Synthesis, Photophysical and Photochemical Properties of a Set of Silicon Phthalocyanines Bearing Anti-Inflammatory Groups

Article abstract of DOI:10.1007/s10895-016-1969-y

In this study, a series of novel silicon (IV) phthalocyanines conjugated axially with anti-inflammatory (sulindac) and triethylene glycol groups has been synthesized. Different synthetic strategies were attempted to obtain the targeted molecules in high yield. The compounds were fully characterized by using different analyses techniques. Our objectives were to generate a system with sulindac group which enhances the singlet oxygen generation and exhibits anti-cancer effect. Therefore, photophysical and photochemical properties of these compounds were investigated in different solvents. The substituent effect on fluorescence quantum yield and singlet oxygen generation was evaluated for efficiency in photodynamic therapy (PDT) as photosensitizer. The molecules exhibited no aggregation tendency, solubility in common organic solvents, high singlet oxygen quantum yield and high photostability in DMSO so these favourable properties make them good candidates as photosensitizer for PDT. In addition, their stabilities were investigated in DMSO, THF, acetonitrile and DMF.

Full text of DOI:10.1007/s10895-016-1969-y

J Fluoresc
DOI 10.1007/s10895-016-1969-y
ORIGINAL ARTICLE
Synthesis, Photophysical and Photochemical Properties of a Set
of Silicon Phthalocyanines Bearing Anti-Inflammatory Groups
Belgin Şahin1 & Sevinc Zehra Topal1 & Devrim Atilla1
Received: 19 August 2016 /Accepted: 3 November 2016
#
Springer Science+Business Media New York 2016
Abstract In this study, a series of novel silicon (IV) phtha-
locyanines conjugated axially with anti-inflammatory
(sulindac) and triethylene glycol groups has been synthe-
sized. Different synthetic strategies were attempted to ob-
tain the targeted molecules in high yield. The compounds
were fully characterized by using different analyses tech-
niques. Our objectives were to generate a system
with sulindac group which enhances the singlet oxygen
generation and exhibits anti-cancer effect. Therefore,
photophysical and photochemical properties of these com-
pounds were investigated in different solvents. The substit-
uent effect on fluorescence quantum yield and singlet ox-
ygen generation was evaluated for efficiency in photody-
namic therapy (PDT) as photosensitizer. The molecules
exhibited no aggregation tendency, solubility in common
organic solvents, high singlet oxygen quantum yield and
high photostability in DMSO so these favourable proper-
ties make them good candidates as photosensitizer for
PDT. In addition, their stabilities were investigated in
DMSO, THF, acetonitrile and DMF.
Introduction
Due to desirable photophysical and photochemical proper-
ties, and easy chemical modifications, phthalocyanines
(Pcs) attract considerable attention as photosensitizers for
photodynamic therapy (PDT) [1–8]. Especially, silicon
phthalocyanines (SiPcs) which have intense absorption
and fluorescence emission in the red visible region, high
singlet oxygen generation and low dark toxicity [9] have
been used in many applications such as photodynamic can-
cer therapy [10], fluorescence based sensors [11] and non-
linear optics [12]. Apart from their desirable photophysical
and photochemical properties, they have axial substitution
ability which prevents aggregation and increases solubility.
By introducing different chemical groups at the axial posi-
tion of SiPc, desirable photochemical and photophysical
properties can be tuned. A number of studies have been
published during the two last decades concerning different-
ly substituted SiPcs for PDT [13–22]. Among these Pc
derivatives, the silicon phthalocyanine (Pc4) has under-
gone phase I for photodynamic cancer therapy [23–25].
As a new approach for cancer theraphy, chemo-
photodynamic therapy is a combination of both PDT and che-
motherapy to maximize therapeutic effect of chemotherapy
and PDT started recently [26, 27]. In this new approach, the
proliferation of cancer cells by chemotherapeutic agents is
prevented while PDT also destroys the cancer cells with the
light interaction of photosensitizer. Nowadays, nonsteroidal
anti-inflammatory drugs (NSAIDs) to inhibit cyclooxygenase
(COX enzyme) are playing a role in the initiation and progres-
sion of cancer growth [28–32].
.
.
.
Keyword Phthalocyanine Silicon Photochemical
.
.
