Preparation and sensor evaluation of a Pacman phthalocyanine

Article abstract of DOI:10.1016/j.tetlet.2007.10.089

We report both the preparation and sensor evaluation of a new metal-free calixarene bridged binuclear phthalocyanine.

Full text of DOI:10.1016/j.tetlet.2007.10.089

Available online at www.sciencedirect.com
Tetrahedron Letters 48 (2007) 9003–9007
Preparation and sensor evaluation of a Pacman phthalocyanine
Shane O’Malley, Benjamin Schazmann, Dermot Diamond and Kieran Nolan*
National Centre for Sensor Research, School of Chemical Sciences, Dublin City University, Glasnevin 9, Ireland
Received 10 May 2007; revised 11 October 2007; accepted 18 October 2007
Available online 22 October 2007
Abstract—We report both the preparation and sensor evaluation of a new metal-free calixarene bridged binuclear phthalocyanine.
ꢀ 2007 Elsevier Ltd. All rights reserved.
The binuclear phthalocyanines have attracted much
interest as potential catalysts for the four electron reduc-
N
N
N
N
H
N
O
H
N
N
tion of water.1 However, little work has been carried out
into their potential use as environmental sensors for hea-
vy metals. In fact, we could not find any previous work
involving the application of non-ionophore metal-free
phthalocyanines in cation sensing applications.2 We
believe that the cofacial metal-free binuclear phthalo-
cyanines, which possess an electron rich core of eight
nitrogens, may offer a unique opportunity for the
potential sensing of soft heavy metals such as silver
and mercury.3 However, cofacial binuclear phthalo-
cyanines prepared in the past use rigid bridges which
do not afford much conformational flexibility, a property
which is desirable in chemoreceptor applications. We
desired to create a new system using a bridge that not
only places two phthalocyanine rings in a cofacial
arrangement, but also allows conformational flexibility.
N
O
Me
Me
Ag+
O
O
N
N
N
O
H
N
N
H
N
N
N
O
Figure 1. Target binuclear phthalocyanine 1.
shown that hard oxygen calixarenes such as 4 (Scheme
1) are not only ineffective at binding hard metals such
as Na+1, K+1 and Ca+2, but are also incapable of coor-
dinating soft metals.5 As a consequence of this, the
calixarene bridge’s ionophore properties are ‘turned
off’ in 1.
Outlined in Figure 1 is our proposed target, a calix4
arene bridged binuclear phthalocyanine (1), the first ever
Pacman phthalocyanine. We chose a calixarene bridge
since the calixarene scaffold would not only allow for
the cofacial placement of two phthalocyanine rings on
the lower rim of the calixarene but would also act as a
molecular lever, allowing for open and closed forms.
Furthermore, the calixarene bridge would impart organ-
ic solubility to the system, which is a necessary require-
ment for immobilisation into polymer membranes.4
The synthetic route used to prepare 1 is outlined in
Scheme 1. The preparation of 2 was achieved by treating
calix4 arene with methyl iodide, potassium carbonate
base in DMF at 70 ꢁC for 1 h. After purification, a
33% yield of 2 was obtained, it should be noted that
trace quantities of the trimethoxy derivative were also
formed, which could be separated by silica gel column
chromatography.
The preparation of the spacer required two steps; ester-
ification of the remaining hydroxy groups of 2 using
NaH and ethyl bromoacetate in DMF at 70 ꢁC for 2
days followed by reduction of the esters to their respec-
tive alcohols. Extra additions of base and ethyl bromo-
acetate were required to drive the esterification reaction
to completion. After purification by column chromato-
graphy, a yield of 50% was obtained for 3. Ester 3 was
We are aware that many calixarene derivatives possess
cation complexing ability, however, past studies have
Keywords: Calixarene; Temperature 1H NMR; Conformation; Ion
selective electrode; Binuclear phthalocyanine; Pacman; Silver selective.
*
Corresponding author. Tel.: +353 017005913; e-mail: kieran.nolan@
dcu.ie
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.089

9004
S. O’Malley et al. / Tetrahedron Letters 48 (2007) 9003–9007
oxygens of the calixarene, which stabilises some of the
conformations present in the solution.
