The effect of substitutents at alkylsulfanyl/arylsulfanyl non-peripherally substituted phthalocyanines: Spectral and photophysical properties, basicity and photostability

Article abstract of DOI:10.1142/S1088424615500832

A series of magnesium, zinc and metal-free derivatives of non-peripherally substituted phthalocyanines (Pcs) bearing alkylsulfanyl or arylsulfanyl groups of different bulkiness was synthesized. Their spectral and photophysical properties including also th

Full text of DOI:10.1142/S1088424615500832

Journal of Porphyrins and Phthalocyanines
J. Porphyrins Phthalocyanines 2015; 19: 1–12
DOI: 10.1142/S1088424615500832
Published at http://www.worldscinet.com/jpp/
The effect of substitutents at alkylsulfanyl/arylsulfanyl
non-peripherally substituted phthalocyanines: Spectral
and photophysical properties, basicity and photostability
Antonin Cidlinaa, Zuzana Pausimovab, Miroslav Miletina, Petr Zimcika◊
and Veronika Novakova*b◊
a Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Kralove,
Charles University in Prague, Heyrovskeho 1203, Hradec Kralove, Czech Republic
b Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove,
Charles University in Prague, Heyrovskeho 1203, Hradec Kralove, Czech Republic
Received 7 June 2015
Accepted 16 July 2015
ABSTRACT: A series of magnesium, zinc and metal-free derivatives of non-peripherally substituted
phthalocyanines (Pcs) bearing alkylsulfanyl or arylsulfanyl groups of different bulkiness was synthesized.
Their spectral and photophysical properties including also the basicity of azomethine nitrogens and
photostability were compared within the series as well as with similar peripherally substituted Pcs. Non-
peripheral position of substituents led to the 70 nm red-shift of Q-band in comparison to the peripherally
substituted Pcs. However, unexpected blue-shift of approximately 50 nm was observed in the series of
non-peripherally substituted Pcs for the most bulky tert-butylsulfanyl derivative caused probably by
extreme distortion of the macrocycle. The substitution had no effect on photophysical properties and
compounds reached FD values 0.74–0.76 and FF 0.053–0.080 for zinc complexes, and FD 0.47–0.51
and FF 0.10–0.17 for magnesium complexes following the rule of heavy atom effect. Generally, non-
peripherally substituted Pcs possessed improved singlet oxygen production in comparison to peripherally
substituted ones. The photostability of the target compounds decreased with the red-shift of their
absorption maxima with the arylsulfanyl derivatives being less photostable. The basicity of azomethine
nitrogens was clearly dependent on the position and the character of substituent. Thus, non-peripherally
substituted Pcs showed extraordinary increased basicity over the peripherally substituted ones with the
most pronounced effect at alkylsulfanyl derivatives.
KEYWORDS: phthalocyanine, non-peripheral substitution, singlet oxygen, fluorescence, basicity,
photobleaching.
photodynamic therapy of cancer [1–4], solar cells [5],
INTRODUCTION
gas sensors [6], organic light emitting devices [7] or
Phthalocyanines (Pcs) are intensively colored synthetic
near infrared fluorescence imaging probes [8]. The near
dyes structurally close to porphyrins with interesting
infrared absorption brings advantages in many of these
spectral, electrochemical and photophysical properties.
applicationsespecially dueto limited spectral competition
Due to extended 18 p-conjugated macrocyclic system,
with other molecules (endogenous chromophores present
they absorb the light in red region beyond 650 nm.
in biological material) and lower light scattering.
Their application can be found in various fields, such as
The position of the Pcs main absorption band (i.e.
the Q-band) can be manipulated by annulation of
additional benzene rings forming, thus, Pcs homologs
◊ SPP full member in good standing
(e.g. naphthalocyanines [9]), by nature and position
*Correspondence to: Veronika Novakova, email: veronika.
of peripheral substituents [10], and partially also by
novakova@faf.cuni.cz, tel:+420495067380, fax:+420495067167
Copyright © 2015 World Scientific Publishing Company

2
A. CIDLINA ET AL.
coordination of different metal cations into the center
[11]. However, higher homologs of Pcs with stronger p–p
interactions suffer usually from increased aggregation
and low solubility leading to the loss of optimal spectral
and photophysical properties. Evidently, the modulation
of the position and character of substituents is the most
effective way for tuning spectral properties of Pcs.
Hence, pronounced bathochromic shift of Q-band was
achieved by substitution in non-peripheral positions
(1,4,8,11,15,18,22,25) of Pc core [11, 12]. Heteroatom
connecting peripheral substituent to the macroclic
core can contribute to the p-electron system shifting,
thus, absorption more to the red part. Accordingly,
alkylsulfanyl or arylsulfanyl substituents are known
to bathochromically shift the Q-band due to efficient
overlapping of its 3p orbitals with p-orbitals of Pc
[13]. Further, it has been systematically demonstrated
that slight distortion of the macrocycle caused by non-
peripheral substitution leads to significant red-shift
of Q-band. This was shown on Pcs bearing different
substituents (i.e. alkyl/aryl- [14], alkyloxy/aryloxy [9]
as well as alkylsulfanyl/arylsulfanyl [11] derivatives)
and proved experimentally as well as by theoretical
calculations [15, 16]. Moreover, the substitution in non-
peripheral positions of the macrocycle is known to reduce
unfavorable aggregation behavior [17, 18].
were included in the study. Only recently, Dumoulin and
co-workers [19] described similar blue shift comparing
two metal-free Pcs bearing tert-butylsulfanyl and
hexylsulfanyl groups attached in non-peripheral positions
and attributed it to the substantially increased distortion
of the former macrocycle based on X-ray structures
and theoretical calculations. In this work, series of
compounds enabling clear comparison of alkylsulfanyl
vs. arylsulfanyl substitution of different bulkiness was
designed. Besides spectral properties, photophysical
evaluation, basicity of azomethine nitrogens as well as
photostability will be of interest in present work.
EXPERIMENTAL
General
All of the organic solvents used in the syntheses
were of analytical grade. Anhydrous butanol for
the cyclotetramerization was freshly distilled from
magnesium, anhydrous quinoline was dried over calcium
hydrideanddistilledunderreducedpressure.Ananhydrous
DMF was purchased from Sigma-Aldrich. Unsubstituted
zinc phthalocyanine (ZnPc) was purchased from Sigma-
Aldrich. All of the other chemicals for the syntheses were
purchased from certified suppliers (i.e. Sigma-Aldrich,
TCI Europe, Acros, and Merck) and used as received.
TLC was performed on Merck aluminum sheets coated
with silica gel 60 F254. Merck Kieselgel 60 (0.040–
0.063 mm) was used for column chromatography. The
melting points were measured on an Electrothermal
IA9200-series digital melting-point apparatus (Electro-
thermal Engineering, Southend-on-Sea, Essex, Great
Britain). The infrared spectra were measured on a Nicolet
Combining above-mentioned knowledge, the target
magnesium non-peripherally substituted Pc with bulky
alkylsulfanyl groups (3Mg, Chart 1) was designed.
Surprisingly, unexpected blue shift was observed (data
shown below). That was why, the series was enlarged
to the other compounds 1M, 2M, 4M and 5M (Chart 1)
of different bulkiness and alkylsulfanyl- or arylsulfanyl-
nature of substituent to explain this feature. Metal
complexes as well as corresponding metal free derivatives
R
1M
2M
S
S
S
S
R
R
S
S
N
N
R
R
R
R
N
N
N
N
N
N
3M
4M
S
S
M
M
N
N
N
N
N
N
N
N
S
S
R
R
S
S
5M
S
6M
M = Mg/Zn/2H
M = Mg/Zn
Chart 1. Structures of investigated compounds 1M–6M
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 2–12

