Synthesis, structure and basic properties of 5,10,15,20-tetrakis[4′-(benzoxazole-2-yl)phenyl]-21,23-dithiaporphyrin

Article abstract of DOI:10.1016/j.molstruc.2021.130406

The synthesis of 5,10,15,20-tetrakis [4 '- (benzoxazol-2-yl) phenyl] -21,23-dithiaporphyrin was carried out by the reaction of metal complex catalysis. In this work, quantum chemical calculations were performed in the DFT approximation (hybrid functional B3LYP) with a set of 6–21 G basis functions. The resulting compound was identified by electron absorption, ¹H NMR spectroscopy and mass spectrometry. The basic properties of heterosubstituted ligand in comparison with the classical porphyrin analogue and unsubstituted TPP were studied by the spectrophotometric titration method in an acetonitrile - perchloric acid system. The basicity constants for the first and second steps and the ranges of existence of the protonated forms of 5,10,15,20-tetrakis [4 '- (benzoxazol-2-yl) phenyl] -21,23-dithiaporphyrin and its classical analog were determined.

Full text of DOI:10.1016/j.molstruc.2021.130406

Journal of Molecular Structure 1238 (2021) 130406
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstr
Synthesis, structure and basic properties of
ꢀ
5,10,15,20-tetrakis[4 -(benzoxazole-2-yl)phenyl]-21,23-dithiaporphyrin
S.G. Pukhovskayaa,∗, Y.B. Ivanovab, A.N. Kiselevb, N.A. Fominab, S.A. Syrbub
a Ivanovo State University of Chemistry and Technology, 153460, Sheremetevsky Pr. 7, 153000 Ivanovo, Russia
b G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, Akademicheskaya St. 1, 153045 Ivanovo, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of 5,10,15,20-tetrakis [4 ’- (benzoxazol-2-yl) phenyl] -21,23-dithiaporphyrin was carried out
by the reaction of metal complex catalysis. In this work, quantum chemical calculations were performed
in the DFT approximation (hybrid functional B3LYP) with a set of 6–21 G basis functions. The resulting
compound was identified by electron absorption, 1H NMR spectroscopy and mass spectrometry. The basic
properties of heterosubstituted ligand in comparison with the classical porphyrin analogue and unsubsti-
tuted TPP were studied by the spectrophotometric titration method in an acetonitrile - perchloric acid
system. The basicity constants for the first and second steps and the ranges of existence of the proto-
nated forms of 5,10,15,20-tetrakis [4 ’- (benzoxazol-2-yl) phenyl] -21,23-dithiaporphyrin and its classical
analog were determined.
Received 14 December 2020
Revised 11 March 2021
Accepted 29 March 2021
Available online 9 April 2021
Keywords:
Synthesis
Heterosubstituted Porphyrins
Basic Properties
© 2021 Elsevier B.V. All rights reserved.
1. Introduction
It is well known that the synthesis of porphyrins with het-
erocyclic substituents is based on the condensation of hetero-
Porphyrins are one of the best-studied classes among all known
macrocyclic systems [1], but the interest in their studies is far
from weakening; instead, it continues to grow. The fact that por-
phyrins and their analogues have such diverse properties is associ-
ated with their specific molecular structure [1-5]. Finding solutions
to the fundamental problems related to this class of compounds
and their practical applications are directly dependent on the op-
timization of the porphyrin synthesis methods and possibility of
chemical modification [6]. There are two methods of porphyrin
macrocycle transformation. One is the substitution of the hydrogen
atoms in the β-positions of the pyrrole rings, in the mesopositions
and at the transannular nitrogen atoms of the macrocycle. The va-
riety of organic and inorganic groups that can be chosen as sub-
stituents makes it possible to obtain a large number of classi-
cal porphyrin structures [7-10]. The second method of macrocycle
transformation is changing the macrocycle itself through hydro-
genation, broadening the conjugation system by adding carbo- or
heterocycles and through replacing one or two transannular nitro-
gen atoms with other donor atoms: O, C, S, Se, and Te [11]. The re-
sult of such transannular modification is porphyrinoids or hetero-
substituted porphyrins, with properties considerably different from
those of classical porphyrins.
cyclic aldehydes that are often difficult to obtain or that produce
a low yield of the final macroheterocycle. A breakthrough in the
preparation of such macroheterocycles was made with the dis-
covery of cross-coupling reactions [12]. The development of the
–
cross-coupling method enabled C H-functionalization of macrocy-
cles catalyzed by transition metal complexes [13].
