Synthesis of water soluble axially disubstituted silicon (IV) phthalocyanines with alkyne & azide functionality

Article abstract of DOI:10.1016/j.dyepig.2015.10.007

Phthalocyanines (Pcs) are a class of photosensitizers (PSs) with a strong tendency to aggregate in aqueous solutions, which has a negative influence on their photosensitizing ability for photodynamic therapy. Four new axially disubstituted, non-aggregated silicon phthalocyanines (SiPcs), containing azide or alkyne functional groups have been synthesized and characterized. The method of synthesis is based on the reaction of silicon phthalocyanine dichloride with variable length poly(ethylene glycol) (PEG) chains in the presence of NaH. All synthesized dyes are highly soluble in alcohols, THF, CH₂ Cl₂, acetone, DMF and other common polar organic solvents, with the PEGylated silicon phthalocyanines (SiPcs) also being soluble in water. Photophysical and electrochemical properties of the dyes have been investigated. The presence of alkyne or azide groups in the phthalocyanine dyes, coupled with their high aqueous solubility, make these compounds useful as building blocks in copper catalyzed Huigsen azide-alkyne cycloaddition reactions (i.e. click chemistry).

Full text of DOI:10.1016/j.dyepig.2015.10.007

Dyes and Pigments 125 (2016) 72e79
Contents lists available at ScienceDirect
Dyes and Pigments
journal homepage: www.elsevier.com/locate/dyepig
Synthesis of water soluble axially disubstituted silicon (IV)
phthalocyanines with alkyne & azide functionality
Yuriy Bandera , Mary K. Burdette , Jamie A. Shetzline b, Ragini Jenkins a b,
b
a
,
b
c
,
,
c
,
b
a, b, *
Stephen E. Creager , Stephen H. Foulger
Department of Materials Science and Engineering, Clemson University, Clemson, SC 29634-0971, USA
Center for Optical Materials Science and Engineering Technologies, Clemson University, Clemson, SC 29634-0971, USA
Department of Chemistry, Clemson University, Clemson, SC 29634-0971, USA
a
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 August 2015
Received in revised form
Phthalocyanines (Pcs) are a class of photosensitizers (PSs) with a strong tendency to aggregate in
aqueous solutions, which has a negative influence on their photosensitizing ability for photodynamic
therapy. Four new axially disubstituted, non-aggregated silicon phthalocyanines (SiPcs), containing azide
or alkyne functional groups have been synthesized and characterized. The method of synthesis is based
on the reaction of silicon phthalocyanine dichloride with variable length poly(ethylene glycol) (PEG)
29 September 2015
Accepted 3 October 2015
Available online 19 October 2015
2 2
chains in the presence of NaH. All synthesized dyes are highly soluble in alcohols, THF, CH Cl , acetone,
DMF and other common polar organic solvents, with the PEGylated silicon phthalocyanines (SiPcs) also
being soluble in water. Photophysical and electrochemical properties of the dyes have been investigated.
The presence of alkyne or azide groups in the phthalocyanine dyes, coupled with their high aqueous
solubility, make these compounds useful as building blocks in copper catalyzed Huigsen azide-alkyne
cycloaddition reactions (i.e. click chemistry).
Keywords:
Phthalocyanine
Silicon
Click chemistry
Water soluble
Synthesis
© 2015 Elsevier Ltd. All rights reserved.
Azide
1. Introduction
to exhibit broad emission characteristics and are not amenable for
use in more complex heterostructures due to their limited chemical
Phthalocyanines (Pcs) and their metal complexes have intense
absorption in the far red region, low dark toxicity, good chemical
stability, and a propensity to generate reactive oxygen species
when excited [1,2]. These properties make Pcs interesting for the
development of new photosensitizers (PS) for photodynamic
therapy (PDT) [3]. Currently, PDT is broadly used in medicine for the
treatment of various conditions, including a variety of cancers
attachment sites. The main goal of this research was the synthesis
of new, versatile, non-aggregated axially disubstituted silicon
phthalocyanine (SiPc) complexes, which can be used in future in-
vestigations either as small molecules or as a part of a larger het-
erostructure. These systems were modified with substituents
containing azide or alkyne functional groups making them
amenable for use in reactions which exploit the copper catalyzed
Huigsen azide-alkyne cycloaddition (i.e. “click chemistry”) [22].
