Synthesis of new water soluble phthalocyanines and investigation of their photochemical, photophysical and biological properties

Article abstract of DOI:10.1016/j.jphotochem.2012.03.010

With the quaternized derivatives (4a and 5a), the synthesis of new Zn(II) and Co(II) phthalocyanines (4 and 5) substituted with 2-(azepan-1-yl)ethoxy moieties are reported. Photochemical and photophysical properties of quaternized Zn(II) and Co(II) phthal

Full text of DOI:10.1016/j.jphotochem.2012.03.010

Journal of Photochemistry and Photobiology A: Chemistry 235 (2012) 56–64
Contents lists available at SciVerse ScienceDirect
Journal of Photochemistry and Photobiology A:
Chemistry
journal homepage: www.elsevier.com/locate/jphotochem
Synthesis of new water soluble phthalocyanines and investigation of their
photochemical, photophysical and biological properties
Canan Uslana, B. S¸ ebnem Sesalana,∗, Mahmut Durmus¸ b
a
˙
Istanbul Technical University, Faculty of Science and Letters, Department of Chemistry, Istanbul, Turkey
b Gebze High Institute of Technology, Department of Chemistry, Gebze 41400, Kocaeli, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
With the quaternized derivatives (4a and 5a), the synthesis of new Zn(II) and Co(II) phthalocyanines (4
and 5) substituted with 2-(azepan-1-yl)ethoxy moieties are reported. Photochemical and photophysical
properties of quaternized Zn(II) and Co(II) phthalocyanines (4a and 5a) are investigated in both dimethyl
sulfoxide (DMSO) and water, while non ionic derivatives in DMSO only. General trends are described for
fluorescence quantum yields, fluorescence lifetimes, singlet oxygen quantum yields and photodegrada-
tion quantum yields. In this work, the effect of substituents and the nature of the metal atoms on the
photochemical and photophysical parameters of new phthalocyanines are discussed. The quaternized
compounds exhibit excellent solubility in water, making them potential photosensitizers for use in pho-
todynamic therapy (PDT) of cancer. This study also showed that the water-soluble quaternized Zn(II)
phthalocyanines strongly bind to blood plasma proteins such as bovine serum albumin (BSA).
© 2012 Elsevier B.V. All rights reserved.
Received 26 August 2011
Received in revised form 1 February 2012
Accepted 11 March 2012
Available online 17 March 2012
Keywords:
Water soluble
Phthalocyanines
Fluorescence
Singlet oxygen
Photodynamic therapy
1. Introduction
During the last decade, our group has been heavily engaged
with the synthesis of phthalocyanines and porphyrazines with
Phthalocyanines (Pcs) are widely used in the design of new
materials such as stable dyes, catalysts, building blocks for nanos-
tructures, active components of optical sensors, semiconductor
and electrochromic devices, memory systems, liquid crystal color
displays, photoelectric transformers of solar energy, etc. [1–5]. Met-
allophthalocyanines (MPcs) attract more attention due to additive
magnetic or biological properties of metals which they are incor-
porated.
Recently, pcs have also been widely used as photosensitizers
in photodynamic therapy (PDT). PDT is a binary treatment that
involves the activation of a tumor-localized photosensitizer with
red light. The excited photosensitizer in triplet state reacts with
molecular oxygen and forms singlet oxygen that destroys malig-
nant tissues [6,7]. For PDT applications, it is important that MPcs
exhibit high absorption coefficients (ε > 105 M−1 cm−1) in visible
region and a long triplet lifetime to produce singlet oxygen [8–13].
In order to overcome the insolubility of unsubstituted phthalo-
cyanine parent molecule, peripheral groups have been extensively
used to enhance solubility. In this sense, long alkyl, alkyloxy, alkyl-
sulfanyl or bulky apolar groups lead to soluble products in common
organic solvents while anionic or cationic substituents (e.g. sulfo
groups, carboxy groups, ammonium groups) result with products
soluble in aqueous media [14,15].
substituents such as quaternized amino groups, and multicyclic
aromatic rings [16–19]. Water soluble phthalocyanines have
appeared as attractive photosensitizers for photodynamic therapy
[20–22]. One limitation of these photosensitizers is their high ten-
dency to form aggregated species in aqueous solution. An efficient
strategy for number of practical uses might be to add some groups
to inhibit aggregation. In this paper we report the synthesis and
investigation of photochemical and photophysical properties of
some phthalocyanines and their quaternized derivatives bearing
four 2-(azepan-1-yl)ethoxy groups which enable the molecules to
dissolve in number of organic solvents as well as water.
In this work, the synthesis, characterization and spectro-
scopic behaviour as well as photophysical (fluorescence quantum
yields and lifetimes) and photochemical (singlet oxygen and
photodegradation quantum yields) properties of new tetrakis-
[2-(azepan-1-yl)ethoxy substituted non-ionic (4 and 5) and
quaternized ionic (4a and 5a) Zn(II) and Co(II) phthalocyanine com-
plexes (Fig. 1) are presented. The aim of our ongoing research is to
synthesize water-soluble phthalocyanines to be used as potential
PDT agents.
2. Experimental
2.1. Materials
∗
All reagents and solvents were of reagent grade quality and
were obtained from commercial suppliers. 2-(Azepan-1-yl)ethanol
Corresponding author. Tel.: +90 212 285 33 03; fax: +90 212 285 63 86.
E-mail address: sungurs@itu.edu.tr (B.S¸ . Sesalan).
