Novel Cyanoarylporphyrazines with Triazole Groups at the Macrocycle Periphery as Potential Sensibilizers of Photodynamic Therapy and Optical Probes of Intracellular Viscosity

Article abstract of DOI:10.1134/S1070363218110154

Novel fluorescent dyes of the cyanoarylporphyrazine series containing peripheral triazole groups have been synthesized. Their photophysical properties and the local viscosity effect on the fluorescence have been studied. The experiments with cell cultures have revealed rapid accumulation of the dyes in the cells cytoplasm. Photo- and dark cytotoxicity of the compounds have been evaluated by means of the MTT test.

Full text of DOI:10.1134/S1070363218110154

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 11, pp. 2339–2346. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © S.A. Lermontova, I.S. Grigoryev, N.N. Peskova, I.V. Balalaeva, V.P. Boyarskii, L.G. Klapshina, 2018, published in Zhurnal
Obshchei Khimii, 2018, Vol. 88, No. 11, pp. 1862–1870.
Dedicated to the 115th anniversary of B.A. Arbuzov’s birth
Novel Cyanoarylporphyrazines with Triazole Groups
at the Macrocycle Periphery as Potential Sensibilizers
of Photodynamic Therapy and Optical Probes
of Intracellular Viscosity
a,b
a
b
S. A. Lermontova , I. S. Grigoryev , N. N. Peskova ,
b
c
a,b
I. V. Balalaeva , V. P. Boyarskii , and L. G. Klapshina *
a
Razuvaev Institute of Organometal Chemistry, Russian Academy of Sciences, ul. Tropinina 49, Nizhny Novgorod, 603137 Russia
*
e-mail: klarisa@iomc.ras.ru
b
Lobachevskii Nizhny Novgorod State University, Nizhny Novgorod, Russia
c
St. Petersburg State University, St. Petersburg, Russia
Received September 13, 2018
Abstract—Novel fluorescent dyes of the cyanoarylporphyrazine series containing peripheral triazole groups
have been synthesized. Their photophysical properties and the local viscosity effect on the fluorescence have
been studied. The experiments with cell cultures have revealed rapid accumulation of the dyes in the cells
cytoplasm. Photo- and dark cytotoxicity of the compounds have been evaluated by means of the MTT test.
Keywords: porphyrazines, template synthesis, ytterbium complexes, photosensibilizers, optical probes of
intracellular viscosity
DOI: 10.1134/S1070363218110154
Tetrapyrrole macrocycles are important compounds
fragment significantly improves the efficiency of
cycnoarylporphyrazine dyes as PDT sensibilizers.
in modern bioorganic chemistry, since they exhibit the
property of selective accumulation in a tumor tissue and
production of singlet oxygen (inducing cascade of
oxidation reactions of cellular components resulting in
the cancer cells death) under irradiation at a proper
wavelength [1]. This concept lays the foundation of
photodynamic therapy (PDT) of oncological diseases.
In contrast to the porphyrins and phthalocyanines
which have been widely applied as PDT agents [2–6],
photosensitizing properties of porphyrazines in the
form of free bases have been less studied [7–9]. The
data on photodynamic activity of tetraaryltetracyano-
porphyrazines have been absent until quite recently
To elucidate the influence of the n-donor nitrogen
atoms introduced in the aryl substituent on the photo-
dynamic activity of porphyrazine, we herein synthesized
novel cyanoarylporphyrazine dyes containing triazole
moieties in the aryl substituents of the macrocycle. We
studied their photophysical properties, the rate of
accumulation in cancer cells, and cytotoxicity under
irradiation and in dark. Overall, we demonstrated the
prospects of those macrocycles use as photosensibilizers
of PDT. As other cyanoarylporphyrazines synthesized
by us [10–13], novel compounds of that series exhibited
high sensitivity of the fluorescence parameters to local
viscosity of their surrounding, which can be utilized in
the development of optical viscosity probes.
[
10, 11]. We have earlier reported the synthesis of
cyanoarylporphyrazines containing para-fluorophenyl
1) and para-benzyloxy (2) groups in the aryl frame of
(
the macrocycle (Scheme 1) [10, 12]. The experiments
with cancer cell cultures have revealed that the
incorporation of n-donor oxygen atom in the aryl
To prepare the cyanoarylporphyrazine bases using
click chemistry methods, we synthesized arylcarbal-
dehydes 5 and 6 bearing a propargyl group.