Photophysical Anti-inflammatory Singlet oxygen
Electronic supplementary material The online version of this article
(doi:10.1007/s10895-016-1969-y) contains supplementary material,
which is available to authorized users.
* Devrim Atilla
We have been interested in synthesis and characterization
of novel SiPcs to develop efficient and selective photosensi-
tizers for PDT [33]. In this study, we designed new asymmet-
ric axially substituted SiPc by presenting with anti-
datilla@gtu.edu.tr
1
Department of Chemistry, Gebze Technical University, Gebze,
41400 Kocaeli, Turkey

J Fluoresc
inflammatory group to enhance anticancer activity of the mol-
ecule and triethylene glycol monomethyl ether group to im-
prove solubility at axial position. The symmetric and asym-
metric derivatives were synthesized to compare substitutent
effect on photophysical and photochemical properties of the
compounds so their electronic absorption and fluorescence
emission as well as singlet oxygen quantum yield of the com-
pounds were investigated in DMF and DMSO. The results in
DMF were very interesting, we provided cleave of the Si-O-C
bond via ester hydrolysis in DMF with characterization of
resulting products through mass spectrometry (MALDI) and
absorption and fluorescence emission spectroscopies.
Calc. 1253,43 for C72H48F2N8O6S2Si; Found: 1325.91 [M +
3H + 3Na]+.
Synthesis of Asymmetric SiPc (2)
0.07 mmol triethylene glycol monomethyl ether solved in
1 ml toluene and 300 μL solution added to a mixture of
SiPcCl2 (0.087 mmol), sulindac (0.09 mmol) and dry potas-
sium carbonate (0.26 mmol) in toluene (30 mL) at the same
time. And then reaction solution refluxed with stirring for
4 day under argon atmosphere. After the reaction mixture
was cooled at room temperature, filtered and washed with
toluene. The solvent was evaporated under reduced pressure.
The crude product was purified by column chromatography
on aluminium oxide with CH2Cl2:MeOH (200:1) as solvent
system and by preparative TLC on silica with CH2Cl2:MeOH
(200:1) as solvent system. At first step of the purification
symmetric derivative (1) and mixture of asymmetric Pc deriv-
ative (2) and symmetric derivative (3) were obtained was col-
umn chromatography. At the second step, 2 and 3 was purely
obtained by preparative TLC on silica with CH2Cl2:
Ethylacetate (7:5) as solvent system. Yield of 2 0.010 g
(10.8%). IR (ATR) vmax/cm−1: 3062 (Ar-H), 2923–2859
(Aliph. C-H), 1684, 1602, 1524, 1467, 1430, 1336, 1290,
1196, 1165, 1122, 1081, 949, 912, 760. 1H NMR (CDCl3) (
δ ppm): 9.7 (s, 8H, Ar-H), 8.3 (s, 8H, Ar-H), 8.0 (s, 4H, Ar-H),
6.7 (m, 1H, Ar-H), 6.3 (s, 1H, Ar-H), 6.0 (m, 1H, Ar-H), 4.4
(m, 1H, Ar-H), 3.2 (m, 5H, aliph-H), 2.9 (m, 5H, aliph-H), 2.5
(s, 2H, aliph-H), 1.7 (s, 2H, aliph-H), 0.7 (s, 2H, aliph-H), 0.3
(s, 2H, aliph-H), 0.2 (s, 3H, aliph-H), −1,8 (s, 2H, aliph-H).
ESI-MS (m/z:1061.22 1127.25 g/mol) ESI-MS (m/z) Calc.
1061.22 for C59H49FN8O7SSi; Found: 1127.25 [M + 4H +
K + Na]+.
Experimental
Materials
Dichlorosilicon (IV) Pc (SiPcCl2) was prepared from
1,3-diiminoisoindoline [34] according to the literature proce-
dure [35]. All reagents and solvents were of synthetic grade
quality and obtained from commercial suppliers.
Equipment
FT-IR spectra were recorded on Perkin Elmer Spectrum 100
FT-IR spectrophotometer. MALDI-TOF MS mass spectrom-
etry analyses were carried out on Bruker microflex LT
MALDI-TOF MS spectrometer using dithranol as a matrix.
1H NMR and 13C NMR spectra were recorded in CDCl3 so-
lutions on a Varian 500 MHz spectrometer.