NaH
DMF
The high temperature 1H NMR spectrum of 5 (Fig. 2) in
nitrobenzene-d5 at 125 ꢁC, again showed a time resolved
spectrum indicating an apparent cone conformation for
the calixarene. However, unlike 4 the spacer methylene
groups could be resolved at 195 ꢁC giving two triplets
at d 4.39 ppm and 4.73 ppm (Fig. 2). The phthalonitrile
protons occurred as a triplet at d 7.73 ppm and a
doublet at 7.40 ppm, however, the other expected
doublet could not be seen as it overlapped with one of
the solvent peaks.
O
O
ethyl bromoacetate
O
O
O
O
O
O
Me
O
Me
Me
Me
70 0
C
H
H
OEt
O
EtO
3
2
CN
CN
DIBAL-H RT
Toluene
NO2
O
O
O
Na2CO3
DMF
Vacuum
O
Me
O
O
O
O
Me
Me
We originally believed that the nitrile groups of 5 should
be able to coordinate soft metal ions such as silver via
the nitrogens of the nitrile groups. However, we found
from ion selective electrode studies that 5 showed no
selectivity for any of the metals screened.9 This can be
explained by the lack of a pre-organisation of the bind-
ing cavity on the lower rim of the calixarene as a result
of the random orientation of the phthalonitrile substitu-
Me
OH
O
O
OH
NC
NC
CN
CN
4
5
Scheme 1.
1
ents, as confirmed by the H NMR spectrum of 5 at
room temperature.
converted to alcohol 4 using DIBAL-H in THF for 24 h
under N2. After purification, a 70% yield of 4 was
obtained. The structure of 4 was confirmed by ESI-
MS, with a [M+Na]+ peak at 787 amu. Bisphthalonitrile
5 was prepared using an SNAr substitution reaction
between 4 and 3-nitrophthalonitrile, with Na2CO3 in
DMF under vacuum for 5 days to give 5 in 25% yield
after column chromatography.6 The presence of 5 was
confirmed by ESI-MS with a [M+Na]+ peak at
1039 amu and a [M+K]+ peak at 1055 amu.
Calixarene 5 was reacted with an eightfold excess of
phthalonitrile in Li/pentanol at 110 ꢁC for 24 h10 to
afford 1, which was isolated by silica gel column chro-
matography using chloroform then THF as eluant. A
small quantity of the isolated phthalocyanine mixture
from this column was dissolved in a minimum amount
of THF and applied to a size exclusion column (Bio-
Beads SX-3).11 The mixture separated into two bands,
the first band was the target binuclear phthalocyanine
1 followed by unsubstituted phthalocyanine. Final puri-
fication of 1 involved precipitation from THF/methanol
to give 1 in an 8% yield. The presence of 1 was confirmed
by MALDI-TOF MS. As expected, the calixarene
bridge imparts excellent solubility for 1 in organic
solvents, even in the absence of substituents on the
peripheral benzo groups of the phthalocyanine rings
(Scheme 2).