Current efforts have been presented of Pcs modified for use in click
chemistry with azide groups [23e25] or alkyne groups [26e31], but
all of these compounds have the substituents in peripheral posi-
tions, with only one SiPc complex having axially attached sub-
stituents containing an alkyne [32]. The main challenge of
peripherally substituted Pcs is their high propensity to aggregate
and their limited synthetic approach [33,34,11]. Axially substituted
Pcs are much less likely to aggregate due to the interruption of the
[4e6]. Pcs used for PDT include zinc phthalocyanines (ZnPcs) [7,8],
aluminum phthalocyanines (AlPcs) [6,9,10], and silicon phthalocy-
anines (SiPcs) [11e14]. However, most of these compounds exhibit
high levels of aggregation in common organic solvents and aqueous
media. Silicon Pcs have a relatively reduced tendency to aggregate
in solution, which accounts for their high solubility and more
pronounced fluorescence lifetimes [15,16]. Despite the large
amount of non-aggregated, axially substituted SiPc derivatives
presented in the past few years [12e14,17e21], these systems tend
p-system by the non-planar substituents issuing from the center
metal atom [35].
For the purpose of increasing the solubility of SiPc complexes in
water and other common organic solvents, we have synthesized a
*
Corresponding author. Department of Materials Science and Engineering,
Clemson University, Clemson, SC 29634-0971, USA.
E-mail address: foulger@clemson.edu (S.H. Foulger).
http://dx.doi.org/10.1016/j.dyepig.2015.10.007
0143-7208/© 2015 Elsevier Ltd. All rights reserved.

Y. Bandera et al. / Dyes and Pigments 125 (2016) 72e79
73
new series of axially disubstituted, non-aggregated SiPcs, contain-
ing either alkyne or azide functionality. These new symmetrical
SiPc complexes can be easily modified by click reactions with other
appropriate small molecules, nano- or micro-particles, polymers,
and proteins. This feature makes them valuable for future in-
vestigations because the nature of the substituents has a strong
influence on the optical and physical parameters of phthalocya-
nines. Photophysical and electrochemical properties of the syn-
thesized compounds have been studied.
dichloromethane and washed with water. The organic solution was
dried with Na SO , filtered, and evaporated under reduced pressure
to yield a brown oil. The crude product was purified by flash col-
umn chromatography on silica. The first eluent was dichloro-
methane, which serves to remove a majority of the impurities. A
2
4
second eluent, acetone, was used to collect the product. Yield:
1
1.63 g (65%), pale yellow oil. H NMR (CDCl
3
)
d
2.43 (t, 1H, J ¼ 2.4 Hz,
CCH), 3.61 (m, 2H, OCH
J ¼ 2.4 Hz, CH CC).
2
), 3.67e3.74 (m, 10H, OCH
2
), 4.21 (d, 2H,
2
2
. Experimental
2.2.2. Synthesis of compound 1b
Compound 1b was synthesized according to the above proce-
2.1. Materials and equipment
dure. The crude product was washed with hexanes twice, decanted,
dried, and used in the next step without further purification. Yield:
1
Silicon phthalocyanine dichloride (SiPcCl
2
), triethylene glycol,
83%, clear oil. H NMR (CDCl
3
)
d
1.83 (s, 1H, OH), 2.43 (t, 1H,
), 4.20 (d, 2H, J ¼ 2.4 Hz,
and polyethylene glycol 600 (PEG 600) were purchased from Sig-
maeAldrich. Other reagents were purchased from Alfa Aesar. All
commercial reagents were used without further purification. All
solvents were dried according to standard methods. Triethylene
glycol and PEG 600 were dried in THF solutions over A4 molecular
J ¼ 2.4 Hz, CCH), 3.60e3.71 (m, 56H, OCH
2
CH CC).
