New highly soluble phenoxy-substituted phthalocyanine and azaphthalocyanine derivatives: Synthesis, photochemical and photophysical studies and atypical aggregation behavior

Article abstract of DOI:10.1016/j.dyepig.2012.03.023

A series of zinc phthalocyanines and corresponding aza-analogues azaphthalocyanines substituted with peripheral 2,6-diisopropylphenoxy substituents containing different functional groups (Br, OCH₃, and OH) were synthesized and their photophysical properties were investigated. UV-vis and ¹H NMR analyses confirmed the non-aggregation behavior of the prepared complexes in most organic solvents. All investigated compounds showed good photophysical and photochemical properties in THF and DMF with Φ_F values in the range of 0.22-0.44 and Φ_Δ values ranging between 0.42 and 0.57. Hydroxylated compounds showed good solubility in polar solvents including ethanol, methanol, acetone and even in aqueous ethanol mixtures. Absorption spectra in aqueous ethanol indicated presence of only monomers even at very low ethanol content in water (0.5% of ethanol in water). Despite this, no fluorescence occurred from approximately 50% of ethanol in water suggesting presence of aggregates that do not differ from monomers in a shape of absorption spectra.

Full text of DOI:10.1016/j.dyepig.2012.03.023

Dyes and Pigments 95 (2012) 351e357
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Dyes and Pigments
journal homepage: www.elsevier.com/locate/dyepig
New highly soluble phenoxy-substituted phthalocyanine and azaphthalocyanine
derivatives: Synthesis, photochemical and photophysical studies and atypical
aggregation behavior
,
a
a
b
a
c
Saad Makhseed a , Ahmad Tuhl , Jacob Samuel , Petr Zimcik , Nouria Al-Awadi , Veronika Novakova
*
a Department of Chemistry, Kuwait University, P.O. Box 5969, Safat 13060, Kuwait
b Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005,
Czech Republic
c Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of zinc phthalocyanines and corresponding aza-analogues azaphthalocyanines substituted with
peripheral 2,6-diisopropylphenoxy substituents containing different functional groups (Br, OCH3, and
OH) were synthesized and their photophysical properties were investigated. UVevis and 1H NMR
analyses confirmed the non-aggregation behavior of the prepared complexes in most organic solvents.
All investigated compounds showed good photophysical and photochemical properties in THF and DMF
with FF values in the range of 0.22e0.44 and FD values ranging between 0.42 and 0.57. Hydroxylated
compounds showed good solubility in polar solvents including ethanol, methanol, acetone and even in
aqueous ethanol mixtures. Absorption spectra in aqueous ethanol indicated presence of only monomers
even at very low ethanol content in water (0.5% of ethanol in water). Despite this, no fluorescence
occurred from approximately 50% of ethanol in water suggesting presence of aggregates that do not
differ from monomers in a shape of absorption spectra.
Received 15 December 2011
Received in revised form
14 March 2012
Accepted 22 March 2012
Available online 22 May 2012
Keywords:
Phthalocyanine
Tetrapyrazinoporphyrazine
Zinc
Singlet oxygen
Fluorescence
Aggregation
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
as a consequence singlet oxygen production is significantly reduced
[2]. Despite the fact that many approaches tried to conquer the
Phthalocyanines (Pcs) and their aza-analogues (AzaPcs) from
tetrapyrazinoporphyrazine group have recently received a great
attention due to their fascinating optical properties which are
currently being exploited in several technological applications [1e4].
Their strong absorption in the region of biological optical window
(600e800 nm), efficiency in generating singlet oxygen, lack of dark
toxicity, flexibility in structural modifications including the central
transition metal and photostability make them promising candi-
dates in photodynamic therapy (PDT) [5e9]. PDT is based on
production of cytotoxic singlet oxygen after irradiation of photo-
sensitizer and achieved success in clinical practice for treatment of
various diseases, mainly cancer [10]. However, the aggregation
behavior of Pcs represents the main concern for the researchers due
to the efficiency limitation of using such material in PDT and other
related applications. The aggregation leads to quenching of the
excited state through nonradiative energy relaxation pathway, and
aggregation behavior in organic solvent [11,12] or in aqueous media
[13e15] there is still a room for many improvements in this area.