THE EFFECT OF SUBSTITUTENTS AT ALKYLSULFANYL/ARYLSULFANYL NON-PERIPHERALLY SUBSTITUTED
3
1
13
6700 spectrometer in ATR mode. The H and C NMR
spectrawererecordedonaVarianMercuryVxBB300NMR
spectrometer or VNMR S500 NMR spectrometer. The
chemical shifts are reported relative to Si(CH3)4 and
were locked to the signal of the solvent. The UV-vis
spectra were recorded using a Shimadzu UV-2600
spectrophotometer. The steady-state fluorescence
spectra were measured using an AMINCO-Bowman
Series 2 luminescence spectrometer. The MALDI-TOF
mass spectra were recorded in positive reflectron mode
on a 4800 MALDI TOF/TOF mass spectrometer (AB
Sciex, Framingham, MA, USA) in trans-2-[3-(4-tert-
butylphenyl)-2-methyl-2-propenylidene]-malononitrile,
which was used as a matrix. The instrument was
calibrated externally with a five-point calibration using
a Peptide Calibration Mix1 kit (LaserBio Laboratories,
Sophia-Antipolis, France). 3,6-Bis(pentan-3-ylsulfanyl)
phthalonitrile (2) [20], 3,6-bis(tert-butylsulfanyl)phthalo-
nitrile (3) [21], 3,6-bis(phenylsulfanyl)phthalonitrile (4)
[11], 3,6-bis(adamantan-1-ylsulfanyl)phthalonitrile (7)
[22], 2,3-dicyano-1,4-phenylene bis(4-methylbenzenesul-
fonate) (8) [23] and the reference compounds 6Mg, 6Zn
[24] were prepared according to previously published
procedures.Thecompound3,6-bis(butylsulfanyl)phthalo-
nitrile (1) [10], 3,6-bis[(2,6-dimethylphenyl)sulfanyl]
phthalonitrile (5) [12] were prepared with a minor
modification described below. Our analytical data for
previously published compounds corresponded well with
those reported.
CH3). 13C NMR (75 Hz, CDCl3): d, ppm 140.8, 139.7,
125.0, 114.8, 50.5, 31.0.
1
3,6-Bis(phenylsulfanyl)phthalonitrile (4). H NMR
(300 Hz, CDCl3): d, ppm 7.92–7.72 (m, 10H, ArH), 7.32 (s,
2H, ArH). 13C NMR (75 Hz, CDCl3): d, ppm 142.8, 134.5,
132.2, 130.2, 130.0, 129.6, 115.1, 113.6.
3,6-Bis[(2,6-dimethylphenyl)sulfanyl]phthalo-
nitrile (5). The finely ground anhydrous potassium
carbonate (235 mg, 1.7 mmol) was sonicated in
anhydrous DMSO (10 mL) for 30 min and then
2,6-dimethylbenzenethiol (120 mg, 0.85 mmol) was
added. Later, compound 8 (100 mg, 0.21 mmol) was
added in one portion and the stirring continued for
next 16 h at room temperature. The reaction was then
quenched by water (50 mL). The mixture was extracted
with ethyl acetate (3 × 15 mL). The combined organic
layers were dried over anhydrous Na2SO4 and solvent
was removed under reduced pressure. The crude product
was purified by column chromatography on silica with
toluene/chloroform (5:1) as the mobile phase (Rf = 0.40).
1
Yield 63 mg (74%) of yellow solid. H NMR (300 Hz,
CDCl3): d, ppm 7.61–7.58 (m, 2H,ArH), 7.52 (d, J = 7 Hz,
4H, ArH), 6.76 (s, 2H, ArH) 2.71 (s, 12H, CH3). 13C
NMR (75 Hz, CDCl3): d, ppm 144.0, 141.7, 130.7, 129.0,
128.9, 127.1, 113.7, 113.4, 21.7.
3,6-Bis(adamantan-1-ylsulfanyl)phthalonitrile (7).
The finely ground anhydrous potassium carbonate (8.2 g,
59 mmol) was sonicated in DMSO (50 mL) for 30 min
and then 1-adamantanethiol (5 g, 30 mmol) was added.
Later, compound 8 (2.78 g, 6 mmol) was added to the
mixture in six portions during the next 1h and the stirring
was continued for 16 h at room temperature. The reaction
was then quenched by water (150 mL). The mixture was
extracted with chloroform (4 × 40 mL). The combined
organic layers were dried over anhydrous Na2SO4 and
solvent was removed under reduced pressure. The crude
product was purified by column chromatography on
silica with toluene and further with toluene/chloroform
(1:1) (Rf = 0.41) as the mobile phase. Yield 2.76 g (96%)
Synthesis of precursors
3,6-Bis(butylsulfanyl)phthalonitrile (1). The finely
ground anhydrous potassium carbonate (5.3 g, 38.4 mmol)
was sonicated in DMSO (50 mL) for 30 min and then
butanethiol (2.9 g, 32.0 mmol) was added. Later, the
compound 8 (6 g, 12.8 mmol) was added to the mixture
in six portions during the next 2 h and stirring continued
for next 16 h at room temperature. The reaction was then
quenched by water (150 mL). The mixture was extracted
with ethyl acetate (3 × 40 mL). The combined organic
layers were dried over anhydrous Na2SO4 and solvent was
removed under reduced pressure. The crude product was
purified by column chromatography on silica with toluene
as the mobile phase (Rf = 0.27). Yield 2.32 g (59%) of
light yellow solid. 1H NMR (300 Hz, CDCl3): d, ppm 7.86
(s, 2H, ArH), 3.38 (t, J = 7 Hz, 4H, SCH2), 2.02 (quint, J =
7 Hz, 4H, SCH2CH2), 1.91–1.75 (m, 4H, CH2CH3), 1.30
(t, J = 7 Hz, 6H, CH3). 13C NMR (75 Hz, CDCl3): d, ppm
141.3, 132.0, 117.0, 113.8, 33.4, 30.6, 21.4, 13.5.
1
of white solid. H NMR (500 Hz, CDCl3): d, ppm 8.12
(s, 2H, ArH), 2.44 (s, 6H, CH2), 2.30–2.25 (m, 12H,
CH + CH2), 2.01 (q, 12H, CH + CH2). 13C NMR (125 Hz,
CDCl3): d, ppm 141.1, 137.7, 125.3, 115.0, 53.2, 43.7,
35.8, 30.1.
Synthesis of macrocycles
General procedure for synthesis of magnesium (II)
complexes. Magnesium turnings (10 eq.) and a small
crystalline of iodine were refluxed in freshly distillated
anhydrous butanol (10–50 mL) for 3 h. Later, the
compound 1–5 (1 eq.) was added and reflux continued
for next 24 h. The reaction mixture was cooled down
and solvent was removed under reduced pressure. The
aqueous solution of acetic acid (50%) (v/v) was added
(about 100 mL) and the mixture was stirred at room
temperature for 1 h. Precipitate was collected by filtration
3,6-Bis(pentan-3-ylsulfanyl)phthalonitrile (2). 1H
NMR (300 Hz, CDCl3): d, ppm 7.9 (s, 2H, ArH), 3.59
(quint, J = 6 Hz, 2H, CH), 2.14–1.92 (m, 8H, CH2), 1.39
13
(t, 12H, CH3). C NMR (75 Hz, CDCl3): d, ppm 141.2,
134.2, 118.8, 114.1, 52.9, 26.6, 11.0.
3,6-Bis(tert-butylsulfanyl)phthalonitrile(3).1H NMR
(300 Hz, CDCl3): d, ppm 8.18 (s, 2H, ArH), 1.76 (s, 18H,
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 3–12

