To fold or to assemble?

Article abstract of DOI:10.1021/ja027186h

We introduce a new class of foldable oligomers consisting of alternating rigid and flexible regions. The rigid segments overlap to give π-stacked folded conformers whose formation is driven mostly by π-π molecular orbital overlaps. As the oligomer concentration increases, the folded molecular structures further self-assemble into larger nanostructures. The dynamic processes of folding and self-organization are monitored with absorption, fluorescence, and NMR spectroscopies. Our results show that folding dominates at low concentrations (<1～ mM) and precedes self-assembly, which occurs over the initial concentration range of 1-100 mM. Copyright

Full text of DOI:10.1021/ja027186h

Published on Web 01/10/2003
To Fold or to Assemble?
Wei Wang, Lin-Song Li, Greg Helms, Hong-Hui Zhou, and Alexander D. Q. Li*
Department of Chemistry and Center for Materials Research, Washington State UniVersity,
Pullman, Washington 99164
Received June 5, 2002 ; E-mail: dequan@wsu.edu
Scheme 1 a
Folding (intramolecular association) and self-assembly (inter-
molecular association) play vital roles in molecular science.1-4
Indeed, folded proteins and their assemblies can accomplish
remarkable functions including catalysis,5 DNA repair,6 and
information translation.7 When driven by the same force, will an
oligomer fold or assemble first? In this report, we describe a class
of oligomers, which consist of rigid chromophores linked by flexible
ethylene glycols. Diagnostic changes occur in 1H NMR, UV-vis,
and fluorescent spectra when the chromophores come into close
contact.
Scheme 1 summarizes the general strategy for synthesizing
oligomers capable of folding and self-organization. First, we
monobenzoylated bis-N,N-(2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)-
ethyl)perylenetetracarboxylic diimide (HPTD) to form a chain
anchor (1a) that permits extension at only one hydroxyl group.
Second, we synthesized the building block of HPTD with one
hydroxyl group protected with dimethoxyl trityl (DMTr) and the
other hydroxyl group activated with phosphoramidite (1b). Thus,
we used the building block (1b) to attack the monobenzoylated
anchor (1a) to synthesize a dimer. The DMTr group was then
removed by hydrolysis to generate the new hydroxy group necessary
for chain extension (2).8 Using this method of coupling followed
by detritylation, we have prepared specific oligomers including
dimer (2), trimer (3), tetramer (4), pentamer (5), and hexamer (6).
In dilute solutions (<1 mM), compound 1 exists as mostly “free”
monomer. The oligomers 2-6, however, exist as “free” folded
structures as evidenced by the upfield shift of the perylene aromatic
proton resonances (Ha and Hb). The chemical shift separation (∆δ)
between Ha (four outer protons) and Hb (four inner protons) is a
reliable indicator of folded structures versus nonfolded structures.
The larger ∆δ values observed for the folded structures arise
because the inner proton (Hb) experiences a larger ring-current than
the outer proton (Ha) when the two aromatic rings are π-stacked.
For free monomer (1), ∆δ is 0.061 ppm, whereas, the ∆δ values
for dimer, trimer, tetramer, pentamer, and hexamer are 0.26 (Figure
1a), 0.33, 0.38, 0.38, and 0.38 ppm, respectively, confirming that
they all exist as folded structures.
Strong exciton-phonon coupling was observed in the folded
nanostructures as the absorption maximum blue shifts by 0.17 eV
from 0f0 transition to 0f1 transition (Figure 1b).9 The relative
intensities of the vibronic bands are governed by the Franck-
Condon factors. The intensity reversal indicates the optimum
overlap has shifted from ø′v′)0|øv)0 in free monomers to
øv′′)1|øv)0 in the folded structures, where ø and ø′ are ground-
and excited-state vibronic wave functions. The strong exciton-
phonon coupling indicates that the HPTD molecules adopt mostly
eclipsed structures with interplanar distance of ∼3.38 Å; this value
is below van der Waals contact, suggesting molecular π-orbital
overlaps.9d
a Conditions: (1) CH2Cl2/N-Ph-IMT, rt; Then I2 (CH2Cl2/Py/H2O; 1:3:
1), rt. (2) CHCl2CO2H/ CH2Cl2, rt. Yield for 1 and 2: ∼74%.
Figure 1. (a) Observed (Ha: circles; Hb: squares) and theoretical (solid
lines) chemical shifts for dimer 2 in TCE (filled) and CHCl3 (open). (b)
Absorption spectra of free monomer 1 and folded oligomers 2-6 at 6.6 µM
monomeric units in CHCl3 with the 0 f 0 transition normalized.
states coupled to a molecular vibration. If there were Frenkel and
CT excitons, the mixing of Frenkel-CT excitations must be small
because unlike solid thin films well-resolved vibronic bands are
observed in the folded oligomers. Thereby, the broadening of the
absorption peaks may be due to exciton coupling and mixing within
the folded nanostructures.9