This work is focused on zinc Pcs and AzaPcs substituted with
eight bulky phenoxy groups inhibiting the aggregation containing
three different functional moieties: Br, MeO and OH. The last
mentioned substitution was expected to provide Pcs and AzaPcs
soluble in more polar solvents which is a good starting point for
potential biological testing. Photochemical and photophysical
properties of synthesized compounds were evaluated in order to
gain insight to the structure-property relationships. Based on
previous findings, zinc complexes have been chosen in this study as
a result of their desirable photophysical and stability properties.
2. Experimental
2.1. Material and method
The
4,5-dichlorophthalonitrile
and
precursor
5,6-
dichloropyrazine-2,3-dicarbonitrile were synthesized by the repor-
ted procedures in the literature [16,17]. Starting from the 2,6-di-iso-
* Corresponding author. Tel.: þ965 24985538; fax: þ965 24816482.
E-mail address: saad.makhseed@ku.edu.kw (S. Makhseed).
0143-7208/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.dyepig.2012.03.023

352
S. Makhseed et al. / Dyes and Pigments 95 (2012) 351e357
propylphenol, 2,6-di-iso-propyl-4-bromophenol and 2,6-di-iso-
propyl-4-methoxyphenol were synthesized and characterized in our
laboratory [18]. 4,5-Bis(2,6-di-iso-propyl-4-bromophenoxy)phtha-
lonitrile (1) and 2,3,9,10,16,17,23,24-octa(2,6-di-iso-propyl-4-
bromophenoxy)phthalocyaninato zinc (II) (5) have been reported
previously by our group [19]. Anhydrous DMF was purchased from
Aldrich and the potassium carbonate was obtained locally. 1H NMR
spectra (400 MHz) were recorded using Bruker DPX 400. IR spectra
were recorded on a Jasco 6300 FTIR. UVeVis studies were done on
a Varian Cary 5 spectrometer and Shimadzu UV-2401Pc spectro-
photometer. Elemental analyses were carried out using Elementar
Vario Micro Cube. Mass analyses were done by electron impact (EI)
and fast atom bombardment (FAB) on a Thermo DFS mass spec-
trometer. Differential scanning calorimetry (DSC) analyses were
carried out on Shimadzu DSC-50. Fluorescence spectra were
obtained using an AMINCO-Bowman series 2 luminescence spec-
trometer (SLM-Amino, Urbana II, U.S.A).
C32H38N4O4, C: 70.82, H: 7.06, N: 10.32. Found C: 71.08, H: 7.3, N:
10.00; MS (EI) (m/z): Calc. 542.289, Found 542 [M]þ.
2.2.4. 2,3,9,10,16,17,23,24-octa(2,6-diisopropyl-4-
methoxyphenoxy)phthalocyaninato zinc(II) (6)
Compound 1 (0.50 g, 0.92 mmol) was reacted with excess of
anhydrous zinc acetate (40 mg, 0.22 mmol) in dry quinoline (10 mL)
at 180 ꢀC under nitrogen for 8 h. The crude product was purified by
column chromatography on SiO2 eluting with hexane/DCM/ethyl
acetate (7:2:1) to give 6 as a green solid. (0.36 g, 70%), M.p over
300 ꢀC; UV/vis (CHCl3): lmax 683 (5.56), 356 nm; IR (KBr)
cmꢁ1:2963, 1606, 1453, 1398, 1336, 1303, 1266, 1185, 1125, 1090,
1039, 888, 846; 1H NMR (400 MHz; CDCl3)
/ppm: 8.28 (s, 8H, ArH),
n/
d
6.97 (s, 16H, ArH), 4.08 (s, 24H, CH3O), 3.45 (sept, 16H, J ¼ 6.8 Hz,
CH),1.27 (br, 96H, CH3); Anal. calc. for C136H164N8O18 Zn (compound
6 þ 2H2O): C 72.4, H 7.30, N 4.95, found C 72.32, H 7.80, N 4.84; MS
(FAB) (m/z): Calc. 2225, Found: 2226 [M þ H]þ.
