A novel diketopyrrolopyrrole (DPP)-based [2]rotaxane for highly selective optical sensing of fluoride

Article abstract of DOI:10.1021/ol400221h

A novel [2]rotaxane based on an orthogonal H-bonded motif and 3,6-di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (DPP) with controlled topicity was successfully constructed, displaying excellent stimulated responses toward anion and solvent polarity. The preorganized host selectively recognized F^- with high optical sensitivity and reversibility via enhanced positive cooperativity and noncovalent interaction by evidence of a shorter fluorescence lifetime.

Full text of DOI:10.1021/ol400221h

ORGANIC
LETTERS
2013
Vol. 15, No. 6
1274–1277
A Novel Diketopyrrolopyrrole
(DPP)-Based [2]Rotaxane for Highly
Selective Optical Sensing of Fluoride
Mandapati V. Ramakrishnam Raju and Hong-Cheu Lin*
Department of Materials Science and Engineering, National Chiao Tung Univeristy,
Hsinchu 30049, Taiwan (ROC)
linhc@mail.nctu.edu.tw
Received January 25, 2013
ABSTRACT
A novel [2]rotaxane based on an orthogonal H-bonded motif and 3,6-di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione (DPP) with controlled
topicity was successfully constructed, displaying excellent stimulated responses toward anion and solvent polarity. The preorganized host
selectively recognized FÀ with high optical sensitivity and reversibility via enhanced positive cooperativity and noncovalent interaction by
evidence of a shorter fluorescence lifetime.
Developing bright and novel functional mechanically
interlocked molecules (MIMs) with controlled topicity for
selective and sensitive anion binding and sensing is of
current research interest in the field of anion supramo-
lecular chemistry owing to their indispensable roles in
biological and chemical processes.1 Due to its unique
chemical properties and significant aspects in pharmacol-
ogy, dental care, and treatment of osteoporosis, the fluo-
ride ion is one of the most intriguing targets among all
anions.2 It is thus imperative to develop MIM based
probes for sensitive and selective sensing of fluoride.
Controlled topology has been elegantly utilized by nature
in the recognition of anionic guests, inspired by many
artificial anion receptors to be developed for the specific
recognition of halides and other anions.3 Myriads of
molecular switches have been reported, due to their
exquisite responsiveness to stimuli4 and the handful of
optical anion sensors;5 however, those switches often
suffered in the recognition of anionic guests in a discrimi-
native fashion. To mimic this, we need a robust signaling
unit (fluorophore) and a cavity with unique topological
constraintsformedinsituby virtue of mechanicalbonding.
Additionally pervasive advantages of chromogenic and
fluorogenic molecular switches have been found because
of their ease in responding to subtle guest interactions in
microenvironments to perceivable outputs.6
(4) (a) Altieri, A.; Bottari, G.; Dehez, F.; Leigh, D. A.; Wong, J. K. Y.;
Zerbetto, F. Angew. Chem., Int. Ed. 2003, 42, 2296. (b) Qu, D. H.; Wang,
Q. C.; Ren, J.; Tian, H. Org. Lett. 2004, 6, 2085. (c) Kwan, P. H.;
MacLachlan, M. J.; Swager, T. M. J. Am. Chem. Soc. 2004, 126, 8638.
(d) Onagi, H.; Rebek, J., Jr. Chem. Commun. 2005, 4604. (e) Li, Y.; Li, H.;
Li, Y.; Liu, H.; Wang, S.; He, X.; Wang, N.; Zhu, D. Org. Lett. 2005, 7,
4835. (f) Lankshear, M. D.; Beer, P. D. Acc. Chem. Res. 2007, 40, 657. (g)
Lin, C.-F.; Liu, Y.-H.; Peng, S.-M.; Lai, C.-C.; Chiu, S.-H. Chem.;Eur. J.
