The Sn(IV)-tetra(4-sulfonatophenyl) porphyrin complexes with antioxidants: Synthesis, structure, properties

Article abstract of DOI:10.1016/j.ica.2018.11.003

Complexes of Sn(IV)-tetra(4-sulfophenyl)porphyrin with antioxidants (methoxydol and ionol) and their precursors (para-cresol and 3-hydroxypyridine) were synthesized. All four complexes were obtained by boiling in aqueous solutions of the p-sulfo substitut

Full text of DOI:10.1016/j.ica.2018.11.003

InorganicaChimicaActa486(2019)468–475
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Research paper
The Sn(IV)-tetra(4-sulfonatophenyl) porphyrin complexes with
antioxidants: Synthesis, structure, properties
⁎
Galina M. Mamardashvilia, , Dmitriy A. Lazovskiya,b, Olga V. Maltcevaa,
Nugzar Zh. Mamardashvilia, Oscar I. Koifmana,b
a G.A. Krestov Institute of Solution Chemistry of the Russian Academy of Sciences, Ivanovo 153045, Russian Federation
b Research Institute of the Chemistry of Macroheterocyclic Compounds, Ivanovo State University of Chemistry and Technology, Sheremetevskiy Av. 7, Ivanovo 153000,
Russian Federation
A R T I C L E I N F O
A B S T R A C T
Keywords:
Complexes of Sn(IV)-tetra(4-sulfophenyl)porphyrin with antioxidants (methoxydol and ionol) and their pre-
cursors (para-cresol and 3-hydroxypyridine) were synthesized. All four complexes were obtained by boiling in
aqueous solutions of the p-sulfo substituted Sn(IV) dihydroxytetraphenylporphyrin with the corresponding
phenols. The structure of the obtained compounds was confirmed by NMR spectroscopy and mass spectrometry
methods and quantum chemical calculations. Fluorescent properties of the diphenol complexes of Sn(IV) por-
phyrins and their photochemical stability in the presence of hydrogen peroxide in buffer media were in-
vestigated. It was shown that complexes with antioxidant ligands (ionol and methoxydol) have higher quantum
yields and are more resistant to macrocycle destruction than complexes with other phenols and Sn(IV) dihy-
droxytetraphenylporphyrinate complexes. The main reasons for higher stability and weak quenching of fluor-
escence intensity are the presence of alkyl groups in the ortho-positions of the phenolic rings in the ionol and
methoxydol molecules.
Sn(IV) porphyrins
Antioxidants
Synthesis
Spectroscopic properties
Fluorescent properties
1. Introduction
axially coordinated antioxidants.
Sn(IV) – porphyrins are ideal basis for constructing axial binding
Nowadays Fluorescent diagnostics (FD) and photodynamic therapy
(PDT) are considered to be the most promising methods of prevention,
diagnosis and treatment, which are widely used in various fields of
medical practice, in particular in oncology, dermatology, cosmetology,
gynecology [1–3]. The advance of photodynamic cancer therapy is
closely related to the design of porphyrin-based sensitizers [4–6].
Currently, porphyrin photosensitizers of several generations have al-
ready been developed and are successfully used. However, in order to
further improve the photodynamic therapy method, it is necessary to
search for the new photosensitizers that have even higher photoactivity,
tumorigenicity, ability to excite in the near infrared spectrum range and
capable of early diagnosis.
assemblies [7–30]: (a) they are resistant to acids in contrast to other
metalloporphyrins, such as Zn(II) and Mg(II) porphyrins; (b) Sn(IV)
porphyrins are diamagnetic with NMR active Sn atom to obtain struc-
tural information; (c) Sn(IV) porphyrins fluoresce and luminesce; (d)
One can reduce Sn(IV) porphyrins easier than other diamagnetic me-
talloporphyrins, and (e) Sn(IV) porphyrins have a strong affinity for
oxygen donor ligands. The overwhelming majority of antioxidants are
organic compounds with phenolic groups.