2.2. Synthesis
2.2.5. 2,3,9,10,16,17,23,24-cta-(2,6-diisopropyl-4-hydroxyphenoxy)
phthalocyaninato zinc(II) (7)
2.2.1. 4,5-Bis(2,6-diisopropyl-4-methoxyphenoxy)phthalonitrile (2)
To the stirred solution of 2,6-di-iso-propyl-4-methoxyphenol
(4.64 g, 22.3 mmol) in dry DMF (50 mL) finely grounded
anhydrous CsF (6.78 g, 44.6 mmol) followed by 4,5-
dichlorophthalonitrile (2 g, 10.1 mmol) were added. The reaction
mixture was heated at 60 ꢀC under nitrogen atmosphere for 24 h.
After cooling the reaction mixture was poured into distilled water.
The precipitate was filtered and washed with distilled water. The
crude product was then recrystallised from methanol to give 2 as
To a solution of compound 5 (0.200 g, 0.1 mmol) in dry DCM
(10 mL), under nitrogen, at 0 ꢀC boron tribromide (0.1 mL, 2 mmol)
was added dropwise. After 6 h the stirring was stopped and the
solution was transferred to a beaker; excess of boron tribromide
was left to evaporate 24 h at room temperature then the reaction
was quenched with distilled water and a purple precipitate crushed
out. The solid was collected, dissolved in ethyl acetate and washed
with water. The organic layer was dried over magnesium sulphate
and evaporated to give 7 as a green solid that was purified by
recrystallization using ethyl acetate/hexane (0.095 g, 56%), M.p
white crystalline solid (4.1 g, 75%), M.p: 192 ꢀC; IR (KBr)
n :
/cmꢁ1
2226 (CN). 1H NMR (CDCl3, 400 MHz)
d/ppm: 6.81 (s, 4H, ArH), 6.8
over 300 ꢀC; UV/vis (EtOH): lmax 677 (5.60), 356 nm; IR (KBr)
cmꢁ1 3406, 2963, 1603, 1482, 1445, 1397, 1338, 1306, 1264, 1220,
1184, 1141, 1089, 1025, 888, 853; 1H NMR (400 MHz; acetone[D6])
n/
(s, 2H, ArH), 3.90 (s, 6H, CH3O), 2.78 (sept, 4H, J ¼ 6.8 Hz, CH), 1.24
(d, 12H, J ¼ 6.8 Hz, CH3), 1.16 (d, 12H, J ¼ 6.8 Hz, CH3). Anal. calc. for
C34H40N2O4, C: 75.53, H: 7.46, N: 5.18. Found C: 75.45, H: 7.84, N:
5.08; MS (EI) (m/z): Calc. 540.3. Found 540 [M]þ.
d
/
ppm: 8.84 (s br, 8OH), 8.28 (s, 8H, ArH), 7.13 (s,16H, ArH), 3.45 (sept,
16H, J ¼ 6.5 Hz, CH), 1.22 (d br, 96H, CH3); Anal. calc. for
C128H148N8O18Zn (compound 7 þ 2H2O): C 71.44, H 6.93, N 5.21,
found C 71.80, H 7.34, N 5.03; MS (FAB)(m/z): Calc. 2113, Found:
2113 [M]þ.
2.2.2. 5,6-Bis(4-bromo-2,6-diisopropylphenoxy)pyrazine-2,3-
dicarbonitrile (3)
Dry potassium carbonate (8.3 g, 60.0 mmol) was added to
a solution of 2,6-di-iso-propyl-4-bromophenol (11.35 g, 45.0 mmol)
and 5,6-dichloropyrazine-2,3-dicarbonitrile (2.9 g, 15.0 mmol) in
dry DMF (150 mL). The reaction mixture was heated at 60 ꢀC for
24 h under nitrogen. On cooling, the reaction mixture was poured
in to distilled water (200 mL). The resulting precipitate was
collected by filtration and washed with water and air-dried. The
crude product was recrystallised from methanol to give 3 as a white
2.2.6. 2,3,9,10,16,17,23,24-octa(4-bromo-2,6-diisopropylphenoxy)-
1,4,8,11,15,22,25-octaazaphthalocyaninato zinc(II) (8)
A mixture of 5,6- Bis(2,6-di-iso-propyl-4-bromophenoxy)pyr-
azine-2,3-dicarbonitrile (3) (1.00 g, 1.6 mmol) and an excess of
anhydrous zinc (II)acetate (40 mg, 0.22 mmol) in dry quinoline
(10 mL) was stirred at 180 ꢀC under nitrogen atmosphere for 6 h.
