Conjugates of 3,4-dimethoxy-4-styrylnaphthalimide and bacteriochlorin for theranostics in photodynamic therapy

Article abstract of DOI:10.1007/s11172-020-2885-5

New conjugates of fluorophore based on 3,4-dimethoxy-4-styryl-1,8-naphthalimide and photosensitizer bacteriochlorin e differing in the nature of spacer fragments were synthesized and their spectral-luminescent properties were studied. The conjugates effic

Full text of DOI:10.1007/s11172-020-2885-5

Russian Chemical Bulletin, International Edition, Vol. 69, No. 6, pp. 1169—1178, June, 2020
1169
Conjugates of 3,4-dimethoxy-4-styrylnaphthalimide and bacteriochlorin
,
for theranostics in photodynamic therapy* **
M. A. Zakharko,a P. A. Panchenko, D. P. Zarezin, V. G. Nenajdenko, D. A. Pritmov,
a,b
c
c
d
d
d
a,b
M. A. Grin, A. F. Mironov, and O. A. Fedorova
aA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
8 ul. Vavilova, 119991 Moscow, Russian Federation.
2
Fax: +7 (495) 135 5085. E-mail: Marina_Zr@mail.ru
Mendeleev University of Chemical Technology of Russia,
b
9
Miusskaya pl., 125047 Moscow, Russian Federation
c
Lomonosov Moscow State University, Department of Chemistry,
Build. 3, 1 Leninskie Gory, 119991 Moscow, Russian Federation
d
Moscow Technological University,
M. V. Lomonosov Institute of Fine Chemical Technologies,
8
6 prosp. Vernadskogo, 119571 Moscow, Russian Federation
New conjugates of fluorophore based on 3,4-dimethoxy-4-styryl-1,8-naphthalimide and
photosensitizer bacteriochlorin е differing in the nature of spacer fragments were synthesized
and their spectral-luminescent properties were studied. The conjugates efficiently generate
singlet oxygen in solution, however, the emission of the naphthalimide fragment of the conju-
gates is quenched to varying degrees as a result of the photoexcitation energy transfer to bacterio-
chlorin.
Key words: 1,8-naphthalimide, styryl dyes, conjugate, theranostics, energy transfer, fluores-
cence, singlet oxygen generation.
Photodynamic therapy (PDT) is an efficient and one
the long-wavelength absorption maximum of which ap-
1
7
of the most gentle cancer treatment methods. PDT is
pears in the region of 760—800 nm, i.e., within the
based on the use of photosensitizers (PS), which upon
excitation by light can enter into photochemical reactions
with oxygen molecules, leading to the formation of reac-
tive oxygen species toxic for cells.1 PS emits part of the
energy of the absorbed photons in the form of fluorescence,
which allows the diagnosis of the tumor. The use of fluo-
rescence visualization in combination with therapy in-
creases the efficiency of PDT; its potential is being studied
in the framework of a modern scientific field called "ther-
anostics".
phototherapeutic window of transparency of biological
tissues (650—850 nm), where the absorption of blood
8
components is minimal. It is the radiation in the IR range
—3
that is most suitable for PDT, since it penetrates the bio-
9
logical tissues the deepest. Bacteriochlorin derivatives are
distinguished by high quantum yields of singlet oxygen
generation, but relatively low fluorescence efficiency. In
addition, natural chlorins are characterized by low values
of the Stokes shift, which worsens the contrast of diagnos-
1
0
tic images.
At present, PSs of various classes of tetrapyrrole mac-
rocycles: porphyrins and their hydrogenated analogs
In this connection, there appeared an idea about de-
velopment of (bis)chromophore theranostics for PDT, the
molecules of which include two covalently bonded func-
tional fragments, a photosensitizer and a fluorophore.
Selective excitation of each of the components of the
system would allow for both the diagnosis of the tumor
and its subsequent removal. The literature describes several
examples of such systems, which are conjugates of PS with
(
chlorins and bacteriochlorins), phthalocyanines, as well
as metal complexes of these compounds, are used in prac-
tice and also undergo clinical trials.4
particularly interesting are derivatives of bacteriochlorin,
—6
Among them,
*
On the occasion of the 65th anniversary of the foundation of
1
1—13
14.15
cyanines,
rhodamines,
and also BODIPY-based
A. N. Nesmeyanov Institute of Organoelement Compounds of
the Russian Academy of Sciences.
1
6,17
dyes.
These types of dyes are characterized by low
values of the difference between the absorption and emis-
sion wavelengths. In addition, as was shown in the
*
* Based on the materials of the International Conference
"
(
Chemistry of Organoelement Compounds and Polymers 2019"
November 18—22, 2019, Moscow, Russia).
1
1—17
works,
the resonance energy transfer process is real-
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1169—1178, June, 2020.
066-5285/20/6906-1169 © 2020 Springer Science+Business Media LLC
1

1
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Russ. Chem. Bull., Int. Ed., Vol. 69, No. 6, June, 2020
Zakharko et al.
ized between the conjugate components, which, depend-
ing on the direction, deteriorates either the photodynamic
or the fluorescent properties of the systems.
In the present work, we synthesized conjugates of dyes
based on 4-styrylnaphthalimide and photosensitizer bac-
teriochlorin BChl-NI1 and BChl-NI2 (Scheme 1) differ-
ing in the nature of the spacer fragment, studied their
spectral-luminescent characteristics, and measured the
efficiency of singlet oxygen generation.
acid29,30 led to naphthalimide derivatives 2a and 2b. Using
the Heck reaction, a 3,4-dimethoxystyrene fragment was
introduced at position 4 of the naphthalimide core of the
2
2,31
latter.
The hydroxy group in the molecule 3a was
replaced with the azide group through the intermediate
chloro derivative 4. Compound 3b was introduced into
the four-component Ugi reaction to synthesize the naphth-
alimide derivative NI2 containing a peptide spacer frag-
ment. The presence of the spacer fragment containing
amide bonds should increase the affinity of the conjugate
The derivative of the second-generation photosensitizer
bacteriochlorin e (compound BChl in Scheme 1) was
selected as the component responsible for the therapeutic
effect of the conjugates, since, along with significant photo-
dynamic efficiency, it is characterized by low dark toxic-
ity, rapid clearance from normal tissues, and low skin
3
2
to biomolecules. The Ugi reaction is a four-component
condensation of isocyanide, a carbonyl compound, an
3
3
amine, and an inorganic or organic acid. This type of
reactions is widely used in combinatorial chemistry for the
synthesis of biologically active compounds, since they
make it possible to obtain a wide variety of products struc-
turally similar to peptides in a single step under mild
1
8
phototoxicity. Derivatives of naphthalic acid imide
(
naphthalimide) were used as fluorophores. Dyes of this
3
4
class are distinguished by significant photostability, high
conditions from available starting reagents. The intro-
duction of an azide-substituted isocyanide into this reac-
tion allows one to construct in one step amino acid de-
values of the Stokes shift, and are widely used as compo-
nents of photoactive systems.1
9—21
The introduction of
3
5,36
electron-donating substituents at position 4 of the naph-
thalimide core results in the appearance of long-wave-
length absorption bands in the spectra of dyes due to charge
transfer from the substituent to the dicarboxyimide group
of naphthalimide, and is also accompanied by an increase
in the fluorescence quantum yield. It is known that naphth-
alimide derivatives containing a styryl moiety at position
rivatives containing an azide fragment,
which can be
3
7
used in subsequent transformations. The structure and
composition of the synthesized compounds were confirmed
by a combination of physicochemical methods of analysis
(see Experimental).