4
A. CIDLINA ET AL.
and washed with water. Purification of the product is
mentioned at each compound below.
(THF): lmax, nm (log e) 775 (5.35), 695 (4.71), 495 (sh)
361 (4.80). 1H NMR (300 Hz, CDCl3/pyridine-d5): d, ppm
7.75 (broad s, 16H, ArH), 7.59–6.84 (m, 32H, ArH). No
1,4,8,11,15,18,22,25-Octakis(butylsulfanyl)phthalo-
cyaninato magnesium (II) (1Mg). The compound 1Mg
was prepared from 1 (1 g, 3.28 mmol) according to general
procedure for synthesis of magnesium complexes. The
crude product was washed thoroughly with methanol and
purified by column chromatography on silica with toluene/
chloroform/THF (40:4:1) as a mobile phase (Rf = 0.32).
Yield 722 mg (70%) of dark green solid. UV-vis (THF):
13
signal was detected in C NMR spectrum. IR: nmax, cm-1
3056, 2785, 2538, 1957, 1884, 1582, 1557, 1475, 1461,
1439, 1320, 1287, 1177, 1107, 918, 791. MS (MALDI):
m/z 1400.1 [M]+.
1,4,8,11,15,18,22,25-Octakis(2,6-dimethylphenyl-
sulfanyl)phthalocyaninato magnesium (II) (5Mg).
The compound 5Mg was prepared from 5 (286 mg,
0.71 mmol) following the general procedure for synthesis
of magnesium complexes. The crude product was purified
by column chromatography on silica with a toluene/THF
(50:1) as a mobile phase (Rf = 0.50). The pure compound
was washed thoroughly with methanol. Yield 179 mg
(47%) of dark brown solid. UV-vis (THF): lmax, nm (log e)
l
max, nm (log e) 776 (5.26), 694 (4.62), 501 (sh), 359 (4.68).
1H NMR (300 Hz, CDCl3/pyridine-d5): d, ppm 7.93 (broad s,
8H, ArH), 3.48 (broad s, 16H, SCH2), 2.14 (quint, J = 7 Hz,
16H, SCH2CH2), 1.92–1.70 (m, 16H, CH2CH3), 1.16 (t, J =
13
7 Hz, 24H, CH3). C NMR (75 Hz, CDCl3/pyridine-d5):
d, ppm 153.5, 132.7, 124.8, 32.11, 31.3, 23.1, 14.1. IR:
max, cm-1 2956, 2929, 2870, 1561, 1463, 1436, 1319, 1284,
788 (5.38), 702 (4.72), 501 (sh), 360 (4.81). H NMR
1
n
1210, 1107, 1084, 926. MS (MALDI): m/z 1240.3 [M]+.
1,4,8,11,15,18,22,25-Octakis(pentan-3-yl)phthalo-
cyaninato magnesium (II) (2Mg). The compound 2Mg
was prepared from 2 (500 mg, 1.51 mmol) according to
general procedure for synthesis of magnesium complexes.
The crude product was washed thoroughly with methanol
and purified by column chromatography on silica
with toluene/THF (20:1) as the mobile phase (Rf =
0.75). Yield 220 mg (43%) of dark brown solid. UV-vis
(THF): lmax, nm (log e) 774 (5.22), 692 (4.60), 505 (sh),
(300 Hz, CDCl3/pyridine-d5): d, ppm 7.36–7.28 (m, 24H,
ArH), 6.88 (s, 8H, ArH), 2.64 (s, 48H, CH3). 13C NMR
(75 Hz, CDCl3/pyridine-d5): d, ppm 144.5, 139.1, 131.4,
130.7, 129.4, 128.8, 124.4, 22.2. IR: nmax, cm-1 3054,
2952, 1561, 1459, 1377, 1212, 1166, 1107, 1053, 988,
916, 517, 769. MS (MALDI): m/z 1624.2 [M]+.
General procedure for synthesis of metal-free
derivatives. The compound 1Mg, 2Mg, 4Mg or
5Mg (1 eq.) was dissolved in THF (40 mL) and
p-toluenesulfonic acid (TsOH) was added (7 eq.). The
reaction mixture was stirred at room temperature for 1 h
protected from light by aluminum foil. Later, the reaction
was quenched by water (50 mL) and precipitate was
collected by filtration. The crude product was washed
with water and thoroughly with methanol. The product
was purified by column chromatography on silica
(mobile phases are mentioned at each compound below)
and thoroughly washed with methanol.
1
363 (4.66). H NMR (500 Hz, CDCl3): d, ppm 7.94 (s,
8H, ArH), 3.76–3.63 (m, 8H, CH), 2.14–1.98 (m, 32H,
13
CH2), 1.25 (t, J = 7 Hz, 48H, CH3). C NMR (125 Hz,
CDCl3): d, ppm 153.2, 136.5, 132.9, 131.8, 130.8, 128.6,
126.7, 50.0, 27.1, 12.1. IR: nmax, cm-1 2964, 1931, 1872,
1558, 1491, 1461, 1377, 1318, 1281, 1205, 1139, 1106,
919. MS (MALDI): m/z 1352.4 [M]+, 1375.4 [M + Na]+,
1391.1 [M + K]+.
1,4,8,11,15,18,22,25-Octakis(tert-butylsulfanyl)phth-
alocyaninato magnesium (II) (3Mg). The compound
3Mg was prepared from 3 (200 mg, 0.66 mmol) according
to general procedure for synthesis of magnesium com-
plexes.Thecrudeproductwaspurifiedbycolumnchromato-
graphy on silica with chloroform/THF (10:1) as a mobile
phase (Rf = 0.41). The pure 3Mg was washed thoroughly
with methanol. Yield 63 mg (31%) of dark green solid.
UV-vis (THF): lmax, nm (log e) 724 (5.08), 657 (4.44), 467
1,4,8,11,15,18,22,25-Octakis(butylsulfanyl)
phthalocyanine (1H). The compound 1H was prepared
from 1Mg (90 mg, 0.072 mmol) according to the general
procedure for synthesis of metal-free derivatives. Mobile
phase: chloroform (Rf = 0.65). Yield 52 mg (59%) of
green solid. UV-vis (THF): lmax, nm (log e) 805 (5.18),
1
718 (4.61), 523 (sh), 350 (4.71). H NMR (300 Hz,
CDCl3/pyridine-d5): d, ppm 7.56 (s, 8H, ArH), 3.21
(broad s, 16H, SCH2), 1.97–1.81 (m, 16H, SCH2CH2),
1.78–1.61 (m, 16H, CH2CH3), 1.09 (t, J = 7 Hz, 24H,
CH3). 13C NMR (75 Hz, CDCl3/pyridine-d5): d, ppm
168.3, 133.4, 129.6, 124.2, 30.4, 29.0, 22.1, 13.2. The
other analytical data correspond to the data published in
literature [10].
1,4,8,11,15,18,22,25-Octakis(pentan-3-yl)phthalo-
cyanine (2H). The compound 2H was prepared from 2Mg
(100 mg, 0.074 mmol) according to the general procedure
for synthesis of metal-free derivatives. Mobile phase:
chloroform/THF (30:1) (Rf = 0.72). Yield 77 mg (78%) of
brown solid. UV-vis (THF): lmax, nm (log e) 802 (5.17),
716 (4.58), 515 (sh), 357 (4.67). nmax/cm-1 3304, 2964,
2931, 2872, 1559, 1460, 1377, 1278, 1225, 1197, 1136,
1
(sh), 375 (4.58). H NMR (300 Hz, CDCl3/pyridine-d5):
d, ppm 8.26 (s, 8H, ArH), 1.62 (s, 144H, CH3) 13C NMR
(75 Hz, CDCl3/pyridine-d5): d, ppm 152.4, 142.5, 139.9,
139.5, 137.2, 134.5, 133.3, 132.2, 41.5, 31.4. IR: nmax, cm-1
2962, 2918, 2894, 2861, 1689, 1553, 1459, 1389, 1362,
1128, 1096, 917, 783. MS (MALDI): m/z 1240.3 [M]+.
1,4,8,11,15,18,22,25-Octakis(phenylsulfanyl)phtha-
locyaninato magnesium (II) (4Mg). The compound 4Mg
was prepared from 4 (500 mg, 1.64 mmol) according to