2
339

2
340
LERMONTOVA et al.
reference. The introduction of triazole group led to
Scheme 1.
noticeable shift of the absorption maximum to longer
wavelength as compared to porphyrazine 1. That
ensured better optical transparency of biological tissue
under irradiation, favorable for PDT.
R
CN
N
NC
R
R
NH
N
N
N
N
A unique feature of cyanoarylporphyrazines is the
combination of high photodynamic activity with strong
sensitivity of the fluorescence parameters to the
medium viscosity. Such fluorescent dyes known as
HN
CN
N
“
molecular rotors” are transformed into the dark state
NC
F
R
1
, 2
(when the excitation energy is fully or partially
consumed on the internal rotation of the fluorophore
molecule rather than fluorescence) upon photo-
excitation in the low-viscosity medium. High local
viscosity of the molecular rotor surrounding prevents
the intermolecular movement, and therefore the
intensity of fluorescence of such molecules is strongly
increased in high-viscous media [14, 15]. The Förster–
Hoffman equation (1) relates quantum yield of
fluorescence (φ) with the solvent viscosity (η), z and α
being numerical parameters.
R =
(1),
O
(2).
Aryltricyanoethylenes prepared from arylcarbalde-
hydes 7 and 8 bearing a triazole fragment (Scheme 2)
were used as starting materials for template self-
assembly of the porphyrazine macrocycle. Method of
the synthesis of free cyanoarylporphyrazine bases is
shown in Scheme 3.
log φ = z + αlog η.
(1)
The described synthetic route has been used by us
earlier [12, 13], and it should be noted that the use of
triazole-containing benzaldehydes as the precursors
did not deteriorate the synthetic capability of the
elaborated approach.
Similar equation is known for another fluorescence
property, lifetime of the excited state τ [Eq. (2)] [16] (η
being viscosity, z and α being numerical parameters,
and k being the rate constant of the emitting transition).
r
log τ = log (z/k
r
) + αlog η.
(2)
Table 1 displays spectral parameters of porphyra-
zines 17 and 18 in water; the data for tetra(4-
fluorophenyl)tetracyanoporphyrazine 1, photophysical
properties and photodynamic properties of which have
been described in detail in earlier [10], are given for
It has been earlier shown that tetra(4-fluorophenyl)-
tetracyanoporphyrazine 1 is a typical fluorescent
molecular rotor [10]. Its high photodynamic activity as
well as the possibility of its use as a sensitive optical
Scheme 2.
O
H
O
Cl
HO
O
H
R
R
3
, 4
5, 6
N3
O
H
O
N
N
N
R
7
, 8
R = H (3, 5, 7), OEt (4, 6, 8).
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NOVEL CYANOARYLPORPHYRAZINES WITH TRIAZOLE GROUPS
2341
Scheme 3.
R
H
R
H
CN
CN
R
CN
CN
R
CN
CN
CH (CN)
KCN, HCl
NCS
2
2
O
NC
NC
7
, 8
9, 10
11, 12
13, 14
O
O
Yb
R
R
CN
CN
N
NC
NC
R
C
NH
N
N
R
CN
N
N
N
N
NC
R
TFA
N
N
N
HN
N
Yb
N
N
N
R
CN
N
R
CN
N
NC
R
NC
R
1
7, 18
15, 16
N
N
R =
O
(7, 9, 11, 13, 15, 17),
(8, 10, 12, 14, 16, 18).
OEt
N
N
N
O
sensor for intracellular viscosity have been demon-
strated in the experiments with cancer cells culture. In
is turn, this opens the possibility to perform real-time
monitoring of cancer cells death from the change in the
fluorescence parameters, since the intracellular vis-
cosity is strongly increased during photodynamic
action [17].
experiments. Using the strong red fluorescence signal,
we determined that the introduced sensibilizer was
accumulated in the cytoplasm of the А431 cells
(epidermoid carcinoma of human skin) near the
nucleus and in the nuclear shell. Accumulation of the
Table 1. Maximums of absorption and fluorescence in red
spectral range and quantum yield of fluorescence of the
prepared porphyrazines 17, 18, and 1 in water (c = 4 μmol/L)
The parameter α reflecting the sensitivity of
fluorescence of the molecular rotors to viscosity is of
Porphyrazine
17
593
4.32
640
0.2
18
591
4.38
650
0.19
1 [10]
579
4.42 [11]
650
0.3
0
.3–0.6 [15]. The data in Fig. 1 show that porphyra-
λ
max (Q-band), nm
zines containing triazole fragments in the cyanoaryl-
porphyrazine macrocycle exhibited the sensitivity to
viscosity close to that for the reference compound 1.
