TTFV-based molecular tweezers and macrocycles as receptors for fullerenes

Article abstract of DOI:10.1021/ol402093a

Hybrids of tetrathiafulvalene vinylogues (TTFVs) and planar arenes were synthesized via the click reaction to form tweezer-like and macrocyclic structures. These compounds were investigated as receptors for fullerenes (C₆₀ and C₇₀) b

Full text of DOI:10.1021/ol402093a

ORGANIC
LETTERS
2013
Vol. 15, No. 17
4532–4535
TTFV-Based Molecular Tweezers and
Macrocycles as Receptors for Fullerenes
Karimulla Mulla, Haseena Shaik, David W. Thompson, and Yuming Zhao*
Department of Chemistry, Memorial University, St. John’s, NL, Canada A1B 3X7
Yuming@mun.ca
Received July 24, 2013
ABSTRACT
Hybrids of tetrathiafulvalene vinylogues (TTFVs) and planar arenes were synthesized via the click reaction to form tweezer-like and macrocyclic
structures. These compounds were investigated as receptors for fullerenes (C60 and C70) by UVꢀvis absorption and fluorescence spectroscopy.
With the increasing application of fullerene-containing
materials in modern materials science and biological tech-
nology, how to detect and separate different types of
fullerenes has captured considerable attention.1 In this
context, the use of various synthetic receptors to form
guestꢀhost inclusion complexes with fullerenes has been
extensively studied.2 From a practical viewpoint, three
important features are desirable for an ideal fullerene
receptor as elaborated below. (1) Selectivity for specific types
of fullerenes. This issue can be tackled by aromatic-rich
molecular and macromolecular hosts which are preorganized
in such shapes as tweezers, rings, helix, cups, and cages, based
upon the notion of concaveꢀconvex complementarity.2,3
(2) Effective sensory function. So far, the chemical sensing
of fullerenes by rapid and noninvasive methods such as
fluorescence spectroscopy has been rarely addressed in the
literature.4 It is worth noting that development of fluores-
cence turn-on sensors for fullerenes is a challenging task,
given that fullerenes usually cause attenuation of emission
when bound to various fluorogenic moieties.4a,5 However,
(1) (a) Wilson, M. A.; Pang, L. S. K.; Vassallo, A. M. Nature 1992,
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Zhu, D. J. Org. Chem. 2006, 71, 3970.
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Soc. 2008, 130, 10674. (f) Marois, J.-S.; Cantin, K.; Desmarais, A.;
Morin, J.-F. Org. Lett. 2008, 10, 33. (g) Wietor, J.-L.; Pantos, G. D.;
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Sanders, J. K. M. Angew. Chem., Int. Ed. 2008, 47, 2689. (h) Perez, E. M.;
Sierra, M.; Sanchez, L.; Torres, M. R.; Viruela, R.; Viruela, P. M.; Ortı,
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K. A.; Cho, W.-S.; Sarova, G. H.; Petersen, B. M.; Bond, A. D.; Becher,
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r
10.1021/ol402093a
Published on Web 08/21/2013
2013 American Chemical Society