2007, 13, 4350. (h) Zhou, W.-D.; Li, J.-B.; He, X.-R.; Li, C.-H.; Lv, J.; Li,
Y.-L.; Wang, S.; Liu, H.-B.; Zhu, D.-B. Chem.;Eur. J. 2008, 14, 754. (i)
Jiang, Q.; Zhang, H. Y.; Han, M.; Ding, Z. J.; Liu, Y. Org. Lett. 2010, 12,
1728. (j) Megiatto, J. D.; Schuster, D. I. Org. Lett. 2011, 13, 1808. (k) Li, H.;
Zhang, H.; Zhang, Q.; Qu, D.-H. Org. Lett. 2012, 14, 5900.
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r
10.1021/ol400221h
Published on Web 03/05/2013
2013 American Chemical Society

The exceptional thermal and light stabilities of 3,6-
di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione
(DPP) and its derivatives along with the remarkable
photophysical properties make them expedient candi-
dates in designing new functional MIMs.7 Since fluoride
ions have a strong reactivity with receptor groups, such as
amine, amide, lactam, urea, thiourea, and phenol, due to
its high electronegativity and small ionic size, miscella-
neous macrocyclic and tweezer-shaped receptors have
been reported.8 However, reports based on [2]rotaxanes
with controllable topology under external stimuli that
have specific anionic guest binding abilities are still due.
Herein, we designed and synthesized a first example of a
DPP stoppered [2]rotaxane 2-P containing an orthogonal
bifurcated pyridineÀpyridine H-bonded motif. This de-
signwas found to be ideal for solvent inducedshuttling and
specific fluoride ion sensing with sensitive chromogenic
and fluorogenic functions along with remarkable reversi-
bilities.5a,9 The key building blocks, i.e., pseudorotaxane 2
and asymmetric diketopyrrolopyrrole derivative 3, were
prepared in good yields. Compound 2 was synthesized
from the monodentate thread 1 and a preformed macro-
cycle-Pd tridentate ligand10 using a palladium active metal
template approach (see Supporting Scheme S1). Novel
asymmetric DPP derivative 3 was prepared from 11 in
three steps. First, compound 11 was monoalkylated with
2-ethylhexyl bromide to acquire compound 12, which was
further alkylated with propargyl bromide to afford 13.
Then, it was brominated by NBS to obtain asymmetric
DPP derivative 3 as shown in Supporting Scheme S1.
The building blocks 2 and 3 were coupled by utilizing
a click reaction strategy to afford metalated [2]rotaxane
2-M, likewise the control axle 1-C was prepared. To
manipulate guest binding capabilities, 2-M was demeta-
lated using potassium cyanide in CHCl3/MeOH to pro-
duce the final [2]rotaxane 2-P as depicted in Scheme 1.
Scheme 1. Synthetic Route of [2]Rotaxane 2-P
the existence of an overwhelming interlocked nature
through an orthogonal bifurcated pyridineÀpyridine
H-bonding between axle and wheel. Moreover, in rela-
tively polar solvent d6-DMSO the observed upfield shifts
for resorcinol protons (7 and 9) along with downfield shifts
for pyridyl protons (12, 13, and 14) and macrocycle amide
protons C suggested that the cycle was translocated to the
resorcinol unit as the H-bonding basicity was increased
(Scheme 1 and Figure 2). Thus, [2]rotaxane presents two
translational isomers under different solvent polarities in
which the macrocycle resides on the pyridine unit in CDCl3
(translational isomer 2-P) and on the resorcinol unit in
DMSO (translational isomer 2-R).11
1
The H NMR spectra of [2]rotaxane 2-P, control axle
1-C, and macrocycle were compared in CDCl3 (Figure 1).
Upfield shifts for axle pyridyl protons (12, 13, and 14) and
macrocycle protons (E and F) along with a 1.5 ppm
downfield shift for macrocycle amide protons C indicated
(6) Lakowicz, J. R. Principles of Fluorescence Spectroscopy; Kluwer
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Rybak-Akimova, E. V. Org. Lett. 2006, 8, 3171. (b) Kaewtong, C.;
Fuangswasdi, S.; Muangsin, N.; Chaichit, N.; Vicens, J.; Pulpoka, B.