The purpose of this work was to obtain the Sn(IV)-tetra(4-sulfo-
phenyl)porphyrin diaxial complexes with antioxidants (methoxydol
(L2) and ionol (L4)) and their precursors (para-cresol and 3-hydro-
xypyridine) as potential objects for photodynamic therapy, containing
simultaneously porphyrin photosensitizer, and an antioxidant that re-
duces side toxicological effects in the lesion and investigation of the
effect of the antioxidant environment of Sn-porphyrin on its fluorescent
properties and quantum yield.
One of the disadvantages of the PDT method is increased radical
formation at all levels, both in cell membranes and in biological fluids,
which leads to inhibition of the activity of antioxidant defense me-
chanisms. Therefore, the problem of design of multifunctional phar-
maceutical system, which would deliver both sensitizer and antioxidant
substances to the lesion simultaneously, is very actual. The prototype of
such systems could be sensitizers based on Sn(IV) – porphyrins with
⁎ Corresponding author at: 1 Akademicheskaya Str., 153045 Ivanovo, Russian Federation.
E-mail address: gmm@isc-ras.ru (G.M. Mamardashvili).
https://doi.org/10.1016/j.ica.2018.11.003
Received 13 July 2018; Received in revised form 1 November 2018; Accepted 4 November 2018
Availableonline09November2018
0020-1693/©2018PublishedbyElsevierB.V.

G.M. Mamardashvili et al.
InorganicaChimicaActa486(2019)468–475
(70%) [M-2(L2)-4(SO3−)]+. 1H NMR, (500 MHz, D2O): 9. 05 (s, 8H, Hβ-
pyrr.), 8.33 (d, J = 7.8 Hz, 8H, ortho-C6H4), 8.16 (d, J = 7.8 Hz, 8H,
meta-C6H4), 5.72 (s, 4H, meta-Ar-L), 3.15 (s, 36H, CH3-L), 1.78 (s, 6H,
CH3-L).
SnP(L3)2: UV–Vis (water), λmax(logε)nm: 594 (4.03), 557 (4.06),
424 (5.02) MS (MALDI-TOF) (m/z): (M = C54H32N6O14S4Sn): 1233.7
(28%) [M]+; 1139.6 (62%) [M-L3]+; 1045.5 (94%) [M-2(L3)]+, 725.5
(765%) [M-2(L3)-4(SO3−)]+
.
1H NMR, (500 MHz,D2O): 9.10 (s, 8H,
H
β-pyrr.), 8.42 (d, J = 7.8 Hz, 8H, ortho-C6H4), 8.20 (d, J = 7.8 Hz, 8H,
meta-C6H4), 6.96 (d, J = 6.9 Hz, 2H, para-Ar-L), 5.18 (t, J = 7.6 Hz, 2H,
meta-Ar-L), 2,19 (d, J = 3.9 Hz, 2H, ortho-Ar-L), 2,03 (s, 2H, orthó-Ar-
L).
SnP(L4)2: UV–Vis (water), λmax(logε) nm: 594 (4.03), 555 (3.54),
421 (5.01) MS (MALDI-TOF) (m/z): (M = C60H44N6O14S4Sn): 1317.7
(25%) [M]+; 1181.6 (62%) [M-L4]+; 1045.5 (92%) [M-2(L4)]+, 725.5
(70%) [M-2(L4)-4(SO3−)]+. 1H NMR, (500 MHz, D2O): 9.09 (s, 8H, Hβ-
pyrr.), 8.40 (d, J = 7.8 Hz, 8H, ortho-C6H4), 8.18 (d, J = 7.8 Hz, 8H,
meta-C6H4), 5.06 (d, J = 6.0 Hz, 2H, meta-Ar-L), 2.72 (q, 4H, -CH2-
CH3), 2.39 (s, 6H, CH3), 1,86 (d, J = 3.7 Hz, 2H, ortho-Ar-L), 1.13 (t,
6H, -CH2-CH3).
Fig. 1. Molecular structures of the SnP(L)2 and ligands (L).
2. Experimental
2.1. Materials
We used commercially available 5,10,15,20-tetra(4-sulfophenyl)
porphyrin, cresol, 3-pyridylphenol (Sigma-Aldrich), methoxidol, ionol
(BION Ltd. Obninsk) (Fig. 1).