general procedure for synthesis of magnesium complexes.
The crude product was purified by column chromatography
on silica with toluene/THF (30:1) as a mobile phase (Rf =
0.33). Yield 308 mg (61%) of dark brown solid. UV-vis
Copyright © 2015 World Scientific Publishing Company
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THE EFFECT OF SUBSTITUTENTS AT ALKYLSULFANYL/ARYLSULFANYL NON-PERIPHERALLY SUBSTITUTED
5
1
1091, 1044, 907. H NMR (300 Hz, CDCl3/pyridine-d5):
d, ppm 7.95 (s, 8H, ArH), 3.81–3.63 (m, 8H, SCH), 2.25–
1.95 (m, 32H, -SCHCH2), 1.27 (t, J = 7 Hz, 48H, CH3). 13C
NMR (75 Hz, CDCl3/pyridine-d5): d, ppm 136.37, 133.62,
132.91, 130.87, 129.18, 127.02, 49.51, 27.03, 11.98. MS
(MALDI): m/z 1330.5 [M]+, 1353.47 [M + Na]+.
the general procedure for synthesis of zinc complexes.
Mobile phase: toluene (Rf = 0.65). Yield 37 mg (75%) of
brown solid. UV-vis (THF): lmax, nm (log e) 777 (5.21),
1
697 (4.59), 510 (sh), 344 (4.62). H NMR (300 Hz,
CDCl3/pyridine-d5): d, ppm 7.81 (s, 8H, ArH), 3.56
(quint, J = 6 Hz, 8H, SCH), 2.01–1.81 (m, 32H,
SCHCH2), 1.10 (t, J = 7 Hz, 48H, CH3). 13C NMR (75 Hz,
CDCl3/pyridine-d5): d, ppm 152.0, 131.7, 125.4, 48.7,
26.0, 11.0. The other analytical data corresponded to the
data published in literature [20].
1,4,8,11,15,18,22,25-Octakis(phenylsulfanyl)
phthalocyanine (4H). The compound 4H was prepared
from 4Mg (129 mg, 0.092 mmol) according to the general
procedure for synthesis of metal-free derivatives. Mobile
phase: toluene/THF (50:1) (Rf = 0.80). Yield 78 mg
(61%) of brown solid. UV-vis (THF): lmax, nm (log e)
1,4,8,11,15,18,22,25-Octakis(phenylsulfanyl)
phthalocyaninato zinc (II) (4Zn). The compound 4Zn
was prepared from 4H (78 mg, 0.056 mmol) according
to the general procedure for synthesis of zinc complexes.
Mobile phase: toluene/THF (50:1) (Rf = 0.33).Yield 67 mg
(82%) of green solid. UV-vis (THF): lmax, nm (log e) 779
(5.27), 695 (4.66), 497 (sh), 352 (4.76). 1H NMR (300 Hz,
CDCl3/pyridine-d5): d, ppm 7.98–7.83 (m, 16H, ArH),
7.52–7.41 (m, 24H, ArH), 7.31–7.25 (m, 8H, ArH). 13C
NMR (75 Hz, CDCl3/pyridine-d5): d, ppm 153.7, 134.1,
134.0, 133.0, 129.9, 129.0, 127.2. The other analytical
data correspond to the data published in literature [12].
1,4,8,11,15,18,22,25-Octakis(2,6-dimethylphenyl-
sulfanyl)phthalocyaninato zinc (II) (5Zn). The compound
5Zn was prepared from 5H (59 mg, 0.37 mmol) according
to the general procedure for synthesis of zinc complexes.
Mobile phase: toluene/THF (50:1) (Rf = 0.49). Yield 48 mg
(78%) of brown solid. UV-vis (THF): lmax, nm (log e) 793
1
802 (4.87), 713 (4.30), 522 (sh), 356 (4.75). H NMR
(300 Hz, CDCl3/pyridine-d5): d, ppm 8.03–7.80 (m,
16H, ArH), 7.57–7.41 (m, 24H, ArH), 7.31–7.22 (m, 8H,
ArH). The other analytical data correspond to the data
published in literature [11].
1,4,8,11,15,18,22,25-Octakis(2,6-dimethylphenyl-
sulfanyl)phthalocyane (5H). The compound 5H was
prepared from 5Mg (136 mg, 0.084 mmol) according
to the general procedure for synthesis of metal-free
derivatives. Mobile phase: toluene/hexane (1:1) (Rf =
0.33). Yield 100 mg (75%) of brown solid. UV-vis
(THF): lmax, nm (log e) 817 (5.29), 725 (4.67), 536 (sh),
1
358 (4.77). H NMR (300 Hz, CDCl3/pyridine-d5): d,
ppm 7.68–7.59 (m, 24H, ArH), 7.23 (s, 8H, ArH), 2.94 (s,
48H, CH3). 13C NMR (75 Hz, CDCl3/pyridine-d5): d, ppm
144.5, 137.8, 133.5, 129.1, 128.3, 125.4, 125.2, 22.1. The
other analytical data correspond to the data published in
literature [12].
1
(5.36), 706 (4.71) 511 (sh), 354 (478). H NMR (300 Hz,
CDCl3/pyridine-d5): d, ppm 7.40–7.20 (m, 24H,ArH), 6.94–
13
General procedure for synthesis of zinc (II)
complexes. The metal-free derivative 1H, 2H, 4H or 5H
(1 eq.) was dissolved in pyridine (15 mL) and anhydrous
zinc acetate was added (7 eq.). The reaction mixture was
heated at reflux for 2 h. Hereupon, the mixture was left to
cool down and water (20 mL) was added. The precipitate
was collected by filtration and thoroughly washed with
water and methanol. The crude product was purified
by column chromatography on silica (mobile phase is
mentioned at each compound below).
6.86 (s, 8H, ArH), 2.63 (s, 48H, CH3). C NMR (75 Hz,
CDCl3/pyridine-d5): d, ppm 153.9, 144.5, 134.4, 132.6,
131.1, 129.5, 129.2, 128.9, 128.4, 124.6, 22.2. IR: nmax, cm-1
3052, 2955, 2920, 2853, 2730, 2457, 1933, 1879, 1771,
1731, 1603, 1558, 1489, 1376, 1319, 1212, 1166, 1137,
1112, 1053, 914, 169. MS (MALDI): m/z 1664.2 [M]+.
Fluorescence measurements
All of the samples were re-purified using preparative
TLC prior the measurement to ensure high purity of the
samples (mobile phases are mentioned in Experimental
part). All of the emission spectra were corrected for the
instrument response. The fluorescence quantum yields
(FF) were determined in THF via the comparative
method using unsubstituted zinc phthalocyanine (ZnPc)
as a reference (FF = 0.32 in THF [25]). Both the reference
and sample were excited at 360 nm. The absorbance at the
Q-band maximum was maintained below 0.05 to limit the
inner filter effect. The value of FF was calculated using
Equation 1 [26]:
1,4,8,11,15,18,22,25-Octakis(butylsulfanyl)phthalo
cyaninato zinc (II) (1Zn). The compound 1Zn was
prepared from 1H (49 mg, 0.04 mmol) according to
the general procedure for synthesis of zinc complexes.
Mobile phase: chloroform (Rf = 0.10). Yield 45 mg
(91%) of green solid. UV-vis (THF): lmax, nm (log e)
1
779 (5.17), 699 (4.57), 507 (sh), 359 (4.68). H NMR
(300 Hz, CDCl3/pyridine-d5): d, ppm 7.76 (broad s, 8H,
ArH), 3.31 (broad s, 16H, SCH2), 2.1–1.89 (m, 16H,
SCH2CH2), 1.82–1.61 (m, 16H, CH2CH3), 1.09 (t, J = 7
Hz, 24H, CH3). 13C NMR (75 Hz, CDCl3/pyridine-d5):
d, ppm 138.24, 129.81, 128.72, 123.69, 31.02, 30.39,
22.12, 13.17. The other analytical data correspond to the
data published in literature [10].
-A R
FS 1−10


