Synthesis and metal-binding studies of a novel pyrene discotic

Article abstract of DOI:10.1016/j.tetlet.2007.11.078

The synthesis of a novel bis-crown quinoxalino[2′,3′:9,10]phenanthro[4,5-abc]phenazine discotic and its binding properties to a series of alkali and alkaline-earth metals is reported. A schematic representation of the binding equilibrium of the sensor to the metal is proposed. The binding constant of the sensor to barium(II) was estimated to be 1.4 × 10⁴ M^-1 based on ¹H NMR studies.

Full text of DOI:10.1016/j.tetlet.2007.11.078

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 238–242
Synthesis and metal-binding studies of a novel pyrene discotic
a
b,
a,
*
*
Fadi M. Jradi, Mohammad H. Al-Sayah and Bilal R. Kaafarani
a
Department of Chemistry, American University of Beirut, Beirut, Lebanon
Department of Biology and Chemistry, American University of Sharjah, Sharjah, United Arab Emirates
b
Received 2 October 2007; revised 9 November 2007; accepted 14 November 2007
Available online 19 November 2007
This Letter is dedicated to Professor Douglas C. Neckers on the occasion of his 70th birthday
0
0
Abstract—The synthesis of a novel bis-crown quinoxalino[2 ,3 :9,10]phenanthro[4,5-abc]phenazine discotic and its binding proper-
ties to a series of alkali and alkaline-earth metals is reported. A schematic representation of the binding equilibrium of the sensor to
4
ꢀ1
1
the metal is proposed. The binding constant of the sensor to barium(II) was estimated to be 1.4 · 10 M based on H NMR
studies.
ꢀ
2007 Elsevier Ltd. All rights reserved.
Crown ether derivatives have been exploited for a wide
The UV–vis spectrum of 1 showed characteristic bands
1
ꢀ1
ꢀ1
range of applications such as optical and photo-
at 286 nm (e = 54,400 M cm ), 404 nm (e = 41,000
2
3
ꢀ1
ꢀ1
18
ꢀ1
ꢀ1
chromic sensing of metal ions, molecular switches
M
cm ), and 426 nm (e = 58,000 M cm ). The
4
5
and elevators, two-photon absorption properties, and
biomedical applications. Crown-ether-based fluores-
cent sensors for alkali and alkaline-earth
addition of barium(II) to the sensor led to a decrease
in the absorption bands at 404 nm and 426 nm, an
increase at 340 nm, and a blue shift followed by absorp-
tion enhancement at the 286 nm band (Fig. 1). This
change in the UV spectrum was observed, with the same
trend, even when the concentration of the metal was
more than that of the sensor.
6
7
,8
1,8–10
metal
cations are an attractive target due to their sensitivity,
selectivity, and potential application in real-time moni-
1
1
toring. Rigid rod-like bis-crowns are especially inter-
esting for their ability to form different extended
1
2
supramolecular arrangements with the metal cations.
1
3
14
Recently, we
and others
have reported novel
On the other hand, the fluorescence spectrum of 1
discotics based on the rigid fluorescent core of
exhibited a maximum emission at 447 nm upon excita-
tion at 350 nm. The addition of barium(II) to 1 led to
0
0
18
quinoxalino[2 ,3 :9,10]phenanthro[4,5-abc]phenazine. In
this Letter, we report the synthesis and binding studies
of a novel bis-crown discotic 1 composed of a quinoxa-
a decrease of its emission at 447 nm and to an increase
at 525 nm (Fig. 2). When the metal concentration was
equal to the concentration of the sensor (but half the
effective concentration of the crown), 1 started to regain
its fluorescence at 450 nm and to lose the emission at
525 nm. These results suggest that the metal was binding
0
0
lino[2 ,3 :9,10]phenanthro[4,5-abc]phenazine core furni-
shed with two 18-crown-6 moieties.
The synthesis of 1 (Scheme 1) started with Friedel–
Crafts alkylation of pyrene (2) to afford 2,7-di-t-butyl-
pyrene (3) which was oxidized using ruthenium(III)
chloride and sodium periodate to yield di-t-butyltetra-
7
,9,12,19–21
to two crown ethers
of two molecules to form
complexes such as S M and S M (Scheme 2). The struc-
2
2
2
ture of these complexes forced two chromophores to be
in close proximity which led to quenching of the emission
at 450 nm and the enhancement at 525 nm. This is
similar behavior to pyrene chromophores that formed
1
5
16
ketopyrene (4). Nitration of the benzo-18-crown-6
5) produced the 4,5-dinitrobenzo-18-crown-6 (6), which
was reduced to yield the 4,5-diaminobenzo-18-crown-6
(
1
6
10,22
(
7). The condensation of 4 and 7 in methanol afforded
excimers once the rings were in close proximity.
1
7
the bis-crown sensor 1.
As the concentration of barium increased, such that
more than 1 equiv of the metal was added, the equilib-
rium shifted toward new complexes in the form of
S M and SM (Scheme 2). These new conformations
*
Corresponding authors. Tel.: +961 3 151451; fax: +961 1 365217
B.R.K.); e-mail addresses: malsayah@ausedu;
bilal.kaafarani@aub.edu.lb
(
2
3
2
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.11.078