2.4. Thermodynamics
The fluorescence spectra were recorded at an excitation wavelength
of 416 nm. The width of the excitation and emission slits was 5 nm.
Absorption and emission spectra were obtained in phosphate buffer
(pH = 7.4) with a concentration of the test compound 1∙10-6 mol/l. The
relative quantum yield was calculated by the formula:
2.2. Equipment
The 1H NMR spectra were recorded in D2O on an Avance 500 in-
strument (Bruker, USA) at an operating frequency of 500 MHz.
Standard – TMS. Electronic absorption spectra were recorded in the
range of 355–800 nm on a Cary 300 spectrophotometer (Agilent, USA).
Fluorescence spectra were recorded in the range of 500–770 nm on the
RF 5301PC spectrofluorimeter (Shimadzu, Japan).
Ix Ast nx2
=
·
st
x
Ist Ax ns2t
where φst is the quantum yield of the standard (dihydroxy-Sn(IV)-meso-
tetra(p-methylphenyl)porphyrin in methanol, φst = 0. 49 [9]), Ix and Ist
are the area under the fluorescence spectra of the studied compound
and standard, respectively, Ax and Ast are the optical density of the
studied compound and the standard, respectively, at the excitation
wavelength, nx and nst are the refractive indices of the solutions with
the studied substance and standard, respectively.
Quantum-chemical simulating of the studied compounds was car-
ried out using the DFT method with the B3LYP hybrid functional in a
mixed basis: 3–21 g for C, N, O, S, H and ECP28MDF VTZ atoms (cc-
pVTZ-PP) for the atom Sn [31–32].
2.3. Synthesis
The kinetic parameters of the photochemical decomposition reac-
tion were obtained according to the procedure described in [34–36].
The effective rate constants (keff) were determined from the change in
the optical density of the solution at working wavelengths (λ ∼
420 nm) at definite time intervals, using a formally first-order equation
with excess peroxide. Irradiation of the cobalt-porphyrin solutions was
carried out using a medium pressure mercury lamp of the TUNGSRAM
20 W F33 type. The light irradiation wavelength range is 380–800 nm,
and the intensity is 13,000 Lux.
Dihydroxy-Sn(IV)-tetra(4-sulfophenyl)porphyrin (SnP(OH)2) was
synthesized by the procedure. Described in [33] by boiling of meso-tetra
(p-sulfophenyl)porphyrin with metallic tin in water for 60 h. Purifica-
tion of the resulting compound was carried out by column chromato-
graphy. We used aluminum oxide as the adsorbent. The eluent was a
mixture of ethanol: water in a ratio of 1: 2.
UV–vis (water), λmax(logε)nm: 593 (4.10), 554 (3.60), 419 (5.40),
MS (MALDI-TOF) (m/z): 1085(98) [M]+ 1H NMR, (500 MHz,CDCl3):
9.10 (s, 8H,β-pyrr.), 8.45 (d, J = 7.8 Hz, 4H, ortho-C6H5), 8.25 (d,
J = 7.8 Hz, 8H, meta-C6H5). -7.02 (2H, OH).
3. Results
The SnP(L1-L4)2 complexes were synthesized by boiling SnP(OH)2
with a 2.5 fold excess of ligands L1, L2, L3 and L4 in water for 2.5, 1.5,
2 and 5 h, respectively. Purification of the resulting compounds from an
excess of the ligand was carried out by column chromatography. The
adsorbent was aluminum oxide. The mixture of ethanol: water in a ratio
of 1:2 was used as eluent.