1010-6030/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.jphotochem.2012.03.010

C. Uslan et al. / Journal of Photochemistry and Photobiology A: Chemistry 235 (2012) 56–64
57
Fig. 1. Synthesis of phthalocyanines (4, 4a, 5 and 5a). (i) K2CO3, N2, DMF, 50 ◦C, 48 h, (ii) for compound 4 Zn(CH3COO)2 and for compound 5 anhydrous CoCl2, pentan-1-ol,
DBU, reflux, N2, 48 h; (iii) dimethyl sulfate, DMF, 120 ◦C, 12 h.
was purchased from Aldrich. 1,3-Diphenylisobenzofuran (DPBF)
and 9,10-antracenediyl-bis(methylene)dimalonoic acid (ADMA)
were purchased from Fluka. All solvents were dried and purified
as described by Perrin and Armarego [23]. 4-Nitrophthalonitrile
[24] was synthesized and purified according to well-known
literature.
and emission spectra were recorded on a Varian Eclipse spectroflu-
orometer using 1 cm path length cuvettes at room temperature.
Photo-irradiations were done using a General Electric quartz
line lamp (300 W). A 600 nm glass cut off filter (Schott) and a
water filter were used to filter off ultraviolet and infrared radi-
ations, respectively. An interference filter (Intor, 670 nm with
a band width of 40 nm) was additionally placed in the light
path before the sample. Light intensities were measured with
a POWER MAX5100 (Molelectron detector incorporated) power
meter.
2.2. Equipment
The IR spectra were recorded on a Ati-Unicam Mattson 1000 FT-
IR spectrophotometer. 1H NMR spectra were recorded on a Varian
Mercury 200 MHz spectrometer in CDCl3 and DMSO-d6. Chemi-
cal shifts were reported (ı) relative to Me4Si as internal standard.
Mass spectra were measured on a Micromass Quatro LC/ULTIMA
LC–MS/MS spectrometer. Elemental analyses were performed with
Thermo Finnigan Flash EA 1112 at 950–1000 ◦C.
2.3. Photophysical parameters
2.3.1. Fluorescence quantum yields and lifetimes
Fluorescence studies of substituted Zn(II) phthalocyanine com-
plexes (4 and 4a) were studied in DMSO. The substituted Co(II)
phthalocyanine complexes (5 and 5a) did not show fluores-
cence due to paramagnetic behavior of Co(II) atom. Fluorescence
Absorption spectra in the UV–vis region were recorded with
a Shimadzu 2001 UV spectrophotometer. Fluorescence excitation

58
C. Uslan et al. / Journal of Photochemistry and Photobiology A: Chemistry 235 (2012) 56–64
5a). A light intensity of 3.18 × 1016 photons s−1 cm−2 was employed
for ˚d determinations.
quantum yields (˚F) were determined by the comparative method
(Eq. (1)) [25,26],
F · AStd · n2
˚
F
= ˚F (Std)
(1)
2.5. Binding studies of quaternized Zn(II) and Co(II)
phthalocyanine complexes to BSA
FStd · A · n2
Std
where F and FStd are the areas under the fluorescence emission
curves of the samples (4 and 4a) and the standard, respectively.
A and AStd are the respective absorbances of the samples and stan-
dard at the excitation wavelengths, respectively. n and nStd are the
refractive indices of solvents used for the sample and standard,
respectively. Unsubstituted ZnPc (˚F = 0.20) [27] was employed
as the standard in DMSO. The absorbance of the solutions at the
excitation wavelength ranged between 0.04 and 0.05.
The binding properties of the water soluble quaternized
phthalocyanine complexes (4a and 5a) to BSA were studied by spec-
trofluorometry at room temperature. An aqueous solution of BSA
(fixed concentration) was titrated with varying concentrations of
the respective samples (4a and 5a) solutions in water. BSA was
excited at 280 nm and fluorescence recorded between 290 and
500 nm. The steady diminution in BSA fluorescence with increase
in quaternized cationic phthalocyanine concentrations was noted
and used in the determination of the binding constants and the
number of binding sites on BSA, according to Eq. (5) [34–36].
Natural radiative (ꢀ0) lifetimes were determined using Pho-
tochemCAD program which uses the Strickler–Berg equation [28].
The fluorescence lifetimes (ꢀF) were evaluated using (Eq. (2)).
ꢀ
ꢁ
ꢀF
(F0 − F)
˚
F
=
(2)
log
= log Kb + n log[Pc]
(5)
ꢀ0
F − F
∞
where F0 and F are the fluorescence intensities of BSA in the absence
2.4. Photochemical parameters
and presence of quaternized cationic phthalocyanine complexes
(4a and 5a), respectively; F , the fluorescence intensity of BSA satu-
2.4.1. Singlet oxygen quantum yields
∞
rated with quaternized cationic phthalocyanine complexes; Kb, the
binding constant; n, the number of binding sites on a BSA molecule;
and [Pc] the concentration of quaternized cationic Pc complexes.