Porphyrins and related macroheterocyclic compounds are ap-
plied in a variety of technological fields as catalysts of practi-
cally important processes, as parts of materials for optical lim-
iters, photosensitizers, solar energy converters, and many other de-
vices [3,6,14,15]. The last few years have seen a rapid development
of the porphyrin application areas, such as diagnostics and treat-
ment of malignancies, anemia, neuropsychic disorders; skin, eye,
and many other diseases [16-19].
Introduction of various heterocyclic substituents and donor
atoms into the porphyrin macrocycle has a great effect on the
porphyrin electronic structure and, thus, changes the physical and
chemical properties of the compounds, preserving their aromatic-
ity. When biologically active molecules are used as substituents,
they improve the useful properties of a compound as a whole.
A serious problem in medicine is the fast emergence of drug-
resistant microbial strains. Since the emergence of antiresistant
bacteria is inevitable, it is absolutely urgent to discover new ac-
tive agents; and among them, benzoxazole derivatives are the most
promising candidates [20,21]. This work presents the results of the
∗
Corresponding author.
ꢀ
E-mail address: svetlana.puhovskaya@mail.ru (S.G. Pukhovskaya).
synthesis of 5,10,15,20-tetrakis[4 -(benzoxazole-2-yl)phenyl]−21,23-
https://doi.org/10.1016/j.molstruc.2021.130406
0022-2860/© 2021 Elsevier B.V. All rights reserved.

S.G. Pukhovskaya, Y.B. Ivanova, A.N. Kiselev et al.
Journal of Molecular Structure 1238 (2021) 130406
dithiaporphyrin (I, S2TPP) and the study of its spectral, acid-base
2.2.2. Synthesis of
ꢀ
properties in comparison with the earlier synthesized classical
5,10,15,20-tetrakis[4 -bromophenyl]−21,23-dithiaporphyrin
ꢀ
ꢀ
analogue - 5,10,15,20-tetrakis[4 -(benzoxazole-2-yl)phenyl]porphyrin
Five grams (11 mmol) of 2,5-bis-(4 -bromophenyl hydrox-
(II, H2PP) [13] - and the easiest to obtain synthetic porphyrin -
5,10,15,20-tetraphenylporphin (III, H2TPP).
ymethyl)thiophene, 150 mL of para-xylene, and 0.75 mL (11 mmol)
of pyrrole were placed into
a 250 mL three-necked round-
bottomed flask equipped with a Dean-Stark trap, a reflux con-
denser, and an air feed pipe. Then the mixture was heated to
the para-xylene boiling point and 1 mL of trifluoroacetic acid was
added from the dropping funnel to 50 mL of para-xylene, with
air simultaneously passed through the mixture. The mixture was
boiled for 1 h and the p-xylene was distilled off with water vapor.
Then the precipitate was filtered, washed with water and dried
at room temperature until its weight became constant. The raw
product was dissolved in dichloromethane and chromatographed
on silica gel with simultaneous dichloromethane elution. The sec-
ond brownish-orange dithiaporphyrin layer was collected, the elu-
ate was evaporated, the product was precipitated with methanol,
filtered and dried at room temperature until its weight became
constant. Yield: 0.63 g (12%). For further purification, the product
was chromatographed on silica gel again.