Org. Lett. 2006, 8, 1561. (c) Kim, J. S.; Quang, D. T. Chem. Rev. 2007,
107, 3780. (d) Sessler, J. L.; Kim, S. K.; Gross, D. E.; Lee, C. H.; Kim,
J. S.; Lynch, V. M. J. Am. Chem. Soc. 2008, 130, 13162. (e) Kim, S. K.;
Lynch, V.; Young, N. J.; Hay, B. P.; Lee, C. H.; Kim, J. S.; Moyer, B. A.;
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Muangsin, N.; Pulpoka, B. Org. Lett. 2012, 14, 4050.
To probe the anion recognition affinities of [2]rotaxane,
we employed 1H NMR titrations of 2-P in CDCl3 overÀa
range of anions, such as FÀ, ClÀ, BrÀ, IÀ, AcOÀ, NO3
,
and H2PO4À, with 3 equiv of respective tetrabutylammonium
salts (Figure S1). Interestingly, no other anions showed any
significant spectroscopic changes except FÀ. Taking this
vivid spectroscopic clue, further titrations were conducted
(9) Barrell, M. J.; Leigh, D. A.; Lusby, P. J.; Slawin, A. M. Z. Angew.
Chem., Int. Ed. 2008, 47, 8036.
(10) (a) Furusho, Y.; Matsuyama, T.; Takata, T.; Moriuchi, T.;
Hirao, T. Tetrahedron Lett. 2004, 45, 9593. (b) Fuller, A. M.; Leigh,
D. A.; Lusby, P. J.; Oswald, I. D. H.; Parsons, S.; Walker, D. B. Angew.
Chem., Int. Ed. 2004, 43, 3914. (c) Leigh, D. A.; Lusby, P. J.; Slawin,
A. M. Z.; Walker, D. B. Angew. Chem., Int. Ed. 2005, 44, 4557. (d)
Crowley, J. D.; Leigh, D. A.; Lusby, P. J.; MaBurney, R. T.; Perret-Aebi,
L.-E.; Petzold, C.; Slawin, A. M. Z.; Symes, M. D. J. Am. Chem. Soc.
2007, 129, 15085. (e) Fuller, A. M.; Leigh, D. A.; Lusby, P. J. J. Am.
Chem. Soc. 2010, 132, 4954.
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1997, 119, 11092. (b) Chiang, P.-T.; Cheng, P.-N.; Lin, C.-F.; Liu, Y.-H.;
Lai, C.-C.; Peng, S.-M.; Chiu, S.-H. Chem.;Eur. J. 2006, 12, 865. (c)
Mateo-Alonso, A.; Ehil, C.; Guldi, D. M.; Prato, M. Org. Lett. 2013, 15, 84.
Org. Lett., Vol. 15, No. 6, 2013
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Figure 1. 1H NMR spectra (CDCl3, 300 MHz, 298 K): (a)
macrocycle, (b) 1:1 mixture of control axle 1-C and macrocycle,
(c) 1-C, (d) [2]rotaxane 2-P. The assignments correspond to the
lettering shown in Scheme 1 (numerical and alphabetical letter-
ing indicating dumbbell part and macrocycle, respectively).
1
Figure 3. Changes in H NMR (300 MHz, d6-DMSO, 298 K)
spectrum of [2]rotaxane 2-R (3 mM) during titration with TBAF
(0À4 equiv). Red circled region indicating the formation of the
HF2À ion. The assignments correspond to the lettering shown in
Scheme 1.
with FÀ. Upon the progressive addition of FÀ, significant
upfield shifts were observed for cavity and thread protons
along with the disappearance of amide NH protons at 1
equiv of FÀ. On further addition, no obvious changes were
observed as shown in Figure S2. Importantly, the [2]rotaxane
precursors, such as 1-C and 2-M, could not show observable
changes with the addition of 3 equiv of FÀ (Figure S3).
