Synthesis and properties of TTFV-hinged molecular tweezers

Article abstract of DOI:10.1016/j.tetlet.2010.10.032

Two molecular tweezers containing a tetrathiafulvalene vinylogue (TTFV) core were synthesized via sequential Sonogashira and Horner-Wadsworth-Emmons (HWE) reactions. The electrochemical and spectroscopic properties of these TTFV tweezers were investigated by UV-vis absorption spectroscopy, cyclic voltammetry, and spectro-electrochemical measurements. The property characterizations suggest potential application in electrochemically-actuated molecular switching devices.

Full text of DOI:10.1016/j.tetlet.2010.10.032

Tetrahedron Letters 51 (2010) 6552–6556
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Synthesis and properties of TTFV-hinged molecular tweezers
⇑
Guang Chen, Stephen Bouzan, Yuming Zhao
Department of Chemistry, Meorial University of Newfoundland, St. John’s, NL, Canada A1B 3X7
a r t i c l e i n f o
a b s t r a c t
Article history:
Two molecular tweezers containing a tetrathiafulvalene vinylogue (TTFV) core were synthesized via
sequential Sonogashira and Horner–Wadsworth–Emmons (HWE) reactions. The electrochemical and
spectroscopic properties of these TTFV tweezers were investigated by UV–vis absorption spectroscopy,
cyclic voltammetry, and spectro-electrochemical measurements. The property characterizations suggest
potential application in electrochemically-actuated molecular switching devices.
Received 8 September 2010
Revised 2 October 2010
Accepted 6 October 2010
Available online 14 October 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Tetrathiafulvalene (TTF) derivatives aside from their traditional
use for organic conducting materials1 have recently attracted
growing attention as building blocks for stimuli-responsive molec-
ular devices such as sensors, switches, and logic gates.1a,2 Of
numerous TTF derivatives, diaryl-substituted vinylogous tetra-
thiafulvalene (TTFV) shows unique conformational switching prop-
erty associated with a simultaneous two-electron redox reaction
occurring on the TTFV moiety.3 Upon oxidation the TTFV scaffold
changes from cis to trans conformation as a result of significant
electrostatic repulsion between the two dithiolium rings. This
switching process is rapid, reversible, and readily actuated by elec-
trochemical or chemical inputs. Taking advantage of this property,
a number of TTFV-based switchable ligands for metal cations has
been previously prepared and investigated.2a,3c,4 Most recently,
our group reported the use of a simple acetylenic TTFV precursor
to selectively construct two distinct types of TTFV-macromole-
cules, shape-persistent macrocycles and linear polymers, wherein
the conformational switching of TTFV dictating the synthetic
consequences.5
electronic properties of TTFV,3–5 the molecular tweezers are
accordingly envisioned to exhibit easy controllability and versatile
adaptability for the preparation of functional molecular switching
devices.
Prior to testing the tweezer-like behavior, proof-of-concept
model compounds need to be prepared. In this Letter, we report
the synthesis and molecular properties of two TTFV-hinged
molecular tweezers, the tip regions of which were designed to
The unique switching property of diaryl-substituted TTFV led us
to envisage its usefulness as a molecular hinge for electrochemi-
cally-actuated molecular tweezers.6 To further explore this con-
cept, we designed a new type of TTFV molecular tweezers. As
shown in Scheme 1, two
p-conjugated functional groups are en-
listed as the ‘tips’ of tweezers, which are connected to a central
TTFV core through rigid covalent linkage. In principle, such TTFV
tweezers would assume a stable V-like molecular shape in the neu-
tral state, giving a ‘close’ form in which the
close enough to allow co-operative ‘griping’ of a guest molecular
species through non-covalent forces such as -stacking or
p-tips are spatially
p
charge-transfer interactions. Upon oxidation, the TTFV molecular
hinge would rotate into a linear trans orientation, thus ‘opening’
the molecular tweezers to release the guest. Given the remarkable
⇑
Corresponding author. Tel.: +1 709 864 8747; fax: +1 709 864 3702.
E-mail address: yuming@mun.ca (Y. Zhao).
Scheme 1. General structure of TTFV-hinged molecular tweezers.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.032