Synthesis
Synthesis of Symmetric SiPc (3)
Synthesis of Symmetric SiPc (1)
Compound 3 was obtained from synthesis of compound 2 as
by-product. It was isolated by column chromatography and
thin layer chromatography as mentioned above. Symmetric
SiPc (3) yield 0.018 g (24.0%) IR (ATR) vmax/cm−1: 3053
(Ar-H), 2920–2850 (Aliph. C-H), 1522, 1471, 1426, 1332,
1284, 1249, 1201, 1165, 1102, 1074, 945, 905, 872, 839,
791, 730. 1H NMR (CDCl3) ( δ ppm): 9.6 (s, 8H, Ar-H), 8.3
(s, 8H, Ar-H), 3.2 (s, 10H, Aliph-H), 3.0 (s, 4H, Aliph-H), 2,7
(s, 4H, Aliph-H), 1.7 (s, 4H, Aliph-H), 0.4 (s, 4H, Aliph-H),
−2.0 (s, 4H, aliph-H).
A mixture of SiPcCl2 (0.087 mmol), sulindac (0.174 mmol)
and dry potassium carbonate (0.27 mmol) in toluene (30 mL)
refluxed with stirring for 4 day under argon atmosphere. After
the reaction mixture was cooled at room temperature, filtered
and washed with toluene. The solvent was evaporated under
reduced pressure. The crude product was purified by column
chromatography on aluminium oxide with CH2Cl2:MeOH
(200:1) as solvent system. Yield 0.012 g (11.0%). Chemical
formula: IR (ATR) vmax/cm−1: 3059 (Ar-H), 2921–2850
(Aliph. C-H), 1687, 1601, 1529, 1465, 1431, 1336, 1290,
1188, 1155, 1122, 1082, 1049, 951, 914, 890, 855, 811, 783,
762, 670. 1H NMR (CDCl3) ( δ ppm): 9.5 (s, 8H, Ar-H), 8.3
(s, 8H, Ar-H), 7.9 (s, 8H, Ar-H), 6.7 (m, 2H, Ar-H), 6.3 (s, 2H,
Ar-H), 6.0 (m, 2H, Ar-H), 4.4 (m, 2H, Ar-H), 3.0 (s, 6H, aliph-
H), 0.9 (s, 4H, aliph-H), 0.3 (s, 6H, aliph-H). ESI-MS (m/z)
Photophysical and Photochemical Measurements
All absorption and emission-based measurements were per-
formed with freshly prepared solutions of the compounds.

J Fluoresc
Absorption and Fluorescence Measurements
corresponding compounds (1, 2 and 3) were calculated using
the following equation where R and RStd were the DPBF
photobleaching rates in the corresponding samples and refer-
ence standard, Iabs and IAStbds were the rates of light absorption
by the samples and standard, respectively.
Absorption spectra were recorded using Shimadzu 2101 UV-
Visible spectrophotometer, and fluorescence emission spectra
were recorded using Varian Cary Eclipse in a 10 mm path
length quartz cell at room temperature.
Std
R:I
ΦΔ ¼ ΦSΔtd
ð2Þ
Abs
Fluorescence Rate Constants
RStd:IAbs
Photoirradiations 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 radiations, respectively. An interference filter
(Intor, 700 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 de-
tector incorporated) power meter.
Fluorescence rate constants were determined using the ϕF
andτF (kF = ϕF/τF).
Fluorescence Lifetime Measurements
Fluorescence lifetimes were recorded using Horiba FL3-2IHR
with a Time Correlated Single Photon Counting (TCSPC) sys-
tem. The instrument was equipped with a nanoLED 670-LH as
the excitation source. During measurements, the Instrument
Response Function (IRF) was obtained from a non-
fluorescence suspension of a colloidal silica (LUDOX 30%,
Sigma Aldrich) in water, held in 10 mm path length quartz cell
and was considered to be wavelength independent.
Result and Discussion
Molecular Design and Solvent Choice
SiPcs have desirable spectral properties such as high fluores-
cence, high singlet oxygen generation and low aggregation due
to axial substitution. Moreover, presence of axial substituents
allows further modification in order to handle desirable proper-
ties for intended application. Many experimental and clinical
studies have demonsrated the effects of NSAIDs. Therefore,
NSAIDs preventing cancer cell proliferation by inhibiting angio-
genesis factors are promising drugs as anticancer agents [28–32].