3.1. Synthesis and characterization
The publications devoted to ligand exchange of hydroxyl groups in
lipophilic dihydroxy-Sn-porphyrins on various phenols and phenolic
derivatives are quite extensive [10–12,18]. They describe the methods
for the synthesis of diphenolic Sn-porphyrins, proposed a mechanism
for ligand exchange, discuss their structure, spectral properties, and the
areas of their possible application. The main method for synthesis of the
diphenolic complexes is heating or boiling of solutions of dihydroxy-Sn
(IV)-porphyrin and the corresponding phenol (phenolic derivative) (pKa
7–11) in anhydrous aprotic nonpolar solvents (benzene, toluene,
chloroform). The ligand exchange reaction time is determined by the
structure of the porphyrin and phenolic molecule. Direct proofs of the
stepwise formation of Sn(IV)TTP bisphenolates, in accordance with
Scheme 1, were obtained by the authors of [10] by 1H NMR
SnP(L1)2: UV–Vis (water), λmax(logε) nm: 594 (4.11), 556 (3.56),
423 (5.05). MS (MALDI-TOF) (m/z): (M = C58H38N4O14S4Sn): 1259.7
(30%) [M]+; 1153.7 (55%) [M-L1−
]
+; 1046.7 (95%) [M-2(L1)]+
;
725.5 (70%) [M-2(L2)-4(SO3−)]+
.
1H NMR, (500 MHz,D2O): 9.02 (s,
8H, Hβ-pyrr.), 8.45 (d, J = 7.8 Hz, 8H, ortho-C6H4), 8.25 (d, J = 7.8 Hz,
8H, meta-C6H4), 5.42 (d, J = 8.7 Hz, 4H, meta-Ar-L), 1.89 (s, 6H, CH3-
L), 1.74 (d, J = 8.7, 4H, ortho-Ar-L).
SnP(L2)2: UV–Vis (water), λmax(logε)nm: 595 (4.07), 558 (3.53),
422 (5.04). MS (MALDI-TOF) (m/z): (M = C74H70N4O14S4Sn): 1483.7
(20%) [M]+; 1264.7 (62%) [M-L2]+; 1045.5 (92%) [M-2(L2)]+, 725.5
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InorganicaChimicaActa486(2019)468–475
Scheme 1. The mechanism of Sn-porphyrins diphenolic complexes formation in aqueous media.
spectroscopy. Direct evidence for the stepwise formation of the bi-
sphenolates of Sn(IV)TTP is shown in Scheme 1. The results of the
studies indicated that this mechanism is not regulated by the pKa de-
pendence, but mainly depends on steric factors due to interactions
between the substituents in phenol with porphyrin mesoaryls.
Our studies show that the aqueous medium is the most suitable
medium for the synthesis of diphenol complexes from solvents in which
dihydroxy-Sn(IV)-tetra(4-sulfophenyl)porphyrin dissolves, and this is
H2O, lower alcohols, DMSO or DMF. The boiling time of solutions of Sn-
porphyrin and the corresponding phenol (L1-L4) in a ratio of 1:2.2 was
from one to 5 h. Like in non-aqueous solvents, there is no direct re-
lationship between the rate of substitution reaction and pKa of phenol
(Fig. 2).
3.2. Structure of SnP(L)2 complexes
The structures of the hydrophilic Sn(IV)-porphyrin complexes syn-
thesized with antioxidants (SnP(L2)2 and SnP(L4)2) and their pre-
cursors were optimized by the DFT B3LYP method. The geometric
parameters and structures are presented in Table 1 and Fig. 3, respec-
tively.
The structure of the complexes studied was optimized to the saddle
point on the PES (potential energy surface) and in all cases is a prac-
tically flat macrocycle.
In
the
series
SnP(OH)2 < SnP(L1)2 < SnP(L3)2 < SnP
(L4)2 < SnP(L2)2, the distance Sn-O increases from 2.02 to 2.10 A. As
in the case of the replacement rate of hydroxy groups by phenols
(Fig. 2), there is no direct correlation between the Sn-O bond length in
the SnP(L)2 complexes and the acid-base properties of L. The in-
troduction of the ethyl group into the ortho-position of hydroxypyridine
leads to the removal of the axial ligand in the SnP(L)2 complex by
0.023 nm. Due to the presence of two tret-butyl substituents in the
ortho-positions of the phenolic ring of all the studied phenols, the ionol
molecules in the SnP(L)2 complex are at the maximum distance from
the porphyrin center of 2.1 nm, which is 0.047 nm higher than in the
SnP(L3)2 complex.