G. Chen et al. / Tetrahedron Letters 51 (2010) 6552–6556
6553
Scheme 3. Synthesis of TTFAQ-TTFV-TTFAQ 5 by HWE reaction.
As shown in Scheme 3, phosphonate 48 was first treated with a
strong base, n-BuLi, at low temperature to form phosphonate ylide.
AQ-TTFV-AQ 3 was next added to react with the in situ generated
phosphonate ylide, affording the desired molecular tweezers 5
which is a TTFAQ-TTFV-TTFAQ triad. The HWE reaction produced
5 in reasonable yields; however, purification of 5 by column chro-
matography was found tedious and tricky. Compound 5 tends to
decompose slowly in contact with silica gel. As a result, the isolated
yield of 5 often showed significant variation as a function of the
duration of column chromatographic separation.
Scheme 2. Synthesis of AQ-TTFV-AQ 3 by Sonogashira coupling.
In addition to the HWE strategy, we have also tried an alterna-
tive Sonogashira coupling route to synthesize compound 5. As
shown in Scheme 4, a mono-iodo substituted TTFAQ precursor 7
was first prepared by a P(OEt)3-promoted olefination reaction9 be-
tween 2-iodoanthraquinone 28c and thione 68 in toluene at 100 °C.
The reaction gave the desired product 7 in 43% yield, along with
the formation of two byproducts 8 and 9 resulting from incomplete
olefination. All these compounds were readily separated and puri-
fied by column chromatography. Cross-coupling of 7 with desily-
lated TTFV 1 under the catalysis of Pd/Cu in Et3N afforded
compound 5, which precipitated out during the reaction. The crude
product could then be easily purified by flushing through a short
silica plug with CHCl3, giving pure 5 in a yield of 62%. The short
separation procedure considerably reduced the undesirable
decomposition of 5 when exposed to silica gel, therefore, ensuring
more consistent and reproducible yields for this reaction.
be anthraquinone (AQ) or anthraquinoid-type
thiafulvalene (TTFAQ), respectively. In the ground state, the AQ
p-extended tetra-
group has a planar
p-framework, whereas TTFAQ takes a sad-
dle-like structure.7 Given the rich electronic properties of AQ
and TTFAQ, the two designed molecular tweezers are thus ex-
pected to show supramolecular interactions with certain aromatic
species via
p-stacking and charge-transfer forces. Moreover, the
tweezers are donor/acceptor molecular arrays that may find
applications in organic electronic materials and molecular switch-
ing devices.7
Scheme 2 illustrates the synthesis of AQ-tipped molecular twee-
zers 3. Acetylenic TTFV precursor 1 was first prepared through the
method we previously reported.5 Removal of the trimethylsilyl
groups in TTFV 1 with K2CO3, followed by Sonogashira coupling
with 2-iodoanthraquinone (2), afforded molecular tweezers 3 in
66% yield. Note that compound 3 is an acceptor–donor–acceptor
triad in electronic structure and hence is referred to as AQ-TTFV-
AQ in the following discussions. With compound 3 in hand, the tar-
geted TTFAQ-tipped tweezers were supposed to be readily obtained
through a twofold Horner–Wadsworth–Emmons (HEW) reaction.
The molecular structures of TTFV-hinged tweezers 3 and 5 were
characterized by IR, NMR, and MS analyses.10 The electrochemical
redox properties of 3, 5, and TTFV precursor 1 were investigated by
cyclic voltammetry (CV), and detailed cyclic voltammograms are
given Figure 1.

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G. Chen et al. / Tetrahedron Letters 51 (2010) 6552–6556
Scheme 4. Synthesis of TTFAQ-TTFV-TTFAQ 5 by Sonogashira coupling.
Figure 1. Cyclic voltammograms of (A) TTFV 1, (B) AQ-TTFV-AQ 3, and (C) TTFAQ-
TTFV-TTFAQ 5. Experimental conditions: analyte (ca. 10À3 M); Bu4NBF4 (0.1 M) as
supporting electrolyte; CH2Cl2 as solvent; glassy carbon as working electrode; Pt
wire as counter electrode; Ag/AgCl as reference; scan rate 0.1 V sÀ1
.
From Figure 1A, it can be seen that TTFV 1 gives a reversible
redox couple at Epa = +0.67 V and Epc = +0.46 V, which are attrib-
uted to a simultaneous two-electron process. In the CV profile of
AQ-TTFV-AQ 3 (Fig. 1B), the TTFV-originated redox wave pair is sig-
nificantly shifted relative to TTFV 1. The Epa value is shifted to less
positive direction at +0.61 V, while Epc to more positive potential at
+0.54 V, indicating increased electrochemical reversibility. The for-
mal oxidation potential (Epa + Epc)/2 of 3 (+0.58 V) is observed to be
slightly greater than that of TTFV 1 (+0.57 V), as a result of the
Figure 2. (A) UV–vis absorption spectra of 1, 3, and 5 measured in CH2Cl2. (B) UV–
vis spectrum of 3 comparing against the spectrum of mixture of 1 and 2 (in 1:2
molar ratio).
electron-withdrawing effect of the AQ groups on the TTFV unit in
3 through
p
-conjugation.2m,8c,d In the negative potential window,