Singlet oxygen quantum yield (˚ꢁ) determinations were car-
ried out using the experimental setup described in literature
[29,30]. Typically, a 3 cm3 portion of the respective substituted
Zn(II) (4 and 4a) and Co(II) (5 and 5a) phthalocyanine deriva-
tives (concentration = 1 × 10−5 M) containing the singlet oxygen
quencher was irradiated in the Q band region with the photo-
irradiation setup described in references [29,30]. Singlet oxygen
quantum yields (˚ꢁ) were determined in air using the relative
method with unsubstituted ZnPc (in DMSO) or ZnPcSmix (in aque-
ous media) as references. DPBF and ADMA were used as chemical
quenchers for singlet oxygen in DMSO and aqueous media, respec-
tively. Eq. (3) was employed for the calculations:
Plots of log[(F − F)/(F − F )] against log[Pc] would provide the val-
∞
0
ues of n (from the slope) and Kb (from the intercept). The changes
in BSA fluorescence intensity were related to quaternized cationic
phthalocyanine concentrations by the Stern–Volmer relationship
(Eq. (6)):
F0BSA
FBSA
= 1 + KSBVSA[Pc]
(6)
BSA
SV
and K
is given by Eq. (7):
Std
R · I
abs
RStd · Iabs
BSA
˚
= ˚Std
(3)
K
= kqꢀF(BSA)
(7)
ꢁ
SV
ꢁ
where F0BSA and FBSA are the fluorescence intensities of BSA in
the absence and presence of quaternized cationic phthalocyanine
complexes (4a and 5a), respectively. K
quenching constant; kq is the bimolecular quenching constant and
ꢀF(BSA) is the fluorescence lifetime of BSA. ꢀF(BSA) is known to be
10 ns [37–39], thus from the values of KSBVSA obtained from the plots
of F0BSA/FBSA versus [Pc], the value of kq may be determined from Eq.
where ˚Sꢁtd is the singlet oxygen quantum yields for the stan-
dard unsubstituted ZnPc (˚Sꢁtd = 0.67 in DMSO) [31] and ZnPcSmix
(˚Sꢁtd = 0.45 in aqueous media) [32]. R and RStd are the DPBF (or
BSA
SV
is the Stern–Volmer
ADMA) photobleaching rates in the presence of the phthalocya-
Std
abs
nine derivatives and standards, respectively. Iabs and I
are the
rates of light absorption by phthalocyanine derivatives and stan-
dards, respectively. To avoid chain reactions induced by DPBF (or
ADMA) in the presence of singlet oxygen [33], the concentration
of quenchers (DPBF or ADMA) was lowered to ∼3 × 10−5 M. Solu-
tions of sensitizer containing DPBF (or ADMA) were prepared in the
dark and irradiated in the Q band region using the setup described
above. DPBF degradation at 417 nm (in DMSO) and ADMA degra-
dation at 380 nm (in water) were monitored. The light intensity
9.54 × 1015 photons s−1 cm−2 was used for ˚ꢁ determinations.
(7).
2.6. Synthesis
2.6.1. Synthesis of 4-(2-(azepan-1-yl)ethoxy)phthalonitrile (3)
4-Nitrophthalonitrile (1) (0.173 g, 1 mmol) and 2-(azepan-1-
yl)ethanol (0.3 mL, 2 mmol) were reacted in dry dimethylfor-
mamide (DMF) (10 mL) at 50 ◦C under N2 atmosphere. Potassium
carbonate (1.38 g, 10 mmol) was added in small portions to the
reaction solution and the addition finished within 2 h. After 72 h,
the reaction mixture was poured into water (100 mL). The mix-
ture was extracted by diethyl ether (15 mL × 4). Organic phase was
dried by sodium sulfate and evaporated. The oily residue was dried
under vacuum overnight and was purified by column chromatogra-
phy over alumina using tetrahydrofuran as eluent. Yield: 96 g (35%).
IR, ꢂmax/cm−1: 3076 (Ar H); 2930 (aliphatic–H); 2853 (O CH2);
2229 (CN); 1596–1490 (Ar
1087–1136 (R)C
(m, 3H, Ar H), 4.14–4.10 (t, 2H, O CH2), 2.99–2.94 (t, 4H, CH2c),
2.75–2.73 (t, 2H, CH2b), 1.68–1.38 (m, 8H, CH2a). MS (MALDI) (m/z):
269.85 [M]+.