2
2.2.3. Synthesis of compound 2a
Methanesulfonyl chloride (3.2 g, 27.94 mmol) was added to the
solution of triethylene glycol (4 g, 26.64 mmol) in dichloromethane
(50 ml). The reaction was cooled with ice. Triethylamine (2.97 g,
29.3 mmol) was added dropwise to the stirred solution. The ice
bath was removed, and the obtained mixture was stirred at room
temperature for 6 h. The reaction mixture was then washed with
1
13
sieves. H and C NMR spectra were recorded on a JEOL ECX300
spectrometer (300 MHz for proton and 76 MHz for carbon).
Chemical shifts for protons are reported in parts per million
downfield from tetramethylsilane and are referenced to residual
protium in the NMR solvent (CDCl3:
d 7.26 ppm, DMSO-d6:
d
2.50 ppm). Electrospray (ESI) mass spectra were obtained using
2 4
water twice. The organic solution was dried with Na SO , filtered,
Finnigan LCQ spectrometer and HP 1100 (HPLC). Absorption spectra
were taken using a PerkineElmer Lambda 950 UV/VIS/NIR spec-
trophotometer. Photoluminescence (PL) spectra were collected
using a Photon Technology International QuantaMaster 60 NIR with
a PMT spectrofluorometer and a Thermo Oriel xenon arc lamp
and evaporated under reduced pressure. The obtained product
contains approximately 10% of bis-methylsulfonylated triethylene
glycol and was used in the next step without additional purifica-
1
tion. Yield: 3.6 g (59%), clear oil. H NMR (CDCl
3
)
d
3.07 (s, 3H), 3.61
OSO ).
(m, 2H, CH
2
OH), 3.67 (m, 4H), 3.76 (m, 4H), 4.37 (m, 2H, CH
2
2
(
1
Thermo Oriel 66902) mated with a Thermo Oriel Cornerstone 7400
/8 m monochromator (Thermo Oriel 7400). Fourier transform
2.2.4. Synthesis of compound 2b
infrared (FTIR) spectra were obtained with a Nicolet 6700 by
Thermo Scientific FT-IR spectrometer and all spectra were
measured with FTIR-ATR with a diamond head.
Cyclic voltammetery was utilized to determine the electro-
chemical characteristics of the SiPc compounds. A three electrode
system was utilized with a platinum disk working electrode, a
platinum coiled wire counter electrode, and a Ag/AgCl reference
electrode with an outer junction to prevent water contamination of
Compound 2b was synthesized according to the above proce-
dure and was used in the next step without additional purification.
1
Yield: 87%, clear oil. H NMR (CDCl
40H), 3.75 (m, 2H), 4.37 (m, 2H, CH
3
)
d
3.07 (s, 3H), 3.58e372 (m,
2
OSO ).
2
2.2.5. Synthesis of compound 3a
Compound 2a (3.6 g, 15.77 mmol) was dissolved in acetonitrile
(20 ml), and sodium azide (2.56 g, 39.38 mmol) was added to the
solution. The obtained mixture was stirred and refluxed for 16 h.
After cooling, the mixture was extracted with dichloromethane and
was washed with water. The organic solution was dried with
the solutions. The Pt disk was polished with 5
runs. 0.1 M TEABF in ACN was used as the electrolyte. For each test,
ml of electrolyte was added to a vial and bubbled with N . A
background scan was collected. After the background had been
collected, 200 L of 11 mM SiPc complexes in ACN were added to
the solution (concentration in solution was 1 mM), and purged with
. Three sweeps were performed from 0 V to 1.6 V and then
to ꢀ1.4 V at 100 mV/s . After the CV of the SiPc derivatives were
completed, 10 L of 25 mM FC in 0.1 M TBABF was added to the
solution, and the scans were repeated in the same manner after
purging with N . The addition of ferrocene resulted in no shifting or
interaction with the SiPcs. FC had a E(1/2) of 0.412 V, and of
mm alumina between
4
2
2
2 4
Na SO , filtered, and evaporated under reduced pressure. The ob-
tained product contains about 10% of bis-azido-derivative, but it
m
was used in the next step without additional purification. Yield:
1
N
2
2.47 g (89%), clear oil. H NMR (CDCl
3
)
d
3.38 (t, 2H, J ¼ 4.8 Hz,
CH
2 3
N ), 3.59e3.79 (m, 10H).
m
4
2.2.6. Synthesis of compound 4a
2
Silicon phthalocyanine dichloride (0.2 g, 0.33 mmol) was mixed
with dry toluene (4 ml), and the solution of compound 3a (0.17 g,
0.97 mmol) in toluene (2 ml) was added to the reaction mixture.