The in vitro studies demonstrated that both prepared
porphyrazines were readily accumulated in the cells.
To confirm the accumulation of the macrocycles in
cancer cells, we performed fluorescence microscopy
log ε
λ
fl, nm (λex = 590 nm)
а
φ , %
a
Quantum yield of fluorescence was referenced to cresol violet (λex
590 nm).
=
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 11 2018

2
342
LERMONTOVA et al.
porphyrazines with triazole fragments in the aryl
substituent exhibited pronounced photodynamic
activity and could be used as photosensibilizers for
PDT. As for the benzyloxy derivatives [12], the
compounds investigated in this study revealed the
reduced dark cytotoxicity in comparison with
porphyrazine 1 [10], which is favorable for the
application in optical anticancer therapy, since this
factor will reduce the damage of healthy tissues in the
absence of irradiation. On the other hand, it should be
noted that the data in Table 2 showed that the triazole-
containing cyanoarylporphyrazines revealed certain
increase in the inhibiting concentration of the photo-
sensibilizer under irradiation conditions [IC (light)],
Viscosity, cP
Fig. 1. Quantum yield of porphyrazines 1, 17, and 18 as
50
function of the medium viscosity.
meaning weakening of the photodynamic effect.
Nevertheless, the obtained data unambiguously
demonstrated that cytotoxicity of novel potential
photosensibilizers containing triazole fragments in the
aryl substituent was largely caused by the photo-
induced cell death rather than the inherent toxicity of
the compounds. That was evidenced by the sufficiently
high ratio IC50(dark)/IC50(light), so called therapeutic
index. This parameter is important, yet the success of
photodynamic therapy is often determined by the
ability of the photosensibilizer to kill cancer cells and
simultaneously induce the systemic immune reaction
of the organism thus coping with the secondary
neoplasms [19]. The probability of such response
cannot be predicted from the MTT test results, since
the massive immune response can be triggered by the
type of the cell death [20]. The cyanoarylporphyrazine
pigments being developed in our research group
exhibit simultaneously the properties of efficient PDT
photosensibilizers and fluorescent molecular rotors;
this opens the way to investigate special features of the
porphyrazines in the tumor cells in the course of the
incubation of the cells culture is shown in Fig. 2. It is
to be seen that porphyrazines 17 and 18 were readily
accumulated by the tumor cells within first 60 min
after their introduction in the culture.
To estimate the photodynamic activity of the novel
tetraaryltetracyanoporphyrazines, we quantified their
dark and photoinduced cytotoxicity towards the A431
cells. Those parameters can be determined using the
MTT test [18], that is the measurement of
concentration of the drug inducing the suppression of
the cells growth or their death by 50% (inhibiting
concentration IC ). That value was measured in dark
5
0
and under light irradiation. Figure 3 displays the plots
of metabolic activity (viability) of the A431 cells as
function of the concentration of porphyrazine 17 (a)
and 18 (b) in dark and under light irradiation; the
measured IC50 values are collected in Table 2. The
obtained data revealed that the novel cyanoaryl-
(
а)
(b)
Incubation time, min
Incubation time, min
Fig. 2. Accumulation of porphyrazine 17 (a) and 18 (b) as function of the incubation time.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 11 2018

NOVEL CYANOARYLPORPHYRAZINES WITH TRIAZOLE GROUPS
а) (b)
2343
(
Concentration, M
Concentration, M
Fig. 3. Metabolic activity (viability) of the A 431 cells as function of the concentration of porphyrazine 17 (a) and 18 (b) in the
2
medium in dark and during irradiation with 635 nm light at dose 20 J/cm .
cancer cells death in real time from the changes in the
intracellular viscosity. This may allow distinguishing
the types of cell death and reveal their relationship to
the efficiency of therapeutic action.