Study of the optical properties of conjugates. The opti-
cal properties of the conjugates BChl-NI1, BChl-NI2 and
their components were studied in acetonitrile (Fig. 1). For
a comparative analysis of the spectral characteristics,
monochromophore derivatives BChl and 3a were used.
Table 1 presents the main spectral characteristics of all
the compounds studied. As can be seen from Fig. 1, a, b,
the absorption spectra of the conjugates correspond to
a superposition of the absorption spectra of bacteriochlorin
(BChl) and dye 3a, which indicates the absence of interac-
tion between the components of the conjugates in the
ground electronic state. Naphthalimide dyes 3a and NI2
upon photoexcitation show intense fluorescence in the
region of 608—618 nm (see Table 1), while a narrow band
with a maximum at 758 nm is observed in the emission
spectrum of bacteriochlorin BChl (see Fig. 1, c).
4
of the naphthalimide core can be used as fluorescent
2
2,23
markers and sensors for cells,
because they have the
ability to penetrate through the cell membrane and inten-
sively luminesce in the cell medium. The previous stud-
2
4,25
ies
of the optical properties of naphthalimide styryl
derivatives showed that 3,4-dimethoxy-4-styrylnaphth-
alimide chromophore efficiently fluoresces in low-polar
media, and being photoexcited in solvents of high polarity
it forms twisted states with charge transfer, while maintain-
ing an intense fluorescent signal. Therefore, to develop
fluorescent navigators for PDT, we selected the structure
of 4-styrylnaphthalimide containing donor methoxy groups
at positions 3 and 4 of the phenyl ring.
Results and Discussion
Photoexcitation of an equimolar mixture of BChl and
a with light of 420 nm wavelength, which is mainly ab-
3
Synthesis of compounds. The copper-catalyzed 1,3-cyclo-
addition reaction was used for covalent bonding of two
chromophores since this reaction proceeds rapidly and
selectively under mild conditions.26 The bacteriochlorin
sorbed by the naphthalimide chromophore, leads to the
appearance of a broad emission signal of 3a in the fluo-
rescence spectra (see Fig. 1, d). At the same time, irra-
diation of conjugate BChl-NI1 with light of the wavelength
corresponding to the dye maximum absorption leads to
the appearance in the fluorescence spectrum of an emis-
sion signal corresponding to the bacteriochlorin residue.
This fact indicates that the process of photoinduced energy
transfer from the fluorophore to the photosensitizer occurs
in the conjugate.
propargyl derivative was synthesized according to the
described procedure.2
7,28
The azide groups were intro-
duced into the aliphatic substituent at the imide nitrogen
atom of the naphthalimide fluorophores NI1 and NI2. The
dyes NI1 and NI2 were obtained from 4-bromonaphthalic
anhydride according to Scheme 1. At the first stage of the
synthesis, the imidation reaction of 4-bromonaphthalic
anhydride 1 with ethanolamine and ε-aminocaproic
In the case of conjugate BChl-NI2, which contains
a peptide spacer, the dye fluorescence is not completely

Theranostics in photodynamic therapy
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 6, June, 2020
1171
Scheme 1
DIPEA is diisopropylethylamine.

1
172
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 6, June, 2020
Zakharko et al.
A
a
b
A
0
0
0
0
.20
0
0
0
0
0
.25
.20
.15
.10
.05
BChl-NI2
BChl-NI1
BChl + 3a
BСhl
3
a
.15
.10
.05
3
00
400
500
600
700
800 λ/nm
300
I/Imax
.0
400
500
600
700
800 λ/nm
I/Imax
c
d
BChl-NI2
BChl-NI1
BChl + 3a
1
1
0
0
0
0
.0
BChl
3
a
0
0
0
.8
.6
.4
.8
.6
.4
.2
0.2
5
00
600
700
800 λ/nm
5
00 550 600 650 700 750 800 λ/nm
Fig. 1. Absorption (a, b) and normalized fluorescence spectra (c, d) of compounds 3а, BChl, BChl-NI1, BChl-NI2 and an equimolar
–
6
–1
mixture of BChl + 3а in acetonitrile. The concentration of all compounds is 2.6•10 mol L . The excitation wavelength for BChl
is 515 nm, for other compounds 420 nm.
Note. Figures 1 and 2 are available in full color on the web page of the journal (http://link.springer.com/journal/volumesAndIssues/11172).
quenched (the ratio of the fluorescence intensity of
intramolecular energy transfer proceeds less efficiently
compared to BChl-NI1. The fluorescence quantum yields
for NI2 and BChl-NI2 were 0.34 and 0.037, respectively
BCHl-NI2 and BChl-NI1 at a wavelength of 610 nm is
4
.4). This indicates that in this molecule, the process of
Table 1. Spectral and photophysical characteristics of BChl, 3a, NI2, BChl-NI1, BChl-NI2 and an equimo-
lar mixture of BChl + 3а in acetonitrile
λabs
λfl
(λ )
I (λ ) (arb. units)
a
φfl
ΦRETb (%) ΦΔc (λ /nm)
ex
Compound
max
max
ex
ex
nm
BChl
356, 516, 748
419
758 (515)
618 (420)
608 (420)
618 (420)
755 (420)
760 (420)
—
—
0.030
0.210
0.340
0.190
0.034
0.037
—
—
0.79 (510)
3
a
—
—
—
NI2
413
—
—
BChl + 3a
BChl-NI1
BChl-NI2
419
355, 515, 748
356, 520, 753
1361650 (420)
6149 (420)
28948 (420)
—
99.5
97.8
0.65 (510)
0.49 (510)
a
The values given correspond to the non-normalized fluorescence emission spectra of compounds BChl-NI1,
BChl-NI2 and an equimolar mixture of BChl + 3a recorded at the same concentration of all compounds
–
6
–1
equal to 2.6•10 mol L
.
b
Energy transfer efficiency.
The quantum yield of singlet oxygen generation (Φ ) was measured in acetone.
c
Δ

Theranostics in photodynamic therapy
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 6, June, 2020
1173
(
see Table 1). The energy transfer efficiency (ΦRET) can
chromophores of conjugate BChl-NI2 (compounds NI2
and BChl) in BSA retain the ability to intensively luminesce
3
8
be estimated using Eq. (1):
(
Fig. 2, b). The observed spectral effects can be related to
ΦRET = 1 – I /ID,0,
(1)
the process of complexation of BChl-NI2 and BSA mol-
ecules mainly due to the formation of hydrogen bonds
between the functional groups of the spacer fragment of
BChl-NI2 and albumin, as well as to the coordination of
aromatic amino acid residues of the protein with chromo-
phores in the conjugate through the π-stacking interac-
D
where ID и ID,0 is the fluorescence intensity of the donor
in the presence and absence of an acceptor, respectively.