In most solvents, oligomers 2-6 exist as folded structures. In
1,1,2,2-tetrachloroethane (TCE), however, we found a minor amount
of unfolded species of the dimer (2). Since folded and unfolded
species are exchanging rapidly, the equilibrium constant Kfold
)
6.1 was determined using eq 1 and the low concentration data (<1
mM, Figure 1a).10 Similarly, Kfold ) 6.2 was estimated from the
intensity ratio of 0f0 and 0f1 transitions from the electronic
absorption spectra (Figure 1b).
δ1 - δobs
δobs - δ2
Excitation of eclipsed stacks of perylenetetracarboxylic diimide
could generate both molecular (Frenkel) and charge transfer (CT)
Kfold
)
(1)
9
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10.1021/ja027186h CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
to higher vibronic ground states (0 f v, v ) 0, 1, 2, 3), thereby
red-shifting the spectra. As the concentration increases (>1mM),
the folded molecular structure further assembles and intensifies the
red emissions (0f3) at the expenses of decreasing green (0f0)
and yellow (0f1) emissions. Although spectroscopic features may
vary in detail, the trimer or higher oligomers predominantly emit
red color (see the graphic in the Table of Contents).
In summary, folding dominates at low concentrations (<∼1
mM); it precedes self-assembling at slightly higher concentrations
(∼1-100 mM). Although both are driven by the same enthalpy
effect, the difference is due to “high” local concentration of foldable
units within an oligomer. At very high concentrations, our model
predicts that self-assembling could precede folding, giving rise to
a completely different aggregate morphology; however, one cannot
investigate this due to solubility limitations.
Figure 2. (a) Plot of experimental folding Kfold (open circles: NMR data;
solid circles: UV-vis data) and self-assembling KSA (solid squares)
constants (TCE) against 1/T, which yields comparable enthalpies. (b)
Theoretical prediction of unfolded dimer [A-A], folded dimer [A2], and
dimer-assembled tetramer [A2:A2] and hexamer [A2:A2:A2].
Acknowledgment. We acknowledge the support of DOE-Los
Alamos, Sub-contract (28893-001-01-35) and the Chemistry De-
partment, the CMR, the NMR center, and College of Sciences at
WSU. We thank the reviewers for helpful discussions.
Scheme 2
Supporting Information Available: Synthetic procedures of 1-6,
1H NMR shifts, fluorescence spectra, and UV-vis model for Kfold
(PDF). This material is available free of charge via the Internet at http://
pubs.acs.org.
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As the oligomer concentrations increase ([Ao] > 1 mM), the Ha
and Hb resonance peaks shift further upfield. The same forces that
drive the oligomer to fold now drive aggregation into larger
nanostructures (Scheme 2). Therefore, we expect these two
processes to have similar enthalpies, and the difference between
folding and self-organization should be largely due to entropic
contributions.
The self-assembly formation constant (KSA) can be determined
by solving an oversimplified equal-KSA power series using observed
chemical shift (δobs) at various concentrations (Figure 1a).11 Fitting
this power series (solid lines in Figure 1a) to the experimental data,
we obtained KSA ) 31 M-1 in TCE and KSA ) 90 M-1 in CHCl3
at 20 °C. Figure 2 shows the van’t Hoff plots [ln K ) ∆S°/R -
∆H° /(RT)] of the variable temperature UV-vis and 1H NMR data
for both the folding (Kfold) and the self-assembling (KSA) processes.
As expected, enthalpies for folding and self-assembling are
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comparable with ∆H° ) - 3.01 ( 0.06 kcal/mol and ∆H°
SA
(dimer) ) - 2.44 (fo0ld.12 kcal/mol. This indicates both folding
and self-assembling of HPTD molecules are exothermic processes
in organic solvents. Self-organization requires more ordering;
therefore, it should have a larger entropy change than that of folding
(10) Here, δ1 is the chemical shift of the free monomer or unfolded dimer, δ2
is the chemical shift of the folded dimer, δobs is the observed chemical
shift in rapid exchange between folded dimer and unfolded dimer.
(11) The theoretical model is described, and the entropy is calculated in Wang,
W.; Li, L.-S. Han, J. J.; Wang, L-Q.; Li, A. D. Q. Manuscript submitted.
into similar final structures. Experimentally, we observed ∆S°
)
fold
-6.60 ( 0.40 cal/mol‚K and ∆S° (mono) ) -17.5 ( 0.7
SA
(12) Folding processes: A-A T A2, ∆S° ) S(A2) - S(A-A); SA
cal/mol‚K,11 indicating that folding is favored by entropy contribu-
fold
processes: A + A T A: A, ∆S°SA ) S(A:A) - 2S(A). Assume S(A2) ≈
tion.12
S(A:A), then ∆S°fold - ∆S° ) 2S(A) - S(A-A) > 0. Thus, ∆S°
>
SA
fold
∆SS°A.
As the foldable oligomers become larger and absorption blue-
shifts to 500 nm (0f1), the photoluminescence favors emissions
JA027186H
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