2.4.2. Photodegradation quantum yields
Photodegradation quantum yield (˚d) determinations were
carried out using the experimental setup described in literature
[29,30]. Photodegradation quantum yields were determined using
Eq. (4),
(C0 − Ct) · V · NA
˚
=
(4)
d
Iabs · S · t
C C); 1169 (C N C); 1309 (Ar N);
where C0 and Ct are the samples (4, 4a, 5 and 5a) concentrations
before and after irradiation, respectively, V is the reaction volume,
NA is the Avogadro’s constant, S is the irradiated cell area, t is the
irradiation time and Iabs is the overlap integral of the radiation
source light intensity and the absorption of the samples (4, 4a, 5 and
O
Ar); 875, 833. 1H NMR (CDCl3): ı 7.70–7.27

C. Uslan et al. / Journal of Photochemistry and Photobiology A: Chemistry 235 (2012) 56–64
59
2.6.2. Synthesis of 2,9(10),16(17),23(24)-tetrakis-
(2-(azepan-1-yl)ethoxy) phthalocyaninatozinc(II) (4)
Anhydrous Zn(CH3COO)2 (0.033 g, 0.185 mmol)
3. Results and discussion
was
3.1. Synthesis and characterization
dissolved in dry pentan-1-ol (3 mL) then 4-(2-(azepan-1-
yl)ethoxy)phthalonitrile (3) (0.1 g, 0.37 mmol) was added to
the mixture under nitrogen in the presence of DBU (3 drops). After
reflux for 48 h, the mixture was cooled to room temperature and
centrifuged (4000 × g) for 3 min. The filtrate was evaporated. 10 ml
tetrahyrofuran was added to the oily residue and the mixture
was centrifuged (4000 × g) for 3 min. The filtrate was evaporated
and the residue was purified by column chromatography over
aluminum oxide using tetrahydrofuran as eluent. Yield: 14 mg
(13%). IR ꢂmax/(cm−1): 3073 (Ar H); 2924 (aliphatic H); 2853
The synthetic procedure of the phthalocyanine complexes (4
and 5) and their quaternized derivatives (4a and 5a) is given in
Fig. 1. 2-(Azepan-1-yl)ethoxy substituted phthalonitrile derivative
(3) was synthesized through base-catalyzed aromatic displacement
of 4-nitrophthalonitrile (1) with 2-(azepan-1-yl)ethanol using
K2CO3 as the base in dry DMF. The reactions were carried out
at 50 ◦C under N2 atmosphere for 48 h. Cyclotetramerization of
the phthalonitrile derivative (3) to the tetra-substituted Zn(II) and
Co(II) phthalocyanines (4 and 5) were accomplished in the presence
of anhydrous Zn(CH3COO)2 and CoCl2 in pentan-1-ol and the crude
product was purified column chromatography using alumina filled
column. Quaternized Zn(II) and Co(II) phthalocyanines (4a and 5a)
were obtained from the reaction of corresponding phthalocyanines
(4 and 5) with dimethyl sulfate in DMF. The structures of the tar-
get compounds were confirmed using IR, 1H NMR, spectroscopy
and mass spectra. The analyses are consistent with the predicted
structures.
(O CH2); 1598–1492 (Ar
C C); 1163 (C N C); 1310 (Ar N);
1087–1135 (R
O
Ar); 873, 833. 1H NMR (CDCl3): ı 7.38–7.03 (m,
12H, Ar H), 4.57 (t, 8H, O CH2), 4.19 (t, 8H, CH2c), 3.16–2.28 (m,
32H, CH2b), 1.79–1.36 (m, 16H, CH2a). UV–vis ꢃmax (nm) (log ε)
CHCl3: 681 (4.45), 614 (2.82), 353 (4.15). MS [m/z]: 1141.95 [M]+.
C64H76N12O4Zn requires C, 67.27; H, 6.70; N, 14.71; found C, 67.42;
H, 6.81; N, 13.98%.
The IR spectra clearly indicated the formation of compounds
(3) with the appearance of absorption band at 2229 cm−1 (C N).
In the 1H NMR spectrum of compound 3, the aromatic protons
were observed at between 7.70 and 7.27 ppm and O CH2 protons
were observed at between 4.14 and 4.10 ppm. c, b and a protons
which had been shown in Fig. 1 were observed at between 2.99 and
2.94 ppm, 2.75 and 2.73 ppm, and 1.68 and 1.38 ppm, respectively.
In the mass spectra of compounds 3 the presence of molecular
ion peak at m/z = 269.85 [M]+ confirmed the proposed structures.
Cyclotetramerization of the dinitrile derivative (3) to the Zn(II)
and Co(II) phthalocyanines (4 and 5) were confirmed by the dis-
appearance of the sharp C N vibration of 2229. The 1H NMR
spectrum of Zn(II) phthalocyanine (4) was obtained as expected.
In the 1H NMR spectrum of Zn(II) phthalocyanine (4) aromatic pro-
tons were observed between 7.38 and 7.03 ppm, etheric O CH2
protons at 4.57 ppm, c protons at 4.19 ppm, b protons between 3.16
and 2.28 ppm, and a protons at 1.79–1.36 ppm (a, b and c protons
respectively represented in Fig. 1).
2.6.3. Synthesis of 2,9(10),16(17),23(24)-tetrakis-
(2-(azepan-1-yl)ethoxy) phthalocyaninatocobalt(II) (5)
Compound 3 (0.1 g, 0.37 mmol) was added to a stirring solu-
tion of anhydrous CoCl2 (0.024 g, 0185 mmol) in dry pentan-1-ol
(5 mL). Then the mixture was refluxed in the presence of DBU (3
drops) under nitrogen. After 48 h, the mixture was cooled to room
temperature and centrifuged (4000 × g) for 5 min. The filtrate was
concentrated by evaporating up to 5 mL and added dropwise to
10 mL of cold hexane. The mixture was filtrated and the precipi-
tate was washed with tetrahydrofuran (10 mL × 5) and dried under
vacuum. Yield: 49.90 mg (47.5%). IR ꢂmax/(cm−1): 3252 (Ar H);
2917 (aliphatic H); 2849 (O CH2); 1522–1405 (Ar
C C); 1184
(C C); 1339 (Ar N); 1060–1120 (R Ar); 850, 820. UV–vis
N
O
ꢃmax (nm) (log ε) DMSO: 665 (4.63), 603 (4.10), 333 (4.52). MS
[m/z]: 1135.95 [M]+. C64H76CoN12O4 requires C, 67.65; H, 6.74; N,
14.79; found C, 67.70; H, 6.67; N, 14.85%.
