One-dimensional optoelectronic nanostructures derived from the aqueous self-assembly of π-conjugated oligopeptides

Article abstract of DOI:10.1021/ja805491d

The aqueous self-assembly of oligopeptide-flanked π-conjugated molecules into discrete one-dimensional nanostructures is described. Unique to these molecules is the fact that the π-conjugated unit has been directly embedded within the peptide backbone by way of a synthetic amino acid with π-functionality that is compatible with standard Fmoc-based peptide synthesis. The peptide-based molecular design enforces intimate π-π communication within the aggregate after charge-screening and self-assembly, making these nanostructures attractive for optical or electronic applications in biological environments. The synthesis and assembly are reported along with spectroscopic and morphological characterization of the new nanomaterials. Copyright

Full text of DOI:10.1021/ja805491d

Published on Web 09/25/2008
One-Dimensional Optoelectronic Nanostructures Derived from the Aqueous
Self-Assembly of π-Conjugated Oligopeptides
Stephen R. Diegelmann, Justin M. Gorham, and John D. Tovar*
Department of Chemistry, Johns Hopkins UniVersity, Baltimore, Maryland 21218
Received July 15, 2008; E-mail: tovar@jhu.edu
Self-assembling supramolecular objects with π-electron func-
tionality are of increasing interest for nanotechnology.1 The vast
majority of these approaches involve the association of molecular
components in organic solvents. Notable exceptions are the water-
soluble rod-coil oligophenylenes, but they are rendered soluble by
oligo(ethylene oxide)s known in many cases to resist specific
biological adhesion.1h Thus, the construction of discrete organic
electronic nanostructures with biologically interactive function in
aqueous environments remains a daunting challenge. We demon-
strate herein how small peptide sequences with π-conjugated
oligomers directly embedded in the backbone promote assembly
into 1-D nanostructures with strong π-π intermolecular electronic
communication under completely aqueous and physiologically
relevant conditions. This important step sets the stage for the
presentation of bioactive small peptides and other molecular
recognition elements on the periphery of the nanostructure. The
synthetic approach is fundamentally different from covalent modi-
fication of preformed nanostructures or single proteins in that the
peptidic structure encourages or enforces the formation of π-stacked
conduits within the assembled objects.2
Synthetic biomaterials whose properties can be regulated by
external stimuli offer useful scaffolds for cell adhesion and growth.3
Figure 1. (A) CD and (B) fluorescence of 2 in basic (dissolved, black
traces) and acidic (assembled, red traces) aqueous solutions. The inset of
panel B depicts a concentrated solution (left) and a gel (right) irradiated at
365 nm. Tapping-mode AFM images and height profiles of the indicated
Biological architectures that incorporate π-conjugated materials are
attracting substantial attention in this regard,4 as evidenced in
polypyrrole-based cell scaffolds and artificial muscles.5 External
line trace of (C) large area and (D) isolated structures formed after assembly
stimuli can also provoke the assembly of biomolecular components
into functional nanostructures. These strategies are inspired by the
formation of ꢀ-amyloid plaques where misfolded soluble proteins
undergo hierarchical assembly to yield fibrils 10-50 nm in diameter
with lengths of several micrometers. A wide diversity of small
peptides form amyloid fibrils, and substantial research efforts seek
to describe their formation,6 prevent their formation, and even use
the process for advanced materials.7
and deposition on freshly cleaved mica surfaces.
Scheme 1. Endgame Construction of Bithiophene Fmoc-Amino
Acid 1 Used To Construct Self-Assembling Peptides Such as 2
The amyloid aggregation paradigm presents an attractive method
to construct well-defined 1-D nanostructures with biologically
responsive and electronically useful properties from molecular
precursors. To harness this process to control π-π interactions,
we will need to embed the π-system directly into the peptide
backbone. As proof of principle, we prepared bithiophene 1 bearing
an Fmoc-protected amine and a free carboxylic acid (Scheme 1
and Supporting Information, S1),8 representing the shortest member
of the oligothiophene class of p-channel organic semiconductors.