2. Experimental
2.1. Materials and equipment
The solvents used in this work (perchloric acid, acetoni-
trile, dichloromethane, toluene, tetrahydrofuran, para-xylene, and
methanol) were purified by the standard methods [22]. Benzalde-
hyde, 4-bromobenzaldehyde, trifluoroacetic acid, benzoxazole, pal-
ladium acetate, palladium tetrakis(triphenylphosphine), copper ac-
etate, potassium carbonate, potassium hydroxide, triphenylphos-
phine, and pyrrole produced by Aldrich were used without purifi-
cation.
For preparative column chromatography, a Merck silica gel with
a particle size of 40–60 μm was used. The compound individuality
was controlled by the TLC method employing Silufol plates with a
layer thickness of 0.5 mm (Merck) and dichloromethane as the elu-
ent (the dichloromethane /methanol ratios were 50:1, 100:1). The
UV–visible spectra were measured on Shimadzu UV-1800 and Hi-
tachi U-2000 spectrophotometers. The acid-base properties of the
porphyrins were studied by spectrophotometric titration. The ex-
perimental techniques and methods of experimental data process-
ing are presented in detail in work [23].
1H NMR (CDCl3, 500 MHz) δ, ppm: 9.73 (s,4H, β-H), 8.69 (s,
4H, β-H), 8.16 (d, 8H, J = 7.94 Hz, Ar), 8.03d (d, 8H, J = 7.32 Hz,
Ar).
MALDI-TOF MS: m/z calculated: C44H24Br4N2S2: 966.1100; de-
termined experimentally: 966.1080 [M]+.
ꢀ
2.2.3. Synthesis of 5,10,15,20-tetrakis[4 -(benzoxazole-2-
yl)phenyl]−21,23-dithiaporphyrin(I)
First, 4.15 mg Pd(OAc)2 (40 mol%), 3.69 mg Cu(OAc)2•H2O (40
Chemically pure perchloric acid (58% aqueous solution), which
has a high dissociation constant (pKa. = 2.8 [24]) in acetonitrile,
was used as the protonating agent. For titration, a working 0.01 M
solution of perchloric acid (HClO4) in acetonitrile was prepared.
The error in the measurement of the corresponding constants was
3–5%.
mol%), 30.3 mg triphenylphosphine (2.5 eq.), 44.68 mg 5,10,15,20-
ꢀ
tetrakis[4 -bromophenyl]−21,23-dithiaporphin
(0.0463
mmol),
(3 mL) toluene, and 44.72 mg benzoxazole (8 eq. 0.3704 mmol)
were placed into a 5 mL flask equipped with a magnetic stirrer
and a reflux condenser. Then the mixture was stirred for 1 min;
31.99 mg of potassium carbonate (5 eq.) were added. After that,
the mixture was stirred again and was simultaneously boiled.
Forty hours later, when the reaction was completed, the reaction
mixture was cooled to room temperature and dichloromethane
(5 mL) was added. The mixture was filtered off, the precipitate
was washed portionwise with dichloromethane (2 × 5 mL), and
the combined organic fractions were evaporated in a vacuum.
To obtain chemically pure compounds, the residue was chro-
matographed on silica gel, which was accompanied by its elution
with a dichloromethane-methanol mixture (100:1). Yield: 23.7 mg
(46%).
2.2. Synthesis
ꢀ
2.2.1. Synthesis of 5,10,15,20-tetrakis(4 -bromophenyl)porphin
2.0 mL of trifluoroacetic acid and 150.0 mL of para-xylene were
placed into a 1 L three-neck flask equipped with a Dean-Stark trap,
a reflux condenser, an air feed pipe, and a dropping funnel. The
mixture was heated to the para-xylene boiling point and a solution
of 13.3 g (72 mmol) of 4-bromobenzaldehyde and 5 g (72 mmol)
of pyrrole was added from the dropping funnel to 150 mL of para-
xylene, with air simultaneously passed through the mixture.