FSF = FSF
(1)
S


FR
1−10-A


1,4,8,11,15,18,22,25-Octakis(pentan-3-yl)phthalo-
cyaninato zinc (II) (2Zn). The compound 2Zn was
prepared from 2H (50 mg, 0.038 mmol) according to
where F is the integrated area under the emission spectrum
and A is the absorbance at the excitation wavelength.
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 5–12

6
A. CIDLINA ET AL.
The superscripts R and S correspond to the reference
and sample, respectively. All of the experiments were
performed in triplicate with the reported data representing
the mean (estimated error 15%).
cell, stirred at room temperature and irradiated for total
time 20 min by using halogen lamp (EMOS, 400 W).
The electronic absorption spectra were measured at
defined irradiation time (typically in 5 min periods).
The incident light was filtered through a water filter
(65 mm) to remove the heat from the light source. The
decomposition of a sample was expressed as a relative
decrease of its absorbance at Q-band maximum in time.
All measurements were performed three times and
presented data represent mean of these three experiments.
Simultaneously, control solutions of 1Mg–6Mg were
measured under the same conditions in the dark. No
changes in electronic absorption spectra of control
solutions were observed without irradiation.
Determination of the singlet oxygen production
All of the samples were re-purified using preparative
TLC prior to the measurement to ensure high purity of the
sample (mobile phases are mentioned in Experimental
part). The quantum yields of the singlet oxygen (FD) were
determined in THF according to a previously published
procedure [27] using the decomposition of a chemical
trap 1,3-diphenylisobenzofuran (DPBF) with ZnPc as a
reference (FD = 0.53 in THF [28]). The detailed procedure
was as follows: 2.5 mL of a DPBF stock solution in THF
(5 × 10-5 M) was transferred into a 10 mm × 10 mm
quartz optical cell and saturated with oxygen for 1 min.
Then, a stock solution of the tested compound in THF
(typically 20 mL) was added to achieve an absorbance
of the final solution in the Q-band maximum of approxi-
mately 0.1. The solution was stirred and irradiated
using a xenon lamp (100 W, ozone-free XE DC short-
arc lamp, Newport). The incident light was filtered
through a water filter (6 cm) and an OG530 cut-off filter
(Newport) to remove the heat and light below 523 nm,
respectively. A decrease of DPBF in the solution as a
function of the irradiation time was monitored at 414 nm.
All of the experiments were performed in triplicate, and
the data presented herein represent the mean of the three
experiments (estimated error: 15%).
RESULTS AND DISCUSSION
Synthesis
In general, synthesis of Pcs is performed by cyclotetra-
merization of precursors, usually substituted phthalo-
nitriles. The precursors 2, 3, 4 and 7 (see Scheme 1) were
prepared via nucleophilic substitution according to the
previously published procedures [12, 20–22]. In these
cases, 2,3-dicyano-1,4-phenylene bis(4-methylbenzene-
sulfonate) (8) [23] and appropriate alkylthiolate or
arylthiolate reacted in the presence of K2CO3 as a base
to give required products in reasonable yields 34–66%.
Thiols needed for the nucleophilic substitution were
commercially available besides 1-adamantanethiol which
was prepared from 1-bromoadamantane according to the
reported procedure [29].
Protonation of azomethine nitrogens
A stock solution (2 mL) of 1Zn, 2Zn, 4Zn, 5Zn or 6Zn
(c = 1 mM) in THF was transferred into the 10 × 10 mm
quartz optical cell and absorption spectrum was
recorded. Then, defined amounts (typically 10 or 50 mL)
of trifluoroacetic acid (TFA) were added and absorption
spectra were measured after each addition. The final
concentration of TFA in the sample ranged from 0.0005%
to 21.5% (v/v) (that corresponds to 0.00065–2.82 M).
Trituration of TFA (0.1 mL TFA in 9.9 mL THF) was
employedinsomecasestoreachrequiredlowconcentration
of TFA in the sample. Finally, tetrabutylammonium
hydroxide (TBAH) in THF (c = 100 mM) (10 or 50 mL)
was added to the sample at the maximum of the mono-
protonated form to confirm the reversibility. The presented
data were corrected for dilution. Data are presented by
plotting the absorbance at Q-band maximum as a function
of the TFA concentration. The association constant K was
calculated from the plotted data using nonlinear regression
in Prism 6 for Windows (GraphPad Software, Inc.).
Methods described in literature for synthesis of
precursors 1 [10] and 5 [12] suffered from low yields,
thus, the reaction conditions were optimized. Regarding
precursor 1, tosyl leaving group (i.e. compound 8 as a
starting material) was used instead of triflate leaving
group in 1,2-dicyano-3,6-bis(trifluorosulfonyl)benzene to
improve the yield from published 19% up to 59%. In the
case of precursor 5, we were not able to achieve the 53%
yield employing the published procedure. Thus, various
reaction conditions were tested such as different bases
(K2CO3, NaOH, CsF), reaction temperatures (-12°C,
room temperature, up to reflux), reaction times (3–60 h),
solvents (THF, DMSO), and air/inert atmosphere. The
best yields were obtained in combination of K2CO3,
anhydrous DMSO, argon atmosphere and room
temperature where the yield was improved up to 74%.
Synthesis of metal-free derivatives 1H [10], 3H
[19], 4H [11], 5H [12], were reported in literature and
were based on lithium assisted cyclotetramerization
in alcohols. However, magnesium and zinc complexes
were also the subjects of interest in this study. Therefore,
cyclotetramerization of 1–5 was performed with
magnesium butoxide as an initiator of the reaction leading
to the formation of magnesium complexes 1Mg–5Mg.
Photostability
A stock solution (2.5 mL) of 1Mg–6Mg (c = 2 μM) in
THF was transferred into the 10 × 10 mm quartz optical
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 6–12