corresponding to free TBAF at À102.5 ppm was upfielded
to À103.8 ppm (Δδ = 1.3 ppm) upon the addition of 2-R
solution (3 equiv) to TBAF. Moreover, the weak doublet
corresponding to HF2 at À143.1 ppm was gradually
À
raiseÀd in its intensity with a declined triplet intensity of
DF2 at À143.5 ppm simultaneously as depicted in
Figure S4.8a Importantly the binding process of 2-R/FÀ
was completely reversible upon the addition of CF3COOH
(TFA, 5 equiv) and provided a spectrum identical to that
of the original rotaxane (Figure S5). Thus, [2]rotaxane
2-R selectively recognized FÀ through a noncovalent
interaction due to a positive cooperativity between the
2,6-dicarboxyamidopyridine receptor (in macrocycle)
and FÀ, and further guest equivalents would deprotonate
the amide cleft and induce a macrocycle shuttling.
Next, we focused on the photophysical properties of
1-C, 2-M, and 2-R under the influence of chemical stimuli
(solvent and anionic guests). To escalate future aqueous
soluble functional MIMs, we further carried out all photo-
physical measurements in DMSO. Both absorption and
fluorescence intensities of [2]rotaxane were sharply de-
creased in the relative polar solvent DMSO (Figure S6),
which lucidly indicated the translocation of the wheel from
pyridine to the resorcinol unit as the H-bond formed
between pyridine and the wheel was disrupted, which is
consistent with our above 1H NMR observations as well as
previous reports.4d,11c
Figure 2. 1H NMR spectra (300 MHz, 298 K): (a) [2]rotaxane
translational isomer 2-P in CDCl3, (b) [2]rotaxane translational
isomer 2-R in d6-DMSO. The assignments correspond to the
lettering shown in Scheme 1.
1
Furthermore, H and 19F NMR titrations were con-
ducted in polar solvent DMSO to appreciate the sensing
ability of [2]rotaxane and to attain a better insight into the
binding interaction of 2-R/FÀ. The 1H NMR spectrum of
2-R showed significant changes upon the addition of FÀ.
As the addition of FÀ reached 1 equiv, the cavity and
thread protons, such as pyridine and the resorcinol unit,
showed upfield shifts. On further addition the spectrum
became broad as well as the amide NH protoÀn C com-
pletely disappeared and formed a strong HF2 peak at
4 equiv of FÀ (Figure 3).
UVÀvis and fluorescence measurements were explored
to probe the optical anion sensing abilities of 2-R, and
significant absorption changes in the absorption maxima
of DPP (564 and 525 nm) and nonfluorogenic axle part
(274 nm) wereobserved. Asdepicted inFigure4a, upon the
gradual addition of TBAF (0À40 equiv), the original
absorption maxima of DPP decreased with two emerging
new peaks at 257 and 451 nm. Simultaneously, the emis-
sion maximum of 2-R at 582 nm (λex = 525 nm) was
Delightfully, the binding mode was clearly revealed by
19F NMR titrations in DMSO, in which the sharp singlet
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Org. Lett., Vol. 15, No. 6, 2013

gradually quenched (Figure 4b). Since the titration pat-
terns of absorption and 1H NMR were complex, we
employed fluorescence titrations to determine the stoichio-
metry and binding constant. Unambiguously, the results
established a 1:1 stoichiometry of the 2-R/FÀ complex and
yielded a binding constant of 2.65 Â 104 MÀ1 (see Figures S7a
and S7b).12,13
DPP in relative polar solvent DMSO. Eventually, this
process facilitates the supramolecular electronic coupling
between DPP and the 2-R/FÀ complex and thus affects the
photophysical properties of the current functional MIM.5d,14
To corroborate the above observations, time-resolved
fluorescence measurements were carried out for the 2-R
and 2-R/FÀ complex probed at 582 nm (excited at 525 nm).
Significantly, as shown in Figure 5, time-resolved fluores-
cencebecame a biexponential decaywiththe lifetime of(τ1)
5.71 ns (69.21%) and (τ2) 2.19 ns (30.79%) from the
original monoexponential decay with a lifetime of (τ1)
5.56 ns. The shorter value can be attributed to the charged
wheel (amide deprotonation by FÀ), and the longer value
represents the intrinsic fluorescence of the DPP fluorophore.