The reaction mixture was poured into stirred methanol (20 mL) on
cooling, and the solid green product was collected by filtration then
washed intensely with warm water and methanol. The crude
product was purified by column chromatography on silica gel
where CHCl3 was used as the eluting solvent. Following the removal
of the solvent by evaporation to give 8 as a green solid (0.40 g, 39%);
powder (7.8 g, 82%); M.p: 203e204 ꢀC; IR (KBr)
n
/cmꢁ1: 2238 (CN);
1H NMR (CDCl3, 400 MHz)
d
/ppm: 7.40 (s, 4H, ArH), 2.76 (sept, 4H,
J ¼ 6.8 Hz, CH), 1.23 (d, 24H, J ¼ 6.4 Hz, CH3), Anal. calc. for
C30H32N4O2Br2, C: 56.33, H: 5.00, N: 8.76, Found C: 56.06, H: 4.91,
N: 8.62; MS (EI) (m/z): Calc. 639.8, Found 640[M]þ.
M.p over 300 ꢀC; UV/vis (DMF): lmax 636 (5.39), 365 nm; IR (KBr)
cmꢁ1: 3390, 2969, 2931, 1576, 1550, 1451, 1420, 1400, 1362, 1213,
1160, 952, 932; 1H NMR (400 MHz; CDCl3)
/ppm: 7.70 (s,16H, ArH),
n/
2.2.3. 5,6-Bis(2,6-diisopropyl-4-methoxyphenoxy)pyrazine-2,3-
dicarbonitrile (4)
d
To the stirred solution of 2,6-di-iso-propyl-4-methoxyphenol
(4.59 g, 22 mmol) in dry DMF (50 mL) finely grounded anhydrous
CsF (6.71 g) followed by 5,6-dichloropyrazine-2,3-dicarbonitrile
(2 g, 10 mmol) was added. The reaction mixture was heated at
60 ꢀC under nitrogen atmosphere for 24 h. After cooling the reac-
tion mixture was poured in to distilled water. The precipitate was
filtered and washed with distilled water. The crude product was
then recrystallised from methanol to give 4 as white crystalline
3.37 (sept, 16H, J ¼ 6.8 Hz, CH), 1.34 (br, 96H, CH3); Anal. calc. for
C120H128 Br8N16O8Zn: C, 54.86; H, 4.88; N, 8.53. Found: C, 55.1; H,
5.20; N, 8.90. MS (FAB) m/z: Calc. 2625, Found: 2625 [M]þ.
2.2.7. 2,3,9,10,16,17,23,24-octa(2,6-diisopropyl-4-methoxyphe
noxy)-1,4,8,11,15,22,25-octaazaphthalocyaninato zinc(II) (9)
5,6-Bis(2,6-di-iso-propyl-4-methoxyphenoxy)pyrazine-2,3-
dicarbonitrile (0.500 g, 0.9 mmol) was reacted with anhydrous zinc
acetate (0.1 g, 0.55 mmol) in quinoline (10 mL) at 180 ꢀC under
nitrogen atmosphere for 6 h. The crude product was purified by
column chromatography on SiO2 eluting with hexane/DCM (4:6) to
solid (4.35 g, 80%); M.p: 190 ꢀC; IR (KBr)
(CDCl3, 400 MHz) /ppm: 6.76 (s, 4H, ArH), 3.87 (s, 6H, CH3O), 2.78
(sept, 4H, J ¼ 6.8 Hz, CH),1.21 (d, 24H, J ¼ 6.1 Hz, CH3); Anal. calc. for
n
/cmꢁ1: 2226 (CN). 1H NMR
d

S. Makhseed et al. / Dyes and Pigments 95 (2012) 351e357
353
give 9 as a green solid (0.360 g, 70%); M.p over 300 ꢀC; UV/vis
(CHCl3): lmax 629 (5.44), 360 nm; IR (KBr)
/cmꢁ1 2970, 1599, 1463,
1402, 1300, 1197, 1161, 1128, 951, 817; 1H NMR (400 MHz; CDCl3)
ppm: 6.97 (s, 16H, ArH), 4.08 (s, 24H, CH3O), 3.33 (sept, 16H,
J ¼ 6.8 Hz, CH), 1.28 (d, 96H, J ¼ 7.21 Hz, CH3); Anal. calc. for
C128H154N16O17Zn (compound 9 þ H2O): C 68.20, H 6.89, N 9.94,
found C 68.26, H 6.87, N 9.75; MS (FAB) (m/z): Calc. 2233,
Found:2233 [M]þ.
not decomposing or aggregating within the experimental period.