The reaction mixture was boiled for 1 hour, with air simulta-
neously passed through it. Then the mixture was cooled to room
temperature, 2 mL of diethanolamine were added, and after that,
the mixture was left overnight. Then the porphyrin precipitate
was filtered, washed with ethanol, and dried at room tempera-
ture until its weight became constant. For purification, the por-
phyrin was dissolved in dichloromethane and chromatographed on
aluminum oxide, Brockman activity grade II, with simultaneous
dichloromethane elution. The porphyrin eluate was evaporated and
precipitated with ethanol. Yield: 5.9 g (35%).
1H NMR (CDCl3, 500 MHz): 9.86 (s, 4H, β-H-thiophene), 8.83
(s, 4H, β-H-pyrrole), 8.59 (s, 4H, β-H), 8.22–8.25 (m, 8H 3 J = 7.8
Ar), 7.75–7.49 (m, 8H, 3 J = 7.8 Hz Ar).
MALDI-TOF MS: m/z calculated: C72H40N6O6S2: 1118.2611; De-
termined experimentally: 1118.2411 [MH]+.
2.2.4. Synthesis of zinc
5,10,15,20-tetrakis[4-(1,3-benzoxazole-2-yl)phenyl]porphyrinate (II)
Porphyrin (II) was synthesized using the method described in
work [13]. The compound chemical purity was controlled by the
TLC method using Silufol plates with the layer thickness of 0.5 mm
("Merck’), and employing dichloromethane as the eluent. The spec-
tral characteristics of the compound agreed with the literature data
[13].
1H NMR (CDCl3, 500 MHz): δ −2.85 (bs, 2H, NH), 7.92 (d, 8H,
J = 8.0 Hz, Ar), 8.10 (d, 8H, J = 8.0 Hz, Ar), 8.87 (s, 8H, H-pyrrole).
Elemental analysis: calculated:% H 2.820; C 56.810; N 6.02; Br
34.35; determined experimentally:%H 2468; C 56,595; N 5632; Br
34,35.
Yield:
visible, λmax
(dichloromethane). 1H NMR δ, ppm: 7.40–7.46
8
mg (14%), vinous-green crystalline powder. UV-
nm (log ε): 427(5.90); 553(4.81); 596(4.67)
(8H); 7,67–
,
m
UV–vis: λmax
515(4.34), 419(5.68) (CHCl3).
,
nm (lgε): 650(3.95), 590(3.89), 549(4.04),
7,71 m (4H); 7,84–7.88 m (4H); 8.40d (8H, 3 J = 7.7 Hz); 8.64d
(8H, 3 J = 7.7 Hz); 9.02 s (8H) (CDCl3).
MALDI-TOF MS: m/z calculated: C44H26Br4N4, 929.8911; deter-
mined experimentally: 929.6612 [M]+.
MALDI-TOF MS: m/z calculated: C72H40N8O4Zn: 1144.25; deter-
mined experimentally: 1144.22 [M]+.
2

S.G. Pukhovskaya, Y.B. Ivanova, A.N. Kiselev et al.
Journal of Molecular Structure 1238 (2021) 130406
7.42 m (6H); 7,65br.s (3H); 7,72br.s (3H); 7,88d (2H, 3 J = 8,2 Hz);
8,06d (2H); 8,36br.d (6H); 8,54br.d (6H); 8,93–9,01 m (8H) (CDCl3).
MALDI-TOF MS: m/z calculated: C65H36BrN7O3Zn: 1105.14; de-
termined experimentally: 1105,05 [M]+.
2.2.5. Synthesis of 5,10,15,20-tetraphenylporphin (III)
Porphyrin (III) was synthesized according to the procedure
described in [10]. 1Н NMR δ, ppm: 8,90
8,29 m (8H, 2,6-H-pH); 7,76–7,84 m (12H, 3,4,5-H-pH); −2,72bs
(2H, NH) (CDCl3). UV-visible: λmax, nm (lgε): 647(3.82), 590(3.86),
550(4.03), 515(4.27), 418(5.67) (CHCl3).
s (8H, β-H); 8,24–
Scheme 1. The first stage.
MALDI-TOF MS: m/z calculated: C44H30N4, 614.4011; deter-
mined experimentally: 614.6065 [M]+.