In this study, a synergic effect is aimed by combining with
NSAIDs and SiPc to maximize therapeutic effect of chemother-
apy and PDT. In our design, sulindac and triethylene glycol
monomethyl ether groups as axial ligand have been chosen for
the anti-cancer properties and to enhance solubility, respectively.
The spectroscopic measurements were performed in DMF
and DMSO because both our target molecules and reference
ZnPc have been soluble in DMF and DMSO. It should be
noted that solvent parameters such as polarity, viscosity etc.
are widely known to influence the absorption and fluores-
cence properties [40–42].
Fluorescence Quantum Yield Determination
Fluorescence quantum yield values (ϕF) were calculated
employing the comparative William’s method. For this pur-
pose, the absorbance and fluorescence spectra of reference
standard (ZnPc) and molecules 1–3 were measured at four
different concentrations under identical conditions. The inte-
grated fluorescence intensities were plotted vs absorbance for
ZnPc (ϕF = 0.18 in DMSO [36] and ϕF = 0.17 in DMF [37]
and corresponding molecules. The ratio of the gradients of the
plots was proportional to the quantum yield. Quantum yield
(ϕF) values were calculated according to followed Equation.
Grad was the gradient of the plot and n was the refractive
index of the solvent.
!
ꢀ
ꢁ
Grad
GradStd
n2
n2Std
ΦF ¼ ΦSFtd
ð1Þ
Singlet Oxygen Quantum Yield Determination
Synthesis and Characterization
The solutions (M = 1 × 10−5 M) containing the singlet oxygen
quencher (~3 × 10−5 M) were irradiated in the Q band region
with the photo-irradiation set-up described in the reference
[38] DPBF was used as chemical quencher and ZnPc was
used as reference photosensitizer (ΦΔ = 0.67 in DMSO [39])
for singlet oxygen measurements. The degradation of DPBF
at 417 nm was monitored by UV-Vis spectrophotometer. The
light intensity 6.54 × 1015 photons s−1 cm−2 was used for the
determinations. Singlet oxygen quantum yields (ΦΔ) of the
The synthetic route of the SiPc complexes (1–3) was given in
Scheme 1. The symmetric and asymmetric Pc derivatives
were synthesized through base-catalysed displacement reac-
tion between SiPcCl2, sulindac and triethylene glycol
monomethyl ether. A lot of synthetic conditions were tested
to obtain in high yield the SiPc derivatives, and they were
summarized at Table S1 as supplementary data. In this work,
we experienced that triethylene glycol monomethyl ether was

J Fluoresc
Scheme 1 Synthetic pathway to
the SiPcs (1–3) i: K2CO3 and
toluene
more reactive than sulindac during synthesis experiments.
Because we obtained only axially symmetric substituted de-
rivative with triethylene glycol monomethyl ether side chain
when all ligands and SiPcCl2 were added reaction media at
same stoichiometric rate 1/1. Therefore, triethylene glycol
monomethyl ether ratio was slightly lowered in comparison
with sulindac, so we obtained the asymmetric SiPc (2) as well as
3. The structure of the compounds were confirmed by IR, 1H–
NMR spectroscopy and ESI-MS spectra. The analysis results
were consistent with the predicted structures as shown in exper-
imental section. The IR spectra clearly indicated formation of
symmetric and asymmetric SiPcs (1 and 2) with the appearance
of absorption bands at 1680–1690 cm−1 (C = O), 1687 cm−1
(C = O) for compound (1), 1684 cm−1 (C = O) for compound
Vis absorption spectrum of 2 in these solvents were shown in
Fig. 1 (Fig. S9 for 1 and Fig. S10 for 3). The UV-Vis spectra of
SiPc complexes 1–3 showed monomeric behaviour in the
studied solvents, showing no aggregation. In addition, their
wavelength maxima in different solvents were very close to
each other indicating no solvatochromic effect. However, ob-
served absorption intensities for 1–3 were different depending
on the solvents. They exhibited the highest absorption inten-
sity in DCM, but nearly same intensity in the other solvents.
1–3 in DMF exhibited Q-band maxima at 689, 681 and
674 nm, respectively. Q band maxima was shifted to red
1
(2). The H–NMR spectra of compounds (1, 2 and 3) were
obtained as expected. The ESI-MS spectra of Pc compounds
showed molecular ion peaks at m/z = 1325.91 [M + 3H +
3Na]+ for (1), 1127.25 [M + 4H + K + Na]+ for (2) supported
the proposed molecular formula for these compounds.