The fluorescence intensity of a mixture of monochromo-
phores BChl and 3a at a wavelength of 600 nm were used
as the ID,0 values and the fluorescence intensity of conju-
gates at a wavelength of 600 nm were used as the I value
(
4
3—45
tions. There are a number of literature
examples of
the complexation of fluorescent markers with BSA, which
is accompanied by a change in their optical characteristics.
D
see Table 1). The calculation was based on the fluores-
4
5
cence intensity values at a wavelength of 600 nm, the ΦRET
values are presented in Table 1.
The authors of the work showed that quenching of the
emission of a fluorophore based on the BODIPY derivative
in a BSA solution is explained by the formation of a non-
fluorescent complex stabilized by specific interactions
(π-stacking and hydrogen bonds).
Upon introduction of a peptide spacer fragment into
the structure of conjugate BChl-NI2, it was assumed that
the resulting theranostic would be able to interact with
components of biological fluids when introduced into the
body. Albumins are one of the most common classes of
plasma protein transporters. The optical properties, bio-
Study of singlet oxygen generation. One of the most
important parameters determining the efficiency of a drug
for PDT is the quantum yield of singlet oxygen generation.
4
6
distribution, and metabolism of drugs may change upon
The method of chemical trap is the simplest practical
approach to its determination. It is based on the addition
of traps of singlet oxygen to the photosensitizer solution,
binding to serum albumin.3
9,40
Therefore, the luminescent
properties of conjugate BChl-NI2 were also studied in
a solution of bovine serum albumin (BSA), an available
protein with a well-studied composition and structure,
which is widely used in biochemistry as a model compound
which are organic compounds able to quantitatively react
1
with O species and form products which do not interfere
2
with spectrophotometric determination of the concentra-
tion of nonoxidized trap in the solution.
4
1,42
in the development of biologically active substances.
The absorption spectra of fluorophore NI2, photosen-
sitizer BChl, and their equimolar mixture in a 10% (wt.)
BSA solution in water are in good agreement with the
absorption spectra of these compounds in acetonitrile
To determine the quantum yields of singlet oxygen
generation of conjugates obtained in this work, we used
1
diphenylisobenzofuran (DPIBF), which is oxidized by O2
to endoperoxide not absorbing in the visible region. Thus,
one can judge the formation of reactive oxygen species in
solution by the fading of the DPIBF band (λmax = 410 nm,
acetone) in the spectrum of a mixture of the photosensitizer
(
cf. Fig. 1, Table 1, Fig. 2, a). In the case of conjugate
BChl-NI2, we observed broadening of absorption bands,
as well as their bathochromic shift by 7—8 nm compared
to the spectrum of an equimolar mixture of chromophores.
In this case, the emission of conjugate BChl-NI2 in BSA
is efficiently quenched (Fig. 2, b). The individual mono-
4
7
and the trap. Carrying out an experiment with a standard
for which the quantum yield of singlet oxygen is known
allows one to calculate this parameter for the photosensi-
I•10–6 (arb. units)
A
a
b
BChl
BChl
1.2
BChl + NI2
NI2
BChl + NI2
0
0
.2
.1
0
NI2
BChl-NI2
1
0
0
0
0
.0
.8
.6
.4
.2
BChl-NI2
BChl-NI2
500 550 600 650 700 750 800 λ/nm
Fig. 2. Absorption (a) and fluorescence spectra (b) of NI2, BChl, BChl-NI2 and an equimolar mixture of BChl + NI2 in 10% (wt.)
4
00
500
600
700
800 λ/nm
–
6
–1
solution of bovine serum albumin (BSA) in water. The concentration of all compounds is 2.6•10 mol L . The excitation wavelength
20 nm.
4

1
174
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 6, June, 2020
Zakharko et al.
tizer under study. Tetraphenylporphyrin (TPP, Φ = 0.7)
3,4-dimethoxy-4-styryl-1,8-naphthalimide containing
a two unit methylene chain (BChl-NI1) and a peptide
fragment (BChl- NI2) as a spacer. The study of the optical
properties of these compounds showed that the fluores-
cence of the naphthalimide component in the conjugates
is quenched due to the energy transfer process. This pro-
cess in conjugate BChl-NI2 proceeds less efficiently than
in BChl-NI1 due to the separation of chromophores in
space. However, the emission of BChl-NI2 is quenched
in a solution of bovine serum albumin as a result of inter-
action with the protein. Besides, the quantum yield of
singlet oxygen for this conjugate was found to be lower
than for BChl-NI1 and free BChl.
Δ
was used as the standard.4
8,49
The changes in the absorption spectra of compounds
of mixtures of conjugates BChl-NI1 and BChl-NI2 with
DPIBF trap upon light irradiation are shown in Fig. 3.
The calculated quantum yields of singlet oxygen generation
(
Φ ) were 0.65 and 0.49 for BChl-NI1 and BChl-NI2,
Δ
respectively (see Table 1). The conjugation of the naph-
thalimide chromophore with bacteriochlorin in the case
of BChl-NI1 does not reduce the photodynamic efficiency
5
0
of the photosensitizer (Φ (BChl) = 0.79). At the same
Δ
time, for BChl-NI2, the efficiency of singlet oxygen gen-
eration turned out to be significantly reduced in com-
parison with BChl. This can be explained by the presence
of a π-excessive benzene ring with two methoxy groups in
the spacer fragment of BChl-NI2, which increases the
probability of the involvement of formed reactive oxygen
species in the oxidation of the conjugate molecules.
In conclusion, we synthesized two previously unde-
scribed conjugates of photosensitizer bacteriochlorin e and
Experimental
1H and 13C NMR spectra were recorded on Bruker Avance
300, Bruker Avance 400, Bruker Avance 500, and Bruker Avance
6
00 NMR spectrometers. Solutions of samples in deuterated
chloroform, DMSO, and dichloromethane were used. Chemical
1
13
shifts of H and C nuclei were determined with an accuracy of
.01 ppm relative to the residual signals of the solvents and re-
0
calculated to the internal standard (tetramethylsilane). Spin—spin
coupling constants were measured with an accuracy of 0.1 Hz.
A
a
1
1
Signals in the NMR spectra were assigned using 2D H— H
1
1
0
0
0
0
.2
.0
.8
.6
.4
.2
1
13
1
13
COSY, H— C HSQC, and H— C HMBC procedures with
0
1
pulsed field gradients. The atomic numbers for describing H and
13
C NMR spectra of the synthesized compounds are given in the
general structural formula of the conjugates in Scheme 1. To
designate the side substituents of the bacteriochlorin residue, we
used the numbers of carbon atoms of the tetrapyrrole ring, to
which the corresponding substituent is attached, and the super-
scripts "1" and "2" to indicate the first or second carbon atom
from the macrocycle. The signals for proton belonging to the
same methylene group, but with different chemical shifts, are
designated with superscripts "a" and "b" without specifying their
position in space relative to the macrocycle plane.