The additional data are presented in Figs. 1S-6S in Supplemen-
tary material. additional material is presented in Figs. 1-6
дополнительный материал представлен на рисунках 1–6. dopoleit-
elny material represented drawings 1–6
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Scheme 2. The second stage.
The quantum-chemical calculations for these compounds were
performed using the Gaussian 9 software package [24]. The 3–
21 G basis set was used to describe the electron-wave functions
of atoms was borrowed from the EMSL library [25,26]. The calcu-
lations for these compounds were made by the DFT method using
the B3LYP hybrid functional. Initially, during the porphyrin macro-
cycle construction, the angles and bonds of the averaged structure
of porphyrins were used. A nitrogen atom with a lone electron
pair was installed in such a way that the lone electron pair would
be directed towards the coordination center. Joint structures have
been fully optimized with no symmetry constraints. After the op-
timization of the geometric parameters, the wave function stability
was tested.
To obtain metal-free ligand (II), the solution of the zinc complex
was treated with an HCl solution in dichloromethane, washed with
water until a neutral reaction, and chromatographed on silica gel,
which was accompanied by its elution with CH2Cl2.
MALDI-TOF MS: m/z calculated: C72H42N8O4: 1080.86; deter-
mined experimentally: 1080.82 [M]+.
Zinc
5,10,15-tris[4-(1,3-benzoxazole-2-yl)phenyl]−20-(4-
bromophenyl)-porphyrinate was also obtained. Eluent: 50:1
DCM/methanol mixture. Yield: 44 mg (80%), vinous-green crys-
talline powder. UV-visible: λmax, nm (log ε): 427 (5.98); 553
(4.81); 597 (4.65) (dichloromethane). 1H NMR δ, ppm: 7.36–
Scheme 3. The third stage.
3

S.G. Pukhovskaya, Y.B. Ivanova, A.N. Kiselev et al.
Journal of Molecular Structure 1238 (2021) 130406
3. Results and discussion
An important part of the synthesis procedure of heterosub-
stituted porphyrins is preparation of initial semi-products. The
ꢀ
procedure of 5,10,15,20-tetrakis[4 -(benzoxazole-2-yl)phenyl]−21,23-
dithiaporphyrin synthesis included three main stages. At
first, the reaction of thiophen with n-butyllithium produced
an organolithium compound that later interacted with
a 4-
bromobenzaldehyde solution in tetrahydrofuran (THF) and formed
ꢀ
2,5-bis(4 bromophenylhydroxymethyl)thiophen with a 75% yield
(scheme 1).
An analysis of the literature data [27,28] shows that the syn-
thesis duration and the yield of heterosubstituted porphyrins to
a large extent depend on the medium of the condensation reac-
tion. For example, Ullman and Manassen [27] demonstrated that
substitution of benzene containing 2% chloroacetic acid for toluene
reduced the reaction duration by a third and increased the prod-
uct yield from 6 to 10%. The use of p-xylene with trifluoroacetic
acid (TFA) additions as the solvent made it possible to signif-
icantly shorten the synthesis procedure (scheme 2) required to
ꢀ
prepare 5,10,15,20-tetrakis[4 -bromophenyl]−21,23-dithiaporphyrin
with a 12% yield.
ꢀ
Further
modification
of
5,10,15,20-tetrakis[4 -
bromophenyl]−21,23-dithiaporphyrin employed metal complex
–
catalysis reactions, namely C H-functionalization of the hetarylat-
–
ing macrocycle. Benzoxazole with an "acidic" C H bond served as
such hetarylating agent.
The reaction was carried out with a Pd(OAc)2/Cu(OAc)2 catalytic
system (40/40 mol%) in the presence of 2.5 eq. triphenylphosphine
as the ligand and 5 eq. K2CO3 in boiling toluene and lasted for
40 h.