The mixture was stirred under a nitrogen atmosphere for 5 min and
sodium hydride (0.023 g, 0.96 mmol) was added. The mixture was
refluxed for 20 h. After cooling, the solution was extracted with
ethyl acetate and was washed with water. The organic solution was
DE
p
7
2
2
8 mV.
.2. Synthesis and characterization data
.2.1. Synthesis of compound 1a
Compound 1a was synthesized according to literature [36]. So-
2 4
dried with Na SO , filtered, and evaporated under reduced pres-
dium hydride (0.32 g, 13.32 mmol) was added to the solution of
triethylene glycol (2 g, 13.32 mmol) in tetrahydrofuran (30 ml). The
obtained mixture was stirred at room temperature for 30 min then
propargyl bromide solution (80%) in toluene (2 g, 13.45 mmol) was
added. The mixture was stirred for 6 h at room temperature and
filtered. The filtrate was evaporated; the residue was extracted with
sure. The residue was washed with hexanes. The organic solution
was decanted away from the insoluble product, and the product
was purified by flash column chromatography on silica with an
eluent of a solution of dichloromethane:acetone (10:1), R
f
¼ 0.3.
The dry product was dissolved in a minimum of dichloromethane
and was added dropwise to hexane solution. The precipitates from

74
Y. Bandera et al. / Dyes and Pigments 125 (2016) 72e79
2 3 2 2 3
Fig. 1. Synthetic route to compounds 1a,b, 2a,b, and 3a,b; (i) Propargyl bromide, NaH, THF, r.t.; (ii) MeSO Cl, Et N, CH Cl , r.t.; (iii) NaN ,m acetonitrile, reflux.
this solution were filtered, collected, and dried. Yield: 0.13 g (45%),
1.0 mmol) in toluene (2 ml) was added to the reaction vessel. The
obtained mixture was stirred under a nitrogen atmosphere for
5 min and sodium hydride (0.023 g, 0.96 mmol) was added. The
mixture was stirred and refluxed for 20 h. After cooling, the mixture
was extracted with ethyl acetate and was washed with water. The
organic solution was collected, dried with Na SO , filtered, and
2 4
evaporated under reduced pressure. Compound 5a was purified by
flash column chromatography on silica with an eluent of a 3:1
ꢁ
1
blue crystals, mp 169e170 C with destruction. H NMR (CDCl
), 1.66
), 2.92 (m, 8H, CH
3
)
d
ꢀ1.91 (t, 4H, J ¼ 5.5 Hz, CH
2
OSi), 0.42 (t, 4H, J ¼ 5.5 Hz, CH
2
(
t, 4H, J ¼ 4.8 Hz, CH
2
), 2.45 (t, 4H, J ¼ 4.8 Hz, CH
2
2
CH
2
N
3
), 8.34 (dd, 8H, J ¼ 3.1 Hz, ArH), 9.63 (dd, 8H, J ¼ 3.1 Hz, ArH).
1
3
C NMR (CDCl
3
)
d
50.36, 54.92, 68.83, 69.24, 69.54, 69.58, 123.78,
þ
1
C
31.03, 136.13, 149.38 (CN). ESI Mass (m/z): calculated for
þ
H
44 40
N
14
O
6
Si [MþNa] 911.29, found 911.0.
dichloromethane:acetone solution, R
f
¼ 0.2. The dry product was
dissolved in a minimum of dichloromethane and added dropwise
to hexanes solution. The precipitates from this solution were
filtered, collected, and dried. Yield: 53%, blue crystals, mp
2.2.7. Synthesis of compound 4b
Compound 4b was synthesized according to the procedure of 4a
with the substitution of compound 3b for compound 3a. Com-
pound 4b was purified by flash column chromatography on silica
ꢁ
1
1
(
72e173 C. H NMR (CDCl
t, 4H, J ¼ 5.5 Hz, CH ), 1.67 (t, 4H, J ¼ 4.8 Hz, CH
J ¼ 2.4 Hz, CCH), 2.46 (t, 4H, J ¼ 4.8 Hz, CH ), 2.98 (t, 4H, J ¼ 4.8 Hz,
CH ), 3.95 (d, 4H, J ¼ 2.4 Hz, CH CC),
), 3.29 (t, 4H, J ¼ 4.8 Hz, CH
3
)
d
ꢀ1.90 (t, 4H, J ¼ 5.5 Hz, CH
2
OSi), 0.40
2
2
), 2.34 (t, 2H,
with an eluent of a solution of dichloromethane:methanol (10:1).
