Bidirectional photoinduced electron-transfer quenching is observed in 4-amino-1,8-naphthalimide-based fluorescent anion sensors

Article abstract of DOI:10.1021/jo8012594

(Chemical Equation Presented) The synthesis and photophysical evaluations of two new fluorescent photoinduced electron-transfer (PET) anion sensors, 1 and 2, is described. These are based on 4-amino-1,8-naphthalimide fluorophores and diarylthiourea anion receptors, connected via a methylene spacer to the imide. The sensing of acetate, phosphate, and fluoride, on all occasions, gave rise to quenching in the fluorescence of 1 and 2, similar to that seen for the structural isomer 3. These results demonstrate that bidirectional PET sensing occurs in such naphthalimide-based anion sensors.

Full text of DOI:10.1021/jo8012594

SCHEME 1. Synthesis of the PET Anion Sensors 1 and 2
Bidirectional Photoinduced Electron-Transfer
Quenching Is Observed in
4-Amino-1,8-naphthalimide-Based Fluorescent
Anion Sensors
Emma B. Veale and Thorfinnur Gunnlaugsson*
School of Chemistry, Center for Synthesis and Chemical
Biology, Trinity College Dublin, Dublin 2, Ireland
gunnlaut@tcd.ie
ReceiVed June 11, 2008
tures, in a similar manner to that seen for the photosynthetic
reaction center. This was first proposed, and demonstrated, by
de Silva and Rice in 1996.12a By using several structural isomers
of pH-based Naph PET sensors (using tertiary amines as
receptors), they showed that the Naph emission was only
“switched on” when the H+ receptors were connected at the
4-amino moiety.12a The theoretical examination for this direc-
tionality was subsequently investigated by Marcus et al.13 who
concluded that this directionality was “due to the difference in
the electronic coupling matrix elements (|V|) for the two
reactions” and that the electron transfer from the 4-amino side
was ∼104 times faster than from the imide side. Such direc-
tionality has also been investigated by Qian et al.14a and Tian
et al.14b using Naph-based pH PET sensors.
The synthesis and photophysical evaluations of two new
fluorescent photoinduced electron-transfer (PET) anion sen-
sors, 1 and 2, is described. These are based on 4-amino-1,8-
naphthalimide fluorophores and diarylthiourea anion recep-
tors, connected via a methylene spacer to the imide. The
sensing of acetate, phosphate, and fluoride, on all occasions,
gave rise to quenching in the fluorescence of 1 and 2, similar
to that seen for the structural isomer 3. These results
demonstrate that bidirectional PET sensing occurs in such
naphthalimide-based anion sensors.
In 2003, we demonstrated, for the first time, the use of the
Naph in PET sensors for anions and that deprotonation could
also occur in competition, or in conjunction, with such hydrogen
bonding.15 Based on aryl thioureas as a hydrogen-bonding
receptor, connected to the Naph at the 4-amino moiety via a
CH2 spacer, we developed sensors such as 3. We showed that
the excited-state of Naph was indeed quenched upon anion
recognition, as the ∆GET became more thermodynamically
favorable upon binding of anions at the thiourea receptor.16
Herein, we demonstrate that such anion sensing is also possible
in the PET sensors 1 and 2, the structural isomers of 3. We
propose that in the case of 1 and 2, such an effect is due to an
enhanced electron-charge density at the receptor site upon anion
sensing, which allows PET to occur from the receptor to the
Naph excited state. To the best of our knowledge, 1-3 are the
first examples of Naph-based anion sensors that give rise to
such bidirectional PET quenching.