In contrast to
a similar tetraphenylporphyrin (TPP) reac-
tion with the main heteroarylation product being trihetaryl-
ꢀ
substituted TPP with
a
small amount of 5,10,15,20-tetrakis[4 -
(benzoxazole-2-yl)phenyl]porphyrin [13], in this case, the yield of
ꢀ
the product – 5,10,15,20-tetrakis[4 -benzoxazole-2-yl)phenyl]−21,23-
dithiaporphyrin – reached 46%. Another product, which was ex-
tracted by monohetarylation, retained three bromine atoms, and
its yield was 10% (scheme 3).
Fig. 1. Optimized structures of (a) (I), (b) (II), obtained by DFT calculations at the
B3LYP/3–21 G level of theory.
The calculations of the geometric parameters for these com-
pounds were carried out by the DFT method using the B3LYP hy-
brid functional (Table 1). The calculation results showed that the
substitution of the sulfur atoms for nitrogen atoms in the macro-
cycle reaction center increased the lengths of the bonds between
the corresponding carbon and the heteroatom. This is the reason
for the radial deformation of tetrapyrrole macrocycle (I). The in-
troduction of peripheral substituents into compounds (I) and (II)
caused out-of-plane distortions of the macrocycles (Fig. 1), in the
form of a ruffled macrocycle conformation. Ruffled conformations
are characterized by in-plane rotation of the pyrrole rings and sig-
nificant out-of-plane displacements of the meso–carbon atoms. It is
known that the noted structural changes also indirectly affect the
electronic structure of the macrocycle, decreasing its aromaticity
and increasing the electron density at the atoms of the porphyrin
coordination center.
Table 1
Geometric parameters of compounds (I) and (II).
Compound (I)
Compounds (II)
˚
bond length A
C3 – C2
1.423
1.387
1.390
2.533
1.729
1.727
1.447
1.334
1.473
2.165
1.374
1.300
3.056
4.520
C3 – C2
1.392
1.387
1.388
2.263
1.384
1.384
1.012
1.465
1.329
1.487
2.161
1.391
1.304
4.199
C2 – C1
C2 – C1
C3 – C4
C3 – C4
C4 – C1
C4 – C1
C4 – S
C3 – N21
C1 – N21
N21 – H
C18 – C19
C18 – C17
C17 – C16
C19 – C16
C19 – N24
C1 – S
C18 – C19
C18 – C17
C17 – C16
C19 – C16
C19 – N24
It is known that porphyrins (H2P) and their heterosubstituted
analogues can be protonated in organic solvents in the presence of
acids at the transannular nitrogen atoms [29,30].
C16 – N24
S – N24
C16 – N24‘
N24 – N22
N24 – N22
Angles, degrees
C20 – C1 – S – C4
C20 – C19 – N24 – C16
C2 – C1 – C20 – C19
C1 – S – C4 – C5
C4 – S – C1
C1 – C20 – C19
C19 – N24 – C16
The basic properties of heterosubstituted perchloric acid ligand
(I) in comparison with classical porphyrin analogue (II) and unsub-
stituted TPP (III) were studied by the spectrophotometric titration
method in an acetonitrile – perchloric acid system at T = 298 K.
To a first approximation (with no solvent involved and with-
out stabilization of the resulting particles by counterions), the acid-
base interaction processes of porphyrins and related macrohetero-
171.9
176.1
−174.3
−172.8
94.3
C20 – C1 – N21 – H
H – N21 – C1 – C2
H – N21 – C4 – C5
H – N21 – C4 – C3
C4 – N21 – C1
8.0
−178.3
−1.9
179.4
109.7
125.5
106.6
121.7
108.1
C1 – C20 – C19
C19 – N24 – C16
4

S.G. Pukhovskaya, Y.B. Ivanova, A.N. Kiselev et al.