The 1H NMR spectra of 3, 4 and 5 were poorly resolved
at room temperature. This result was expected as lower
rim intramolecular hydrogen bonding is lost. To resolve
1
the H NMR spectra of the calixarenes a series of high
temperature 1H NMR studies on 3, 4 and 5 were under-
taken. We initially used DMSO-d6 as the NMR solvent,
however, we could not dissolve 3 in DMSO-d6.7 We
chose an alternative solvent, nitrobenzene-d5, which
offers both a superior temperature range to DMSO-d6
and can readily solubilise less polar molecules.8
A UV–vis analysis of 1 (Fig. 3) revealed a typical
broadening and blue shift of the phthalocyanine
Q-band. Further analysis of the spectrum indicated that
1 existed as a conformational mixture of cofacial and
open forms. The peak observed at 630 nm was assigned
to the coupled cofacial or ‘clamshell’ conformation,
whereas the peaks at 700 and 650 nm are due to the
uncoupled absorption of the open form.12
The results of the temperature studies on 3, 4 and 5 are
shown in Figure 2. At 150 ꢁC, we observed a timed aver-
age spectrum for 3 resulting from rapid conformational
changes. As a result, the structure resolves into a cone
conformation with a pair of doublets for the bridging
methylene protons at d 3.49 ppm and 4.47 ppm; a singlet
at 4.53 ppm, a quartet at 4.34 ppm and a triplet at
1.35 ppm for the ethyl acetate substituents. Calixarene
4 also gave a poorly resolved 1H NMR spectrum at
room temperature. Resolution of the 1H NMR of 4
was partially achieved in nitrobenzene-d5 at 150 ꢁC
(Fig. 2). Again, a time averaged spectrum for 4 was
obtained with a pair of doublets at d 3.55 ppm and
4.40 ppm. However, the pendent glycol groups could
not be properly resolved even at 195 ꢁC. We believe that
the pendent alcohol groups are involved in intramole-
cular hydrogen bonding with the lower rim phenoxy
To evaluate the cation complexing ability of 1, the
ligand was incorporated into a PVC membrane based
ion selective electrode (ISE). A blank membrane was
also prepared, which was identical in composition to
the membrane containing 1, except that no ionophore
was present (ion-exchange salt only).13 A comparison
of the two membranes served as a rapid means to
ascertain the selectivity induced by 1. The potentio-
metric response of ISEs to each of a series of cations
is shown in Figure 4. The blank membrane, containing
no element of cavity pre-organisation, resulted in a

S. O’Malley et al. / Tetrahedron Letters 48 (2007) 9003–9007
9005
Figure 2. High temperature 1H NMR study in nitrobenzene-d5: (a) 3, (b) 4, (c) 5 and (d) expanded region showing the methylene spacer protons of 5.
CN
N
N
N
N
H
O
H
N
N
N
N
O
CN
Me
Me
O
O
O
O
O
O
Me
O
Me
N
Li/pentanol
O
N
N
O
H
N
N
H
N
N
CN
CN
O
NC
NC
N
5
1
Scheme 2.
Hofmeister order of selectivity, showing a preference for
Hg2+ and Ag+, which are the most lipophilic cations
tested. ISEs containing 1 appeared to suppress the
Hg2+ response resulting in overall Ag+ selectivity as
dictated by the complexing properties of 1.
We believe that the binding occurs through interaction
of the phthalocyanine rings with the silver cation. This
conclusion is based on the fact that 5 did not possess any
silver selectivity, therefore eliminating the possibility of
the ether oxygens of the calixarene bridge coordinating

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S. O’Malley et al. / Tetrahedron Letters 48 (2007) 9003–9007
References and notes
1. (a) Leznoff, C. C.; Greenberg, S.; Marcuccio, S. M.;
Minor, P. C.; Seymour, P.; Lever, A. B. P. Inorg. Chim.
Acta 1984, 89, L35–L38; (b) Leznoff, C. C.; Marcuccio, S.
M.; Greenberg, S.; Lever, A. B. P.; Tomer, K. B. Can. J.
Chem. 1985, 63, 623–632; (c) Leznoff, C. C.; Greenberg, S.;
Svirskaya, P. I.; Tomer, K. B.; Lever, A. B. P. Can. J.
Chem. 1985, 63, 3057–3069; (d) Leznoff, C. C.; Lam, H.;
Nevin, W. A.; Kobayashi, N.; Janda, P.; Lever, A. B. P.
Angew Chem., Int. Ed. Engl. 1987, 26, 1021–1023; (e)
Hempstead, M. R.; Lever, A. B. P.; Leznoff, C. C. Can. J.
Chem. 1987, 65, 2677–2684; (f) Lam, H.; Marcuccio, S.
M.; Svirskaya, P. I.; Greenberg, S.; Lever, A. B. P.;
Leznoff, C. C.; Cerny, R. L. Can. J. Chem. 1989, 67, 1087–
1097.
2. It should be noted that work has been carried out on
the application of metallated phthalocyanines in anion
sensing. See: (a) Xu, W. J.; Chai, Y. Q.; Yuan, R.; Liu, S.
L. Anal. Bioanal. Chem. 2006, 385, 926–930; (b)
Ganjali, M. R.; Poujavid, M. R.; Shamsipur, M.; Pours-
aeri, T.; Rezapour, M.; Javanbakht, M.; Sharghi, H.