The hydroxyl groups of SnP(OH)2 are most rapidly replaced by
unsubstituted pyridinol L3. Slowly, the hydroxyl groups in SnP(OH)2
are replaced by ionol molecules. Although the ionol is a ligand with the
lowest acidity, however, its presence in two orthotertbutyl groups in the
ortho-positions plays a major role in its low reactivity, which un-
ambiguously prevents the ligand exchange, but does not exclude this
possibility. The mechanism of substitution of hydroxyl groups in SnP
(OH)2 for phenols in aqueous media, most probably, is analogous to the
mechanism presented in Scheme 1. The step wised substitution process
is also confirmed by 1H NMR spectroscopy data, which will be discussed
below.
The angle < LeOeOeL in complexes of the diaxial complexes al-
lows one to estimate the angle of inclination of the aromatic ring of the
ligand with respect to the porphyrin ring, i. e. degree of their con-
jugation (π-π-interaction) [7]. Among the four studied phenols, the
strongest conjugation between a macrocycle and a ligand appears to
occur in the case of the SnP(L)2 complex.
The mass spectra analysis of the synthesized Sn(IV) complexes
confirms that in both cases both hydroxyl groups are replaced by mo-
lecules of the phenol derivatives. The most intense peaks in the mass
spectra of SnP(L1-4)2 are peaks corresponding to diphenyl complexes.
The main process of fragmentation of the diphenyl complexes SnP (L1-
Table 1
Structural parameters of SnP(L)2.
System
r(Sn-O), Å
r(Nпиpp-Nпиpp), Å
< LeOeOeL, °
SnTPPS4(OH)2
SnTPPS4-(L1)2
SnTPPS4-(L2)2
SnTPPS4-(L3)2
SnTPPS4-(L4)2
2.017
2.056
2.103
2.048
2.071
4.26 (4.28)
4.20
180
91.6
97.6
88.5
89.5
4.19
4.21
Fig. 2. Dependence of the formation time of SnP(L)2 complexes (molar ratio of
4.23
1:2.5) on the nature of the ligand (from pKa value).
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G.M. Mamardashvili et al.
InorganicaChimicaActa486(2019)468–475
Table 2
Positions of proton siganals of 1H NMR spectra of the L1-L4 in free state and as axial complexes.
H1
H2
H3
H4
H5
3-Me
t-Bu
5-Et
н
δ
δ
δ
δ
δ
δ
δ
δ
7.00 d
1.74 d
н
6.72 d
5.42 d
6.97 s
5.72 s
7.29 t
5.18 t
7.08 d
5.06 d
н
6.72 d
5.42 d
6.97 s
5.72 s
н
7.00 d
1.74 d
н
2.51 s
1.89 s
2.31 s
1.78 s
H
н
L1
SnP-L1
L2
SnP-L2
L3
SnP-L3
L4
н
1.43 s
3.15 s
н
н
8.09 d
2.19 d
7.56 d
1.86 d
7.38 d
6.79 d
н
8.28 s
2.03 s
н
н
н
2.55 s
2.39 s
н
1.31 q; 2.82 t
1.13 q; 2.72 t
SnP-L4
4) 2 is the detachment of the M-L bonds (the detachment of one or two
axial ligands) and the detachment of the sulfo groups from the phenyl
fragments in the macrocycle. In general, such compounds are char-
acterized by the following series of ions [M + 2L]+, [M + L]+, [M]
+, [M−4 (SO3−)]+. The main intense peaks in the mass spectra of
the studied complexes are presented in the experimental section and on
Fig. S1.
porphyrin ring in Table 2.
The sharpness of each 1H NMR signal at 298 K indicates on the free
rotation of the phenyl ligands around the outer axial center [17].
Comparative studies of NMR spectra of diphenolic Sn-tetra-
phenylporphyrins substituted and unsubstituted in ortho positions show
that for mono-ortho-bromo-substituted tetraphenylporphyrins, the pre-
sence of a bromine atom on one side of the porphyrin macrocycle leads
to the cleavage of aromatic signals related to two different axial ligands.