Scheme 1. Synthesis of TTFV-Arene Tweezers 3aꢀc via Click
Scheme 2. Synthesis of TTFV-Based Macrocycles 5a and 5b via
Click Reactions
Reactions
turn-on sensing gives significant advantages compared with
turn-off sensing, including good signal-to-noise ratio, high
sensitivity, and reduced false signaling. (3) Controllable
reversibility in interactions with fullerenes. Such a function
requires certain switching mechanism(s) to be integrated in
the molecular design of fullerene receptors and is beneficial
for supramolecular separation of various fullerenes.6
TTFV 1 via a well established click reaction, i.e., a Cu-
catalyzed alkyneꢀazide coupling reaction (CuAAC).7b,8
The click reactions were conducted in THF at 60 °C for
several hours in the presence of CuI and i-Pr2EtN, afford-
ing the desired TTFV tweezers 3aꢀc in high yields ranging
from 83% to 91%. The molecular structures of 3aꢀc were
confirmed by various spectroscopic characterizations,
and their tweezer-like molecular shapes were evidenced
by the single crystal X-ray structure of an analogous
dianthryl-TTFV compound.7c
In a similar manner, TTFV 1 was coupled with diazido-
arene 4a or 4b via the CuAAC reaction, wherein the
amounts of TTFV 1 and respective diazido-arene were
controlled at a 1:1 ratio. The click reactions led to the for-
mation of [2 þ 2] macrocyclic adducts 5a and 5b in yields
of 47% and 54% respectively (Scheme 2), which are
quite efficient for a one-pot cyclization process. The
relatively high yields can be attributed to a “templating
effect” imposed by the Cu(I) catalyst, for it is known
that the triazole group resulting from the click reac-
tion can coordinate to transition metal ions to form stable
complexes.9 It is proposed that such an effect enhances the
preorganization of reactive intermediates to favor macro-
cyclization over other possible side reactions.
The supramolecular interactions of tweezers 3aꢀc with
C60 and C70 fullerenes were investigated by UVꢀvis and
fluorescence titration experiments conducted in chloro-
benzene. Of great interest are the fluorescence responses of
these compounds to C60 and C70 fullerenes. Dinaphthyl-
TTFV 3a and macrocycle 5a did not show any significant
fluorescence changes upon titration of fullerenes, likely
due to their arene units (i.e., naphthalene and benzene)
being very poor fluorophores. For tweezers 3b,c and
macrocycle 5b, the arene units (anthracene and pyrene)
are much better fluorophores. These compounds show
moderatetoweakfluorescence, asa resultof the quenching
effect by the central electron-donating TTFV unit via a
photoinduced electron transfer (PET) mechanism.7b Upon
addition of C60 fullerene, dianthryl-TTFV 3b showed only
a slight degree of fluorescence enhancement (Figure 1A).
To develop new fullerene receptors with the three features
above-mentioned, we identified the diphenyl-substituted
tetrathiafulvalene vinylogue (TTFV) as a key building
block for the following reasons. First, TTFVs and deriv-
atives are good electron donors with highly reversible
redox activities.7a Therefore, integration of a TTFV moiety
into a fullerene receptor system should further strengthen
the binding with fullerenes via πꢀπ stacking and/or charge-
transfer interactions. Second, diphenyl-TTFVs exhibit re-
dox-controlled structural switchability. For instance, the
structure of a diphenyl-substituted TTFV adopts a pseudo-
cisoid, V-shaped conformation in the neutral state and
is switched to a transoid conformation upon oxidation.7
Finally, the regular V-shape of a neutral diphenyl-TTFV
upon covalent expansion can lead to tweezer-like and
macrocyclic structures, which in turn would create suitable
π-cavities for hosting fullerenes. Based on the above ratio-
nales, we have designed and synthesized a new class of TTFV-
arene hybrids as fullerene receptors. The compounds are
divided into two distinctive types;molecular tweezers and
macrocycles;in terms of molecular structures and shapes.
Scheme 1 outlines the synthesis of a series of TTFV-
based molecular tweezers 3aꢀc. Three azido-arenes 2aꢀc,
where the aryl groups are 1-naphthyl, 9-anthryl, and
1-pyrenyl respectively, were chosen to react with acetylenic
(6) (a) Zhang, C.; Wang, Q.; Long, H.; Zhang, W. J. Am. Chem. Soc.
2011, 133, 20995. (b) Stefankiewicz, A. R.; Tamanini, E.; Pantos, G. D.;
Sanders, J. K. M. Angew. Chem., Int. Ed. 2011, 50, 5725.
(7) (a) Zhao, Y.; Chen, G.; Mulla, K.; Mahmud, I.; Liang, S.;
Dongare, P.; Thompson, D. W.; Dawe, L. N.; Bouzan, S. Pure Appl.
Chem. 2012, 84, 1005. (b) Mulla, K.; Dongare, P.; Thompson, D. W.;
Zhao, Y. Org. Biomol. Chem. 2012, 10, 2542. (c) Mulla, K.; Zhao, Y.;
Dawe, L. N. Acta Crystallogr. 2012, E68, o3298. (e) Hapiot, P.; Lorcy,
D.; Tallec, A.; Carlier, R.; Robert, A. J. Phys. Chem. 1996, 100, 14823.
(f) Carlier, R.; Hapiot, P.; Lorcy, D.; Robert, A.; Tallec, A. Electrochim.
Acta 2001, 46, 3269.
(8) (a) Hein, J. E.; Fokin, V. V. Chem. Soc. Rev. 2010, 39, 1302.
(b) Meldal, M.; Tornøe, C. W. Chem. Rev. 2008, 108, 2952.
(9) Lau, Y. H.; Rutledge, P. J.; Watkinson, M.; Todd, M. H. Chem.
Soc. Rev. 2011, 40, 2848.
Org. Lett., Vol. 15, No. 17, 2013
4533