0.5 mg/mL, and the cells were incubated during 4 h.
The medium was removed, and the formed colored
crystals of MTT-formazan were dissolved in 100 μL of
DMSO. The absorbance of the solutions at 570 nm
was read using a Synergy MX plate spectrophotometer
(BioTek, USA). Cells viability was estimated from the
ratio of absorbance of the formazan solution in the
sample to that in the reference (without irradiation and
without porphyrazine). When dark cytotoxicity was
determined, the samples were not irradiated.
EXPERIMENTAL
IR spectra of the suspensions in Vaseline oil were
recorded using an FSM 1201 spectrometer. Electronic
absorption spectra were recorded using a PerkinElmer
1
Lambda 25 spectrometer. Н NMR spectra were
To investigate the dynamics of porphyrazines 17
and 18 accumulation, the cells were incubated
overnight in a 96-well plate with glass bottom (8000
cells per a well). Then the medium was exchanged
with the medium containing 5 μmol/L of porphyrazine
recorded using a Bruker Avance II+ instrument [400
1
13
(
H), 100 ( C)] at 25°С. Steady-state fluorescence was
studied using a PerkinElmer LS 55 spectrometer
(
(
wavelength range 300–800 nm). Mass spectra
MALDI TOF) were obtained using a Bruker Microflex
1
5
1
7 or 18. Fluorescence of the samples (excitation at
90 nm and registration at 640 nm) was measured 5,
0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 270,
LT mass spectrometer. Dynamic viscosity of the binary
ethanol(methanol)–glycerol mixtures was measured
using an SVM 3000 Stabinger viscometer (Anton Paar)
with accuracy ±0.35%. Dissolution of porphyrazines
was performed by mechanical stirring and ultrasonication
during at least 15 min.
and 300 min after addition of the dye, without removal
or washing of the cells (since the fluorescence was
multiply enhanced in the cells in comparison with the
medium). The spectrum of porphyrazine in the medium
was recorded independently. The accumulation values
were normalized to the signal obtained 300 min after
the compound addition.
Viability of the cell culture was estimated by means of
the MTT assay [18]. The cells were plated on a 96-well
plate (4000 cells per a well) and incubated overnight.
After that, the medium was replaced with 100 μL of
the medium containing porphyrazine 17 or 18 in the
appropriate concentration. The cells were incubated
during 4 h, and then the medium was exchanged with a
fresh portion. The cells were illuminated using a light
Table 2. The IC50 values of photodynamic activity and dark
toxicity of porphyrazine with different peripheral aryl groups
IC50(light), IC50(dark),
Porphyrazine
IC50(dark)/IC50(light)
mol/L
mol/L
diode array to ensure uniform irradiation of the plate
–
7
6
6
6
–6
2
1
2
1
[10]
[12]
8.0×10
1.0×10
2.7×10
3.5×10
6.9×10
4.0×10
3.0×10
2.5×10
8.6
40.0
11.1
7.1
[
21]. The irradiation dose was 20 J/cm (615–635 nm) at
2
–
–
–
–5
–5
–5
the areal power 20 mW/cm . 24 h after the irradiation,
-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium
3
7
bromide (МТТ reagent, Alfa Aesar, UK) was
introduced to the medium up to the final concentration
18
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 11 2018

2
344
LERMONTOVA et al.
Synthesis and analysis of the compounds were
300 μL of freshly prepared 1 M. aqueous solution),
CuSO ·5H O (0.06 mmol), and 24 mL of a tert-
butanol–water mixture (1 : 2) was stirred at room
temperature during 20–24 h, diluted with 100 mL of
water, and cooled. The precipitate was filtered off,
washed with water several times, and dried.
performed using anhydrous solvents. 4-Hydroxybenz-
aldehyde, ethylvaniline, propargyl chloride, benzyl
chloride, sodium azide, malonodinitrile, and N-chloro-
succinimide were purchased from Sigma Aldrich. Bis-
4
2
(
indenyl)ytterbium was prepared as described else-
where [22].