It mimics amino acid building blocks commonly employed in solid-
phase peptide synthesis (SPPS) and enables direct incorporation
of bithiophene into the backbones of known ꢀ-sheet forming motifs
to yield molecules such as 2.7e Previously, complex nonsymmetric
π-systems have been embedded within soluble biological motifs.9
With 2, environmental conditions that promoted carboxylate charge
screening (e.g., HCl or CaCl2) initiated self-assembly resulting in
the macroscopic formation of self-supporting gels suggestive of
entangled 1-D structures.
The IR spectrum for 2 displayed characteristic ꢀ-sheet amide I
bands at 1630 and 1641 cm-1 accompanied by minor random-coil
contributions.8 Circular dichroism (CD) of freely soluble 2 showed
no meaningful absorption while assembled 2 had intense absorptions
only associated with the π-conjugated unit (Figure 1A). Molecularly
dissolved 2 exhibited a low-energy absorption λmax at 320 nm.
Excitation at 320 nm triggered strong photoluminescence at 380
nm (Figure 1B). Upon assembly, the absorption profile remained
comparable but the emission was dramatically quenched. The
bisignate CD response crossing over at 320 nm (coincident with
the absorption λmax) is a classic signature for exciton-coupled
chromophores in chiral environments. Although formal H-ag-
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10.1021/ja805491d CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
structures with semiconductive π-systems. We are currently explor-
ing the scope of this assembly in terms of the π-conjugated amino
acids and the bioactive peptide sequences used during SPPS, as
well as the environmental conditions required to initiate assembly.
Understanding how these variables impact supramolecular associa-
tion will allow us to engineer and evaluate numerous biologically
relevant and electronically functional nanostructures in a rapid
manner.
Acknowledgment. We thank Johns Hopkins University for
financial support and Prof. D. H. Fairbrother for generous AFM
use. We thank M. Cline (Toscano Laboratory) and Dr. J. M.
McCaffery for instrumental assistance and G. Vadehra for early
synthetic assistance. S.R.D. acknowledges support from the NSF
as an IGERT Fellow through JHU’s Institute for NanoBioTech-
nology.
Figure 2. Energy-minimized illustration of ꢀ-sheets and π-stacks as line
drawings and space-filling models (left, thiophenes in yellow) and the helical
twist sense along a model aggregate (center, hydrogens omitted).
gregates require blue-shifted absorptions, the lower oscillator
strength of 2 may have led to less-pronounced effects. The natural
propensities for ꢀ-sheets to adopt macromolecular twists would also
dictate twisted H-aggregates.10 Although X-ray diffraction was
inconclusive, the photophysics associated with the spectroscopic
behavior above lead us to conclude that the bithiophene π-systems
intimately associate within a twisted chiral environment imposed
by ꢀ-sheet interactions throughout the assembled structure.
Atomic force microscopy (AFM) of gel samples deposited on
mica revealed 1-D nanostructures with heights ranging from 2 to 6
nm (Figure 1C,D). Given that 2 is ca. 42 Å in length, these objects
are consistent with coiled tape-like or even more complex fibrillar
structures, early thermodynamic sinks on the assembly energy
landscape that spans from free molecule to large amyloid-like fiber.
The rigidity of these structures is evident in the larger height profiles
near crossover junctions. In some cases we resolved 1-D structures
resting over a monolayer of flat tapes passivating the mica surface
(ca. 1 nm in height) attributed to strong interactions between flat
tapes and the highly polar mica surface.8,11 The influence of the
backbone-embedded quadrupole moment of the π-cloud must play
a role in affecting peptide-surface interactions: nanostructures
deposited on nonpolar substrates did not show any evidence for
monolayer passivation.8
Supporting Information Available: Experimental details, charac-
terization data, and additional microscopy. This material is available
free of charge via the Internet at http://pubs.acs.org.
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In conclusion, we report a new class of peptides bearing internal
π-conjugated segments that can be manipulated and assembled into
1-D nanostructures in completely aqueous and physiologically
relevant [Ca2+] environments. The clear photophysical changes
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