The mass spectra of phthalocyanine compounds showed molec-
ular ion peaks at m/z = 1141.95 [M]+ for 4, 1135.95 [M]+ and for
5 support the proposed formula for these compounds. Elemen-
tal analysis results of these compounds were consistent with the
expected ones. Quaternized tetra-substituted Zn(II) phthalocya-
nines (4a and 5a) are soluble in water, DMF and DMSO. No major
change in the IR spectra was found after quaternization. The mass
spectra of quaternized Zn(II) and Co(II) phthalocyanines (4a and
5a) confirmed the proposed structure, with the molecular ion being
easily identified at 1395.3 [M]+ for 4a, 1388.08 [M]+ for 5a (ioniza-
tion methods were ESI-MS+ and MALDI for 4a and 5a, respectively).
2.6.4. General route for the synthesis of quaternized
2,9(10),16(17),23(24)-tetrakis-(2-(azepan-1-yl)ethoxy)
phthalocyaninatozinc(II) (4a) and quaternized 2, 9(10), 16(17),
23(24)-tetrakis-(2-(azepan-1-yl)ethoxy)
phthalocyaninatocobalt(II) (5a)
These complexes were prepared according to the method pre-
viously reported [12]. Compound 4 (or 5) (70 mg, 0.061 mmol) was
heated to 120 ◦C in freshly distilled DMF (5 mL) and excess dimethyl
sulfate (0.1 mL) was added dropwise. The mixture was stirred at
120 ◦C for 12 h. After this time, the mixture was cooled to room
temperature and the product was precipitated with hot acetone
and collected by filtration. The blue solid product was washed suc-
cessively with hot ethanol, ethyl acetate, THF, chloroform, hexane
and diethyl ether. The resulting hygroscopic product was dried over
phosphorous pentoxide.
3.2. Ground state electronic absorption and fluorescence spectra
The ground state electronic spectra of the studied neutral (4 and
5) and quaternized cationic (4a and 5a) Zn(II) and Co(II) phthalocya-
nine complexes exhibited characteristic absorptions in the Q band
region at nearby 680 nm for Zn(II) phthalocyanine complexes (4 and
4a) and 665 nm for Co(II) phthalocyanine complexes (5 and 5a) in
DMSO, Table 1. The absorptions in the B band region were observed
at nearby 350 nm for Zn(II) phthalocyanine complexes (4 and 4a)
and 320 nm for Co(II) phthalocyanine complexes (5 and 5a) in
DMSO (Fig. 2a and b). The absorption spectra exhibited monomeric
behavior for Zn(II) phthalocyanine complexes (4 and 4a) evidenced
by a single (narrow) Q band in DMSO which is typical of metal-
lated phthalocyanine complexes (Fig. 2a). The Q bands of the Co(II)
phthalocyanine complexes (5 and 5a) exhibited as splayed peaks
4a: Yield: 34.2 mg (40%). IR ꢂmax/(cm−1): 3059; 2943; 1765;
1716; 1606; 1485; 1468; 1398; 1365; 1207; 1083; 1056; 1000;
853. 1H NMR (DMSO-d6): ı 7.93–7.31 (m, 12H, Ar H), 4.13 (t, 8H,
O
CH2), 3.83 (t, 24H, N CH2b), 3.10 (s, 12H, N CH3), 2.08–1.61 (m,
32H, CH2a). MS [m/z]: 1395.3 [M]+. C68H88N12O12S2Zn requires C,
58.55; H, 6.36; N, 12.05; found C, 58.49; H, 6.22; N, 13.01%.
5a: Yield: 40.2 mg (47%). IR ꢂmax/(cm−1): 2935; 1708; 1608;
1464; 1336; 1186; 1092; 1045; 998; 848; 748. UV–vis ꢃmax (nm)
(log ε) DMSO: 668 (4.53), 603 (4.13), 318 (4.60). MS [m/z]: 1388.08
[M]+. C68H88CoN12O12S2 requires C, 58.82; H, 6.39; N, 12.10; found
C, 58.95; H, 6.26; N, 12.20%.

60
C. Uslan et al. / Journal of Photochemistry and Photobiology A: Chemistry 235 (2012) 56–64
Table 1
Absorption, excitation and emission spectral data for substituted zinc(II) and cobalt(II) phthalocyanines in DMSO and water.
Compound
Solvent
Q band ꢃmax (nm)
log ε
Excitation ꢃEx (nm)
Emission ꢃEm (nm)
Stokes shift ꢁStokes (nm)
4
4a
DMSO
DMSO
H2O
DMSO
DMSO
H2O
683
683
639, 678
665
668
5.11
4.77
4.30, 4.19
4.63
4.53
684
684
–
–
–
696
693
–
–
–
13
10
–
–
–
5
5a
627, 669
4.22, 4.15
–
–
–
Fig. 2. Absorption spectra of: (a) substituted non-ionic and ionic Zn(II) Pc complexes (4 and 4a) in DMSO, (b) substituted non-ionic and ionic Co(II) Pc complexes (5 and 5a)
in DMSO, (c) ionic Zn(II) and Co(II) Pc complexes (4a and 5a) in water, (d) substituted ionic Zn(II) Pc complex (4a) in DMSO and water. Concentration = 1 × 10−5 M.
(Fig. 2b) suggesting that aggregation of these complexes in DMSO.
In water, the absorption spectra of quaternized cationic complexes
(4a and 5a) showed cofacial aggregation, as evidenced by the pres-
2
ence of two non-vibrational peaks in the Q band region (Fig. 2c
and d), Table 1. The lower energy (red-shifted) absorption bands at
678 nm for 4a and 669 nm for 5a are due to the monomeric specie,
A
A
1.6
B
while the higher energy (blue-shifted) absorption bands at 639 for
4a and 627 for 5a are due to aggregated specie.