1
80
Melting points were determined in capillaries on a Mel-
tempII instrument and were not corrected.
4
00
450
600
λ/nm
IR spectra were recorded on a Magna IR (Nicolet) Fourier-
transform spectrometer (transmittance, at a temperature of
0±1 °C).
Electron impact mass spectra were measured on a Finnigan
A
b
2
0
0
0
0
0
.8
.6
.4
.2
PolarisQ instrument (ion trap). The energy of ionizing electrons
was 70 eV. The samples of compounds in solutions (1 wt.%) of
CH Cl or CHCl (0.2 μL) were placed into quartz micro am-
2
2
3
poules, which were inserted into a heated tip of a direct-inlet
rod. Thermomass spectrograms were studied during stepwise (in
5
0 °С) heating of ampoules from 50 to 150 °С. Before heating
the samples, a thermomass spectrogram of an empty ampoule in
the same temperature range was usually obtained, confirming
the absence of any contamination of the ampoule and rod.
A MicroTOF-Q instrument was used for studies by high
resolution mass spectrometry (HRMS). Solutions in dichloro-
methane or methanol were used for studies by electrospray
ionization (ESI) mass spectrometry. MALDI mass spectra were
measured on a Bruker Ultraflex TOF/TOF time-of-flight mass
spectrometer (matrix dihydroxybenzoic acid (DHB)).
240
4
00
450
600
λ/nm
Fig. 3. Changes in the absorption spectra in solutions of contain-
–
5
–1
ing DPIBF (4.0•10 mol L ) BChl-NI1 during 0—180 s (a)
and BChl-NI2 during 0—240 s (b) in acetone upon irradiation
with light of 510 nm wavelength.
Electronic absorption spectra were recorded on a Varian Cary
5G dual-channel spectrophotometer, fluorescence spectra were

Theranostics in photodynamic therapy
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 6, June, 2020
1175
recorded on a Fluorolog 3-221 spectrofluorimeter at a tempera-
ture of 20±1 °С. The observed fluorescence was detected at right
angles to the excitation beam. Fluorescence spectra were cor-
rected with respect to the sensitivity of the measuring photomul-
tiplier tube. Absorption and fluorescence spectra were recorded
using spectroscopically pure acetonitrile and acetone from
Aldrich and Acros, as well as a solution (10 wt.%) of lyophilized
bovine serum albumin (PanEco) in distilled water purified in the
TKA Smart2Pure system.
(1.5 g, 5.41 mmol) and 6-aminocaproic acid (0.711 g, 5.42 mmol)
in 95% ethanol (50.0 mL) was refluxed until the mixture of the
white suspension became a clear brown solution (~4 h). The
reaction mixture was cooled to ~20 °C. The precipitate formed
was collected by filtration, washed with cold 95% EtOH on the
filter, and dried to obtain 1.405 g (67%) of product 2b. M.p.
1
159—161 °С (cf. Ref. 26: m.p. 161 °С). H NMR (400.13 MHz,
DMSO-d , 20.9 °С), δ: 1.27—1.43 (m, 2 Н, СН (СН ) СООН);
6
2
2 2
1.45—1.58 (m, 2 Н, СН СН СООН); 1.58—1.71 (m, 2 Н,
2
2
fl
Quantum yields of fluorescence (φ ) were determined in
СН (СН ) СООН); 2.15—2.26 (m, 2 Н, СН СООН); 3.96—4.06
2 2 3 2
air-saturated solutions at a temperature of 20±1 °С with respect
(m, 2 Н, СН N); 7.96—8.04 (m, 1 Н, Н(6)); 8.23 (d, 1 Н, Н(3),
2
to the standard coumarin 481 in acetonitrile (φfl = 0.08).
51
J = 7.9 Hz); 8.35 (d, 1 Н, Н(2), J = 7.9 Hz); 8.51—8.62 (m, 2 Н,
5
2
Quantum yields were calculated using the relation (2):
Н(5), Н(7)); 11.99 (br.s, ОН).
Synthesis of 3,4-dimethoxy-4-styryl-substituted derivatives
of naphthalimide 3a,b (general procedure). Compound 2a (1 eq.)
,
(2)
was added to a suspension of catalysts Pd(OAc) and (o-tol) P
2
3
in a mixture of DMF and Et N, followed by the addition of
3
where ϕifl and ϕ fl are the quantum yields of the analyzed solution
a corresponding styrene (1.2 eq.). The reaction was carried out
for 10—15 h at 110 °С in an argon atmosphere. Upon the reaction
completion (TLC monitoring, PhH—EtOH (10 : 1, v/v), the
reaction mixture was cooled to ~20 °С. The product was ex-
tracted from the reaction mixture with dichloromethane, the
combined extracts were washed several times with water and
0
and the standard, respectively, A and A are the absorption of
i
0
the analyzed solution and the standard, S and S are the areas
i
0
under the fluorescence curve of the analyzed solution and the
standard, n and n are the refractive indices of the solvents of
i
0
the test compound and the standard.
dried with Na SO . Then, CH Cl was removed on a rotary
To determine the quantum yield of singlet oxygen by the
chemical trap method, we used freshly prepared solutions of TPP
standard, DPIBF, BChl, and conjugates BChl-NI1, BChl-NI2
in acetone. A mixture of the studied compound and the trap
2
4
2
2
evaporator. The product was purified by column chromatography
or recrystallization. This procedure is an adaptation of procedures
for carrying out the Heck coupling reaction described earlier.27
2
-(2-Hydroxyethyl)-6-[(E)-2-(3,4-dimethoxyphenyl)ethen-
(
DPIBF) was irradiated with light with λ = 510 nm in a quartz
yl]-1Н-benzo[d,e]isoquinoline-1,3(2Н)-dione (3a). Crude prod-
cuvette (l = 1 cm) in a Fluorolog 3-221 spectrofluorimeter using
a xenon lamp as a source of light. The optical density of the trap
was detected by the absorption spectra of the solution obtained
on a Varian Cary 5G spectrophotometer at a wavelength of
uct (0.600 g) was obtained from compound 2a (0.446 g, 1.4 mmol)
and Pd(OAc) (3.7 mg, 0.02 mmol), (o-tol) P (23.3 mg, 0.08 mmol),
2
3
3
,4-dimethoxystyrene (0.249 mL, 1.68 mmol), DMF (18.0 mL),
and Et N (2.7 mL). Purification by column chromatography on
4
10 nm. The quantum yield of singlet oxygen generation of the
studied samples was determined by the formula (3):
3
silica gel (eluent CH Cl —MeOH (100 : 2)) gave pure product
2
2
1
3
a (0.485 g, 84%). M.p. 199—200 °С. Н NMR (600.13 MHz,
DMSO-d , 27 °C), δ: 3.62—3.68 (m, 2 Н, СН OH); 3.82 (s, 3 Н,
6
2
,
(3)
ОMe(14)); 3.89 (s, 3 H, ОMe(13)); 4.16 (t, СН СН OH,
2
2
J = 6.4 Hz); 4.80 (t, 1 Н, ОН, J = 6.0 Hz); 7.02 (d, 1 Н, Н(15),
where А /А is the optical density per standard photosensitizer/
studied photosensitizer at a wavelength of excitation; V /V is the
slope of the linear segment of the graph of the dependence of
optical density at a wavelength of 410 nm on the exposure time
for mixtures of a photosensitizer with the standard of the studied
photosensitizer with DPIBF in acetone; Φ is the quantum yield
of singlet oxygen of the photosensitizer standard in the solvent
J = 8.3 Hz); 7.32 (dd, 1 Н, Н(16), J = 8.3 Hz; J = 1.9 Hz);
0
i
1
2
7.51—7.57 (m, 2 Н, Н(10), H(12)); 7.91 (dd, 1 Н, Н(6),
0
i
J = 8.7 Hz, J = 7.2 Hz); 8.08 (d, 1 Н, Н(9), J = 16.1 Hz); 8.21
1
2
(d, 1 Н, Н (3), J = 7.9 Hz); 8.48 (d, 1 Н, Н(2), J = 7.9 Hz); 8.54
(d, 1 Н, Н(7), J = 7.2 Hz); 9.01 (d, 1 Н, Н(5), J = 8.7 Hz).