1
2
R
f
¼ 0.4. Yield: 66%, dark blue oil. H NMR (CDCl
3
)
d
ꢀ1.92 (t, 4H,
), 1.66 (t, 4H,
), 2.96 (t, 4H, J ¼ 4.8 Hz,
), 3.37 (m, 8H, CH ), 3.44 (m, 4H,
), 8.33 (dd, 8H, J ¼ 3.1 Hz, ArH), 9.62
2
2
2
J ¼ 5.5 Hz, CH
2
OSi), 0.37 (t, 4H, J ¼ 5.5 Hz, CH
), 2.44 (t, 4H, J ¼ 5.2 Hz, CH
), 3.21 (t, 4H, J ¼ 5.2 Hz, CH
), 3.51e3.69 (m, 70H, CH
2
13
8
.34 (dd, 8H, J ¼ 3.1 Hz, ArH), 9.63 (dd, 8H, J ¼ 3.1 Hz, ArH). C NMR
J ¼ 4.8 Hz, CH
2
2
(CDCl
3
)
d
54.85, 58.29, 68.72, 68.84, 69.48, 69.53, 69.75, 74.47,
CH
CH
2
2
2
þ
7
9.76, 123.79, 131.0, 136.13, 149.37 (CN). ESI Mass (m/z): calculated
2
2
13
for C50
H
46
N
8
O
8
Si [MþNa]þ 937.31, found 937.13.
(
6
1
dd, 8H, J ¼ 3.1 Hz, ArH). C NMR (CDCl
3
) d 50.79, 54.80, 68.68,
9.46, 69.90, 70.16, 70.20, 70.39, 70.48, 70.54, 70.69e70.81 (m),
þ
23.77, 130.98, 136.10, 149.34 (CN). ESI Mass (m/z): calculated for
2.2.9. Synthesis of compound 5b
compound 4b avg. C86
H124N14
O
26 Si [MþH]þ 1797.87, found mul-
Compound 5b was synthesized according to the procedure of 5a
tiple peaks starting from 1963 (See Supplementary Information).
with the substitution of compound 1b for compound 1a. Com-
pound 5b was purified by flash column chromatography on silica.
Two eluents were employed. The first eluent was ethyl acetate and
was used to remove the majority of impurities. The second eluent
was a 3:1 solution of dichloromethane:methanol and was used to
2.2.8. Synthesis of compound 5a
Silicon phthalocyanine dichloride (0.2 g, 0.33 mmol) was mixed
with dry toluene (4 ml) and the solution of compound 1a (0.19 g,
Fig. 2. Synthetic route to compounds 4a,b and 5a,b; (i) Reaction conditions: NaH, toluene, reflux.

Y. Bandera et al. / Dyes and Pigments 125 (2016) 72e79
75
Fig. 3. ESI Mass analysis of 5b, positive ionization.