All experiments were performed three times and the data pre-
sented in the paper represent a mean of these three experiments.
Estimated error ꢂ10%. Singlet oxygen quantum yield (FD) was
calculated by using the following equation (Eq. (2)):
n
d/
R kSIaRT
FDS
¼
FD
(2)
kRIaST
where k is a slope of a plot of the dependence of ln (A0/At) on
irradiation time t, with A0 and At being the absorbance of the DPBF
at monitoring wavelength before irradiation and after irradiation
time t, respectively. IaT is a total amount of light absorbed by the
dye. Superscripts R and S indicate reference and sample, respec-
tively. IaT is calculated as a sum of intensities of the absorbed light Ia
at wavelengths from 506 nm to 800 nm (step 0.5 nm). Light under
506 nm is completely filtered off by HOYA G filter and light above
800 nm is not absorbed by the dyes. Ia at given wavelength is
calculated using Beer’s law (Eq. (3)).
2.2.8. 2,3,9,10,16,17,23,24-octa(4-hydroxy-2,6-diisopropylphe
noxy)-1,4,8,11,15,22,25-octaazaphthalocyaninato zinc(II) (10)
Complex 10 was synthesized and purified using the similar
procedure adopted for 7 (0.120 g, 60%); M.p over 300 ꢀC; UV/vis
(EtOH): lmax 625(5.35), 360 nm; IR (KBr)
1482, 1445, 1397, 1338, 1264, 1184, 1089, 1025, 888, 853; 1H NMR
(400 MHz; acetone[D6]) /ppm: 8.66 (br s, 8OH), 7.06 (s, 16H, ArH),
n
/cmꢁ1 3406, 2963, 1603,
d
3.34 (sept, 16H, J ¼ 6.5 Hz, CH), 1.30 (br, 96H, CH3); Anal. Calc. for
C120H140N16O18Zn (compound 10 þ 2H2O): C 66.73, H 6.53, N 10.38,
found C 66.55, H 6.84, N 9.97; MS (FAB) (m/z): Calc. 2121, Found:
2121 [M]þ.
ꢂ
ꢃ
Ia ¼ I0 1 ꢁ eꢁ2:3A
(3)
Where transmittance of the filter at given wavelength stays for I0
and absorbance of the dye at this wavelength stays for A.
2.3. Photophysical and photochemical parameters
2.3.1. Fluorescence quantum yields
2.4. Study of aggregation properties
Fluorescence quantum yields (FF) of the studied Pcs and AzaPcs
were determined in THF and DMF and calculated by using the
following equation (Eq. (1)) [20]:
Absolute ethanol (99%, SigmaeAldrich) was used to prepare
200
200 ꢃ with premixed ethanol/water mixtures (from pure ethanol
to pure water) to obtain final 1.0 M solution that was used for
absorbance measurements. For fluorescence measurements, the
solutions were further diluted to obtain maximum absorbance of
0.05 in Q-band (for excitation wavelengths and calculations see
above). Refractive indices were measured for each ethanol/water
ratio (see Supporting Information) and used to correct FF values
according to Eq. (1).
mM stock solutions of 7 and 10. The stock solution was diluted
!
ꢀ
ꢁ
ꢀ
ꢁ2
R
FS
FR
1 ꢁ 10ꢁA
nS
nR
FFS
¼
FFR
(1)
S
m
1 ꢁ 10ꢁA
Where FF is the fluorescence quantum yield, F is the area under the
fluorescence emission curve, A is the absorbance at the excitation
wavelength and n is the refractive index of the solvent. Superscripts
R and S indicate reference and sample, respectively. Unsubstituted
zinc (II) phthalocyanine (ZnPc) was used as the reference
(FF(chloronaphthalene) ¼ 0.30 [21]). Both reference and sample were
excited at the same wavelength (lexc ¼ 591 nm for AzaPcs,
lexc ¼ 611 nm for Pcs). In order to avoid inner filter effect, absor-
bance at Q-band maximum was kept below 0.05. All experiments
were performed three times and the data presented in the
paper represent a mean of these three experiments. Estimated
error ꢂ10%. Excitation spectra were collected by observing fluo-
rescence signal usually at 700 nm or 740 nm for AzaPc and Pc,
respectively.
