Synthesis of functional molecular rod oligomers

Article abstract of DOI:10.1039/b815099k

We are presenting the synthesis of a phenylene ethynylene-based rod containing an Fmoc protected amino group and an activated acid which can be applied to peptide couplings. This linear amino acid analogue is applied to the synthesis of di-, tri- and pent

Full text of DOI:10.1039/b815099k

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Synthesis of functional molecular rod oligomers†
Casper S. Andersen and Kurt V. Gothelf*
Received 29th August 2008, Accepted 2nd October 2008
First published as an Advance Article on the web 5th November 2008
DOI: 10.1039/b815099k
We are presenting the synthesis of a phenylene ethynylene-based rod containing an Fmoc protected
amino group and an activated acid which can be applied to peptide couplings. This linear amino acid
analogue is applied to the synthesis of di-, tri- and pentamers. The pentamer has a molecular mass of
6.5 kDa and is characterized by 1H NMR spectroscopy and MALDI-TOF MS. The method has
potential for the formation of long macromolecular oligomers.
During the last two decades it has been demonstrated that
individual organic molecules can possess electronic properties
very similar to those of silicon-based components.1 Wires, rec-
tifiers, memory units, and transistors are among the molecular
components that have been synthesized and tested.2 The major
obstacle for the realization of electronic circuits constructed from
individual molecules remains our lacking capability in assembling
the molecular building blocks into predetermined networks. Tour
et al. demonstrated the synthesis of molecular wires of up to
16 nm, which is impressive for a monodisperse organic molecule.3
Fig. 1 Structure of building block 1.
New solution phase and solid phase strategies were developed
to obtain these molecular wires. However, how to connect the
wire to other components, junctions and/or electrodes remains
an unsolved problem.
are pursuing. Furthermore, the module contains an Fmoc pro-
tected amino group and an activated ester for assembly by peptide
couplings. The terminal groups are protected salicylaldehydes,
which can potentially be deprotected after the first coupling for
the formation of metal salen bridges between the modules. Here
we demonstrate the synthesis of this compound and its application
to the synthesis of di-, tri- and pentamers by peptide couplings.
For construction of the terminal aryl moiety in 1 consisting
of a protected salicylaldehyde and a functional group for peptide
couplings, compound 4 was synthesized as outlined in Scheme 1.
According to a previously reported procedure,6 compound 2 was
formylated in a Duff reaction followed by acetal formation. The
resulting acid 3 is a hydrophilic and unstable compound, and
was benzylated on the phenol and the carboxyl groups to give
the stable compound 4 in an overall yield of 28% from 2. As
an alternative strategy we also tested the introduction of MOM
protective groups, but the resulting product was difficult to purify
and the reactions containing MOM-protecting groups led to poor
yields in the subsequent Sonogashira reactions.
One of the most studied classes of compounds for molecular
electronics—and in particular for wires—are the oligo(phenylene
ethynylene)-based components.1,2 The commonly used method
for preparation of oligo(phenylene ethynylene)s is the Sono-
gashira cross-coupling reaction between terminal acetylenes and
arylhalides.4 These reactions most often proceed with yields
ranging from 60 to 90%, accompanied by alkyne dimerization
as the most common byproduct. However, compared to the
efficiency of the single coupling cycles in oligonucleotide and
peptide synthesis (often >99%), the yields obtained in Sonogashira
reactions are not sufficiently high for the development of an
iterative synthesis of phenylene ethynylene oligomers using higher
numbers of units.
In previous studies we have applied the oligonucleotide-
functionalized molecular rod assembly of oligomers,5–7 whereas
here we present a method of assembling molecular rods by peptide
synthesis. The key molecular building block 1 (Fig. 1) contains
distinct features for application in peptide synthesis and possesses
the potential for subsequent chemical reactions. It is based on
a phenylene ethynylene backbone. Two dodecyloxy chains are
attached to the central part of the aryl rod to improve the solubility
of the intermediates and the macromolecular assemblies that we
Scheme 1 Synthesis of compound 4 in an overall yield of 28% from
compound 2.
Danish National Research Foundation: Centre for DNA Nanotech-
nology, Department of Chemistry and Interdisciplinary Nanoscience Center
(iNANO), Langelandsgade 140, 8000 Aarhus C, Denmark. E-mail: kvg@
chem.au.dk; http://www.cdna.dk; Fax: +45 8619 6199; Tel: +45 89423907
† Electronic supplementary information (ESI) available: Experimen-
tal procedures, and NMR and MS characterization data. See DOI:
10.1039/b815099k
The central 2,5-bis(dodecyloxy)-1,4-diethynylbenzene 5 was
prepared from hydroquinone according to modified literature
procedures.8 The Sonogashira reaction between 4 and 5, construct-
ing the molecular backbone by the formation of 6, proceeded in
58 | Org. Biomol. Chem., 2009, 7, 58–60
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61% yield (Scheme 2). By the treatment of 6 with LiOH in THF,
the diacid 7 was obtained quantitatively. In parallel studies we
have formed the diacid of a compound similar to 7, but without
the dodecyloxy groups; however, this compound was completely
insoluble in any solvent and impossible to purify. Compound
7 was—on the contrary—soluble in THF and after treatment
with dicyclohexylcarbodiimide (DCC) and pentafluorophenol,
compound 8 was obtained in 77% yield after crystallization.
Scheme 2 Formation of compound 8.
Scheme 4 Formation of monodisperse oligomers (dimer 11, trimers 12
and 13 and pentamer 14).
The reaction of compound 8 with mono 1-N-Fmoc-1,5-
diaminopentane with the aim of preparing 1 is a reaction which
gives an almost 2:1 ratio of compounds 1 and 9 in 40% and 19%
yields, respectively, along with recovery of 20% of the unreacted
starting material (Scheme 3). The Fmoc protecting groups in
diamide 9 were removed upon base treatment to give the diamine
building block 10.
equivalents of 1 at rt in the presence of DMAP. The product was
purified by precipitation and obtained in 60% yield. To obtain the
pentamer the Fmoc protecting groups in 12 were removed by mild
base treatment to yield diamine 13. Finally, reaction of 13 with two
equivalents of 1 gave the pentamer 14 in 75% yield. The identity
of pentamer 14 was verified by MALDI-TOF mass spectrometry
and 1H-NMR spectroscopy.
In summary we have demonstrated the synthesis of two conju-
gated molecular rods 1 and 10, both containing an oligo(phenylene
ethynylene) backbone and functional headgroups containing pro-
tected salicylaldehydes and functionalities for peptide couplings.
The building blocks have been applied to the formation of
oligomers such as dimer 11, trimers 12 and 13 and pentamer 14.
The pentamer is a macromolecular structure with a molecular
mass of 6.5 kDa as verified by MALDI-TOF mass spectrometry.
As we have previously demonstrated for the DNA-directed
assembly of similar structures,5 the protected salicylaldehydes
in the products can potentially be deprotected and applied to
the formation of metal-salen complexes, which are coplanar,
and furthermore such structures have potential as conducting
molecular wires.
Notes and references
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Scheme 3 Synthesis of compounds 1 and 10.
With the molecular building blocks 1 and 10 at hand we
were ready to test their applicability for coupling into oligomeric
structures.
By treatment of 2.0 equivalents of compound 1 with hex-
anediamine in THF/pyridine and in the presence of N,N -
dimethylaminopyridine (DMAP) the dimeric structure 11 was
formed and isolated in 94% yield (Scheme 4). Under similar
conditions the trimer 12 was formed by mixing diamine 10 with 2.1
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