1
3
C NMR (150.91 MHz, DMSO-d , 30.0 °С), δ: 41.77
6
0
(NCH CH OH), 55.54 (OMe(13)), 55.72 (OMe(14)), 57.80
2 2
used for the experiment.
(CH OH), 109.94 (C(12)), 111.67 (C(15)), 120.34 (C(1)), 120.75
2
6
-Bromo-2-(2-hydroxyethyl)-1Н-benzo[d,e]isoquinoline-
,3(2Н)-dione (2а). A solution of ethanolamine (0.65 mL,
0.80 mmol) in ethanol (10.0 mL) was added dropwise to a stirred
(C(9)), 121.72 (C(16)), 122.50 (C(8)), 122.95 (C(3)), 126.78
(C(6)), 128.18 (C(8a)), 128.93 (C(4a)), 129.53 (C(11)), 130.53
(C(2)), 130.71 (C(7)), 130.84 (C(5)), 135.33 (C(10), 141.41
(C(4)), 149.04 (C(13)), 149.77 (C(14)), 163.32 (C(8b)), 163.61
1
1
suspension of 4- bromonaphthalic anhydride 1 (2.0 g, 7.22 mmol)
in 95% ethanol (30.0 mL) at 60 °С. The reaction mixture was
refluxed for 6 h (until it became clear) and cooled to ~20 °С.
Product 2a was collected by filtration as a white powder and
washed on the filter with pure ethanol to obtain 1.939 g (84%)
–
1
(C(8c)). IR (KBr pellets), ν/cm : 3498 (νOH); 2935, 2882 (νCH);
1690, 1652 (νC=O). MS, m/z (I (%)): 404 (16), 403 [M]+ (59),
401 (13), 373 (15), 361 (22), 360 (100), 359 (21), 342 (12),
328 (16), 284 (11).
of product 2a. M.p. 202—204 °С (cf. Ref. 25: m.p. 203—204 °С).
(E)-6-[6-(3,4-Dimethoxystyryl)-1,3-dioxo-1H-benzo[d,e]-
isoquinolin-2(2H)-yl]hexanoic acid (3b). Product 3b (0.103 mg,
85%) was obtained from compound 2b (0.1 g, 0.257 mmol),
1
H NMR (300.13 MHz, CDCl , 21.3 °С), δ: 2.26 (br.s, 1 Н,
3
ОН); 3.90—4.10 (m, 2 Н, СН ); 4.38—4.58 (m, 2 Н, СН );
2
2
7
(
(
.82—7.94 (m, 1 Н, Н(6)); 8.07 (d, 1 Н, Н(3), J = 7.8 Hz); 8.45
Pd(OAc) (1.0 mg, 0.005 mmol), (o-tol) P (4.3 mg, 0.014 mmol),
2
3
d, 1 Н, Н(2), J = 7.8 Hz); 8.61 (d, 1 Н, Н(7), J = 8.6 Hz); 8.68
d, 1 Н, H(5), J = 7.0 Hz).
4-dimethylaminostyrene (0.046 mL, 0.309 mmol), DMF
(4.0 mL), and Et N (1.5 mL). Purification was carried out by
3
6
-(6-Bromo-1,3-dioxo-1H-benzo[d,e]isoquinolin-2(2H)-yl)-
hexanoic acid (2b). A mixture of 4-bromonaphthalic anhydride 1
column chromatography on silica gel with gradient elution with
a solvent mixture of chloroform—methanol (from pure CHCl3

1
176
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 6, June, 2020
Zakharko et al.
to the ratio in the mixture 200 : 1). M.p. 153 °С (with decomp.).
(d, 1 Н, Н(7), J = 7.3 Hz); 9.03 (d, 1 Н, Н(5), J = 8.8 Hz).
6 2
CH N ), 48.29 (CH N ), 55.55 (OMe(14)), 55.73 (OMe(13)),
2 3 2 3
1
13
H NMR (400.13 MHz, DMSO-d , 19.5 °С), δ: 1.30—1.43 (m,
C NMR (150.91 MHz, DMSO-d , 30.0 °С), δ: 38.50 (NCH -
6
1
1
Н, CH (CH ) COOH); 1.53—1.60 (m, 1 Н, CH CH COOH);
2
2 2
2
2
.62—1.69 (m, 1 Н, CH CH N); 2.22 (t, 1 Н, СН СООН,
109.96 (C(12)), 111.68 (C(15)), 119.94 (C(1)), 120.69 (C(9)),
121.79 (C(16)), 122.14 (C(8)), 123.04 (C(3)), 126.88 (C(6)),
128.22 (C(8a)), 128.97 (C(4a)), 129.51 (C(11)), 130.80 (C(2)),
131.01 (C(7)), 131.19 (C(5)), 135.56 (C(10)), 141.78 (C(4)),
149.04 (C(13)), 149.82 (C(14)), 163.29 (C(8b)), 163.59 (C(8c)).
2
2
2
J = 7.3 Hz); 3.83 (s, 3 Н, Me(14)); 3.91 (s, 3 Н, Me(13)); 4.05
(
7
t, 2 Н, CH N, J = 7.4 Hz); 7.03 (d, 1 Н, Н(15), J = 8.4 Hz);
2
.33 (d, 1 Н, Н(16), J = 8.4 Hz); 7.53—7.57 (m, 2 Н, Н(12),
Н(10)); 7.92 (t, 1 Н, Н(6), J = 7.9 Hz); 8.09 (d, 1 Н, Н(9),
J = 16.0 Hz); 8.22 (d, 1 Н, Н(3), J = 7.8 Hz); 8.48 (d, 1 Н, Н(2),
J = 7.8 Hz); 8.55 (d, 1 Н, Н(7), J = 7.4 Hz); 9.02 (d, 1 Н, Н(5),
–
1
IR (KBr pellets), ν/cm : 2956, 2923 (νCH); 2102 (νN ); 1696,
3
+
1654 (νC=O). MS, m/z (I (%)): 428 [M] (26), 400 (51), 382 (34),
J = 8.6 Hz). 13C NMR (150.93 MHz, DMSO-d , 25.0 °С), δ:
373 (100), 342 (40), 298 (35), 273 (31), 227 (21), 213 (20), 202 (36).