3. Result and discussion
3.1. Synthesis and characterization
Fig. 1 shows the synthetic route for the target Pc (5e7) and
AzaPc (8e10) derivatives. The starting phthalonitrile (1, 2) and
pyrazine-2,3-dicarbonitrile (3, 4) precursors were prepared in
a good yield from the aromatic nucleophilic substitution reaction
between 4,5-dichlorophthalonitrile or 5,6-dichloropyrazine-2,3-
dicarbonitrile respectively with the appropriately functionalized
phenolate. The synthesis of zinc complexes (5, 6, 8 and 9) was
achieved by metal-ion mediated cyclotetramerisation reaction of
the corresponding precursors (1e4) in dry quinoline using anhy-
drous zinc acetate. Subsequent demethylation of Pc 6 and AzaPc 9
using an excess of BBr3 in DCM gave Pc 7 and AzaPc 10, respec-
tively. The routine characterization techniques such as UVevis, IR,
elemental analysis and fast atom bombardment mass spectros-
copy (FAB MS) gave results consistent with the proposed struc-
tures for all the prepared complexes along with their satisfactory
purities. Pcs and AzaPcs exhibited well-resolved 1H NMR
spectra with sharp peaks in both aromatic and aliphatic region
implying that the aggregation behavior is absent (see Supporting
Information). The NMR spectra of starting precursors and their
corresponding complexes were almost identical and showed
exactly the same excellent quality spectra apart from the chemical
shifts resulting from the ring current effect of the aromatic
macrocycle which caused the deshielding effects [26]. This is
2.3.2. Singlet oxygen quantum yields
The measurements of singlet oxygen quantum yields (FD) were
performed in DMF and THF based on decomposition of a chemical
trap 1,3-diphenylisobenzofuran (DPBF) [22]. ZnPc was used as
a reference compound (FD
¼ 0.56 [23,24], FD
¼ 0.53 [25]).
(DMF)
(THF)
In detail the procedure was as follows: 2.5 mL of a stock solution of
DPBF (5 ꢃ10ꢁ5 M) in DMF or THF was transferred into a 10 ꢃ 10 mm
quartz optical cell and bubbled with oxygen for 1 min. Defined
amount (usually 30 ml) of concentrated stock solution of the tested
compound in DMF or THF was then added. Absorbance of the final
solution in Q-band maximum was always about 0.1. The solution
was stirred and irradiated for defined times using a halogen lamp
(Tip, 300 W). Incident light was filtered through a water filter
(6 cm) and an orange HOYA G filter to remove heat and light under
506 nm, respectively. Decrease of DPBF concentration in DMF or
THF solution with irradiation time was monitored at 415 nm
or 414 nm, respectively. No significant changes in Q-band shape or
intensity were observed indicating that the Pcs and AzaPcs were

354
S. Makhseed et al. / Dyes and Pigments 95 (2012) 351e357
Fig. 1. The synthesis of ZnPcs and ZnAzaPcs. Reagents and conditions: i) CsF or K2CO3, DMF, 60 ꢀC, 24 h, ii) zinc acetate, quinoline, 180 ꢀC, 6e8 h, iii) BBr3/DCM 0e5 ꢀC, 6 h.
consistent with the previous reports which showed that the iso-
lated forms of complexes in either dilute or concentrated solution
appeared to be intrinsically related to the conformation adapted
by the eight peripheral bulky groups which efficiently suppressed
the cofacial interactions between the macrocycle cores as revealed
by both UVeVis (see below) and 1H NMR spectroscopic techniques
[11,26]. The synthesized compounds showed characteristic
absorption spectra with B-bands located in area around 360 nm
and a Q-bands located over 630 nm. The B-band was found more
intense for all AzaPcs when compared to corresponding Pcs
(Fig. 2). Interestingly, the Q-bands of all AzaPcs were strongly
blue-shifted by approximately 50 nm when compared with cor-
responding Pcs (Fig. 2). This observation has already been made
previously [27], and recently explained by molecular calculations
to be due to stronger destabilization of LUMO than HOMO
by pyrazine rings in AzaPcs when compared to benzene rings in
Pcs [28].