Anal. Sci. 2003, 19, 995–999; (c) Shahrokhian, S.;
Taghani, A.; Moattar, F. Electroanalysis 2002, 14, 1621–
1628.
3. Other pyrrole based macrocycles that have shown heavy
metal/cation selectivity: calixpyrroles (a) Park, S. S.; Jung,
S. O.; Kim, S. M.; Kim, J. S. Bull. Korean Chem. Soc.
1996, 17, 405–407; porphyrins (b) Zhang, X. B.; Han, Z.
X.; Fang, Z. H.; Shen, G. L.; Yu, R. Q. Anal. Chim. Acta
2006, 562, 210–215; (c) Gupta, V. K.; Jain, A. K.;
Maheshwari, G.; Lang, H.; Ishtaiwi, Z. Sens. Actuators,
B 2006, 117, 9–106.
Figure 3. The electronic spectrum of 1 at 10ꢀ6 M in CHCl3.
silver.9 Also fluorimetric experiments were carried out
on 1 in the presence of Ag+. We found that the fluores-
cence of 1 decreased upon the addition of silver cations
demonstrating that the two phthalocyanine rings of 1
are ‘sandwiching’ the silver ions.
In conclusion, we have reported the first example of the
application of a metal-free binuclear phthalocyanine for
the sensing of a heavy metal. A study of the broader sen-
sor characteristics such as concentration response
ranges, slopes and formal selectivity coefficients, as cal-
culated by Nernstian equations of 1 are underway.
4. (a) Diamond, D.; Nolan, K. Anal. Chem. 2001, 73, 23A;
(b) Bohmer, V.; Harrowfield, J.; Vicens, J. Calixarenes
2001; Kluwer Academic, 2001.
5. (a) Buhlmann, P.; Pretsch, E.; Bakker, E. Chem. Rev.
¨
1998, 98, 1593; (b) McMahon, G.; Wall, R.; Nolan, K.;
Diamond, D. Talanta 2002, 57, 1119; (c) Schazmann, B.;
McMahon, G.; Nolan, K.; Diamond, D. Supramol. Chem.
2005, 17, 393.
Acknowledgement
We wish to thank The Irish Research Council for Sci-
ence, Engineering and Technology for financial support
(Grant Number SC/02/331).
6. Preparation of 5,11,17,23-tetra-tert-butyl-25,27-diethyl-
eneoxyphthalonitrile-26,28-dimethoxycalix[4]arene 5: 3-
Nitrophthalonitrile (0.95 g, 5.5 mmol),
4
(1.05 g,
Host
Hg2+
Ag+
1
-2.70 0.01
0
Pb2+
Cu2+
Co2+
-2.06 0.18
-2.34 0.19
-2.99 0.15
Cd2+
Zn2+
H+
Mg2+
Ca2+
Li+
-2.85 0.16
-3.05 0.16
-1.02 0.10
-3.03 0.18
-3.00 0.18
-1.91 0.18
-0.75 0.13
-1.04 0.08
K+
Na+
Figure 4. ISE results for 1. Reproducibility based on three ISE’s. Note: I is the primary ion Ag+ and J is the interferant specified. The Separate
Solutions Method (SSM) was used where logaI = logaJ = ꢀ2.3.

S. O’Malley et al. / Tetrahedron Letters 48 (2007) 9003–9007
9007
1.37 mmol) and K2CO3 (0.76 g, 5.5 mmol) were stirred
under vacuum in anhydrous DMF (15 cm3) for five days.