The sensing of anions, through the modulation of ground- or
excited-state changes, has become a very active area of reserch
in recent times within the field of supramolecular chemistry.1-7
Of the many examples developed to date, the internal charge
transfer (ICT) excited state based 4-amino-1,8-naphthalimide
(Naph) chromophore has been a popular choice in such
sensors.8,9 This is because it strongly absorbs and emits at long
wavelengths, features that are highly desirable for sensing in
competitive media.9 In particular, the Naph have been exploited
in the design of fluorophore-spacer-receptor-based photoin-
duced electron-transfer (PET) sensors.1,9 Indeed, we have
recently demonstrated its use in the fluorescent PET sensing of
Zn(II)10 as well as in the colorimetric sensing of anions.1,11 In
all these cases, the receptors were connected to the Naph moiety
at the 4-position. This is due to the “push-pull” nature of the
ICT excited state of Naph (caused by the electron-donating
amine and the electron-withdrawing imide), which gives rise
to a charge-separated excited state. This favors PET quenching
of the Naph excited state by electron-rich receptors located at
the 4-postion. For this reason, PET quenching from receptors
connected via the imide moiety is normally prevented.12-14
Hence, directional PET quenching occurs in such Naph struc-
(1) (a) Gunnlaugsson, T.; Glynn, M; Tocci (ne´e Hussey) , G. M.; Kruger,
P. E.; Pfeffer, F. M Coord. Chem. ReV. 2006, 250, 3094. (b) Gunnlaugsson, T.;
Ali, H. D. P.; Glynn, M.; Kruger, P. E.; Hussey, G. M; Pfeffer, F. M.; dos Santos,
C. M. G.; Tierney, J.; J. Fluoresc. 2005, 15, 287.
(2) Sessler, J. L.; Gale, P. A.; Cho, W. S. Anion Receptor Chemistry; Royal
Society of Chemistry: Cambridge, UK, 2006.
10.1021/jo8012594 CCC: $40.75
Published on Web 09/18/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 8073–8076 8073

The synthesis of 1 and 2 is shown in Scheme 1. The starting
material 4 (see the Supporting Information), which yielded 1,
was formed by reacting first 4-aminobenzylamine with 4-nitro-
1,8-naphthalic anhydride in EtOH in 90% yield. Catalytic
hydrogenation of 4, using 3 atm of H2 pressure, in the presence
of 10% Pd/C catalyst for 24 h, gave the diamine 6 in 86% yield.
In a similar manner, compound 5 (see the Supporting Informa-
tion), which yielded 2, was formed from 4-chloro-1,8-naphthalic
anhydride in 70% yield. Subsequent reaction in neat pyrrolidine,
under reflux for 18 h, gave 7 after aqueous workup in 71% yield.
The two sensors 1 and 2 were then formed from 6 and 7,
respectively, by treating these intermediates with 4-(trifluorom-
ethyl)phenyl isothiocyanate in DMF and CHCl3, respectively,
by stirring at room temperature for 5 days under an atmosphere
of argon. The resulting precipitate was collected by suction
filtration and washed with cold CHCl3 and, in the case of 2,
also by purification using column chromatography on flash silica
(gradient elution CH2Cl2/MeOH 0 f 98:2). This gave 1 and 2
in 78 and 72% yields, respectively, as highly colored powders.
Both sensors showed characteristic resonances in their 1H NMR
(400 MHz, DMSO-d6; See Figures S1 and S2 (Supporting
FIGURE 1. Changes in the absorption spectra of 1 (18 µM) upon
-
titration with H2PO4 (TBA) in DMSO (0 f 44 mM). Inset: The
relative changes in the ICT band at 438 nm.
Information) for 1 and 2) spectra for the thiourea protons, the
Naph moiety, and for 1, the 4-amino protons (see Figure S3
(Supporting Information) for compounds 4-7).
The photophysical properties of 1 and 2 were evaluated in
DMSO solution. The absorption spectra of both sensors showed
the presence of the ICT band of Naph, with λmax at 438 nm
(log ꢀ ) 5.19 M-1cm-1) and 454 nm (log ꢀ ) 15.30 M-1 cm-1),
for 1 and 2, respectively. For both, a second band also appeared
at higher energy (centered at ca. 285 nm), assigned to their
corresponding π-π* transitions.