THE EFFECT OF SUBSTITUTENTS AT ALKYLSULFANYL/ARYLSULFANYL NON-PERIPHERALLY SUBSTITUTED
7
R
R
R
R
R
R
S
S
S
S
N
N
N
N
OTs
R
1
4
R
R
R
R
R
R
R
R
R
R
R
R
N
N
N
N
N
HN
NC
NC
NC
NC
i)
ii)
iii)
iv)
Mg
Zn
N
N
N
N
N
N
RSH
N
N
NH
N
N
N
2
3
5
7
OTs
R
N
N
S
S
8
1 - 5 or 7
R
R
R
R
R
R
1M - 5M
1M - 5M or 7M
1M - 5M
Scheme 1. Synthetic pathway for target compounds. (i) K2CO3, DMSO, rt, 16 h. (ii) Mg(OBu)2, BuOH, I2, reflux, 24 h. (iii) TsOH,
THF, rt, 30 min. (iv) Zn(OAc)2, pyridine, 60 min
Generally, the magnesium cation can be released from
the center of Pcs under acidic solution. Thus, treatment
of magnesium complexes with p-toluenesulfonic acid
(TsOH) afforded the metal-free derivatives 1H, 2H, 4H
and 5H. Finally, the zinc complexes 1Zn [10], 2Zn [20],
4Zn and 5Zn were synthesized from the corresponding
metal-free derivatives by the reaction with zinc acetate
(Scheme 1). This reaction sequence reduced the tedious
purification after cyclotetramerization to one (purification
of magnesium complexes). The metal exchange
procedures proceeded in high yields with limited amount
of side products that were easily removed. The treatment
of 3Mg with TsOH or trifluoroacetic acid (TFA) caused
rapid decomposition of the macrocycle and no product
formation was registered. Missing stabilization effect
of central cation together with the pronounced steric
hindrance of tert-butylsulfanyl groups leading to the
extremedistortionofthemacrocyclemaybethereasonfor
the instability of such macrocycle. Indeed, low stability
of 3H has been recently pointed out in literature by the
authors who succeeded in isolation of this unstable and
strongly distorted macrocycle [19]. As a consequence,
3H was not prepared despite the fact that different
methods were tried (removal of central magnesium
under acidic conditions, direct cyclotetramerization
using LiOBu as the initiator, etc.) even considering the
method that was recently reported. Also, direct synthesis
of 3Zn via metal cation template effect with zinc acetate
in anhydrous pyridine or quinoline was not successful.
Traces of 3Zn were obtained using cyclotetramerization
in butanol with catalytic amount of DBU and anhydrous
zinc acetate. The structure could not be unequivocally
confirmed and only absorption spectrum was taken. The
position of Q-band at 721 nm in THF (see Fig. S2) was
comparable with 3Mg (724 nm, see Table 1) suggesting,
thus, proper product. Due to the missing analytical data,
this compound was not included in further photophysical
studies.
successful as well. The template method using anhydrous
zinc acetate in high boiling solvent (quinoline, DMF)
also failed and only dark decomposition products were
observed. Lithium butoxide is known as the strongest
initiator of the cyclotetramerization, however, only
traces of presumably metal-free product were detected
by UV/vis absorption spectrum in the reaction mixture
with the Q-band maximum in expected area (Fig. S1).
Nevertheless, the structure could not be confirmed, thus,
this compound was not discussed in the following parts
of the paper. Extreme bulkiness of adamantyl that is even
bigger than tert-butyl most likely produced macrocycle
with even lower stability than for 3H.
Absorption spectra
The electronic absorption spectra of all target
macrocycles were measured in THF and the obtained
data are summarized in Table 1 and Fig. 1. The absorption
spectraofmetalcomplexeshadtypicalhighenergyB-bands
ranging from 340 nm to 430 nm and low energy Q-bands
in range from 724 nm to 793 nm. The sharp and unsplit
Q-bands of all investigated compounds indicated that only
monomeric species are present in solution without any
aggregates. As obvious from Fig. 1, extinction coefficients
were directly proportional to the red-shift of Q-band
ranging for example for magnesium complexes from
120000 M-1.cm-1 (lmax at 724 nm) up to 240000 M-1.cm-1
(lmax at 788 nm). In accordance with non-peripheral
Pcs published in literature [10], Q-bands of all target
compounds (besides 3Mg, that was specific, see below)
were significantly shifted to the red (approx. of 70 nm)
in comparison to similar peripherally substituted Pcs (see
Table 1). The Q-band positions in the series of magnesium
complexes appeared at 724 nm (tert-butylsulfanyl,
3Mg) <<774 nm (pentan-3-ylsulfanyl, 2Mg) ~775 nm
(phenylsulfanyl, 4Mg) ~776 nm (butylsulfanyl, 1Mg)
<788 nm (2,6-dimethylphenylsulfanyl, 5Mg) (Fig. 1,
Table 1). The position of the Q-band of both alkylsulfanyl
and phenylsulfanyl substituents was similar leading to
suggestion of limited effect of phenyl ring on the electronic
structure. This is in agreement with conclusions reported
recently for metal-free 4H [11]. More bulky 5Mg was
red-shifted for more than 10 nanometers in comparison
All attempts to cyclotetramerize precursor
7
bearing bulky 1-adamantylsulfanyl groups either
with magnesium butoxide in butanol or magnesium
octanoxide in octanol failed to produce the desired
product. Cyclotetramerization in butanol with anhydrous
zinc acetate and butoxide generated by DBU was not
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 7–12