(E)-N-{2-[(2-Azidoethyl)amino]-2-oxoethyl}-N-(2,4-dimeth-
oxybenzyl)-6-[6-(3,4-dimethoxystyryl)-1,3-dioxo-1H-benzo-
[d,e]isoquinolin-2(2H)-yl]hexanamide (NI2). A solution of acid 3b
(237 mg, 0.5 mmol) in DMSO (1.5 mL) and 2-azidoethyliso-
cyanide (58 mg, 0.6 mmol) were added to a solution of 2,4-di-
methoxybenzylamine (100 mg, 0.6 mmol) and a 37% (wt.) solu-
tion of formaldehyde (45 μL, 0.6 mmol) in methanol (8 mL).
The reaction mixture was stirred at ~20 °C for 24 h (the reaction
progress was monitored by TLC). Upon reaction completion,
the solvents were evaporated in vacuo, the dry residue was dis-
solved in dichloromethane. The solution was washed with brine
6
2
(
(
4.12 (CH CH COOH), 25.91 (CH (CH ) COOH), 27.14
2 2 2 2 2
СН СООН), 33.48 (СН СООН), 39.79 (CH N), 55.43
2 2 2
OMe(14)), 55.60 (OMe(13)), 109.78 (C(12)), 111.53 (C(15)),
20.07 (C(1)), 120.61 (C(9)), 121.64 (C(16)), 122.24 (C(8)),
22.87 (C(3)), 126.71 (C(6)), 128.00 (C(8a)), 128.84 (C(4a)),
29.41 (C(11)), 130.51 (C(2)), 130.70 (C(5), C(7)), 135.27
C(10)), 141.40 (C(4)), 148.92 (C(13)), 149.65 (C(14)), 163.07
+
(
E)-2-(2-Chloroethyl)-6-(3,4-dimethoxystyryl)-1H-benzo-
[
d,e]isoquinoline-1,3(2H)-dione (4). A solution of compound 3а
and dried with Na SO , after which CH Cl was evaporated
2 4 2 2
(
0.192 g, 0.46 mmol) in POCl (3 mL) was maintained for 1.5 h
in vacuo using a water-jet pump. Purification of the product by
column chromatography (SiO , CH Cl —MeOH) gave com-
3
at 80—90 °С with a reflux condenser and a calcium chloride tube.
After distilling off the phosphorus oxychloride in vacuo, the
2
2
2
1
pound NI2 (236 mg, 63%) as a yellow oil. H NMR (400 MHz,
CDCl ), δ: 1.41—1.51 (m, 2 H); 1.69—1.82 (m, 4 H); 2.25—2.35
product was purified by column chromatography (SiO , CH Cl ) to
2
2
2
3
obtain the target compound 4 (0.200 g, 97%). M.p. 195—197 °С.
(m, 1 H); 2.47—2.54 (m, 2 H); 2.98 (s, 1 H); 3.32—3.43 (m, 5 H);
3.77—4.07 (m, 11 H); 4.16 (t, 2 H, JH,H = 7.3 Hz); 4.49 (s, 1 H);
4.74—4.81 (m, 1 H); 6.42—6.61 (m, 2 H); 6.74 (br.s, 1 H);
6.90—6.97 (m, 2 H); 7.16—7.28 (m, 3 H); 7.66—7.76 (m, 2 H);
1
H NMR (400.13 MHz, DMSO-d , 27 °С), δ: 3.82 (s, 3 Н,
6
ОMe(14)); 3.84—3.96 (m, 5 Н, CH Cl, OMe(13)); 4.41 (t, 2 Н,
2
CH CH Cl, J = 6.8 Hz); 7.03 (d, 1 Н, Н(15), J = 8.3 Hz); 7.33
2
2
(
d, 1 Н, Н(16), J = 8.3 Hz, J = 1.7 Hz); 7.52—7.62 (m, 2 Н,
7.93 (d, 1 H, J
= 7.8 Hz); 8.38—8.48 (m, 1 H); 8.51—8.59
1
2
H,H
1
3
Н(10), Н(12)); 7.90—7.96 (m, 1 Н, Н(6)); 8.10 (d, 1 Н, Н(9),
J = 16.2 Hz); 8.23 (d, 1 Н, Н(3), J = 8.0 Hz); 8.50 (d, 1 Н, Н(2),
J = 8.0 Hz); 8.57 (d, 1 Н, Н(7), J = 7.3 Hz); 9.04 (d, 1 Н, Н(5),
(m, 2 H). C NMR (100 MHz, CDCl , the product is a mixture
3
of rotamers, the signals of the second rotamer are indicated in
brackets), δ: 24.8 (24.6), 26.9 (26.6), 27.8 (27.7), 29.6, 32.7
(32.4), 38.7 (38.8), 40.1 (40.1), 48.2, 50.6 (50.2), 55.3 (55.2),
55.9 (55.6), 81.3, 98.6, 103.8, 109.2, 111.2, 115.8, 120.8, 121.0,
121.3, 122.9, 123.5, 126.5, 128.6, 129.1, 129.3, 129.6 (129.9),
131.0 (131.0), 135.2, 141.6, 149.2, 149.9, 158.3, 160.8, 163.9,
J = 8.0 Hz). 13С NMR (100.61 MHz, DMSO-d , 27.0 °С), δ:
6
4
1
1
1
1
1
0.83 (NCH CH Cl), 55.58 (OMe(13)), 55.78 (OMe(14)),
2 2
09.93 (C(12)), 111.69 (C(15)), 119.98 (C(1)), 120.70 (C(9)),
21.89 (C(16)), 122.18 (C(8)), 123.09 (C(3)), 126.95 (C(6)),
28.27 (C(8a)), 129.02 (C(4a)), 129.52 (C(11)), 130.88 (C(2)),
31.09 (C(7)), 131.28 (C(5)), 135.65 (C(10)), 141.86 (C(4)),
49.08 (C(13)), 149.84 (C14)), 163.25 (C(8b)), 163.54 (C(8c)).
164.2, 169.8 (169.5), 174.6 (174.3). IR (ATR ZnSe), ν/cm–1
:
1638, 1653, 1691, 2108, 2940, 3219. HRМS (ESI), m/z, found:
+
749.3301. [М + H] . Calculated for C41H45N O : 749.3293.