G. Chen et al. / Tetrahedron Letters 51 (2010) 6552–6556
6555
two reversible redox wave pairs are observed, which are typical of
the successive two-step reduction of AQ and indicate no electronic
communication between the two AQ groups.8c Of interest is the
cyclic voltammogram of TTFAQ-TTFV-TTFAQ 5 (Fig. 1C). In the ano-
dic scan, only one oxidation peak is observed at +0.68 V. The cur-
rent intensity of this peak suggests it arise from simultaneous
oxidation at the central TTFV and the two TTFAQ moieties involv-
ing total 6 electrons. In the cathodic scan, however, two reduction
peaks are seen at +0.55 V and +0.23 V, respectively. The former is
likely due to the reduction of the central TTFV unit, while the latter
corresponds to the reduction of the two TTFAQ moieties. The CV
patterns of 5 reveal a significant degree of electronic contact be-
tween the TTFV and TTFAQ groups within the molecule.
The electronic absorption properties of molecular tweezers 3
and 5 were investigated by UV–vis absorption spectroscopy. Figure
2A compares the absorption spectra of 1, 3, and 5. TTFV 1 shows an
absorption band at 380 nm in the low-energy region. In the spec-
trum of AQ-TTFV-AQ 3, a notable absorption shoulder at 460 nm
along with broad long-wavelength absorption tail extending to
ca. 580 nm is observed. To clarify the origin of this band, UV–vis
spectrum of a 1:2 mixture of TTFV 1 and AQ 2 was determined
and compared with the spectrum of 3 (Fig. 2B). The absence of such
a low-energy absorption band in the UV–vis profile of the mixture
of 1 and 2 confirms that the long-wavelength shoulder and tail in
the spectrum of 3 is due to intramolecular charge transfer (ICT).
This conclusion is in agreement with the CV results, indicating very
significant electronic interaction between the TTFV and AQ moie-
ties through acetylenic linkage. The absorption spectrum of
TTFAQ-TTFV-TTFAQ 5 shows a broad low-energy band peaking at
416 nm, the origin of this band can be assigned to overlapped
8c,d
*
p?p
transition bands of TTFV and TTFAQ.
To gain a deeper insight into the redox process, UV–vis spectro-
electrochemical analyses were performed on compounds 1, 3, and
5. Detailed experimental results are shown in Figure 3. The absorp-
tion band of TTFV 1 at 380 nm is observed to decrease with
increasing applied potential ( Fig. 3A). In the meantime, a new
long-wavelength absorption band emerges with
a peak at
642 nm and a shoulder at 713 nm. This band is ascribed to the
characteristic absorption of dication [TTFV]2+. In the spectro-elec-
trochemical measurements of AQ-TTFV-AQ 3, a similar long-wave-
length band is observed to grow with increasing applied potential,
indicating the formation of [TTFV]2+. The ICT band of 3 at 380 nm is
observed to steadily reduce as the oxidation of TTFV progresses,
while the absorption due to AQ at ca. 360 nm remains unchanged.
For TTFAQ-TTFV-TTFAQ 5, a broad band peaking at 650 nm grows
with increasing applied potential. Concomitantly, the absorption
band at 416 nm shows a significant decrease and a band at ca.
330 increases notably. According to the CV data, the spectral
changes in Figure 3C are attributed to the simultaneous formation
of [TTFV]2+ and [TTFAQ]2+ in compound 5 during electrolysis. Over-
all, the spectro-electrochemical studies corroborate that the TTFV
units in molecular tweezes 3 and 5 undergo a two-electron oxida-
tion process similar to TTFV precursor 1 upon electrochemical oxi-
dation. Given the already known conformational switching
behavior of TTFV 1 taking place in electrochemical redox reaction,5
it is reasonably to believe that the conformations of the two molec-
ular tweezers 3 and 5 should be electrochemically controllable as
proposed in Scheme 1.
Figure 3. UV–vis spectral changes with increasing applied potential steps during
electrolysis. Experimental conditions: Bu4NBF4 (0.1 M) as supporting electrolyte;
CH2Cl2 as solvent; Pt mesh as working electrode; Pt wire as counter electrode; Ag/
AgCl as reference.
suggests usefulness in the preparation of molecular switching de-
vices. We are currently investigating the supramolecular guest–
host chemistry of this type of TTFV molecular tweezers, and further
results will be disclosed in due course.
Acknowledgments
The authors thank NSERC, CFI, and Memorial University of New-
foundland for funding support.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.10.032.
In summary, two new TTFV-hinged molecular tweezers with AQ
or TTFAQ as the side groups were synthesized via sequential Sono-
gashira and HWE reactions. Electrochemical and spectroscopic
analyses revealed significant electronic communications between
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G. Chen et al. / Tetrahedron Letters 51 (2010) 6552–6556
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128.8, 128.4, 126.7, 126.6, 126.5, 126.43, 126.36, 126.2, 126.0, 125.7, 125.63,
125.57, 125.4, 123.8, 123.4, 123.0, 121.5, 121.4, 90.48, 90.45, 19.3, 19.2, 19.1;
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837 cmÀ1; MALDI-TOF MS (+eV) m/z calcd for C76H58S24 1737.7836, found
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