4-[(1-Benzyl-1,2,3-triazol-4-yl)methoxy]benzalde-
Benzyl azide was prepared according to the
procedure in [23]. A mixture of 20 mL of ethanol,
mL of water, benzyl chloride (25 mmol) and sodium
azide (38 mmol) was stirred at boiling (95°С) during
0–24 h. After cooling down, the mixture was diluted
hyde (7). Yield 92%, light pink solid, mp 104–105°С.
1
H NMR spectrum (CDCl ), δ, ppm: 5.28 s (2H,
3
3
CH N), 5.56 s (2H, CH O), 7.10 d (2H, J = 8.7 Hz),
2
2
7.30–7.31 m (2H), 7.38–7.40 m (3H), 7.58 s (1H,
1
3
2
CHN), 7.84 d (2H, J = 8.7 Hz), 9.89 s (1H, СНО). C
NMR spectrum (CDCl ), δ , ppm: 54.34, 62.20,
with 100 mL of water. The product was exctracted
with a CH Cl –hexane mixture (3×30 mL). The extract
3
С
115.10, 122.83, 128.15, 128.91, 129.20, 130.38,
131.97, 134.32, 143.65, 163.13, 190.74. Mass spectrum
2
2
was washed several times with saturated solution of
NaCl, and then the solvent was distilled off under
+
+
(ESI ), m/z: 316.1048 [M + Na] .
1
reduced pressure. Yield 82%. H NMR spectrum
4-[(1-Benzyl-1,2,3-triazol-4-yl)methoxy]-3-ethoxy-
(
CDCl ), δ, ppm: 4.38 s (2H), 7.35–7.45 m (5H).
3
benzaldehyde (8). Yield 89%, light grey solid, mp 124–
1
Aldehydes 5 and 6 were synthesized via alkylation
125°С. H NMR spectrum (CDCl ), δ, ppm: 1.44 t
3
of 4-hydroxybenzaldehyde and ethylvaniline via a
procedure adopted from [24]. A mixture of 15 mL of
DMF, the aldehyde (25 mmol), propargyl chloride
(3H, СН CH О, J = 7.0 Hz), 4.13 q (2H, СН CH О,
3
2
3
2
J = 7.0 Hz), 5.36 s (2H, CH N), 5.54 s (2H, CH O),
2
2
7.20 d (1H, J = 7.9 Hz), 7.26–7.28 m (2H), 7.37–7.43
1
3
(
24 mmol), K СО (25 mmol), and KI (0.25 mmol)
m (5H), 7.58 s (1H, CHN), 9.84 s (1H, СНО).
C
2
3
was stirred at 40°С during 20–24 h. After cooling
down to ambient temperature, 100 mL of water was
added. The precipitate was filtered off, washed with
water several times, and dried.
NMR spectrum (CDCl ), δ , ppm: 14.61, 54.30, 63.18,
3
С
64.50, 110.69, 113.22, 122.98, 126.43, 128.14, 128.87,
129.16, 130.69, 134.33, 149.34, 153.30, 190.95. Mass
+
+
spectrum (ESI ), m/z: 360.1316 [M + Na] .
4
-(Prop-2-yn-1-yloxy)benzaldehyde (5). Yield 72%,
Aryltricyanoethylenes were prepared as described
in [26]. 0.56 g (10 mmol) of malonodinitrile and
2 drops of piperidine were added to a solution of
10 mmol of arylbenzaldehyde 7 or 8 in 100 mL of
EtOH. The reaction mixture was stirred during 24 h at
room temperature. The precipitate was filtered off,
washed with water (4×80 mL), and dried at room
temperature under reduced pressure.
1
white crystals, mp 78–80°С. H NMR spectrum
CDCl ), δ, ppm: 2.59 t (1H, HC≡СCH О, J = 2.4 Hz),
.80 d (2H, HC≡СCH О, J = 2.4 Hz), 7.11 d (2H, J =
.7 Hz), 7.88 d (2H, J = 8.7 Hz), 9.92 s (1H, СНО).
C NMR spectrum (CDCl ), δ , ppm: 55.95, 76.37,
(
3
2
4
8
2
1
3
3
С
7
7.55, 115.19, 130.61, 131.89, 162.38, 190.77. Mass
spectrum (ESI ), m/z: 183.0420 [M + Na] .
+
+
4
-(Prop-2-yn-1-yloxy)-3-ethoxybenzaldehyde (6).