Table 1. Binding Constants for TTFV Tweezers and
Macrocycles with Fullerenes Obtained from Global Spectral
Analysis of the Fluorescence Spectral Titration Data
complexation
ratio (H/G)
log β11
(Mꢀ1
log β12
(Mꢀ2
host
guest
)
)
3b
3b
3c
3c
5b
5b
C60
C70
C60
C70
C60
C70
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
1:1
1:1
1:1
1:2
1:2
4.90 ( 0.05
4.87 ( 0.04
4.72 ( 0.03
ꢀ
11.10 ( 0.06
10.11 ( 0.11
ꢀ
Figure 1. Fluorescence spectral changes of (A) 3b upon addi-
tion of C60 (λex = 350 nm), (B) 3b upon addition of C70 (λex
350 nm), (C) 3c upon addition of C60 (λex = 375 nm), (D) 3c
upon addition of C70 (λex = 375 nm), (E) 5b upon addition of
Figure 2. (A) Fluorescence spectral changes of 3b upon addition
of C70 in the presence of a large excess of C60 (λex = 350 nm).
CPK models of optimized molecular structures for the com-
plexes of (B) 3b with C60, and (C) 3b with C70.
=
C
60 (λex = 350 nm), (F) 5b upon addition of C70 (λex = 340 nm).
When 3b was titrated with C70, however, significant
fluorescence enhancement was observed (Figure 1B). In
contrast, dipyrenyl-TTFV 3c and macrocycle 5b showed
prominent fluorescence turn-on responses to both C60 and
the binding events, and it can be concluded that increasing
the degree of π-conjugation of the arene units facilitates the
binding with fullerenes as well as enhances the fluorescence
turn-on responses.
C
70 (Figure 1C to 1F). In particular, 3c led to a 11.4-fold
From the binding studies, dianthryl-TTFV tweezer 3b
appears to show a very high selectivity for C70 over
C60 (Table 1). Such a property suggests potential use in
selective sensing and recognition of C70. To test this kind
of sensory performance, fluorescence titration of C70 to
a solution of 3b in the presence of a large excess of
C60 (>1000 mol equiv) was conducted and the results are
shown in Figure 2A. To our satisfaction, a significant fluor-
escence turn-on response to C70 was still retained in this
titration experiment, demonstrating the remarkable efficacy
of tweezer 3b in discriminating trace C70 out of excessive C60.
The high selectivity of 3b in terms of binding with
enhancement at the end point of titration with C60 and
a 4.4-fold enhancement with C70. The fluorescence turn-on
properties are likely originated from the interactions of
electron-accepting fullerenes with the electron-donating
TTFV moiety in the excited state, which attenuates non-
radiative decay pathways including the PET mechanism.
The spectral titration data were subjected to a global
spectral analysis using the SPECFIT program to determine
the binding stoichiometry and binding constants.3b,7b,10
Meaningful spectral fitting could not be attained from
the UVꢀvis titration results due to the complex spectral
overlap of various colorful species. The fluorescence data,
however, allowed good spectral fitting to be achieved to
quantitatively elucidate the binding properties. Dianthryl-
TTFV 3b exhibits selective affinity for C70 only, whereas
dipyrenyl-TTFV 3c shows a strong affinity for C60 and
C70 with similar binding constants. Obviously, the planar
arene “tips” of the TTFV tweezers play an important role in
C
As shown in Figure 2B, the optimized structure for the 1:1
70 can be rationalized by a molecular mechanics study.11
complex of 3b and C60 shows πꢀπ contacts only between
C
C
60 and the two anthracene units. The spherical shape of
60 does not allow the central TTFV moiety to be involved
(11) Molecular mechanics calculations were done using the SYBYL
force field implemented in the Spartan’10 software (Wave function, Inc.,
Irvine, CA). Alkyl chains were replaced with H atoms to save computa-
tional expense.
€
(10) Gampp, H.; Maeder, M.; Meyer, C. J.; Zuberbuhler, A. D.
Talanta 1985, 32, 251.
4534
Org. Lett., Vol. 15, No. 17, 2013