In the phthalocyanine complexes, aggregation is dependent on
the concentration and nature of the solvent, type of the substituents
C
D
1.2
E
F
on the phthalocyanine framework, nature of the metal ions in
the phthalocyanine cavity and temperature of medium [40]. In
the aggregated state, the electronic structure of the phthalocya-
nine rings are perturbed resulting in alternation of the ground and
excited state electronic structures [41]. The aggregation behavior of
the Zn(II) phthalocyanine complexes (4 and 4a) was investigated
at different concentrations in DMSO (Fig. 3, for complex 4 as an
example). The Beer–Lambert law was obeyed for both of these com-
plexes at concentrations ranging from 1.4 × 10−5 to 4 × 10−6 M. The
studied Zn(II) phthalocyanine complexes (4 and 4a) did not show
aggregation in DMSO.
0.8
0.4
0
F
300
400
500
600
700
800
Wavelength (nm)
Fig. 3. Absorption spectra of 4 in DMSO at different concentrations: 14 × 10−6 (A),
12 × 10−6 (B), 10 × 10−6 (C), 8 × 10−6 (D), 6 × 10−6 (E) and 4 × 10−6 M (F) (inset: plot
of absorbance versus concentration).

C. Uslan et al. / Journal of Photochemistry and Photobiology A: Chemistry 235 (2012) 56–64
61
400
300
200
100
0
2
of quaternized cationic Zn(II) phthalocyanine complex (4a) is also
higher than neutral Zn(II) phthalocyanine complex (4). The kF value
of complex 4a is lower than complex 4 in DMSO.
1.6
1.2
0.8
0.4
0
3.4. Singlet oxygen quantum yields
The singlet oxygen occurs because of the energy transfer
between the triplet state of photosensitizers and ground state
molecular oxygen. The singlet oxygen quantum yields (˚ꢁ), give an
indication of the efficiency of the compounds as photosensitizers
in photocatalytic applications where singlet oxygen is required for
example Type II mechanism for PDT. In this study, the ˚ꢁ values
were determined using a chemical method (using DPBF in DMSO
and ADMA in water as singlet oxygen quenchers). The disappear-
ance of quencher (DPBF or ADMA) was monitored using UV–vis
spectrophotometer (Fig. 5a using DPBF in DMSO for complex 4a
and Fig. 5b using ADMA in water for complex 5a). Many factors may
affect the magnitude of the singlet oxygen quantum yield of photo-
sensitizer such as triplet excited state energy, ability of substituents
and solvents to quench the singlet oxygen, the triplet excited state
lifetime and the efficiency of the energy transfer between the triplet
excited state and the ground state of oxygen. There was no decrease
in the Q band absorption of formation of the studied phthalocyanine
complexes during ˚ꢁ determinations (Fig. 5).
Emission
Excitation
Absorption
600
500
700
800
Wavelength (nm)
Fig. 4. Absorption, excitation and emission spectra of 4 in DMSO. Excitation wave-
length: 650 nm.
The studied Zn(II) phthalocyanine complexes (4 and 4a) are flu-
orescent, while the studied Co(II) phthalocyanine complexes (5 and
5a) are not fluorescence in DMSO due to paramagnetic behavior of
Co(II) atom in the phthalocyanine cavity. Fig. 4 shows fluorescence
emission, absorption and excitation spectra of complex 4 in DMSO
as an example of the studied Zn(II) phthalocyanine complexes.
Fluorescence emission peaks of substituted Zn(II) phthalocyanine
complexes (4 and 4a) were listed in Table 1. The observed Stokes
shifts were within the interval (∼10–20 nm) observed for Zn(II)
Pc complexes. Both studied Zn(II) phthalocyanine complexes (4
and 4a) exhibited similar fluorescence behavior in DMSO. The
excitation spectra were similar to absorption spectra and both
were mirror images of the fluorescent spectra for studied Zn(II)
phthalocyanine complexes (4 and 4a) in DMSO suggesting that the
molecules did not show any degradation during excitation. In aque-
ous media, the water soluble quaternized Zn(II) phthalocyanine
complexes (4 and 4a) are not fluorescent. Aggregated MPc com-
plexes are not known to fluorescence [42] since aggregation lowers
the photoactivity of molecules through dissipation of energy.
Table 2 shows that the ˚ꢁ values of Zn(II) phthalocyanine com-
plexes are higher than Co(II) phthalocyanine complexes in both
DMSO and water, except for the ˚ꢁ values of complex 5a is higher
than corresponding Zn(II) phthalocyanine complex (4a) in water.
In general, the ˚ꢁ values of the phthalocyanine derivatives are
higher in DMSO than water due to the aggregation of these com-
plexes in latter solvent. The ˚ꢁ value of quaternized cationic Zn(II)
1.2
(a)
1
0.8
0.6
0.4
0.2
0
3.3. Fluorescence quantum yields and lifetimes
The fluorescence quantum yields (˚F) for neutral and quat-
ernized cationic Zn(II) phthalocyanine complexes (4 and 4a) in
DMSO are given in Table 2. The ˚F values of the studied Zn(II)
phthalocyanine complexes (4 and 4a) are lower than unsubstituted
Zn(II) phthalocyanine (˚F = 0.20) in DMSO, suggesting that more
quenching of substitution of the 2-(azepan-1-yl)ethoxy groups on
the phthalocyanine framework. The neutral Zn(II) Pc complex (4)
showed larger ˚F values compared to the corresponding qua-
ternarized cationic Zn(II) phthalocyanine complex (4a) in DMSO.