An “ideal” PET sensor should not display changes in its
absorption spectra of the fluorophore upon recognition at the
receptor site.7,10,15 Indeed, this was found to be the case for 1
and 2 upon titration with anions such as AcO- and H2PO4- (as
their tetrabutylammonium salt solutions). This is demonstrated
in Figure 1, for 1, upon titration with H2PO4-, where no
significant changes were observed up to 100 equiv of the anion
(see Figure S4, Supporting Information). However, some
changes were observed in the absorption window of 320 - 360
nm, which were assigned to the diarylthiourea receptor. These
signified the formation of a hydrogen bonding complex between
the anion and the thiourea protons in the ground state.8a,14,15
Similarly, for AcO- (see Figures S5 and S6, Supporting In-
formation), Cl-, and Br-, no significant changes were observed
in the structure of the ICT band. However, in the case of F-,
significant changes were seen in the ICT band of 1 at high
concentration of F-, where a long wavelength absorption band
was observed at 529 nm and a second transition developed at
332 nm, with concomitant isosbestic points at 476 and 300 nm,
respectively, Figure 2. These results are in agreement with that
previously observed for 3, where at a high concentration of F-
deprotonation of the 4-amino moiety,8a with concomitant
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-
changes in the absorption spectra, and the formation of HF2
occurred.1,14,18 Importantly, these spectral changes were reversed
upon addition of competitive hydrogen-bonding solvents, e.g.,
MeOH (see later). In contrast, such changes were not seen in
the ICT band of 2, which lacks the 4-amino protons (Figure
S7, Supporting Information).
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8551. (b) de Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T.; Huxley,
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also: de Silva, A. P.; Goligher, A.; Gunaratne, H. Q. N.; Rice, T. E. ArkiVoc
2003, 7, 229.
The changes in the fluorescence emission of 1 and 2 were
next investigated. Excitation of their ICT absorption bands gave
rise to long wavelength emission, centered at 528 and 533 nm
for 1 and 2, respectively. The fluorescence quantum yield (ΦF)
for 1 was determined as 0.41, while for compound 2, it was
significantly reduced to ΦF ) 0.01. This reflects the effect that
the bulkier 4-amino tertiary amine has on the excited-state
(13) Gao, Y. Q.; Marcus, R. A J. Phys. Chem. A 2002, 106, 1956.
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8074 J. Org. Chem. Vol. 73, No. 20, 2008

FIGURE 4. Changes in the fluorescence emission spectra of 1 (15 µM)
upon titration with F- (TBA) in DMSO (0 f 32 mM).
FIGURE 2. Changes in the absorption spectra of 1 (18 µM) upon
titration with F- (TBA) in DMSO (0 f 32 mM).
quenched for H2PO4-, but to a lesser extent (Figure S10,
Supporting Information).
To further explore this phenomenon, 1 (Figure 4) and 2
(Figure S11, Supporting Information) were titrated with F-,
which is known to bind strongly to (or lead to deprotonation
of)18 thiourea-based anion receptors.8a,18 Indeed, a very effective
quenching (ca. 90%) was observed, with no changes in λmax
.
This further demonstrates the efficiency of PET from the
receptor; prompted by the anion recognition event. The use of
HO-, which should lead to deprotonation of the thiourea moiety
and hence produce a highly electron-rich “receptor”, also gave
rise to efficient quenching (Figure S12, Supporting Information).
For 2, the titration of F- also quenched the excited state, but to
a lesser extent than seen for 1 (ca. 50%,).
FIGURE 3. Changes in the fluorescence emission spectra of 1 (18 µM)
upon titration with H2PO4- (TBA) in DMSO (0 f 44 mM). Inset: The
relative changes at 528 nm as a function of -log [H2PO4-].
To quantify the above changes in the Naph emission of 1
and 2, we analyzed the emission changes19 using the nonliner
regression analysis program SPECFIT. The results of these
fittings and the corresponding speciation distribution diagrams
are shown in the Supporting Information (see Figures S13-23
and Table S1). For 1, and then in the case of H2PO4- only, the
1:1 stoichiometry was observed, with log ꢀ of 3.50 ( 0.03.
Similar results, log ꢀ of 3.24 ( 0.05, were observed for 2.
Furthermore, these values are similar to that observed for 3,
with log ꢀ ) 3.1.15 In a similar manner, the binding of AcO-
also gave rise to 1:1 binding stoichiometry (other were also
determined),20 with log ꢀ ) 4.23 ( 0.02 and 4.20 ( 0.04 for
1 and 2, respectively, which suggests that the primary vs tertiary
4-amino substitute does not affect the sensitivity of the anion
recognition at the receptor site to a large extent. These are, once
more, similar in magnitude to that observed for 315 (Table S2,
Supporting Information). Hence, these results clearly demon-
strate that the location of the anion receptor does not significantly
influence the sensitivity in these structural isomers. Furthermore,
the selectivity and the percent of Naph quenching follow the
same trend as seen for 3 (Table S2, Supporting Information).