8
A. CIDLINA ET AL.
Table 1. Absorption and photophysical data of investigated compounds in THF at room temperaturea
b
b
Cpd.
Substitution
-SBu
Central metal
l
max, nm
lem, nm
Dl, cm-1
FF
FD
K, M-1
1
Mg
2H
Zn
776
805
779
774
802
777
724
775
802
779
788
817
793
699
697
801
840
806
802
840
804
758
799
834
804
805
845
812
709
707
402
517
430
451
564
432
620
388
478
399
268
406
295
202
203
0.13
0.49
0.052
0.75
0.51
0.096
0.76
0.47
0.47
0.064
0.74
0.48
0.049
0.74
0.23
0.68
0.048
0.069
0.10
513
493
2
-S(pentan-3-yl)
Mg
2H
Zn
0.032
0.053
0.10
3
4
-StBu
Mg
Mg
2H
Zn
-SPh
0.17
0.061
0.080
0.12
6.11
5
-S(2,3-Me2)Ph
Mg
2H
Zn
0.064
0.076
0.23
9.34
0.53
6 [25]
-StBu
Mg
Zn
0.16
aAbsorption maximum at Q-band (lmax), emission maximum (lmax), stokes shift (Dl), quantum yield of singlet
oxygen production (FD), quantum yield of florescence (FF), association constant of reaction with TFA in THF
(K). b Mean of three independent measurements, estimated error 15.
52 nm in comparison to 1Mg was observed and does not
correspond with the distortion effect leading to small
red-shift reported often in literature. This effect may be
attributed to extreme distortion of the Pc macrocycle
caused by steric hindrance of bulky tert-butyl substituents.
The extreme distortion of metal-free Pc with the same
substitution (3H) was recently demonstrated by X-ray
structure, and the hypsochromic shift of its Q-band
maximum (750 nm in THF, i.e. shift of 55 nm compared
to hexylsulfanyl derivative) was explained to be due to
decreased conjugation potency of the benzo rings to the
central pyrrolic rings [19]. Interestingly, the reported blue
shift of 55 nm between tert-butylsulfanyl and hexylsulfanyl
derivatives in metal-free Pcs is exactly the same as the blue
Fig. 1. Electronic absorption spectra (1 mM) of 1Mg (green
dashed line), 2Mg (red dotted line), 3Mg (blue double dot-
dashed line), 4Mg (purple dot-dashed line) and 5Mg (black
full line) in THF. Inset: enlarged Q-band area of normalized
absorption spectra
shift observed in our series in magnesium Pcs substituted
with tert-butylsulfanyl (3Mg) and butylsulfanyl (1Mg)
indicating similarly decreased conjugation.
The similar dependences described above for
magnesium complexes were observed also for zinc and
metal-free derivatives (Figs S1 and S2). Considering the
metal-free derivatives, they had the absorption maxima
over 800 nm with sharp unsplit shape of Q-band. Despite
the loss of macrocycle symmetry due to presence of
central hydrogens, unsplit character of spectra is typical
for metal-free Pcs absorbing in near-infrared region [11].
to 4Mg. Origin of the shift may have two explanation.
The more bulky 2,6-dimethylphenyl substituent may
lead to slightly more distorted macrocycle than in case
of 4Mg. The distortion of the Pc ring in non-peripherally
substituted derivatives was reported several times to
lead to small bathochromic shift [11, 15]. Alternatively,
the pushing effect of methyls in ortho positions may
contribute to a small red shift. Unexpectedly, significant
hypsochromic shift of absorption maxima of 3Mg of
Fluorescence and singlet oxygen quantum yields
Fluorescence emission and singlet oxygen production
were studied in THF because of good solubility and
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 8–12

THE EFFECT OF SUBSTITUTENTS AT ALKYLSULFANYL/ARYLSULFANYL NON-PERIPHERALLY SUBSTITUTED
9
32], thus, their FF and FD were significantly lower in
comparison to metal complexes.
Protonation of azomethine nitrogens
The protonation of azomethine nitrogens is usually
deduced from the typical changes in electronic
Fig. 2. Normalized emission spectra of 1Mg (green dashed
line), 2Mg (red dotted line), 3Mg (blue double dot-dashed
line), 4Mg (purple dot-dashed line) and 5Mg (black full line) in
THF. Spectra are corrected for the instrument response
non-aggregating behavior of target compounds in this
solvent. The quantum yields of fluorescence (FF) and
singlet oxygen quantum yields (FD) were determined
using unsubstituted zinc phthalocyanine (ZnPc, FF(THF)
=
0.32 [25] and FD(THF) = 0.53 [28]) as a reference. The
shape of the emission spectra were typical for Pcs with a
small Stokes shift (Figs 2 and S3). The excitation spectra
were also recorded and they perfectly mirrored the
absorption spectra which proves only monomeric forms
of Pcs in the solution without presence of any aggregates
(Figs S4 and S5). Thus, the FF and FD determination was
not affected by aggregation at all. The obtained data are
summarized in the Table 1. The different substitution of
target compounds within the series did not significantly
affected photophysical properties and the values of FF
and FD differed only in relation to the central metal
following the rule of heavy atom effect [30]. According
to this rule, the presence of heavy atoms in the molecule
increases the probability by which the compound
undergoes intersystem crossing that leads to the higher
singlet oxygen production and a concomitant decrease of
other competitive relaxation pathways, e.g. fluorescence
emission. Therefore, magnesium complexes 1Mg–5Mg
reached values of FF in the range of 0.10–0.17 while zinc
complexes in the range of 0.053–0.080 only. Regarding
FD, zinc complexes of target Pcs possessed higher
values (0.74–0.76) than their corresponding magnesium
derivatives (0.47–0.51). Interestingly, the strong
steric distortion of 3Mg macrocycle did not influence
significantly the photophysical properties that were
fully comparable with other magnesium complexes in
the series. In comparision to corresponding peripherally
substituted Pc (i.e. 6Zn), it was obvious that shifting
the substituent to the non-peripheral positions caused
significant improvement of singlet oxygen production
(6Zn of FD is 0.65 only) on the account of fluorescence
emission (FF of 6Zn is 0.28). Metal-free Pcs usually
dissipate energy also by different pathways [25, 31,
Fig. 3. (a) Changes in absorption spectra of 2Zn in THF (1 μM)
after addition of TFA. Spectra are corrected for dilution; (b)
Decrease of absorbance at Q-band maxima of 1Zn (green full
line, open circle), 2Zn (red full line, cross), 4Zn (purple full
line, full circle), 5Zn (black full line, full square) and 6Zn
(black dashed line, open triangle) in THF (1 mM) after stepwise
addition of TFA. Absorbance at Q-band was normalized to be
one for each sample solution without TFA
Copyright © 2015 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2015; 19: 9–12