Characterizatin related spectra were presented in Fig. S1–S8.
Absorption and Fluorescence Emission-Based
Photocharacterization
The electronic absorption spectra of SiPc complexes were
recorded in DCM, CHCl3, DMF, DMSO and THF. The UV-
Fig. 1 UV-Vis absorption spectra of 2 in different solvents (10 μM)

J Fluoresc
Table 1 UV-Vis spectra related
data for the compounds 1–3
in DMF
Compound Solvent Q band max, nm (log ε) Qsh band max, nm (log ε) B band max, nm (log ε)
1
2
3
DMF
DMF
DMF
689 (5.29)
681 (5.35)
674 (5.32)
660 (4.42)
650 (4.55)
644 (4.44)
353 (4.88)
359 (4.89)
355 (4.80)
region by the axial substitution of SiPc with triethylene glycol
monomethyl ether and sulindac groups. UV-Vis spectra of the
all compounds in DMF showed no aggregation in the studied
concentration range between 1 μM and 10 μM with obeying
the Lambert-Beer law (See Fig. S11, Fig. S12, Fig. S13).
Their absorption maxima and logarithmic values of molar
absorption coefficients in DMF were summarized in Table 1.
The fluorescence emission spectra of the molecules in
DMSO and DMF were shown in Fig. 2a and Fig. S14 and
the related data were listed together with the Stoke’s shifts in
Table 2. Upon excitation at 640–657 nm, molecules 1–3 in
DMF showed fluorescence emission at 699, 691 and 681,
respectively. To calculate the fluorescence quantum yields,
the fluorescence area integration of the molecules versus (vs)
absorbance were plotted in DMSO and DMF (See Fig. 2b and
Fig. S14). The fluorescence quantum yields (ΦF) of com-
pounds 1–3 in DMSO were found as 0.25, 0.28 and 0.27,
respectively. Upon excitation at 643–657 nm, the molecules
1–3 in DMF exhibited fluorescence emission at 703, 694 and
683 nm with a fluorescence quantum yield (ΦF) of 0.25–0.28,
respectively. The determined ΦF values of these compounds in
DMF and DMSO were very close indicating no
solvatochromic effect. ΦF values of 1–3 were higher than
ZnPc whereas lower than SiPcCl2 in the both solvents.
Fluorescence Lifetime and Fluorescence Rate Constants
The fluorescence decay profiles of the compounds were
shown in Fig. 3 in DMSO and Fig. S15 in DMF. All the
compounds showed single exponential decay in the both sol-
vents. The fluorescence lifetimes decreased in the order of 1
(τF = 6.58 ns) > 2 (τF = 5.91 ns) > 3 (τF = 5.43 ns) in DMF and
1 (τF = 6.39 ns) > 2 (τF = 5.48 ns) > 3 (τF = 5.02 ns) in DMSO
(See Table 2). Lifetime values of the symmetric sulindac de-
rivative (1) in both solvents were higher than of other deriva-
tives. Axial tethering of sulindac groups to SiPc core caused
longer fluorescence lifetimes compare to SiPcCl2
(τF = 5.06 ns in DMF and τF = 4.50 ns in DMSO).
Presumably, these longer lifetime values can be attributed to
the electron with drawing nature of the sulindac groups. It is
worth nothing that SiPcs exhibit higher fluorescence quantum
yields as well as high fluorescence lifetime than zinc
derivatives.
Using ΦF and τF values, fluorescence rate constants (kF)
were calculated, and represented in Table 2. Compound 3
exhibited the highest kF in the both solvents even better than
ZnPc, whereas all the compound have lower kF values than
SiPcCl2 in the both solvents. The obtained results indicated
that presence of sulindac/ triethylene glycol monomethyl ether
groups at axial position caused fluorescence quenching to be
increase intersystem crossing (ISC).
Stability
To check the compounds stability in DMSO, THF, acetonitrile
and DMF, their absorption and emission wavelength maxima
and the intensities were periodically recorded with using the
solutions stored in dark. There was no time-related spectral
change in all solvents for all the compounds in except of DMF.