remove the remaining impurities and to wash the product from the
2.3. Results & discussion
1
silica. R
f
¼ 0.2. Yield: 64%, dark blue oil. H NMR (CDCl
3
)
d
ꢀ1.92 (t,
4
H, J ¼ 5.5 Hz, CH
2
OSi), 0.37 (t, 4H, J ¼ 5.5 Hz, CH
2
), 1.64 (t, 4H,
2.3.1. Synthesis and characterization
The new axially disubstituted SiPc complexes 4a,b and 5a,b
were synthesized starting from commercially available silicon
J ¼ 4.8 Hz, CH
CH ), 3.20 (m, 4H, CH
.49e3.71 (m, 80H, CH
2
), 2.44 (m, 6H, J ¼ 4.8 Hz, CH
), 3.36 (m, 4H, CH
), 4.21 (d, 4H, J ¼ 2.4 Hz, CH
2
and CCH), 2.96 (m, 4H,
), 3.44 (m, 4H, CH ),
CC), 8.34 (dd,
2
2
2
2
3
8
d
2
2
2 2
phthalocyanine dichloride (SiCl Pc), as presented in Figure 2. SiCl
13
H, J ¼ 2.8 Hz, ArH), 9.62 (dd, 8H, J ¼ 2.8 Hz, ArH). C NMR (CDCl
3
)
Pc reacts with modified triethylene glycols of variable molecular
weights in the presence of NaH in a toluene solution. The reaction
requires high temperatures and leads to the nucleophilic substi-
tution of two chlorine atoms with good yields of the final products
after purification. For this method, the nucleophilic substituent
54.80, 58.53, 68.68, 69.21, 69.43, 69.46, 69.89, 70.20, 70.38, 70.47,
7
0.52, 70.68 (m), 74.69, 79.77, 123.77, 130.99, 136.10, 149.35(CN).
þ
ESI Mass (m/z): calculated for compound 5b avg. (n ¼ 10e11)
C
90 126
H N
8
O
28 Si [MþK]þ 1817.83, found 1818.40.
Fig. 4. 1H NMR spectrum of 5b in CDCl
. Methylene groups closest to the SiPc ring have the highest upfield shift.
3

76
Y. Bandera et al. / Dyes and Pigments 125 (2016) 72e79
Fig. 5. Absorption of 4a,b and 5a,b in methanol at a concentration of 5 mg/mL.
ligands can vary. [21] As key intermediates, we used either tri-
ethylene glycol derivatives (1a or 3a) with azide or alkyne terminal
groups and the corresponding PEG 600 derivatives (1b or 3b). The
synthetic pathway to compounds 1a,b and 3a,b is described in
Figure 1.
Compounds 1a,b were synthesized in one step from triethylene
glycol or PEG600 by the nucleophilic substitution of one hydrogen
in the hydroxyl group to the propargyl group. The reaction was
performed in THF in the presence of NaH and propargyl bromide.
Compounds 3a,b were synthesized in two steps from the same
starting material used for the synthesis of 1a,b. The first interme-
diate is mesylates (2a,b). The reaction of triethylene glycol with a
small excess of methanesulfonyl chloride in dichloromethane
yields 2a. The obtained compound 2a contains a small amount of
bismesylated derivative, but it can be used in the next step without
additional purification because disubstituted impurities will not
Fig. 6. Absorption (pink) and emission (green) of (a) 4b and (b) 5b in water at a
concentration of 5 g/mL. Excitation at 630 nm. (For interpretation of the references to
color in this figure legend, the reader is referred to the web version of this article.)
m
react with SiPcCl
5
2
2
in the final stage of the synthesis of compound
a. Compound 2b was synthesized similarly to 2a. Treatment of
a,b with sodium azide in refluxed acetonitrile yields mono-azide
The closer the atoms of the axial substituents are to the point of
attachment to the SiPc ring, the larger the upfield shift of the
methylene groups in the proton spectrum. The obtained NMR
spectrum corresponds to previous reports for similar compounds
derivatives of triethylene glycol and PEG 600 (3a,b) with high
yields.
1
All synthesized axially disubstituted SiPcs were verified by H,
C NMR, and ESI Mass analyses. The presence of azide groups in
PEGylated SiPc (4b) was also confirmed by FTIR analysis. The azide
[11,13,21]. Alkyne protons in modified triethylene glycols 1a,b and
13
PEGylated SiPcs 5b show a triplet at 2.43 ppm, while, for the shorter
analog 5a, the signal is shifted to 2.34 ppm. The same behavior is
ꢀ1
groups on 4b have a strong absorption at 2098 cm
(see
observed for CH
from 3.37 ppm (3a,b and 4b) is shifted to 2.93 ppm in compound
a. Aromatic protons in the final SiPcs show two, well-separated
2
protons attached to the azide group; the triplet
1
Supplementary Information). The H NMR spectra of the final
products 4a,b and 5a,b shows the shielding of the axial substituent
protons by the electron cloud of the SiPc ring. Well-separated,
upfield shifted triplets, starting from ꢀ1.92 ppm, show methylene
protons (cf. Figure 4).