However, the lifetime values of 1-C and 2-M remained
constant from their original monoexponential decay even
in the presence of FÀ (see Figures S11a and S11b).
Figure 4. (a, b) UVÀvis and fluorescence spectral changes of 2-R
(1 Â 10À5 M in DMSO) upon the addition of TBAF in DMSO (0À
40 equiv), respectively. Inset pictures in (a) and (b) indicate naked
eye color changes as well as fluorescence changes under UV light
(365 nm) upon the addition of TBAF, respectively (λex = 525 nm).
Further selectivity of the [2]rotaxane host system was
verified by titrations of anions, such asClÀ, BrÀ, IÀ, AcOÀ,
NO3À, and H2PO4À. Importantly, none of the above
anions could show noticeable changes in either the absorp-
tion or emission spectra. Moreover, to strengthen the
selectivity of [2]rotaxane, we did control titrations on its
precursors 1-C and 2-M. However, their responses were
trivial under similar conditions (see Figures S8aÀS8f).
The observable naked eye color change of 2-R from pink
to pale green upon the addition of TBAF was consistent
with our absorption trends. Other anions could not change
the color, as their sizes were too large to interact with the
cavity. Moreover, 1-C and 2-M did not show any obvious
color changes with all anions (see Figures S9aÀS9d).
Remarkably, the onÀoffÀon fluorescence etiquette of
the 2-R/FÀ complex was successfully achieved via the
alternative addition of FÀ and TFA up to four cycles,
which proved the excellent chromogenic and fluorogenic
functions along with reversibility of this novel functional
molecular switch. To verify the dramatic color change and
fluorescence quenching of the DPP molecule, we further
carried out electrochemical titrations of 2-P with FÀ (see
Figures S10a and S10b). A dramatic cathodic shift of
ΔE1/2 = 450 mv at 1 equiv of FÀ was observed, and a
further addition of FÀ showed a steady cathodic perturba-
tion, which is consistent with our 1H NMR and UVÀvis
titration trends. Based on these results, we infer that the
smallest anion FÀ could be easily percolated into the
macrocycle to form H-bonding with the 2,6-dicarboxy-
amidopyridine unit, and further guest equivalents would
deprotonate the amide cleft to induce the shuttling of the
charged wheel over the thread and toclose the proximity of
Figure 5. Time resolved fluorescence spectral changes of
[2]rotaxane 2-R before and after the addition of TBAF.
In summary, a bright DPP functionalized [2]rotaxane
was synthesized and well characterized. The preorganized
cavity formed in rotaxane by virtue of mechanical bond
enhanced stimulated responses toward solvent and FÀ via
noncovalent interactions. It was demonstrated spectro-
scopically that the [2]rotaxane 2-R host could selectively
recognize FÀ with remarkable chromogenic, fluorogenic,
and reversible functions. A prevailing time-resolved fluo-
rescence profile proved the sensitivity of 2-R in contrast to
its precursors. As the complex quenching mechanism was
coupled withbothcharged macrocycle shuttling and chem-
ical stimuli, the electron or energy transfer between
macrocycle and fluorophore could not be easily differen-
tiated. Further kinetic and transient absorption studies are
currently underway in our laboratory, which will be re-
ported in due course. Hence, this design of functional MIMs
could be ideal for developing future allosteric anion sensors.
Acknowledgment. We thank the National Science
Council of Taiwan (ROC) for financial support of this
project through NSC 99-2113-M-009-006-MY2 and NSC
99-2221-E-009-008-MY2.
Supporting Information Available. Synthetic proce-
dures, supporting Figures S1ÀS11, and compound char-
acterization data (IR, 1H, 13C NMR, and MALDI-TOF
mass). This material is available free of charge via the
Internet at http://pubs.acs.org.
(12) Strutt, N. L.; Forgan, R. S.; Spruell, J. M.; Batros, Y. Y.;
Stoddart, J. F. J. Am. Chem. Soc. 2011, 133, 5668.
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The authors declare no competing financial interest.
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