6
8
–
1
IR (KBr pellets), ν/cm : 2980, 2918 (νCH); 1690, 1652 (νC=O),
Synthesis of conjugates BChl-NI1 and BChl-NI2 (general
). MS, m/z (I (%)): 423 [M + 2]+ (35), 422 (27), 421
procedure). Bacteriochlorin e propargyl-15 ,17 -dimethoxy-13 -
amide BChl (1 equiv.) was dissolved in dichloromethane and
stirred for 10 min in a flow of argon. Then, copper(I) iodide
(0.36 equiv.), DIPEA (26 eq.), and a corresponding naph-
thalimide derivative NI1 or NI2 (1.1 eq.) were added. The reac-
tion mixture was stirred for 1—2 h in a flow of argon at ~20 °C
2
3
1
7
[
(
95 (ν
C=Cl
+
M] (100), 386 (14), 359 (28), 328 (20), 312 (15), 284 (22), 273
17), 202 (16).
(
E)-2-(2-Azidoethyl)-6-(3,4-dimethoxystyryl)-1H-benzo[d,e]-
isoquinoline-1,3(2H)-dione (NI1). Chloro derivative 4 (118 mg,
0
.28 mmol) and NaN (109 mg, 1.68 mmol) were dissolved in
3
DMF (5.5 mL) and maintained at 100 °С with a reflux con-
(the reaction completion was monitored by TLC, CH Cl —
2 2
denser for 6 h. Then the reaction mixture was diluted with water
MeOH (40 : 1, v/v). The reaction mixture was washed with
water, the combined extracts were dried with Na SO and con-
and the product was extracted with CH Cl (3×10 mL), the
2
2
2
4
combined organic extracts were washed with water and kept over
centrated on a rotary evaporator. The product was purified by
TLC and recrystallization.
a drying agent for ~14 h. The solvent was evaporated in vacuo to
obtain a pure product NI1 (0.100 g, 83%). M.p. 173 °С (with
Conjugate BChl-NI1. Product BChl-NI1 (24.4 mg, 50%) was
obtained from BChl (30 mg), CuI (3 mg), NI1 (20 mg), DIPEA
1
decomp.). H NMR (600.17 MHz, DMSO-d , 30.0 °С), δ: 3.63
6
(
t, 2 Н, СН N , J = 6.2 Hz); 3.81 (s, 3 Н, ОMe(14)); 3.89 (s, 3 Н,
(0.2 mL), and CH Cl (3 mL). M.p. 105 °С (with decomp.).
2
3
2 2
1
ОMe(13)); 4.29 (t, 2 Н, СН СН N , J = 6.2 Hz); 7.02 (d, 1 Н,
Н NMR (500.13 MHz, CD Cl , 25 °С), δ: –1.37 (s, 1 Н, NH,
2 2
2
2
3
2
Н(15), J = 8.4 Hz); 7.33 (dd, 1 Н, Н(16), J = 2.0 Hz, J = 8.4 Hz);
pyrrole); –1.34 (s, 1 H, NH, pyrrole); 1.06 (t, 3 H, H(8 ),
1
2
1
7
.52—7.58 (m, 2 Н, Н(10), H(12)); 7.93 (dd, 1 Н, Н(6)),
J = 7.3 Hz); 1.61 (d, 3 H, H(18 ), J = 7.2 Hz); 1.64—1.74 (m, 1 H,
1
a
1
J = 7.3 Hz, J = 8.8 Hz); 8.08 (d, 1 Н, Н(9), J = 16.0 Hz); 8.22
H(17 )); 1.87 (d, 3 H, H(7 ), J = 7.2 Hz); 2.00—2.17 (m, 2 H,
1
2
1
a
1b
2a
(
d, 1 Н, Н(3), J = 7.9 Hz); 8.50 (d, 1 Н, Н(2), J = 7.9 Hz); 8.58
H(8 ), H(17 )); 2.17—2.24 (m, 1 H, H(17 )); 2.33—2.44 (m,

Theranostics in photodynamic therapy
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 6, June, 2020
1177
1
b
2b
1
1
3
H, H(8 )); 2.50—2.60 (m, 1 H, H(17 )); 3.15 (s, 3 H, СОMe);
СН СН ), 33.46 (CH CO), 36.65 (CH NHCO), 37.82 (C(15 )),
2
2
3
2
1
1
.19 (s, 3 H, Me(12 )); 3.56 (s, 3 H, Me(2 )); 3.57 (s, 3 H,
СООMe); 3.68 (s, 3 H, СООMe); 3.88 (s, 3 Н, C(14)OMe);
39.71 (CHCONH), 46.96 (C(7)), 47.42 (CH CH , triazole),
2 2
48.61 (C(18)), 50.08 (CH CH , triazole), 52.01 (COOCH ),
2 2 3
3
4
4
.90 (s, 3 Н, C(13)OMe); 4.10—4.20 (m, 2 H, H(17), H(8));
.21—4.29 (m, 1 H, H(7)); 4.29—4.37 (m, 1 H, Н(18)); 4.52—
52.73 (COOCH ), 53.66 (C(17)), 55.75 (OMe, styryl), 55.80
3
(OMe, styryl), 56.34 (OMe), 56.38 (OMe), 57.54 (C(8)), 96.09
(C(10)), 98.07 (C(5)), 98.47 (C(21´), C(19´)), 98.92 (C(20)),
104.37 (C(22´)), 105.14 (C(14)), 109.57 (C(12´)), 111.71
(C(15´)), 116.61 (C(17´)), 120.12 (C(1´)), 121.07 (C(16´)),
122.46 (C(3´), C(8´)), 124.55 (CH, triazole), 126.24 (C(6´)),
128.00 (C(4a´), C(1)), 128.29 (C(8a´)), 128.54 (C(2)), 129.41
(C(7´)), 129.62 (C(11´)), 129.99 (C(9´)), 130.24 (C(13), C(15)),
130.37 (C(2´)), 130.65 (C(5´)), 132.03 (C(3)), 132.43 (C(12)),
133.87 (C(4)), 134.03 (C(11)), 134.26 (C(10´)), 140.55 (C(4´)),
.64 (m, 2 H, CH CH , triazole); 4.70—4.78 (m, 2 H, CH CH ,
2
2
2
2
a
triazole); 4.78—4.86 (m, 1 H, CH NHCO); 4.96—5.04 (m, 1 H,
2
b
1a
CH2 NHCO); 5.06 (d, 1 H, H(15 ), J = 18.8 Hz); 5.29 (d, 1 H,
H(151b), J = 18.8 Hz); 6.84 (d, 2 H, H (15´), J = 8.2 Hz);
6
.93—7.04 (m, 3 H, H(12´), Н(10´), H(16´)); 7.16 (t, 1 H,
NHCO, J = 5.4 Hz); 7.42 (d, 1 H, H(9´), J = 16.0 Hz); 7.54—7.65
m, 2 H, Н(3´), Н(6´)); 7.98 (s, 1 Н, СН, triazole); 8.29 (d, 1 H,
(
H(2´), J = 7.3 Hz); 8.37 (d, 1 H, H(5´), J = 8.3 Hz); 8.41 (d, 1 Н,
H(7´), J = 7.0 Hz); 8.52 (s, 1 H, H(10)); 8.72 (s, 1 H, H(5));
145.06 (NHCH C, triazole), 149.68 (C(13´)), 150.52 (C(14´)),
2
1
3
9
.28 (s, 1 H, H(20)). C NMR (125.76 MHz, CD Cl , 25 °С),
158.98 (C(20´)), 161.38 (C(18´)), 163.22 (C(19)), 164.13
(C(8c´)), 164.24 (C(8b´)), 165.91 (C(9)), 166.81 (C(16)), 168.25
(C(6)), 169.49 (NHCO), 170.04 (NHCO), 174.02 (2 COOMe),
2
2
2
1
1
1
δ: 11.08 (C(8 )), 12.00 (C(12 )), 13.99 (C(2 )), 23.49 (C(18 )),
1
1
1
2
2
3
(
(
(
9
1
1
3.92 (C(7 )), 29.83 (C(17 )), 30.46 (C(8 )), 31.44 (C(17 )),
1
3.54 (CH CO), 36.56 (CH NHCO), 38.11 (C(15 )), 40.21
174.67 (NICH CH CONH), 198.42 (COMe). MS (MALDI),
3
2
2 2
+
CH CH , triazole), 47.20 (C(7)), 48.37 (C(18)), 48.50
m/z: 1428.02 [M ]. Calculated: 1427.66.