4
downfield shifted multiplets.
Figure 3 shows the ESI mass analysis of SiPc 5b. Multiple peaks
þ
are separated by 44 mass units [OCH
2
CH
2
]
starting from
Table 2
Table 1
Molar extinction coefficient and fluorescence quantum yield of all four silicon
phthalocyanine derivatives. Solvent is methanol. bSolvent is toluene with 1% pyri-
dine. Excitation at 665 nm.
a
Absorption and emission of 4a,b and 5a,b in methanol at a concentration of 5 mg/mL.
Excitation at 630 nm.
εa (M cm)ꢀ1
ꢀ1
f
F
b
Compound
labs (nm)
lem (nm)
Compound
4a
4b
5a
5b
352, 606, 671
358, 607, 676
354, 604, 672
355, 604, 672
683
680
681
680
4a
4b
5a
5b
259,900
209,200
208,600
218,500
0.50
0.51
0.52
0.51

Y. Bandera et al. / Dyes and Pigments 125 (2016) 72e79
77
þ
molecular ion M . Compound 4b shows similar results (see
of similar SiPcs, which indicates that there is minimal aggregation
in this system. It should also be noted that 4b has just a slight J-
aggregate peak, with 5b having quite a large J-aggregate peak,
which agrees with the absorption spectra obtained for both of these
molecules. J-aggregates occur when the dye has self associated
with itself and are characterized by a longer emission wavelength
than the “isolated” dye molecule. J-aggregates are undesirable in
this case because they represent a path of non-radiative energy
transfer, which will decrease singlet oxygen generation when the
dye is utilized in PDT [37].
Supplementary Information).
SiPcs 4a,b and 5a,b are soluble in alcohols, acetone, dichloro-
methane and other common, polar, organic solvents excluding
diethyl ether. PEGylated SiPcs 4b and 5b have good solubility in
water. Crude products were easily purified by flash column chro-
matography on silica.
2
.3.2. Photophysical properties
The UVeVis absorption spectra of 4a,b and 5a,b, in methanol,
The molar extinction coefficient (ε) and fluorescence quantum
are displayed in Figure 5. The relevant spectroscopic parameters are
summarized in Table 1. All synthesized SiPcs showed a sharp,
intense, well-defined absorption peak (Q-band) at 671e676 nm
along with two vibrational bands at 604 and 645 nm, and a B-band
at 330e360 nm, depending on the particular SiPc. These absorption
bands are indicative of a non-aggregated SiPc for all newly syn-
thesized SiPcs. The same results were obtained in THF and DMSO;
all compounds did not show any aggregation. The maximum fluo-
rescence emission for compounds 4a,b and 5a,b, in methanol,
occurred at 680 nm when excited at 630 nm.
yield (
f
F
) for all synthesized phthalocyanines were calculated. The
¼ 0.3) and 1% pyridine in
data is summarized in Table 2. ZnPc (
f
F
toluene solution as a standard was used for fluorescence quantum
yield calculations. [38] All silicon phthalocyanine derivates had a
much greater fluorescence quantum yield than the standard ZnPc,
which indicates that the SiPc derivatives have more electrons that
fluoresce upon excitation and relaxation. This is beneficial because
less electrons, upon relaxation, go toward non-radiative energy
transfers. Therefore, it can be concluded that silicon phthalocya-
nines are good candidates for use as photosensitizers in PDT as they
have a higher propensity to fluoresce and generate singlet oxygen.
To further support this claim, the molar extinction coefficient was
calculated for all derivatives. It was found that all derivatives had
The absorption spectra for SiPcs 4b and 5b, in water, is provided
in Figure 6. PEGylated SiPc 4b, was dissolved in water at a con-
mg/mL, and it showed a strong absorption peak at
76 nm, which is characteristic of non-aggregated SiPc. The water
centration of 5
6
molar
60,000 M cm with methanol as the solvent. These values are
in good agreement with the value found for zinc phthalocyanine
extinction
coefficients
between
200,000
and
solubility of 4b is 3 mg/mL. Compound 5b shows a strong Q band in
water at 720 nm, which suggests that the dye molecules are self-
associating. The water solubility of 5b is 0.2 mg/mL. The aggrega-
tion behavior of 5b can be explained by the presence of lipophilic
alkyne groups at the end of the PEG chains; it decreases solubility in
water and makes aggregation easier. Increasing the length of the
PEG chains in SiPcs could allow for new dyes with even greater
solubility in water. The emission spectra of both 4b and 5b show J-
aggregates at 761 nm and 757 nm, respectively. This red-shifted
peak does suggest that there are aggregates of 4b and 5b form-
ing, but these peaks are much less pronounced than in the spectra
ꢀ
1
ꢀ1
2
(
ε ¼ 281,800) when dissolved in pyridine. [39] Unfortunately, zinc
phthalocyanine is only soluble in pyridine so an exact comparison
between the standard and the silicon phthalocyanine derivatives
could not be made.