Journal of Molecular Structure 1238 (2021) 130406
Fig. 2. Changes in the UV-visible spectra in the acetonitrile – perchloric acid system in the process of titration with perchloric acid in acetonitrile at 298 K of: a) compound
(I) (Cporph = 6.30 10−6 mol/L), b) compound (II) (Cporph = 3.07 10−5 mol/L) in the acetonitrile – perchloric acid system; c) respective titration curves of compound (I) with
•
•
the analytical wavelengths of 437 and 461 nm; d) respective titration curve of compound (II) with the analytical wavelength of 421 nm.
cycles in acidic media can be described by Eqs. (1-2) [31]:
The total values of the basic ionization constants of protonated
forms (I) in comparison with their classical analogue – H2TPP – in
the acetonitrile – perchloric acid system at 298К were determined
by Eq. (3); their values are given in Table 2.
Kb1
H4P2+
H3P+ + H+
(1)
(2)
ꢀ
pKb = −lgKb = pH − −lgInd
(3)
Kb2
H3P+
H2P + H+
Here, Kb is the basicity constant at the first and second steps,
Ind is the indicator ratio for compound (I) at the first [S2P]/[HS2P+]
and second [HS2P+]/[H2S2P2+] protonation steps, respectively, for
compound (II) – [H2PP]/[H3PP+] [H3PP+]/[H4PP2+] – the рН values
were calculated by the method described in [23] by formula (4):
ꢀ
where Н2Р, H3P+, and H4P2+ are the molecular, mono- and doubly-
protonated ligand forms (the notation for classical porphyrins (II)
and (III), for compound (I) was used: S2P, HS2P+, and H2S2P2+, re-
spectively).
pH = −2.48 − 2.65 lg CHC104
(4)
The spectrophotometric studies of compounds (I) and (II) in the
acetonitrile – perchloric acid system showed that as the perchlo-
ric acid concentration increased, two families of spectral curves
were formed in the electronic absorption spectra, each with its
own set of isobestic points. These experimental data confirm that
there were two stages in the protonation process. The changes
in the UV-visible spectra during the titration and the titration
curves are shown in Fig. 2. By distinguishing the two families of
isobestic points on the UV-visible spectra, we were able to deter-
mine the concentration intervals of existence (of protonated forms
(I) and (II)) and spectral characteristics of the intermediate mono-
protonated form for HS2P+ (Fig. 3). The parameters of the UV-
visible spectra of the molecular and resulting protonated forms are
given in Table 2.
The error in the calculation of the constants during the experi-
ment did not exceed 3–5%.
Taking into account the processes of basic dissociation of pro-
tonated forms (1–2), and material-balance Eq. (5), as well as the
proportionality of the optical density of the dissolved substance to
its concentration, according to the Lambert–Bouguer–Beer law, we
determined the distribution of the concentrations of the molecular
and protonated forms of the studied compound in titration pro-
cesses (6–9) (Fig. 2 for compound (I)).
C0 = CS P + CHS P + CH S P2+ = 100%
(5)
+
2
2
2
2
AS P · Kb1 · Kb2 + AHS P · 10−pH · Kb1 + 10(−pH)2 · AH S P2+
+
2
2
2
2
At =
(6)
(−pH)2
Kb1 · Kb2 + 10−pH · kb2 + 10
5

S.G. Pukhovskaya, Y.B. Ivanova, A.N. Kiselev et al.
Journal of Molecular Structure 1238 (2021) 130406
Table 2
Indicators of base ionization constants and spectral characteristics of molecular and protonated forms of porphyrins (I) –
(III) in the acetonitrile – perchloric acid system at T = 298 K.
Porphyrin
λ(lgε∗)
pK1
pK2
ꢀpK
H2TPP
H4TPP2+
413(5.02)
441(5.04)
437(5.3)
512(3.56)
546(3.12)
589(2.92)
–
646(2.96)
661(4.17)
698(4.05)
–
–
19.80[26]
–
–
S2TPP
HS2TPP+
518(4.46)
549sh(4.20)
635(3.99)
707(4.17)
733sh(4.23)
591(3.51)
614sh(3.70)
9.88
9.85
19.73
22.31
463(5.1)
–
616(4.25)
2+
H2S2TPP
475(5.04)
421(4.96)
456(4.97)
704(4.23)
516(3.84)
–
–
H2PP
H4PP2+
553(3.70)
–
647(3.37)
667(4.25)
12.30
10.01
∗
ε ((mol/L)–1.cm–1) is the molar absorption coefficient (molar extinction coefficient); the error in three parallel series
of experiments was 1–3%.