2-{4-[(1-Benzyl-1,2,3-triazol-4-yl)methoxy]phenyl}-
1
Yield 90%, white crystals, mp 79–80°С. H NMR
spectrum (CDCl ), δ, ppm: 1.50 t (3H, СН CH О, J =
.0 Hz), 2.57 t (1H, HC≡СCH О, J = 2.4 Hz), 4.18 q
1,1-dicyanoethylene (9). Yield 58%, light yellow solid.
–1
1
IR spectrum, ν, cm : 2226 (C≡N). H NMR spectrum
(CDCl ), δ, ppm: 5.27 s (2H, CH N), 5.55 s (2H,
3
3
2
7
2
3
2
(
2H, СН CH О, J = 7.0 Hz), 4.87 d (2H, HC≡СCH О,
CH O), 7.10 d (2H, J = 8.9 Hz), 7.29–7.31 m (2H),
3
2
2
2
J = 2.4 Hz), 7.17 d (1H, J = 8.2 Hz), 7.44–7.47 m
7.37–7.39 m (3H), 7.57 s (1H, CHN), 7.64 s [1H,
1
3
13
(
2H), 9.88 s (1H, СНО). C NMR spectrum (CDCl ),
CH=C(CN) ], 7.89 d (2H, J = 8.9 Hz). C NMR
3
2
δС, ppm: 14.62, 56.67, 64.56, 76.54, 77.69, 110.78,
13.14, 125.98, 130.99, 149.45, 152.37, 190.94. Mass
spectrum (ESI ), m/z: 227.0679 [M + Na] .
spectrum (CDCl ), δ , ppm: 54.40, 62.33, 79.12,
113.24, 114.32, 115.91, 122.97, 124.47, 128.20,
128.98, 129.24, 133.41, 134.27, 143.14, 158.74, 163.34.
3
С
1
+
+
Synthesis of triazoles was performed via a proce-
dure from [25]. A mixture of the aldehyde (6 mmol),
benzyl azide (6 mmol), sodium ascorbate (0.6 mmol,
2-{4-[(1-Benzyl-1,2,3-triazol-4-yl)methoxy]-3-
ethoxyphenyl}-1,1-dicyanoethylene (10). Yield 81%,
–
1
light yellow solid. IR spectrum, ν, cm : 2224 (C≡N).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 11 2018

NOVEL CYANOARYLPORPHYRAZINES WITH TRIAZOLE GROUPS
2345
1
H NMR spectrum (CDCl ), δ, ppm: 1.43 t (3H,
2-{4-[(1-Benzyl-1,2,3-triazol-4-yl)methoxy]phenyl}-
3
СН CH О, J = 7.0 Hz), 4.11 q (2H, СН CH О, J =
1,1,2-tricyanoethylene (13). Yield 90%, yellow solid.
3
2
3
2
–
1
1
6
7
.9 Hz), 5.35 s (2H, CH N), 5.53 s (2H, CH O), 7.17–
IR spectrum, ν, cm : 2233, 2225 (C≡N). H NMR
spectrum (CDCl ), δ, ppm: 5.30 s (2H, CH N), 5.55 s
2
2
.36 m (8H), 7.62 s (1H, CHN), 7.67 s [1H, CH=C
3
2
1
3
(CN)2]. C NMR spectrum (CDCl ), δ , ppm: 14.53,
(2H, CH O), 7.15–7.40 m (8H), 7.57 s (1H), 8.09 s
3
С
2
1
3
54.44, 63.06, 64.76, 78.78, 112.27, 113.49, 113.65,
114.34, 124.82, 127.92, 128.20, 128.96, 129.21, 130.69,
134.25, 149.28, 153.73, 159.12.
(1H, CHN). C NMR spectrum (CDCl ), δ , ppm:
3 С
54.46 62.56, 88.08, 93.17, 111.86, 113.79, 116.44,
121.80, 123.11, 128.22, 129.03, 129.27, 129.85, 132.47,
1
34.17, 140.29, 164.47. Mass spectrum, m/z (I , %):
rel
+
Synthesis 2-aryl-1,1,2-tricyanoethanes 11 and 12.
.62 g (25 mmol) of KCN dissolved in 80 mL of water
+
+
366 (22) [М] , 367 (75) [М + 1] , 368 (25) [М + 2] .