Comparing DMSO and water, while the quaternarized neutral Zn(II)
phthalocyanine complex (4a) is fluorescent in DMSO, this com-
plex is not fluorescent in water. This is attributed to aggregation
as discussed above.
Fluorescence lifetime (ꢀF) to be related to the average time a
fluorophore stays in its excited state before emission. The type of
substituents on the framework, nature of using solvent, concentra-
tion and aggregation affect fluorescence lifetime of phthalocyanine
compounds. Lifetimes of fluorescence were calculated using the
Strickler–Berg equation. Using this equation, a good correlation
has been found [26] between experimentally and the theoretically
determined fluorescence lifetimes for the unaggregated molecules
as is the case for DMSO in this work. The ꢀF value is slightly higher
for quaternized cationic Zn(II) phthalocyanine complex (4a) when
compared to neutral Zn(II) phthalocyanine complex (4) in DMSO.
The natural radiative lifetime (ꢀ0) and the rate constants for
fluorescence (kF) values are also given in Table 2. The ꢀ0 value
300
400
500
600
700
800
Wavelength (nm)
0.8
0.6
0.4
0.2
0
(b)
300
400
500
600
700
800
Wavelength (nm)
Fig. 5. A typical spectrum for the determination of singlet oxygen quantum yield
of: (a) 4a in DMSO using DPBF as a singlet oxygen quencher and (b) 5a in water
using ADMA as a singlet oxygen quencher. Concentration = 1 × 10−5 M (inset: plots
of DPBF or ADMA absorbance versus time).

62
C. Uslan et al. / Journal of Photochemistry and Photobiology A: Chemistry 235 (2012) 56–64
Table 2
Photophysical and photochemical parameters of substituted zinc(II) and cobalt(II) phthalocyanine complexes in DMSO and water.
a
Compound
˚
F
ꢀF (ns)
ꢀ0 (ns)
kF (×108 s−1
)
˚
d
˚
ꢁ
4
4a
0.081
0.12
H2O
DMSO
DMSO
H2O
0.71
1.96
–
–
–
8.76
16.37
–
–
–
–
1.14
0.61
–
–
–
1.38 × 10−4
2.08 × 10−5
4.09 × 10−4
7.86 × 10−4
1.42 × 10−5
1.65 × 10−5
0.62
0.36
0.26
0.007
0.012
0.84
5
5a
–
–
a
kF is the rate constant for fluorescence. Values calculated using kF = ˚F/ꢀF.
1.8
1.8
1.6
1.6
1.4
1.2
1
0.8
0.6
0.4
y = -0.0008x + 1.5404
R² = 0.9898
1.4
0 sec
0.2
0
1.2
60 sec
0
100
200
300
400
120 sec
180 sec
240 sec
300 sec
360 sec
Time (sec)
1
0.8
0.6
0.4
0.2
0
300
400
500
600
700
800
Wavelength (nm)
Fig. 6. The photodegradation of 4 in DMSO showing the disappearance of the Q-band at 1-min intervals (inset: plot of Q band absorbance versus time).
phthalocyanine complex (4a) is higher in DMSO than in water.
However, the ˚ꢁ value of quaternized cationic Co(II) phthalocya-
nine complex (5a) is higher in water than in DMSO. The higher
singlet oxygen generation capability of the studied complexes
(especially in water) makes them appropriate candidate photosen-
sitizers for PDT applications. Quaternized cationic Pc complexes (4a
and 5a) showed lower ˚ꢁ values when compared to corresponding
neutral complexes (4 and 5) in DMSO, suggesting that the quater-
nization of the Zn(II) Pc complexes caused the decrease in the ˚ꢁ
values.
showed lower ˚d values, suggesting that the substitution of the
2-(azepan-1-yl)ethoxy groups on the phthalocyanine framework
decreasing the stability of the phthalocyanine complexes, but the
quaternization of these groups resulted in the increase in the sta-
bility of the quaternized cationic phthalocyanine complexes.
3.6. Binding of quaternized cationic Zn(II) and Co(II)
phthalocyanine complexes to BSA
Fig. 7 shows the changes in the fluorescence emission spec-
tra of BSA in the presence of different concentrations of 5a (as an
example) in water. The quaternized cationic phthalocyanine com-
plexes are mixtures of aggregated and unaggregated species. The
3.5. Photodegradation studies
The stability of photosensitizers under light irradiation is impor-
tant for those molecules intended for use in photocatalysis. The
decreasing of the absorption spectra without any distortion of
the shape confirms photodegradation not associated with photo-
transformation into different forms of MPc absorbing in the visible
region. The spectral changes observed for all the complexes (4, 4a,
5 and 5a) during confirmed photodegradation under light irradia-
tion occurred without phototransformation (Fig. 6 as an example
for complex 4 in DMSO).
All the studied Zn(II) Pc complexes showed about the same sta-
bility with ˚d of the order of 10−4. The ˚d values, found in this
study, are similar with Zn(II) Pc complexes having different sub-
stituents on the phthalocyanine ring in the literature [42]. It was
reported in literature that stable Pc molecules show ˚d values as
low as 10−6 and unstable ones show ˚d values of the order of 10−3
[42].