Each day Na2CO3 (0.19 g, 1.37 mmol) and 3-nitropht-
halonitrile (0.23 g, 1.37 mmol) were added to force the
reaction to completion. On day six, the reaction mixture
was then poured onto ice water (50 ml), filtered and the
solid was washed with hot water (2 · 25 ml). The crude
brown solid was purified by column chromatography
using 70:30 hexane/ethyl acetate, to give a light green solid
(0.34 g, 0.34 mmol, 25% yield) 1H NMR: (CDCl3) d (ppm)
(195 ꢁC); 1.7, (m, 18H, t-Bu); 1.9, (m, 18H, t-Bu); 3.55, (d,
4H, J = 13.0 Hz, Ar-CH2-Ar); 3.84, (s, 6H, 2Me); 4.43, (t,
4H, J = 5.0 Hz, CH2 spacer); 4.47, (d, 4H, J = 13.0 Hz,
Ar-CH2-Ar); 4.76, (t, 4H, J = 5.0 Hz, CH2 spacer); 6.67,
(s, 4H, ArH); 7.36, (s, 4H, ArH); 7.40, (d, 2H, J = 7.6 Hz,
ArH); 7.72, (t, 2H, J = 7.6 Hz, ArH). ESI m/z: 1039
using chloroform as eluant, followed by THF. Then a
second silica gel column was carried out on all bands
collected from the first column using THF as the mobile
phase. The phthalocyanine crude (0.03 g) was then
dissolved in THF and applied to a size exclusion column
(Bio-Beads SX-3, it should be noted that 0.03 g is the
optimum loading for the size exclusion column) using
THF as mobile phase. Two bands were collected, the first
band was 5, followed by unsubstituted phthalocyanine.
The binuclear band was then rerun on the size exclusion
column. This binuclear was then columned again on a
silica gel column using THF as eluant. A blue compound
was obtained in 0.017 g, 0.01 mmol, 8% yield. MALDI-
TOF m/z: 1790.28 (M+1).
11. (a) O’Malley, S.; Alhashimy, N.; O’Mahony, J.; Kieran,
A.; Pryce, M.; Nolan, K. Tetrahedron Lett. 2007, 48, 681–
684; (b) Nolan, K. J. M.; Leznoff, C. C.; Hu, M. Synlett
1997, 593–595.
(M+Na+), 1055 (M+K+) IR:
(KBr [cmꢀ1]):
3500 cmꢀ1m(O–H), 3000 cmꢀ1m(But).
7. Duggan, P. J.; Sheahan, S. L.; Szydzik, M. L. Tetrahedron
12. Dodsworth, E. S.; Lever, A. B. P.; Seymour, P.; Leznoff,
C. C. J. Phys. Chem. 1985, 89, 5698–5705.
Lett. 2000, 41, 3165.
8. Terekhov, D. S.; Nolan, K. J. M.; McArthur, C. R.;
Leznoff, C. C. J. Org. Chem. 1996, 61, 3034–3040.
9. Schazmann, B.; O’Malley, S.; Nolan, K.; Diamond, D.
Supramol. Chem. 2006, 18, 515–522.
13. The preparation and the use of ion selective electrodes
(ISEs): Potentiometric membranes were prepared using
250 mg of 2-nitrophenyl octyl ether, 125 mg PVC,
6.5 mmol ligand 5 and 2.7 mmol of potassium tetrakis(4-
chlorophenyl) borate dissolved in dry THF and evapo-
rated slowly. The ISEs referred to as the blank were
prepared in an identical fashion but contained no ligand 5.
The electrochemical cell used consisted of a double
junction reference electrode and a PVC membrane work-
ing electrode in the following arrangement: AgjAgClj3 M
10. Preparation of 5,11,17,23-tetra-tert-butyl-26,28-dimeth-
oxycalix[4]arene(diethyleneoxy) binuclear phthalocyanine
1: Lithium (0.03 g, 4.28 mmol) was added to 3 ml of
pentanol in a 10 ml round-bottom flask and heated to
60 ꢁC for 30 min under nitrogen to form the lithium
alkoxide. To this reaction flask, 5 (0.1 g, 0.122 mmol) and
phthalonitrile (0.14 g, 1.10 mmol) were added to the
reaction mixture and this was then heated at 110 ꢁC under
nitrogen for 24 h. The reaction mixture was cooled to
room temperature and poured into 1 N HCl. A blue
precipitate was formed and collected by centrifugation and
was further washed, first with water and then methanol.
Chromatography was carried out on a silica gel column
KClk0.1 M
LiOAcksample
solutionjPVC
mem-
branej0.01 M NaCljAgCljAg. Membranes were condi-
tioned in 0.01 M sodium chloride for 12 h and deionised
water for half an hour prior to ISE titrations. The
potentiometric cell was interfaced to a PC using a
National Instruments SCB-68 4-channel interface. All
ISE measurements were performed in triplicate.