, P. G. Science 1997,
277, 1793-1796. (b) Prince, R. B.; Saven, J. G.; Wolynes, P. G.; Moore,
J. S. J. Am. Chem. Soc. 1999, 121, 3114-3121.
Figure 4. SEC traces of metathesis products from 1 and 2 in CH3CN at 5
mM rt for 6 d (a); reaction mixture from (a) was then heated at 40 °C for
another 6 d (b); 1 and 2 equilibrated at 40 °C in CH3CN at 5 mM for 6 d
(c); reaction mixture from (c) was then cooled to rt and equilibrated for
another 6 d (d); reaction mixture from (a) was diluted with CHCl3 (e) or
CH3CN (f) to 2.5 mM and equilibrated at rt for another 6 d.
(12) The reaction was allowed to proceed up to 16 d, but no significant
molecular weight change was observed after 6 d.
(13) All the molecular weight data are based on SEC analysis in THF calibrated
by standard polystyrene samples (actual molecular weight of 1 and 2 is
ca. 1.2 kDa).
(14) Equilibrium constant of the imine metathesis was assumed not to be greatly
affected by the solvent polarity (refs 5 and 6a).
(15) The reaction was also conducted at lower concentration (e.g., 0.5 mM) in
acetonitrile, and polymer products of similar molecular weight were
obtained, supporting the premise that folding, rather than aggregation, is
the dominant driving force for the polymerization.
toward a lower degree of polymerization; the molecular weight was
independent of the pathway followed and only depended on the
equilibration conditions. These results fully support the notion that
the polymerization is reversible and that molecular weight adjusts
in response to environmental changes.
(16) Hill, D. J.; Moore, J. S. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 5053-5057.
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