2
2
CH CH , triazole), 51.96 (COOCH ), 52.69 (COOCH ), 53.50
2
2
3
3
C(17)), 56.38 (OMe, styryl), 56.41 (OMe, styryl), 57.77 (C(8)),
This work was financially supported by the Russian
Science Foundation (Project No. 16-13-10226). The study
of the optical properties of BChl-NI1-2 conjugates, as well
as their characterization by NMR spectroscopy, was fi-
nancially supported by the Ministry of Science and Higher
Education of the Russian Federation using the equipment
of the Center for molecule composition studies of the
A. N. Nesmeyanov Institute of Organoelement Compounds
of the Russian Academy of Sciences.
6.83 (C(10)), 98.02 (C(5)), 98.59 (C(20)), 105.19 (C(14)),
09.91 (12´), 111.88 (C(15´)), 120.65 (C(1´)), 121.18 (C(9´)),
21.40 (C(16´)), 122.81 (C(8´)), 123.68 (C(3´)), 123.85 (CH,
triazole), 126.94 (C(6´), 126.59 (C(6´)), 129.08 (C(3)), 129.12
C(8a´)), 129.76 (C(11´)), 129.80 (C(11)), 129.93 (C(4a´)),
(
1
1
1
30.77 (C(5´)), 131.60 (C(2´)), 131.64 (C(7´)), 132.27 (C(12)),
32.33 (C(2)), 132.64 (C(4)), 133.91 (C(15)), 134.33 (C(13)),
35.67 (C(10´)), 142.36 (C(4´)), 144.81 (s, triazole), 149.93
(
C(13´)), 150.78 (C(14´)), 163.84 (C(8b´)), 164.18 (C(19)),
1
1
64.47 (C(8с´)),165.90 (C(9)), 166.56 (C(16)), 168.75 (C(6)),
69.22 (NHCO), 173.89 (COOMe), 173.94 (COOMe), 198.76
References
+
(
MeCO). MS (MALDI), m/z: 1108.12 [M ]. Calculated: 1107.49.
–
1
IR (KBr pellets), ν/cm : 1733 (νС=О), 1695 (νC=C, triazole),
1
652 (νNH—C=O), 1513 (νNH—C=O), 1434 (νN=N, triazole).
1. R. R. Allison, K. Moghissi, Clin. Endosc., 2013, 46, 24—29;
DOI: 10.5946/ce.2013.46.1.24.
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DIPEA (0.2 mL), and CH Cl (3 mL). M.p. 100 °С (with de-
2
2
1
comp.). H NMR (600.13 MHz, CD Cl , 18 °С), δ: –1.70 (s, 1 Н,
2
2
2
NH, pyrrole); –1.57 (s, 1 H, NH, pyrrole); 1.01 (t, 3 H, H(8 ),
1
J = 7.3 Hz); 1.45—1.64 (m, 4 H, CH CH , triazole, СН (17 ));
2
2
2
1
1а
1
.69 (d, 3 H, H(18 ), J = 7.3 Hz); 1.84—1.99 (m, 4 Н, Н(8 ),
1
1b
2a
Н(7 )); 2.18—2.38 (m, 4 Н, Н(8 ), CH CH , triazole, H(17 ));
2
2
2
b
2
.53—2.62 (m, 1 Н, H(17 )); 3.06 (s, 3 H, COMe); 3.13 (s, 3 H,
1
1
Me(12 )); 3.42 (s, 3 H, Me(2 )); 3.60 (s, 3 H, COOMe); 3.66
s, 3 H, OMe); 3.69 (s, 3 H, OMe); 3.78 (s, 3 H, COOMe);
.52—3.84 (m, 4 H, CH CONH, CH CH , triazole); 3.93 (s, 3 H,
(
3
2
2
2
OMe, styryl); 3.94 (s, 3 H, OMe, styryl); 4.14—4.32 (m, Н(8),
H(17), H(7), H(18)); 4.50 (t, 2 H, СН СH , triazole, J = 5.0 Hz);
.92 (dd, 1 Н, CH NHCO, triazole, J = 14.7 Hz, J = 5.4 Hz);
.01—5.18 (m, 2 H, H(15 ), CH NHCO, triazole); 5.40—5.49
m, 1 H, H(15 )); 6.22—6.37 (m, 3 H, H(21´), H(10´), H(19´));
.36—6.52 (m, 2 H, H(22´), H(3´)); 6.70 (s, 1 Н, Н(12´)); 6.75
d, 1 Н, Н(16´), J = 8.2 Hz); 6.78—6.86 (m, 2 Н, Н(9´),
2
2
a
4
5
2 1 2
1
a
b
2
1
b
(
6
(
NHCO)); 6.89 (d, 1 Н, H(15´), J = 8.2 Hz); 7.08—7.14 (m, 1 Н,
Н(6´)); 7.55 (d, 1 Н, Н(5´), J = 7.6 Hz); 7.58 (d, 1 Н, Н(2´),
J = 7.1 Hz); 7.98 (s, 1 Н, СН, triazole); 8.04 (d, 1 Н, Н(7´),
J = 7.0 Hz); 8.21 (s, 1 Н, Н(10)); 8.33 (t, 1 Н, NHCO,
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3
J = 5.0 Hz); 8.66 (s, 1 Н, Н(5)); 9.27 (s, 1 Н, Н(20)). C NMR
2
1
(
1
2
150.93 MHz, CD Cl , 19 °С), δ: 11.09 (C(8 )), 11.98 (C(12 )),
2 2
1
1
1
4.01 (C(2 )), 23.54 (C(18 ), 23.85 (C(7 )), 24.98 (NI-СН ),
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1
1
2
9.76 (C(17 )), 30.18 (C(8 )), 31.45 (C(17 )), 32.46 (NI-

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Received February 10, 2020;
in revised form April 20, 2020;
accepted April 28, 2020
10.3390/molecules24020351.