F. M. Jradi et al. / Tetrahedron Letters 49 (2008) 238–242
239
O
O
O
RuCl ; NaIO
4
t
-BuCl
3
CH Cl ; CH CN
AlCl3
4%
2
2
3
O
8
37%
2
3
4
O
O
O
O
O
O
O
O
O
O
O
NO2
NO2
O
O
O
O
NH2
NH2
HNO3
H
2
, 50 PSI
Pd, methanol
95%
2
H SO4
9
5%
O
O
O
5
6
7
Hb
O
Hb
Ha
O
O
O
O
N
N
O
O
O
O
CH OH
3
4
+
7
3
7%
O
O
N
N
O
1
Scheme 1. Synthesis of 1.
1.2
1
equiv
0
0
0
0
1
1
2
3
4
.0
.1
.25
.5
.0
.5
.0
.0
.0
0
0
0
0
.8
.6
.4
.2
0
270
320
370
420
470
Wavelength (nm)
Figure 1. UV–vis spectra of 1 (50 lM) upon the addition of Ba(ClO solution (1 mM) in CH Cl /CH CN (1:1).
4
)
2
2 2 3
placed the chromophores far away from each other
resulting in enhanced emission at 447 nm and a decrease
in the emission at 525 nm. Once the concentration of the
metal was double that of the sensor or more, the addi-
tion of further metal had little effect on the fluorescence
profile of 1 (Fig. 3). All the crowns were then complexed
to metals and the main complex present in the solution
9
,12
was in the form of SM (Scheme 2).
2
Titration of 1 with calcium(II) yielded an analogous
emission response to that of barium; however, the
quenching of fluorescence was to a lower extent

240
F. M. Jradi et al. / Tetrahedron Letters 49 (2008) 238–242
4
3
3
2
2
1
1
0
0
.0
.5
.0
.5
.0
.5
.0
.5
.0
equiv
0
0
0
0
.00
.05
.10
.15
0.20
0
0
0
0
.30
.39
.49
.68
0.86
400
450
500
550
600
Wavelength (nm)
Figure 2. Fluorescence spectra of 1 (50 lM) upon titration with Ba(ClO
4
)
2
solution (1 mM) in CH
2
Cl
2
/CH
3
CN (1:1).
1
S
M
S M
S M
S M
2
2
2
S M
2
2
S M
2
3
SM2
Scheme 2. Proposed schematic representation of the binding equilibrium of 1 (S) to the metal (M).
(
Fig. 3). This was attributed to the smaller size of
The complexation of crown sensors to metal ions was
1
23,24
calcium ions, which favored binding to one crown-
ether.
also detected through H NMR spectroscopy.
The
7
,9,12
25
Thus, the binding equilibrium (Scheme 2)
titration with a barium perchlorate solution of 1 led
shifted with calcium toward S M and/or S M to a les-
to a significant downfield shift of the methylene protons
2
2
2
ser extent than with barium. As expected, potassium had
an even lower influence on the emission of 1 than cal-
cium due to the lower charge while sodium and lithium
presented insignificant effects (Fig. 3).
(H , Scheme 1) of the crown ethers from 4.48 ppm to
b
4.70 ppm. The change in this chemical shift became
insignificant after the barium(II) concentration reached
double that of the sensor (or the same as the effective

F. M. Jradi et al. / Tetrahedron Letters 49 (2008) 238–242
241
1
.9
.8
.7
.6
.5
.4
0
0
0
0
0
0
+
Li
+
Na
+
K
+
+
+
Ca
Ba
+
0
0.5
1
1.5
2
2.5
3
3.5
4
Equiv of Metal
Figure 3. The normalized change in the emission intensity of 1 (50 lM) at 447 nm (F = emission intensity of complex, F
0
= initial emission intensity)
Cl /CH CN (1:1).
upon titration with solutions (1 mM) of LiPF (e), NaPF (j), KPF (n), Ca(ClO Æ4H O (s), and Ba(ClO (d) in CH
6
6
6
4
)
2
2
4
)
2
2
2
3
concentration of the crown ether) (Fig. 4). This indi-
cated that the metal-crown complexation resulted in a
9.65 ppm as the concentration of the metal increased
to reach half that of the sensor (Fig. 4). This suggested
that when the two crown ethers bound the metal to form
1
:1 complex (SM ) once enough metal had been added.
2
The binding constant for the binding of discotic 1 to
complex S M, the aromatic protons were located in the
shielding cone of the ring current of the other molecule
producing an upfield shift (an average shift of all the
2
4
ꢀ1
26
barium(II) was estimated to be 1.4 · 10 M
.
On the other hand, the change in the chemical shift of
possible conformations of S M). Then, these signals
2
the aromatic protons (H , Scheme 1) showed a behavior
started to shift downfield as the concentration increased,
and reached 7.87 ppm, when 2 equiv of the metal had
been added. This implied that when the concentration
of the added metal was more than half that of the sensor
a
that supported the suggested dynamic equilibrium
observed in the fluorescence studies (Scheme 2). The
signals of Ha shifted upfield from 9.69 ppm to
0
0
0
.25
0.2
.15
Ha
Hb
0.1
.05
0
-0.05
0
0.5
1
1.5
2
2.5
3
3.5
4
Equiv of Ba++
Figure 4. The change in the chemical shifts (Dd) of the aromatic (H
solution (10 mM) in CDCl /CD CN.
a
b 4 2
) and the crown ether protons (H ) of 1 (1 mM) upon titration with Ba(ClO )
3
3