in the π-interactions with C60. The lack of contact between
60 and the central TTFV moiety thus accounts for the very
C
weak binding as well as insignificant fluorescence changes in
the titration results. The 1:1 complexation of 3b with C70, on
the contrary, shows that apart from the C70 and anthracene
interactions, one of the dithiole rings of the TTFV also has
direct πꢀπ contact with C70 (Figure 2C). The ellipsoidal
shape of C70 makes a very good fit in the π-cavity created by
the dianthryl-TTFV framework of tweezers 3b, rendering it a
highly selective receptor for C70 over C60. The direct contact
between C70 and the TTFV unit is believed to hinder the PET
and hence lead to fluorescence enhancement.
Figure 3. CPK models of optimized molecular structures for
the complexes of (A) C60@3c, (B) C70@3c, (C) 2C60@5b, and
(D) 2C70@5b.
In contrast to dianthryl-TTFV 3b, the relatively larger
π-surface of the dipyrenyl groups in 3c gives rise to
more intimate πꢀπ contact with C60 and C70 fullerenes
(see Figure 3A and B), resulting in strong binding strength
but without particular selectivity. The interactions of macro-
cycle 5b with C60 or C70 follow a 1:2 binding ratio as disclosed
by global spectral analysis. Modeling studies suggest that this
unique binding feature is attributable to the “bucket”-like
molecular shape of macrocycle 5b, which is preorganized well
to allow for two molecules of fullerenes to be loaded inside its
extended π-cavity (Figure 3C and 3D).
Finally, controllability over reversible interactions of
fullerenes with TTFV-arene hybrids was investigated.
The TTFV moiety is known to undergo reversible proto-
nation/deprotonation processes associated with dramatic
conformational changes.7a,12 Such properties have been
recently applied by our group to achieve reversible wrap-
ping and release of single-walled carbon nanotubes using
a TTFV-phenylacetylene polymer.12 Herein we expected
the same reversible mechanism to control the binding
and release of fullerenes. To demonstrate this property,
the complexes of macrocycle 5b and C60 were subjected
to titration with trifluoroacetic acid (TFA). For clear data
analysis, two absorption bands at 334 and 646 nm were
monitored by UVꢀvis spectroscopy. The absorption at
334 nm isdue to three colorful species: free C60, free5b, and
5b/C60 complexes. Figure 4A shows that, upon titration of
5b with C60, the absorption at 334 nm follows a bell-shaped
trend with a maximum at the point where ∼1.5 equiv of
Figure 4. (A) Absorbance of 5b (7.0 μM) at 334 nm as a function
of [C60]. (B) Absorbance of 5b (6.1 μM) and C60 (30.3 μM) at
334 nm as a function of [TFA]. (C) Absorbance of 5b (4.3 μM)
at 334 nm as a function of [TFA]. (D) Absorbance of 5b (6.1 μM)
and C60 (30.3 μM) at 646 nm as a function of [TFA]. All
titrations were done in chlorobenzene at rt.
In conclusion, we have not only prepared a series of
TTFV-arene based molecular tweezers and macrocycles
but also studied their supramolecular interactions with C60
and C70 fullerenes. Our results point to a great potential in
achieving selectively sensing and separation of different
fullerenes by molecular tailoring of TTFV-arene hybrids.
C60 is added. Figure 4B shows the absorbance changes of
5b/C60 complexes at 334 nm as a function of increasing
[TFA]. The plot exhibits aninverted bell-shapedtrend with
the minimum coinciding with the midpoint of titration.
As a comparison, the titration of 5b with TFA exhibits only a
decreasing trend for the absorbance at 334 nm (Figure 4C),
while monitoring the absorbance at 646 nm, which is
the signature absorption band for the protonated
TTFV,12b reveals a continuous increase of protonated
TTFV cations (Figure 4D). Based on these titration
analyses, the spectral trend in Figure 4B can be convin-
cingly assigned to the dissociation of the complexes of
2C60@5b with increasing protonation of the TTFV
moieties in macrocycle 5b.
Acknowledgment. We acknowledge NSERC, Canada
Foundation of Innovation (CFI), and Memorial Univer-
sity for financial support.
Supporting Information Available. Synthetic proce-
dures and spectroscopic characterization for new com-
pounds and relevant analysis of spectral data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(12) (a) Liang, S.; Chen, G.; Peddle, J.; Zhao, Y. Chem. Commun.
2012, 48, 3100. (b) Liang S.; Chen, G.; Zhao, Y. J. Mater. Chem. C 2013,
1, 5477ꢀ5490.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 17, 2013
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