In DMF, compounds 1 and 2 were not stable, while symmetric
derivative bearing only triethylene glycol monomethyl ether
chain (3) was quietly stable in DMF even after one month. The
absorption and emission maxima of molecules 1 and 2 includ-
ing axially substituted sulindac group by ester bond were
Fig. 2 (a) Fluorescence emission spectra of 1–3 in DMSO
(Absorbance = ~0.10), (b) Fluorescence integrated area vs absorbance
of 1–3 and ZnPc in DMSO

J Fluoresc
Table 2 Photophysical and photochemical properties related data of compounds 1–3 in DMF and DMSO
Compound
Solvent
λex (nm)
ΔλST (nm)
ΦF
τF (ns)
kF (×10−6) (s−1
)
ΦΔ
em
max
ex
max
λ
(nm)
λ
(nm)
1
DMF
657
657
650
652
645
645
640
643
645
645
699
703
691
694
681
683
676
682
675
678
689
693
681
678
674
673
670
673
669
672
10
10
10
8
0.25
0.25
0.27
0.28
0.28
0.27
0.17a
0.18c
0.52f
0.44f
6.58
6.39
5.91
5.48
5.43
5.02
3.36
3.59d
5.40
5.37
38.0
39.1
45.7
47.4
51.6
53.8
50.6
50.1
96.3
81.9
0.23
0.27
0.23
0.28
0.31
0.41
0.56b
0.67e
0.12f
0.15f
DMSO
DMF
2
DMSO
DMF
3
7
DMSO
DMF
10
6
ZnPc
SiPc(Cl)2
DMSO
DMF
9
6
DMSO
6
a Data from ref. [37]
b Data from ref. [43]
c Data from ref. [36]
d Data from ref. [44]
e Data from ref. [39]
f Data from ref. [50]
gradually shifted to blue region with starting first day. The
appearance of these spectral changes in DMF with time indi-
cated that this difference was associated with ester bonds at 1
and 2. This change attributed to the nature of DMF which can
release formate by decomposition [45–47]. We concluded that
this formate anion could induce to ester bond hydrolysis.
After 10 days, ~10 nm blue shifted new absorption and
emission bands of 1 were formed to be the proof of occurrence
of the new molecule with time (See Fig. 4a, Fig. S16A and
Fig. S17A). The recorded absorption and emission maxima of
new occurred molecule which was decomposed form of com-
pound 1 were compared to the maxima of SiPc(OH)2, and
fully overlap maxima between decompose form of 1 and
SiPc(OH)2 were obtained. Compound 2 exhibited similar
spectral change in periodical measurements (See Fig. 4b,
Fig. S16B and Fig. S17B). These cleavages were also proved
by mass spectra of stored DMF solutions of these compounds
(See Fig. 5a and b). From the obtained data from UV-Vis,
fluorescence and MASS spectroscopy, we concluded that the
Fig. 4 Fluorescence emission spectra of compounds 1 (a) and 2 (b) in
DMF after 1 day and 10 days (~10 μM)
Fig. 3 Fluorescence decay time analysis of molecules 1–3 in DMSO

J Fluoresc
sulindac groups of compound 1 were removed by ester bond
cleavage in DMF, and compound 1 was turned into
SiPc(OH)2. It was stressed this cleavage was observed only
in DMF, and no spectral change with time was occurred in
DMSO, THF and acetonitrile. Besides, this situation was not
observed for 3. Therefore, all measurements in DMF were per-
formed with freshly prepared solutions of compounds 1 and 2.
singlet oxygen determination related spectra for molecules 1,
3 and ZnPc in DMSO were shown in Fig. S18, Fig. S19 and
Fig. S20, respectively. The singlet oxygen generation related
spectra of compounds 1–3 and ZnPc in DMF were presented
in Fig. S21, S22, S23 and S24, respectively. ΦΔ values of
molecules 1–3 were found as 0.27, 0.28 and 0.41 in DMSO
and 0.23, 0.23 and 0.31 in DMF, respectively. 3 exhibited
highest singlet oxygen generation in both solvents. All mole-
cules exhibited higher ΦΔ values compare to SiPcCl2 in the
both solvent (ΦΔ = 0.12 in DMF and ΦΔ = 0.15 in DMSO
[48]). Note that singlet quantum yields of the compounds in
DMSO were higher than in DMF, and this can be attributed
the presence of amine groups in DMF causes possible
quenching of the singlet oxygen [48].