Hence, we conclude that provided the electron density of the
receptor is sufficient; it will overcome the barrier proposed by
de Silva et al.12 and Marcus at al.,13 and bidirectional PET
quenching becomes allowed. This is an important observation
as it permits the development of other supramolecular systems
based on our design, where either the 4th or the imide or both
positions of the Naph structure can be functionalized with anion
receptors.
properties of 2.17 In our previous study, 3 was found to have
ΦF ) 0.71.15 While this difference in quantum yield between
3 and 1 is not considerable (ca. a factor of 2), it clearly indicates
that the excited state of 1 is quenched, most likely by PET from
the receptor moiety. This would suggest that bidirectional
electron transfer should be allowed in the structural isomers 1
and 2 in a similar manner to that observed for 3.
To investigate this, we carried out fluorescence titrations using
various anions capable of binding to the thiourea receptor moiety
via linear “Y-type” bonding interactions, with concomitant high
binding affinities.18 Upon titration with H2PO4 and AcO-
-
(Figure S8, Supporting Information) significant changes were
indeed observed in the fluorescence emission spectra of Naph.
For H2PO4-, Figure 3, the fluorescence emission was quenched
by ca. 60% at the end point. This quenching is of similar
magnitude as was observed for 3 under identical conditions.15
Moreover, no significant shifts were observed in λmax for 1. The
changes in the ICT band at 532 nm as a function of -log
[H2PO4-] are shown in the inset in Figure 3 and demonstrate
typical sigmoidal behavior, which is classically observed for
1:1 binding in PET sensors.7,9,10 Upon addition of competitive
hydrogen-bonding solvents such as MeOH, the emission was
“switched on”, demonstrating the reversibility for the anion
recognition at the thiourea receptor (Figure S9, Supporting
Information, for H2PO4-). Furthermore, since no significant
changes were observed in the absorption spectra (Figure 1), then
these results clearly demonstrate that PET is active upon anion
recognition in 1 and that this new design enables bidirectional
PET quenching in such Naph based anion sensors. In a similar
manner, for 2, the Naph fluorescence emission was also
In summary, the results from our investigation establish that
PET quenching of the Naph excited state in 1 and 2 is obserVed
upon anion recognition and that the location of the anion
(18) (a) Lowe, A. J.; Pfeffer, F. M. Chem. Commun. 2008, 1871. (b) Dos
Santos, C, M.; G.; McCabe, T.; Gunnlaugsson, T. Tetrahedron Lett. 2007, 48,
3135. (c) Evans, L. S.; Gal, e, P. A.; Light, M. E.; Quesada, R. Chem. Commun.
2006, 965. (d) Gunnlaugsson, T.; Kruger, P. E.; Jensen, P.; Pfeffer, F. M.; Hussey,
G. M. Tetrahedron Lett. 2003, 44, 8909.
(19) (a) Plush, S. E.; Gunnlaugsson, T. Org. Lett. 2007, 9, 1919. (b) Harte,
A. J.; Jensen, P.; Plush, S. E.; Kruger, P. E.; Gunnlaugsson, T. Inorg. Chem.
2006, 45, 9465.