242
F. M. Jradi et al. / Tetrahedron Letters 49 (2008) 238–242
(
but not less than the concentration of 1) complex S M2
13. Kaafarani, B. R.; Lucas, L. A.; Wex, B.; Jabbour, G. E.
2
Tetrahedron Lett. 2007, 48, 5995–5998.
formed. This conformation locked the chromophore
rings in a fixed position placing the aromatic protons
(
and caused a downfield shift. Once the concentration
of the metal was double or more than that of the sensor,
the equilibrium shifted toward the formation of complex
1
1
1
4. Hu, J.; Zhang, D.; Jin, S.; Cheng, S. Z. D.; Harris, F. W.
Chem. Mater. 2004, 16, 4912–4915.
5. Hu, J.; Zhang, D.; Harris, F. W. J. Org. Chem. 2005, 70,
H ) away from the shielding cone of the other ring
a
7
07–708.
6. Pike, J. D.; Rosa, D. T.; Coucouvanis, D. Eur. J. Inorg.
Chem. 2001, 761–777.
SM where the downfield shift of H was mainly due to
the electrostatic effect of the metal.
2
a
17. Synthesis of 2,25-bis(1,1-dimethylethyl)-7,8,10,11,13,14,
16,17,19,20,30,31,33,34,36,37,39,40,42,43-eicosahydro-
00 00 0 0
1,4,7,10,13,16]hexaoxacyclooctadecino[2 ,3 :6 ,7 ]quin-
oxalino[2 ,3 :9,10]phenanthro[4,5-abc][1,4,7,10,13,16]hexa-
oxacyclooctadecino[2,3-i]phenazine (1): A mass of 492 mg
[
0
0
In summary, we have reported the synthesis of a novel
0
0
bis-crown quinoxalino[2 ,3 :9,10]phenanthro[4,5-abc]-
phenazine discotic. We have presented preliminary
results on its binding activity and proposed a schematic
representation of the binding equilibrium of the sensor
to the metal. Further studies on this and other related
crowns are currently in progress.
(
7
1.31 mmol) of 4 was refluxed with 900 mg (2.63 mmol) of
in 100 mL of methanol for 48 h under an argon
atmosphere. The solution was cooled, filtered, and the
solid obtained was washed with cold methanol to afford
1
4
80 mg (37%) of a brownish solid 1, mp >300 ꢁC.
H
NMR (CDCl
3
7
3
, 300 MHz): d 1.75 (18H, s), 3.74 (8H, s),
.79 (8H, m), 3.87 (8H, m), 4.10 (8H, br s), 4.48 (8H, br s),
.64 (4H, s), 9.72 (4H, s). C NMR (CDCl , 75 MHz): d
1
3
3
Acknowledgments
31.49, 35.91, 69.11, 70.49, 70.76, 71.00, 107.02, 123.06,
1
24.73, 129.39, 139.01, 140.75, 160.42, 162.97. HRMS-
+
MALDI (m/z): [M+H] : calcd for
87.4750; found, 987.4799.
8. Spectroscopic titration. A solution of 1 (50 lM, 2 mL) in
CH Cl /CH CN (1:1) placed into a 1 · 1 cm cuvette was
titrated with a solution of the metal (1 mM, CH Cl
56 67 4 12
C H N O ,
This work was supported by the University Research
Board (URB) of the American University of Beirut
9
1
(
AUB), the Lebanese National Council for Scientific
2
2
3
research (LNCSR), the Royal Society of Chemistry,
and the FRG07-002 Grant of the American University
of Sharjah (AUS). The authors are grateful for this
support. B.R.K. thanks AUB for a Junior Faculty
Research Grant.
2
2
/
CH CN (1:1)) that contained 1 (50 lM). Aliquot amounts
3
of the metal solution were added to the cuvette via a
syringe until a total of 4 equiv of the metal had been added
(the number of additions was around 20 with an increase
in the amount of metal solution added). The UV–vis
spectrum and emission spectrum (kex = 350 nm) were
scanned after each addition.
References and notes
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CDCl
3
3
/CD CN (1:1) placed in an NMR tube was titrated
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3
/CD CN
3
7
8
9
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to the NMR tube via a syringe until a total of 4 equiv of
the metal were added (the number of additions was
around 17 with an increase in the amount of metal
1
solution added). A H NMR spectrum was recorded after
46, 3183–3186.
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a
)
1
1
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b
lected data was analyzed using a non-linear least square
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a 2:1 crown-to-metal binding process.
1
26. Klod, S.; Kleinpeter, E. J. Chem. Soc., Perkin Trans. 2
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