Being non-aggregated compounds, new SiPc derivatives can be
modified by “click” reactions with appropriate small molecules,
polymers, nano or microparticles, or proteins (cf. Figure 7). An
example of such a system is presented in Figure 8, where the
Fig. 7. Possible routes, which employ SiPcs (4a,b and 5a,b), to construct complex systems via “click” reactions. See Fig. 8 for a specific example.

78
Y. Bandera et al. / Dyes and Pigments 125 (2016) 72e79
phthalocyanine ring due to the central silicon atom being redox
inactive.
The prediction of LUMO energies through a CV route can often
be quite poor due to the difficulty in assigning the voltage for the
oxidation process due to its irreversibility; therefore, Table 3 also
presents LUMO (LUMOop) energies based on the difference of CV-
derived HOMO values and the energy at the experimentally
observed electronic absorption band edge. Clearly, there is a good
agreement between the CV and optically derived bandgaps, where
the difference between these values is no greater than 0.11 eV for all
the compounds.
3. Conclusion
New axially disubstituted, non-aggregated silicon phthalocya-
Fig. 8. Photoluminescence spectra of 67 nm poly(propargyl acrylate) (PA) particles
surface modified with 4a,b through copper(I)-catalyzed azide alkyne cycloaddition
nines (SiPcs), containing azide or alkyne groups have been syn-
thesized and characterized. All obtained SiPcs are highly soluble in
common polar, organic solvents with the PEGylated derivatives
(
CuAAC). Particles dispersed in DMSO. Excitation wavelength was 630 nm.
(
4b and 5b) being soluble in water and other physiologically
relevant buffers. The presence of azide and alkyne functional
groups in dye molecules, and their high fluorescence and solubi-
lity in various solvents make these new compounds useful as a
versatile building block in “click” reactions, allowing for the syn-
thesis of a broad spectrum of new compounds for use in
biomedical imaging and cancer therapies. The synthetic pathway
presented in this paper can be applicable for the synthesis of a
variety new axially disubstituted SiPc derivatives with alkyne or
azide groups.
photoluminescence spectra of 67 nm poly(propargyl acrylate) (PA)
particles, which have been surface modified with 4a,b (PA/SiPcs)
through copper(I)-catalyzed azide alkyne cycloaddition (CuAAC), is
presented. Clearly, the attachment of the fluorophores to the par-
ticles have not significantly altered their spectral profile since both
exhibit an emission peak at ca. 680 nm.
Previously studied, similar, axially disubstituted PEGylated SiPcs
have been shown to be potent photosensitizers and have consistent
photocytotoxicity [11,13,21]. The properties of these new phthalo-
cyanines (4a,b and 5a,b) are good candidates for photodynamic
therapy (PDT) and the PA/SiPcs assemblies are currently being
investigated as phototsentizers with an enhanced permeability and
retention (EPR) effect.
Acknowledgments
The authors thank the Gregg-Graniteville Foundation and the
National Science Foundation (DMR-1507266) for financial support.
2
.3.3. Electrochemical measurements
Voltammograms were analyzed in order to derive onset po-
Appendix A. Supplementary data
tential (Eonset), half-wave potentials (E(1/2)), peak to peak potential
separation for reversible processes ( (mV)) and peak separation
between the first oxidation and first reduction (Egap). The results
are presented in Table 3. The voltammograms exhibit one irre-
versible one electron transfer oxidation process that has an Eonset of
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.dyepig.2015.10.007.
DE
p
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