Singlet Oxygen Quantum Yields
Singlet oxygen quantum yields (ΦΔ) of 1–3 were determined
in DMSO and DMF to investigate the solvent effect on singlet
oxygen generation. 3-Diphenylisobenzofuran (DPBF) was
used as a singlet oxygen quencher in this chemical method.
A decrease in DPBF absorbance in the presence of the com-
pound 2 in DMSO by light irradiation was monitored using
UV-Vis spectrophotometer as shown in Fig. 6, and the other
As a result, the axially substitution of SiPc core with
triethylene glycol and sulindac groups which are very suitable
for PDT applications [20, 21, 49] increased the singlet oxygen
Fig. 5 MALDI-TOF MS spectra
of compound 1 (a) (m/z:1253.43
[M + 3H + 3Na]+:1325.91 g/mol)
and 2 (b) (m/z:1253.43 [M +
3H + 3Na]+:1325.91 g/mol) in
DMF solution after stored for
10 days

J Fluoresc
Fig. 6 The spectrum of the
determination of singlet oxygen
quantum yield for 2 in DMSO,
inset: The plot of absorbance
change of DPBF vs time
generation compared to SiPcCl2 derivative. On the other
hand, the nature of the substituents also affected the amount
of the produced singlet oxygen because the triethylene glycol
monomethyl ether substituted SiPc derivative (3) generated
more singlet oxygen than 1 and 2.
Conclusion
In this study, we have reported the synthesis of SiPc deriva-
tives bearing anti-inflammatory groups at the axial positions
and their photophysical and photochemical properties in
DMSO and DMF. The axial moieties reduced self-
aggregation of 1–3 in both solvents in which they exhibited
high fluorescence quantum yields and lifetimes, even higher
than ZnPc. The longer lifetimes but slightly lower fluores-
cence quantum yields were obtained for the SiPcs bearing
sulindac groups (1 and 2) because of the electron-with draw-
ing nature of this group comparing 3. The substituent effect on
singlet oxygen generation was investigated, and triethylene
glycol monomethyl ether groups induced slightly higher sin-
glet oxygen generation when compared to sulindac groups.
The obtained high singlet oxygen quantum yields indicated
the potential of these molecules as photosensitizers for Type II
photodynamic applications where singlet oxygen generation
As mentioned above, 1 and 2 were decomposed by cleav-
age of ester bond in DMF, and 1 convert to SiPc(OH)2.The
singlet oxygen generation of 1 and 2 in DMF after 10 days
were also investigated in order to determine the ΦΔ values
belonging to decomposed forms of 1 and 2 (See Fig. 7 for 2
and Fig. S25 for 1). The determined ΦΔ values were com-
pared to ΦΔ value of SiPc(OH)2 (ΦΔ = 0.28) [50] to demon-
strate our ester bond cleavage hypothesis in DMF, implying
that about sulindac groups cleavage regenerate the OH func-
tion. As a result, ΦΔ values of 1 and 2 were increased from
0.23 to 0.28 and from 0.23 to 0.29, respectively. These en-
hanced ΦΔ values which were very close to the value of
SiPc(OH)2 supported also this hypothesis.
Fig. 7 The spectrum of the
determination of singlet oxygen
quantum yield for 2 in DMF after
10 days, inset: The plot of
absorbance change of DPBF
vs time

J Fluoresc
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is required. Their stabilities were also checked in different
solvents and some spectral changes for axially substituted
compound 1 and 2 with ester bond were obtained in DMF.
The spectral changes and analysis showed that ester bond
hydrolysis took place in DMF. Interestingly, singlet oxygen
quantum yields of the products obtained the result of decom-
position were higher than the stable form. We concluded that
these molecules are good candidates as combined chemother-
apy agent and photosensitizer for cancer treatment. Because
cancers cells are more acidic than normal cells, the sulindac
group could be cleaved when these compounds reach the can-
cer cells. As a result, the hydrolysed SiPc complexes could
serve as photosensitizer with higher singlet oxygen yield and
sulindac serve as chemotherapy agent for cancer treatment.
Acknowledgements The Scientific and Technological Research
Council of Turkey (TUBITAK) is gratefully acknowledged (project
114Z463 coupled to the COST Action CM1106).
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