1000
A
800
B
[Pc]=0
C
600
400
200
0
D
E
F
[Pc]=saturated
440
G
290
340
390
490
Wavelength (nm)
The neutral Zn(II) and Co(II) phthalocyanine complexes (4 and
5) showed higher ˚d values when compared to the unsubstituted
ZnPc (˚d = 0.26 × 10−4) [43] in DMSO, whereas, the quaternized
cationic Zn(II) and Co(II) phthalocyanine complexes (4a and 5a)
Fig. 7. Fluorescence emission spectral changes of BSA (C = 3.00 × 10−5 M) on
addition of varying concentrations of 5a in water. [5a]: A = 0, B = 1.66 × 10−6
,
C = 3.33 × 10−6, D = 5.00 × 10−6, E = 6.66 × 10−6, F = 8.33 × 10−6 M, G = saturated with
5a.

C. Uslan et al. / Journal of Photochemistry and Photobiology A: Chemistry 235 (2012) 56–64
63
Table 3
Binding and fluorescence quenching data for interaction of BSA with quaternized zinc(II) and cobalt(II) phthalocyanine complexes in water.a
BSA
SV
Compound
Solvent
K
(×105 M−1
)
kq (×1013 M−1 s−1
)
Kb (×10−6 M−1
)
n
4a
5a
H2O
H2O
1.14
0.90
1.14
0.90
2.63
3.80
1.02
1.28
a
˚F(BSA) = 0.118 [44].
4a
5a
total concentrations of the complexes are mixture of the monomer
and aggregated species. The BSA fluorescence at 348 nm is mainly
attributable to tryptophan residues in the macromolecule. BSA
and the respective quaternized cationic phthalocyanine complexes
exhibit reciprocated fluorescence quenching on one another; hence
it was possible to determine Stern–Volmer quenching constants
(KSV). The slope of the plots shown at Fig. 8 gave KSV values which
are listed in Table 3. These values suggest that BSA fluorescence
quenching is more effective for cationic Zn(II) phthalocyanine com-
plex (4a) than cationic Co(II) phthalocyanine complex (4a) in water.
Using the approximate fluorescence lifetime of BSA [38,39], the
bimolecular quenching constant (kq) was determined using Eq. (7).
0
-0.2
-0.4
-0.6
-0.8
-1
These values are of the order of 1013
M
−1 s−1, which exceed the
-1.2
-5.9
proposed value of 1010 −1 s−1 for diffusion-controlled (dynamic)
M
-5.8
-5.7
-5.6
-5.5
log[Pc]
-5.4
-5.3
-5.2
-5.1
-5
quenching (according to the Einstein–Smoluchowski approxima-
tion) at room temperature [44].
Fig. 9. Determination of quaternized Zn(II) (4a) and Co(II) (5a)
This also, is an indication that the mechanism of BSA quenching
by cationic phthalocyanine complexes (4a and 5a) is not diffusion-
controlled (i.e., not dynamic quenching, but static quenching). The
kq value is larger for cationic Zn(II) phthalocyanine complex (4a)
than cationic Co(II) phthalocyanine complex (5a) in water. The
binding constants (Kb) and number of binding sites (n) on BSA were
obtained using Eq. (5) and the results are shown in Table 3. The slope
of the plots shown at Fig. 9 gave n values and the intercepts of these
plots gave Kb values. The values of Kb and n are typical of MPc–BSA
interactions in aqueous solutions [35,45].
The higher Kb value for cationic Co(II) phthalocyanine com-
plex (5a) implies that this phthalocyanine complex binds more
strongly to BSA than the cationic Zn(II) phthalocyanine complex
(4a), suggesting that less aggregation behavior of Co(II) phthalo-
cyanine complexes in water (Fig. 2c). The decrease in the intrinsic
fluorescence intensity of tryptophan with ionic phthalocyanine
concentration indicates that these complexes readily bind to BSA,
which implies that the phthalocyanine molecules reach subdo-
mains where tryptophan residues are located in BSA. This also
suggests that the primary binding sites of these molecules are very
close to tryptophan residues, since the occurrence of quenching
requires molecular contact.
phthalocyanines–BSA binding constant (and number of binding sites on BSA).
[BSA] = 3.00 × 10−5 M and [Pc] = 0, 1.66 × 10−6, 3.33 × 10−6, 5.00 × 10−6, 6.66 × 10−6
,
8.33 × 10−6 M in water.
4. Conclusion
In conclusion, this work has described the synthesis, spectral,
photophysical and photochemical properties of new peripherally
tetrakis-(2-azepan-1-yl)ethoxy substituted non-ionic and quat-
ernized ionic Zn(II) and Co(II) phthalocyanine complexes. The
quaternized complexes exhibited excellent solubility in water, but
they showed aggregation in this solvent. These complexes gave
good ˚ꢁ values. In particular, quaternarized ionic Co(II) phthalo-
cyanine complex (5a) has high ˚ꢁ value (0.84) in water. Thus, these
complexes exhibit potential as Type II photosensitizers for PDT of
cancer. This work will certainly enrich the hitherto scanty literature
on the potentials of cationic Zn(II) and Co(II) phthalocyanines as
photosensitizers in PDT. This study reveals that the water-soluble
complexes bind strongly to serum albumin; hence they can easily
be transported in the blood.
Acknowledgements
This study was supported by Research Fund of Istanbul Technical
University, TUBITAK (project no. 110T800 and 110T527) and Gebze
High Institute of Technology.
2
4a
5a
1.8
1.6
1.4
1.2
1
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