1
was added to a solution of 2-aryl-1,1-dicyanoethylene
2-{4-[(1-Benzyl-1,2,3-triazol-4-yl)methoxy]-3-
1
2
0 or 12 (12 mmol) in 150 mL of EtOH, and then
40 mL of water was added. The so obtained mixture
ethoxyphentyl}-1,1,2-tricyanoethylene (14). Yield
–
1
67%, yellow solid. IR spectrum, ν, cm : 2224 (C≡N).
1
was stirred during 45 min at room temperature, and
then 6 mL of 37% HCl was added. After cooling on a
water bath, the precipitate was filtered off, thoroughly
washed with water, and dried at room temperature and
reduced pressure.
H NMR spectrum (CDCl ), δ, ppm: 1.45 t (3H,
3
СН CH О, J = 7.0 Hz), 4.11 q (2H, СН CH О, J =
3
2
3
2
6.9 Hz), 5.38 s (2H, CH N), 5.54 s (2H, CH O), 7.28–
2
2
1
3
7.40 m (7H), 7.57 s (1H), 7.64 s (1H, CHN). C NMR
spectrum (CDCl ), δ , ppm: 14.44, 54.42, 63.21,
3
С
6
1
5.04, 87.26, 93,24, 111.72, 113.82, 113.88, 122.16,
23.22, 126.48, 128.22, 129.00, 129.24, 134.19, 140.25,
2
-{4-[(1-Benzyl-1,2,3-triazol-4-yl)methoxy]phenyl}-
1
,1,2-tricyanoethane (11). Yield 95%, white solid. IR
spectrum, ν, cm : 2226 (C≡N). H NMR spectrum
CDCl ), δ, ppm: 4.46 d. d (2H, CHCH, J = 32.1,
–
1
1
142.93, 149.44, 155.11. Mass spectrum, m/z (Irel, %):
+
409 (100) [М] .
(
3
5
.5 Hz), 5.28 s (2H, CH N), 5.53 s (2H, CH O), 7.05 d
Synthesis of ytterbium complexes 15 and 16. A
2
2
(
2H, J = 8.3 Hz), 7.28–7.43 m (9H), 7.54 s (1H, CHN).
solution of 2.3 mmol of the corresponding 2-aryl-1,1,2-
tricyanoethylene 13 or 14 in a degassed THF (5 mL)
was added in small portions under inert atmosphere to
a solution of 0.25 g (0.46 mmol) of bisindenyl
complex of ytterbium(II) in 5 mL of THF. After
1
3
C NMR spectrum (CDCl ), δ , ppm: 29.77, 38.15,
3
С
5
1
4.39, 62.12, 109.64, 115.24, 116.16, 120.76, 123.06,
28.21, 128.96, 129.24, 129.68, 134.31, 143.14, 159.97.
2
-{4-[(1-Benzyl-1,2,3-triazol-4-yl)methoxy]-3-
1
day, the solution was filtered under vacuum. To
ethoxyphenyl}-1,1,2-tricyanoethane (12). Yield 62%,
white solid. IR spectrum, ν, cm : 2226 (C≡N). H
NMR spectrum (CDCl ), δ, ppm: 1.41 t (3H,
СН CH О, J = 6.9 Hz), 4.09 q (2H, СН CH О, J = 7.0
–
1
1
remove the unreacted 2-aryl-1,1,2-tricyanoethylene
and its complex with ytterbium, the obtained solution
was washed with degassed toluene until discoloration.
The product was dried under reduced pressure.
3
3
2
3
2
Hz), 4.32 d. d (2H, CHCH, J = 32.1, 5.5 Hz), 5.28 s
(
7
2H, CH N), 5.53 s (2H, CH O), 6.98–7.39 m (8H),
Synthesis of porphyrazines 17 and 18. A solution
of 0.14 mmol of the corresponding ytterbium complex
15 or 16 in 2 mL of trifluoroacetic acid was stirred at
room temperature during 30 min, and then 30 mL of
water was added. The formed precipitate was centri-
fuged off and thoroughly washed with water to neutral
reaction. The product was purified by column
chromatography (silica gel 60, 40–60 μm, eluent—THF).