3.2. Photophysical and photochemical properties
Photophysical and photochemical properties of all studied Pcs
and AzaPcs were determined in DMF and THF. All compounds
showed strong fluorescence signal after excitation with a shape of
the fluorescence emission spectra characteristic for similar
compounds (Fig. 3). The Stokes shifts were very small (Table 1).
Interestingly, the Stokes shift around 4e5 nm was observed for Pcs,
but almost doubled for AzaPcs (approximately 7e9 nm). As
mentioned above, all compounds were present in the monomeric
form which was further confirmed by comparison of the fluores-
cence excitation spectra with the absorption spectra. Both spectra
superposed (Fig. 3) indicating that only monomeric form is present
in solution. The aggregates have different absorption spectra than
monomers but they usually do not fluoresce besides few exceptions
of J-dimers [29,30]. For this reason, a perfect accordance of exci-
tation and absorption spectra may serve as a confirmation of fully
monomeric form. Fluorescence quantum yields (FF) were of typical
range for zinc complexes of Pc and AzaPc [31]. An observation was
made from the data presented in Table 1, that the FF values of
Fig. 2. Absorption spectra of compounds 7 (full line) and 10 (dashed line) in ethanol.
Spectra were normalized to the same absorption in Q-band.
Fig. 3. Normalized absorption (dashed), emission (dotted) and excitation (full, over-
laps with absorption spectrum) of compound 10 in THF.

S. Makhseed et al. / Dyes and Pigments 95 (2012) 351e357
355
Table 1
Photochemical and photophysical properties of studied compounds in DMF and THF.a
b
b
Complex
Substituent
Core
FF
FD
Q-band lmax (nm)
lem (nm)
Stokes shift (nm)
5
6
7
8
9
10
Br
OCH3
OH
Br
OCH3
OH
Pc
Pc
Pc
AzaPc
AzaPc
AzaPc
0.25/0.27
0.21/0.23
0.23/0.27
0.30/0.39
0.28/0.34
0.22/0.44
0.59/0.57
0.59/0.57
0.54/0.50
0.57/0.53
0.55/0.51
0.42/0.50
676/676
679/678
678/677
629/627
629/626
628/624
681/680
683/682
683/681
638/634
637/633
636/630
5/4
4/4
5/4
9/7
8/7
8/6
Estimated error 10%.
a
Presented as value in DMF/value in THF.
Mean of three independent experiments.
b
AzaPcs were always higher than those of Pcs and that the values for
the same compound in THF exceeded those in DMF.
macrocycle are apparently too weak to induce any difference in
photophysical and photochemical properties.
Singlet oxygen quantum yields (FD) were determined using
decomposition of its chemical scavenger 1,3-diphenylisobenzofuran
(DPBF). Singlet oxygen is considered as the main phototoxic species
in PDT and that is why a rate of its production belongs among the
important parameters of all new photosensitizers [32]. The FD of all
compounds in this work exceeded the value of 0.50 indicating very
good singlet oxygen production that is fully satisfactory for potential
application in PDT. Focusing on the data in Table 1, reverse conclu-
sions than those raised for FF could be made. Pcs were shown to be
stronger singlet oxygen producers than AzaPcs and higher FD values
were usually obtained in DMF than in THF. A simple conclusion can
be made that Pc core supports energy dissipation from excited state
through singlet oxygen more than AzaPc with the same substitution
pattern. On the other hand, AzaPc core seems to be a stronger fluo-
rophore, an important fact which may lead to development of fluo-
rescent probes in future. The results are in good agreement with
a previously published data where Pcs and AzaPcs with the same
peripheral substituents were compared [33]. Focusing on the nature
of peripheral substitution, an increase of FD on the account of FF
could be expected for compounds 5 and 8 substituted with bromine
due to heavy atom effect. This well-known phenomenon was
demonstrated on several examples showing that substitution by
heavy atoms changes excited states deactivation pathways by
preferring intersystem crossing over fluorescence [34,35]. However,
no significant increase of singlet oxygen production or decrease of
fluorescence was observed for compounds 5 and 8. Changes in
electron density transmitted inductively from bromo substituent to
3.3. Aggregation behavior
The assessment of aggregation behavior for the prepared
complexes (5, 6, 8 and 9) was done by recording the absorption
spectra in different organic solvents (CH2Cl2, CHCl3, THF and DMF)
(Supporting Information). The single unperturbed Q-band peak,
a typical of non-aggregated species, was the characteristic feature
of each complex spectrum. Interestingly, the hydroxylated deriva-
tives (7 and 10) were highly soluble in methanol, ethanol and
acetone and showed no evidence of self association as shown by the
position and the appearance of the intense Q-band as well as strong
fluorescence. For example, the absorption spectra of complexes 7
and 10 showed a monomeric character (i.e. single sharp Q-band at
lmax 677 and 625 nm, respectively) even at concentration of
100
mM. The shape of the spectra remained constant and their
molar extinction coefficients obeyed the BeereLambert law in wide
range of concentration from 0.25
Supporting Information).