10
A. CIDLINA ET AL.
absorption spectra such as decrease of Q-band maximum
and formation of a new red-shifted band [33, 34]. The
zinc complexes were chosen for the purposes of this
study because magnesium complexes may undergo
undesirable demetalation under acidic conditions.
Compound 6Zn was introduced into the study to enable
comparison with similarly peripherally substituted Pc.
Stepwise addition of TFA into the THF solution of
studied compounds led to decrease of Q-band maximum
with concomitant increase of absorption close to 900 nm
(Figs 3a and S6). Unfortunately, the formation of
the new red-shifted band could not be optimally
studied due to the limitation of instrument. However,
presence of several isosbestic points in the spectra
clearly confirmed the formation of mono-protonated
form from non-protonated one and also showed that
the decrease of Q-band maximum was not caused by
decomposition of the sample but can be attributed
solely to the protonation of azomethine nitrogens atom.
Finally, tetrabutylammonium hydroxide was always
added into the solution of mono-protonated form of
studied compounds leading to the restoration of original
Q-band shape. This fact confirmed reversibility of the
whole process without decomposition.
Absorbance in Q-band maximum during titration was
plotted as a function of acid concentration (Fig. 3b) and
association constants (K) of Pcs reaction with TFA in
THF were calculated (Table 1). As obvious from Fig. 3b
and K values, basicity of the azomethine nitrogens
was found to be extremely different within the series.
The strongest basicity was observed for alkylsulfanyl
derivatives 1Zn and 2Zn with K in a range of ~500 M-1.
Steric effects in arylsulfanyl derivatives 4Zn and 5Zn
are a likely cause of somewhat lower basicity of their
azomethine nitrogens with K in the range of ~10 M-1 that
is, however, still far above the basicity of the nitrogens
in peripherally substituted 6Zn with K = 0.53 M-1.
Increased basicity of non-peripherally substituted Pcs
over the peripherally substituted ones has already been
noted in literature [4, 34]. In particular, for alkyloxy
derivatives it was explained by stabilization of the
protonated forms by intramolecular hydrogen bonds
between proton attached to the azomethine nitrogen and
either oxygen [34]. Although the hydrogen bonding is not
expected with the sulfur atoms, the distance between the
sulfurs in adjacent units of non-peripherally substituted
Pcs has been reported to be close to twice the van der
Waals radius [12] of the chalcogen and that is why the
van der Waals interaction may stabilize the azomethine
protonated form. Such interaction is obviously missing in
peripherally substituted Pcs. On the other hand, different
basicity of present series can be the result of different
distortion of the macrocycle. Indeed, substantially
increased basicity of nitrogens in highly distorted non-
peripherally octaphenyl substituted metal-free and zinc
Pcs has been reported [34, 35]. However, clear evidence
for presented compounds cannot be given now. Evidently,
Fig. 4. Changes in absorption spectra after light irradiation of
(a) 2Mg and (b) 1Mg in THF (2 mM) at rt; (c) Photostability of
1Mg (green full line, open circle), 2Mg (red full line, cross),
3Mg (blue full line, full triangle), 4Mg (purple full line, full
circle), 5Mg (black full line, full square) and 6Mg (black dashed
line, open triangle) after light irradiation (EMOS, 400 W)
in THF at rt
the definite explanation of different basicity of target Pcs
is challenging and needs to be studied further.
Photostability
Photobleaching of Pcs and related compounds upon
light irradiation is a well-known undesirable feature.
Copyright © 2015 World Scientific Publishing Company
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THE EFFECT OF SUBSTITUTENTS AT ALKYLSULFANYL/ARYLSULFANYL NON-PERIPHERALLY SUBSTITUTED
11
Decomposition of 1Mg–5Mg on light was observed
even during synthesis and storing the samples that was
why the products were kept in the dark. The extent of
photobleaching was studied in THF by the mean of
absorption spectroscopy. Compound 6Mg was introduced
into the study to compare the photostability of non-
peripherally substituted Pcs with similar peripherally
substituted Pc. The significant decrease of absorbance
at all wavelength without any new-band formation was
observed after irradiation in almost all cases (Figs 4a and
S7) suggesting full decomposition of the macrocycles
to small molecules. Only in the case of 1Mg, the
decrease in Q-band maximum was accompanied by its
blue shift for 10 nm (Figs 4b and S7a). Considering the
fact that alkylsulfonyl Pcs are typically blue shifted in
comparison to alkylsulfanyl Pcs [36], this blue shift in
1Mg during decomposition can be attributed to oxidation
of thioethers to alkylsulfinyl and alkylsulfonyl groups.
This was detected only for the Pc with the least sterically
demanding substituent (n-butylsulfanyl) indicating that
the photooxidation of the thioether linkage in Pcs is
inhibited by more bulky substituents. The decrease of
absorbance in the Q-band maximum was subsequently
plotted as a function of time and is depicted in Fig. 4c.
Non-peripherally substituted Pcs proved to be less stable
than peripherally substituted 6Mg. The photostability
increased in series 5Mg < 4Mg < 2Mg < 1Mg < 3Mg
 6Mg. These data are in accordance with the literature,
where macrocycles absorbing at higher wavelengths
are usually less photostable [14, 15]. Arylsulfanyl
substituted Pcs showed more pronounced decomposition
upon light exposer than the alkylsulfanyl as almost
complete decomposition of the macrocycles 4Mg and
5Mg was observed within less than 15 min of irradiation.
The control samples of 1Mg–6Mg kept under the same
conditions but in the dark showed no change in their
absorption spectra.
of shifting the absorption maximum to the red part of the
spectrum due to increased distortion of the macrocycle
[11, 12, 16]. In the case of 3Mg, the extreme distortion
of the macrocycle disrupted probably the p-electron
system of the macrocycle similarly as published recently
by Dumoulin at co-workers for the corresponding metal-
free Pc [19].
Bulkiness and the type of non-peripheral substituent
(alkylsulfanyl vs. arylsulfanyl) did not affect the
photophysical properties such as quantum yields of
singlet oxygen production and fluorescence emission
and the values of FD and FF differed only in respect
to the central metal following the rule of heavy atom
effect. Interestingly, FD values of non-peripherally
substituted Pcs reached significantly higher values than
for similar peripherally substituted Pcs that make them
promising candidates to be used as photosensitizers in
photodynamic therapy. However, the choice of a properly
bulky non-peripheral substituent should be considered
to achieve desirable red shift of absorption maxima and
diminish aggregation, but concurrently to avoid excessive
distortion of macrocycle, which could cause reverse
hypsochromic spectral shift.
The basicity of azomethine nitrogens was clearly
dependent on the position and also the character of
substituent. Thus, non-peripherally substituted Pcs
showed increased basicity than similar peripherally
substituted ones with K values in THF higher for several
orders of magnitude. Furthermore, the basicity was
even more pronounced at alkylsulfanyl derivatives than
arylsulfanyl most likely due to steric effects.
The target compounds were shown to be more prone
to photodecomposition than corresponding peripherally
substituted Pc with the pronounced decomposition at
arylsulfanyl derivatives.
Acknowledgements
This work was supported by Czech Science
Foundation (No. 13-27761S) and Charles University in
Prague (SVV 260 183). The authors would like to thank
Jiří Kuneš for the NMR measurements, and Juraj Lenčo
for the MALDI-TOF MS measurements.
CONCLUSION
A series of magnesium, zinc and metal-free non-
peripherally alkylsulfanyl and arylsulfanyl substituted
Pcs was prepared and their spectral and photophysical
properties were studied. Their properties (i.e. position
of Q-band maximum, FD and FF, basicity of azomethine
nitrogens, photostability) were compared within the
series as well as discussed in comparison with similar
peripherally substituted Pcs.
Supporting information
Figures S1–S7 are given in the supplementary material.
This material is available free of charge via the Internet at
http://www.worldscinet.com/jpp/jpp.shtml.
In accordance with literature data, the shifting of
the substituents from peripheral to non-peripheral
positions of Pc caused ~70 nm red-shift of Q-band.
However, unexpected blue shift of approximately 50 nm
was observed for 3Mg bearing extremely bulky tert-
butylsulfanyl substituents compared to 1Mg bearing
n-butylsulfanyl groups. This interesting phenomenon
contradicts the well-known widely described knowledge
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