2
2
1
3
.61 s (1H, CHN), 7.66 s (1H, CH=C(CN) ). C NMR
2
spectrum (CDCl ), δ , ppm: 14.63, 29.86, 38.68, 54.43,
3
С
6
1
1
3.32, 64.89, 77.22, 109.40, 112.59, 114.93, 115.43,
20.87, 121.19, 123.03, 128.21, 128.95, 129.22, 134.26,
49.88, 149.94.
Synthesis of 1-aryl-1,1,2-tricyanoethylenes 13 and
4. 1.20 g (9.0 mmol) of N-chlorosuccinimide was
1
added to a solution of 2-aryl-1,1,2-tricyanoethane 1 or
2 (6.4 mmol) in 100 mL of Et O. The reaction
Tetra{4-[(1-benzyl-1,2,3-triazol-4-yl)methoxy]-
1
phenyl}tetracyanoporphyrazine (17). Yield 23%,
2
–
1
mixture was stirred at cooling (ice bath). After 1 h,
50 mL of water was added, the organic layer was
separated off, and the mixture was washed with water
3×150 mL). The solvent was removed under reduced
black solid, mp >300°С. IR spectrum, ν, cm : 3394
1
(N–H), 2193 (C≡N), 1603 (C=C); 1218, 1030 (C –O–C).
Ar
Electronic absorption spectrum (H O), λmax, nm: 359
2
(
(Soret band), 593 (Q-band). Mass spectrum, m/z: 1465
+
pressure, and the product was sublimed under reduced
pressure.
[M] . Found, %: C 68.95; H 3.90; N 23.02.
C H N O . Calculated, %: C 68.75; H 3.98; N 22.91.
84
58 24
4
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 11 2018

2
346
LERMONTOVA et al.
Tetra{4-[(1-benzyl-1,2,3-triazol-4-yl)methoxy}-3-
ethoxyphenyl}tetracyanoporphyrazine (18). Yield
Klapshina, L.G., and Kuimova, M.K., J. Mater. Chem.
B), 2015, vol. 3, p. 1089. doi 10.1039/c4tb01678e
11. Lermontova, S.A., Grigor’ev, I.S., Ladilina, E.Y.,
Balalaeva, I.V., Shilyagina, N.Y., and Klapshina, L.G.,
Russ. J. Coord. Chem., 2018, vol. 44, p. 301. doi
(
–
1
2
3
7%, black solid, mp >300°С. IR spectrum, ν, cm :
403 (N–H), 2196 (C≡N), 2879, 2935 (C–H), 1596
(
C=C); 1216, 1037 (C –O–C). Electronic absorption
Ar
1
0.1134/S1070328418040061.
spectrum (H O), λ , nm: 362 (Soret band), 591
2
max
+
12. Lermontova, S.A., Grigor’ev, I.S., Peskova, N.N.,
Ladilina, E.Y., Balalaeva, I.V., Klapshina, L.G., and
Boyarskii, V.P., Russ. J. Gen. Chem., 2017, vol. 87,
no. 3, p. 479. doi 10.1134/S1070363217030173
(
Q-band). Mass spectrum, m/z: 1641 [M] . Found, %:
C 67.56; H 4.41; N 20.67. C H N O . Calculated, %:
92
74 24
8
C 67.22; H 4.54; N 20.45.
1
3. Lermontova, S.A., Grigorev, I.S., Shilyagina, N.Yu.,
Peskova, N.N., Balalaeva, I.V., Shirmanova, M.V., and
Klapshina, L.G., Russ. J. Gen. Chem., 2016, vol. 86,
no. 6, p. 1330. doi 10.1134/S1070363216060189
ACKNOWLEDGMENTS
This study was financially supported by the
Ministry of Education and Science of Russian
Federation (project no. 6.3099.2017) and Russian
Science Foundation (project no. 18-73-00194).
14. Haidekker, M.A. and Theodorakis, E.A., J. Biol. Eng.,
2010, vol. 4, p. 11. doi 10.1186/1754-1611-4-11
1
1
5. Kuimova, M.K., Chimia, 2012, vol. 66, no. 4, p. 159.
doi 10.2533/chimia.2012.159
6. Förster, T. and Hoffmann, G., Zeit. Phys. Chem., 1971,
CONFLICT OF INTERESTS
No conflict of interest was declared by the authors.
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