mM to 100 mM (Fig. 4 and
Interestingly, ethanol solutions of compounds 7 and 10 can be
mixed with water in various ratios and the compounds remain still
fully dissolved (tested up to 0.5% of ethanol in water). Surprisingly,
the shape of the Q-band remained mostly unchanged and the
absorption spectrum indicated presence of only monomeric form
(Fig. 5 and Supporting Information). However, when the solutions
containing more than 50% of water were exposed to UV light
(366 nm) no fluorescence occurred (Supporting Information). For
this reason, a careful analysis of behavior of these compounds in
Fig. 4. Absorption spectra of compound 10 in ethanol at different concentrations
Fig. 5. Absorption spectra of compound 10 in ethanol/water mixtures. Numbers
ranging from 100
m
M to 0.25
mM. Spectra from 100
mM to 10
m
M were measured in
represent content of ethanol in water. Concentration of the sample was kept at 1.0 mM
cuvettes with 1 mm optical pathlength. Inset: Dependence of extinction coefficient in
in all cases. Inset: Normalized spectra of compound 10 in ethanol (dashed) and water
Q-band on concentration.
containing 10% of ethanol (full).

356
S. Makhseed et al. / Dyes and Pigments 95 (2012) 351e357
spectra. This behavior may be closely connected with extremely
bulky peripheral substituents precluding close approximation of
two molecules.
4. Conclusion
Zinc phthalocyanines and their heteroatomic analogues azaph-
thalocyanines peripherally substituted with bulky phenoxy moie-
ties containing different functional groups were prepared and their
photophysical and photochemical properties have been investi-
gated. The fluorescence and singlet oxygen quantum yields of the
studied complexes gave good indication of their potential as
photosensitizer in PDT applications. All complexes showed truly
non-aggregating behavior in most organic solvents. Interestingly,
the hydroxylated derivatives (7 and 10) exhibited unusual aggre-
gation properties in ethanol/water mixtures at lower than 50%
content of ethanol. Fluorescence measurements of the last
mentioned compounds indicated strong aggregation but the
absorption spectra retained character typical for monomeric
species besides slightly lower extinction coefficient. These results
pointed out the importance of fluorescence determination during
assessment of aggregation behavior since the absorption
measurements could easily lead to incorrect interpretation.
Acknowledgments
The authors acknowledge the support of this work by Kuwait
University, (Grant Numbers SC01/09, GS01/01 and GS01/05). The
work was also supported by Czech Science Foundation, grant P207/
11/1200. One of the authors (A.T.) wishes to thank the College of
Graduate Studies, Kuwait University for a Ph.D. candidacy.
Fig. 6. Dependence of extinction coefficient (full squares) and fluorescence quantum
yield (open circles) of compound 10 (A) and 7 (B) on content of ethanol in water.
Extinction coefficients were measured at concentration of 1.0 uM for all data. Excita-
tion wavelengths for fluorescence quantum yield determination were 591 nm and
611 nm for 10 and 7, respectively.
Appendix A. Supplementary data
solutions containing different ethanol/water ratios was performed.
As obvious from Fig. 5, the absorption spectra remained unchanged
from absolute ethanol up to approximately 50% of ethanol in water
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.dyepig.2012.03.023.
(concentration of the dyes was kept constant at 1.0 mM for all tested
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explanation is that Pc 7 and AzaPc 10 form atypical type of aggre-
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