In the case of the presence in the porphyrin of one ortho-Br-substituted
phenyl ring, the rotation of the axial ligand relative to the porphyrinate
plane becomes more limited. This leads to a decrease in the strong-field
shifts of the aromatic signals of the phenols in comparison with those
cases in which the free rotation of the phenyl ligands around the ex-
ternal axial center is unrestricted.
3.3. NMR-spectroscopy
As for lypophilic diphenolic Sn-porphyrinic complexes, in 1H NMR
spectra of all hydrophilic SnP(L)2 complexes, the very large chemical
shifts for protons of ortho-phenolic group are observed as a result of the
time-averaged orientation and proximity of these nuclei to the
It can be assumed that somewhat smaller strong-field shifts of the
signals of the aromatic protons of pyridinol L4 in the SnP(L)2 complex
compared to the L3 ligand are also associated with some limitation of
its free rotation due to the presence of an ethyl group in the ortho
position of pyridinol L4.
The strong-field shifts of aromatic meta-proton signals in alkyl-
phenol (L1) are greater than in trialkylphenol (L2), which agrees well
with the association of the mobility of spatially hindered phenol (L2).
At the same time, it was quite unexpected that the signals of the tret-
butyl groups in the SnP(L2)2 complex were slightly weaker than in
unbound phenol. The reason of the weakly-field shift can be a strong
disshielding action of the porphyrin macrocycle due to its strong re-
pelling effect. For example, the signals of tret-butyl groups in calix[4]
arene in the conformation of the 1,3-alternative are usually manifested
in weaker fields in comparison with the proton signals of the tret-butyl
groups of the stereoisomer cone because they are in the disshielding
zone of two adjacent aryl fragments.
SnP(L2)2
The time dependent NMR spectroscopy data of the the SnP(L1)2
complex presented on Fig. 4, confirming the stepwise mechanism of
hydroxyl groups substitution for the obtained complex. 1H NMR spectra
in D2O at 298 K – (a) of SnP(OH)2 solution at the first time after the
addition of 2.2 equivalents of L1 (4-methylphenol); b) after 1 h boiling,
c) after 2 h boiling. Spectrum (a) show signals of porphyrin (⋄) and
phenol (ο) in free form; (b) – signals of porphyrin (•) and phenol (•) in
bound form - the ratio of signals of phenol and porphyrin in bound form
corresponds to a complex of 1:1 composition; (c) – the ratio of signals of
phenol and porphyrin in bound form corresponds to a 2:1 complex.
3.4. Spectrophotometric and fluorescent studies.
UV–vis spectra in the investigation of the diaxial complexes of Sn-
porphyrins are poorly informative. The UV–vis of the SnP(OH)2 com-
plex has two Q-bands in the 500–650 nm region and a Soret band at
417 nm. The ligand exchange of hydroxyl groups in the SnP(OH)2
complex for various phenolic derivatives leads to very small bath-
ochromic. Shifts of the absorption bands - no more than 2–3 nm in the
UV–vis spectra (Table 3). The UV–vis spectra of different diphenolic
complexes differs among themselves only in intensity. The absence of
significant differences in the UV–vis spectra indicates an almost
SnP(L4)2
Fig. 3. Optimized structures: SnP(L2)2, SnP(L4)2.
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G.M. Mamardashvili et al.
InorganicaChimicaActa486(2019)468–475
Fig. 4. 1H NMR spectra in D2O at 298 K – (a) SnP(OH)2 at the first time after the addition of 2.2 equivalents of L1 (4-methylphenol); b) after 1 h boiling; c) after 2 h
boiling.
Table 3
Absorption Data of SnP(L)2 in a phosphate buffer (pH = 7.4).
Complex
Soret band (λ, nm)
UV–vis data
log ε
log ε
Q-bands (λ, nm)
SnP(OH)2
SnP(L1)2
SnP(L2)2
SnP(L3)2
SnP(L4)2
420
423
422
424
421
5.01
5.05
5.04
5.02
5.01
554, 593
556, 594
558, 595
557, 592
555, 594
3.58, 4.09
3.56, 4.11
3.53, 4.07
3.57, 4.06
3.54, 4.03
identical energy of optical transitions from the ground state to singlet
electronic excited states.