J. Org. Chem. Vol. 73, No. 20, 2008 8075

1-[4-(6-Amino-1,3-dioxo-1H,3H-benzo[de]isoquinolin-2-ylm-
ethyl)phenyl]-3-p-tolylthiourea (1). Compound 1 was synthesized
by treating 6 (0.1 g, 0.315 mmol, 1 equiv) with 4-(trifluorometh-
yl)phenyl isothiocyanate (0.06 g, 0.315 mmol, 1 equiv) in DMF
and stirring the reaction mixture at rt for 5 days under argon. The
solvent was reduced in volume azeotropically with toluene under
reduced pressure, and the product was then precipitated into water,
collected by suction filtration, and dried. The product was then
dissolved in DCM and washed with water (×3) and brine, and the
organic layer was dried over MgSO4, filtered, and evaporated to
dryness to yield 1 as a yellow solid (0.11 g, 78%) after recrystal-
lization from EtOH: mp 178-179 °C; δH (400 MHz, (CD3)2SO)
10.0 (2H, s, NH × 2), 8.61 (1H, d, J ) 8.5 Hz, Ar-H7), 8.44 (1H,
d, J ) 7.0 Hz, Ar-H2), 8.20 (1H, d, J ) 8.5 Hz, Ar-H5), 7.71 and
7.63 (5H, m, Ar-H6, Ar-H2′, Ar-H6′ and Ar-H3′, Ar-H5′), 7.49
(2H, s, NH2), 7.35 (2H, d, J ) 8.5 Hz, Ar-H9′, Ar-H11′), 7.30
(2H, d, J ) 8.5 Hz, Ar-H8′, Ar-H12′), 6.86 (1H, d, J ) 8.0 Hz,
Ar-H3), 5.18 (2H, s, CH2); δC (100 MHz, (CD3)2SO),180.0, 164.3,
163.3, 153.4, 143.9, 138.3, 134.9, 134.7, 131.7, 130.2, 130.0, 128.3,
125.9, 124.5, 124.2, 123.4, 123.2, 122.1, 119.8, 108.7, 107.7, 42.5;
m/z 467 (M + H)+; νmax (neat sample)/cm-1 3235, 2924, 1629,
1318, 1100, 1065. Anal. Calcd for C27H22N4O2S: C, 69.51; H, 4.75;
N, 12.01. Found: C, 69.21; H, 4.50; N, 11.81.
1-[4-(1,3-Dioxo-6-pyrrolidin-1-yl-1H,3H-benzo[de]isoquinolin-
2-ylmethyl)phenyl]-3-p-tolylthiourea (2). Compound 2 was syn-
thesized by treating 7 (0.099 g, 0.267 mmol, 1 equiv) with
4-(trifluoromethyl)phenyl isothiocyanate (0.054 g, 0.267 mmol, 1
equiv) in CHCl3 and stirring the reaction mixture at rt for 5 days
under argon. The resulting precipitate was collected by suction
filtration and washed with CHCl3 to yield the product as a red solid
(0.1 g, 72%) after purification by recrystallization from EtOH
followed by column chromatography on flash silica (gradient elution
DCM/MeOH 0 f 2%): mp 158 - 159 °C; δH (400 MHz, CDCl3),
8.62 (1H, d, J ) 8.5 Hz, Ar-H7), 8.59 (1H, d, J ) 7.5 Hz, Ar-H2),
8.43 (1H, d, J ) 9.0 Hz, Ar-H5), 8.0 (1H, br s, NH), 7.78 (1H, br
s, NH), 7.64 and 7.54 (8H, m, Ar-H) 7.26 (1H, d, J ) 8.0 Hz,
Ar-H6), 6.82 (1H, d, J ) 8.5 Hz, Ar-H3), 5.39 (2H, s, CH2), 3.82
(4H, s, CH2), 2.13 (4H, s, CH2); δC (100 MHz, CDCl3), 179.6,
164.9, 164.0, 152.9, 141.3, 137.4, 135.2, 133.8, 132.4, 1314, 131.3,
130.2, 125.9, 125.8, 125.3, 124.1, 123.0, 122.4, 122.1, 109.8, 108.5,
53.2, 42.8, 26.0; m/z 543 (M + Na)+; νmax (neat sample)/cm-1 2968,
1678, 1304, 1108, 1064, 1015. Anal. Calcd for C31H28N4O2S: C,
71.51; H, 5.42; N, 10.76. Found: C, 71.21; H, 5.52; N, 10.51.
receptor does not affect the sensitivity or the selectivity of the
anion sensing to a great extent. We are currently exploring these
important results in the study of other anion sensing systems
based on 1-3.