porphyrin (II)); Kb1 and Kb2 are the basicity constants of processes
2+
(1) and (2); At, AS2P, AHS2P+, AH2S2P
are the optical densities of
the solutions corresponding to the neutral and ionized forms of
2+
porphyrin (I) or AH2P, AH3P+, AH4P
for porphyrin (II)).
The introduction of bulky substituents into the para- positions
of the four phenyl fragments of compound (II) increases the basic
properties of the ligand in comparison with H2TPP due to addi-
tional deformation of the macrocycle.
Further modification of compound (II), namely the replacement
of two pyrrole nitrogen atoms of the reaction center with more
electropositive sulfur atoms, as could be expected, reduces the ba-
sic properties of compound (I) by ~ 2.5 orders of magnitude in
comparison with (II). However, it should be said that in compar-
ison with H2TPP, the basicity of (I) becomes only slightly lower
(the changes are within the experimental error). This fact is ev-
idently associated with the mutually opposing action of several
factors: the electron effect of the benzoxazole substituent and in-
crease in the macrocycle deformation because of the bigger diam-
eter of the transannular sulfur atoms in comparison with nitrogen
[32,33]. Both factors make the compound basic properties stronger
(I). Lower basicity, i.e. partial negative charges on the central nitro-
gen atoms, causes redistribution of the electron density due to the
introduction of less electronegative sulfur atoms.
4. Conclusion
In summary, the present study provides an insight into the de-
sign of the classical and heterosubstituted ligand of porphyrin-
inspired macrocycles. The reaction of metal complex cataly-
ꢀ
sis was used to synthesize 5,10,15,20-tetrakis[4 -(benzoxazole-2-
ꢀ
yl)phenyl]−21,23-dithia (I) and 5,10,15,20-tetrakis[4 -(benzoxazole-
2-yl)phenyl]porphyrin (II). The geometric parameters for these
compounds were calculated by UV-visible spectroscopy. The UV-
visible spectra show that there is distinct stepwise protonation
in both porphyrins. The molecular and resulting protonated forms
were characterized by absorption spectra.
Fig. 3. Distribution of concentrations and spectra of the molecular (1) and doubly
protonated (2) forms during the titration of compound (I) (a) and compound (II)
(b).
Declaration of Competing Interest
kb1 · kb2
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared to
influence the work reported in this paper.
CS P
=
· 100%
(7)
(8)
(−pH)2
2
kb1 · kb2 + 10−pH · kb2 + 10
10−pH · kb2
+
CHS P
=
· 100%
(−pH)2
2
kb1 · kb2 + 10−pH · kb2 + 10
CRediT authorship contribution statement
(−pH)2
10
· kb2
CH S P2+
=
· 100%
(9)
(−pH)2
2
2
S.G. Pukhovskaya: Conceptualization, Methodology, Software,
Data curtion. Y.B. Ivanova: Visualization, Investigation, Writing –
original draft. A.N. Kiselev: Writing – review & editing. N.A. Fom-
ina: Software, Validation. S.A. Syrbu: Supervision.
kb1 · kb2 + 10−pH · kb2 + 10
Here: CS2P, CHS2P+, CH2S2P
are the concentrations of the neu-
2+
tral and ionized forms of porphyrin (I) or CH2P, CH3P+, CH4P
for
2+
6

S.G. Pukhovskaya, Y.B. Ivanova, A.N. Kiselev et al.
Journal of Molecular Structure 1238 (2021) 130406
Acknowledgements
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The work was financially supported by the Russian Foundation
for Basic Research, grant No. 19–03–00214 A, and was carried out
on the equipment of the Upper Volga Region Center of Physico-
Chemical Research.
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