Experimental Section
6-Amino-2-(4-aminobenzyl)benzo[de]isoquinoline-1,3-dione
(6). Compound 6 was synthesized by hydrogenating 4 (0.50 g, 4.30
mmol, 1 equiv) in MeOH/DCM (2:1) at 3 atm pressure in the
presence of 10% Pd/C catalyst (0.2 equiv) for 24 h. The reaction
mixture was then diluted with MeOH, filtered through Celite, and
washed with MeOH. The filtrate and washings were evaporated
under reduced pressure to yield the product as an orange solid (0.39
g, 86%): mp 287-288 °C; δH (400 MHz, (CD3)2SO) 8.67 (1H, d,
J ) 8.0 Hz, Ar-H7), 8.44 (1H, d, J ) 7.0 Hz, Ar-H2), 8.20 (1H,
d, J ) 8.5 Hz, Ar-H5), 7.66 (1H, t, J ) 8.0 Hz, Ar-H6), 7.57 (2H,
br s, NH2), 7.34 (2H, d, J ) 8.0 Hz, Ar-H2′, Ar-H5′), 7.10 (2H, d,
J ) 8.0 Hz, Ar-H3′, Ar-H4′), 6.87 (1H, d, J ) 8.0 Hz, Ar-H3),
5.18 (2H, s, CH2); δC (100 MHz, (CD3)2SO) 164.3, 163.3, 153.5,
135.1, 134.7, 131.7, 130.3, 130.1, 129.2, 124.5, 122.0, 121.1, 119.8,
108.7, 107.6, 42.5; m/z 318 (M + H)+, 340 (M + Na)+; νmax (neat
sample)/cm-1 3318, 3182, 1674, 1570. Anal. Calcd for C19H15N3O2:
C, 71.91; H, 4.76; N, 13.24. Found: C, 71.61; H, 4.79; N, 13.54.
2-(4-Aminobenzyl)-6-pyrrolidin-1-ylbenzo[de]isoquinoline-
1,3-dione (7). Compound 7 was synthesized by treating 5 (0.30 g,
0.89 mmol) with pyrrolidine (3.4 g, 4 mL, 56.1 mmol) and stirring
the reaction mixture at reflux temperature for 18 h. The reaction
mixture was then filtered hot through Celite, and the filtrate was
poured immediately into ice-cold water and stirred for 1 h. The
resulting precipitate was then collected by suction filtration, washed
with ice-cold water, and dried over BaO to yield the product as a
red/brown solid (0.234 g, 71%) after recrystallization from EtOH
and subsequent purification by dry column chromatography on flash
silica (DCM/MeOH 0 f 2%): mp 175-177 °C; HRMS 394.1541
([M + Na]+, C23H21N3O2 requires 394.1531); δH (400 MHz, CDCl3)
8.57 (2H, d, J ) 7.0 Hz, Ar-H7, Ar-H2), 8.43 (1H, d, J ) 8.5 Hz,
Ar-H5), 7.52 (1H, t, J ) 7.5 Hz, Ar-H6), 7.42 (2H, d, J ) 8.0 Hz,
Ar-H2′, Ar-H5′), 6.80 (1H, d, J ) 8.5 Hz, Ar-H3), 6.63 (2H, d, J
) 8.0 Hz, Ar-H3′, Ar-H4′), 5.30 (2H, s, CH2), 4.28 (4H, s, CH2),
2.10 (4H, s, CH2); δC (100 MHz, (CDCl3) 164.9, 164.1, 152.6,
145.5, 133.5, 131.9, 131.2, 131.1, 130.5, 128.1, 123.0, 122.6, 122.5,
114.9, 110.8, 108.4, 53.1, 42.8, 26.0; m/z 394 (M + Na)+; νmax
(neat sample)/cm-1 3476, 3011, 1654, 1406, 1001. Anal. Calcd for
C23H21N3O2: C, 74.37; H, 5.70; N, 4.31. Found: C, 74.07; H, 5.50;
N, 4.21.
Acknowledgment. We thank TCD, SFI, Enterprise Ireland,
and IRCSET for financial support.
Supporting Information Available: Synthesis and char-
acterization of 4-7, Figures S1-S21, and Tables S1 and S2.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(20) For both 1 and 2, a second binding interaction was also observed at
higher anion concentration (Table S1 for details). The fitting for F-, for both 1
and 2, also gave rise to 1:1 and 1:2 binding interactions, signifying the
deprotonation of the thiourea moiety. These changes mirrored that observed for
3 (ref 15). It was difficult to obtain reliable binding constants from the fitting of
2 for F-, most likely due to concomitant deprotonation events.
JO8012594
8076 J. Org. Chem. Vol. 73, No. 20, 2008