Significantly more important information about the structure of the
investigated objects can be obtained by fluorescence spectra (Fig. 5,
Table 4).
The fluorescent properties of the stationary state of the studied
complexes were investigated by excitation at 416 nm, where Sn-por-
phyrin has the maximum absorption (as a reference for comparison
meso-tetra(p-sulfophenyl)porphyrin). The fluorescence spectra of all
SnP(L)2 compounds have bands at 607 and 663 nm, which are typical
for Sn(IV)tetraphenylporphyrin. The effect of L1-L4 ligands on the
fluorescent properties of the Sn-porphyrinate macrocycle is observed
only in the case of their axial coordination on the Sn (IV) cation. Just
additives of the investigated ligands to the solution of SnP(OH)2. do not
lead to a decrease in fluorescence (Table 4), i.e. the L1-L4 molecules
themselves are not quenchers with respect to SnP(OH)2.
Fig. 5. Fluorescence spectra of the obtained complexes: (1) – SnP(OH)2, (2) –
SnP(L2)2, (3) – SnP(L4)2, (4) – SnP(L3)2, (5) – SnP(L1)2 at pH = 7.4, T = 298 K,
λex = 416 nm (Csolv = 1.5·10−6 mol/l).
The observed decrease of the quantum yield of the Sn-porphyrin
fragment in the axial coordination of various oxygen-containing mole-
cules on it is due to the inductive-resonance migration of energy-
spontaneous energy transfer from the Sn-porphyrin fragment (donor) to
the axial ligand (acceptor) by a nonradiative way.
Sn (IV) dihydroxy porphyrins possess
a comparatively strong
fluorescence, and the replacement of hydroxy groups with various
phenolic derivatives, results in quenching of fluorescence intensity
[9,18].
Quenching of the fluorescence of the Sn-porphyrin fragment is also
observed with axial coordination of larger molecules – hydroxy-sub-
stituted porphyrins, sapphirines and other macrocycles [23,27–28].
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G.M. Mamardashvili et al.
InorganicaChimicaActa486(2019)468–475
Table 4
The main reason for this is the presence of alkyl substituents in ortho-
positions in the phenols L2 and L4. In the case of spatially hindered
phenols, such as the antioxidants methoxydol and ionol, quenching of
fluorescence intensity of Sn-porphyrin fragments occurs to a lesser de-
gree than one would expect. The diagram in Fig. 6b this deviation φ
from the assumed value is shown in blue.
Emission Data of of SnP(L)2 in a phosphate buffer (pH = 7.4) (λex 416 nm).
pКa
L
Quantum yield
% Quenching
SnP(OH)2
–
0.18
0.04
0.17
0.12
0.15
0.18
–
SnP(L1)2
10.3
10.8
8.7
8.9
–
88
6.5
33
17
0
SnP(L2)2
The higher quantum yield of the SnP(L2)2 and SnP(L4)2 complexes,
than might be expected, can be explained byseveral reasons. The first,
the presence of alkyl substituents in the ortho-positions of the phenols
leads to an increase in the Sn-L distance (Table 1), which reduces the
probability (intensity) of the inductive-resonance migration of energy,
all other conditions being equal, and hence the quenching of the
fluorescence occurs at a lower degree. However, the absence of any
explicit relationship between the distance in the complex between the
donor (porphyrin macrocycle) and the acceptor (phenol) and its φ (Fig.
S3) indicates that this factor is not the only one. An important point can
be not only the distance, but the presence of an alkyl layer (alkyl
groups) between the aromatic porphyrin and phenolic rings, especially
two tret-butyl groups in the ionol, which prevents spontaneous energy
transfer from the Sn-porphyrin fragment (donor) to the phenolic ligand
acceptor), blocking the dipole-dipole interactions between the donor
and the acceptor of the energy migration process.
SnP(L3)2
SnP(L4)2
SnP(OH)2 + (L1 ÷ L4) (1:2)
As was shown in work [9], the ability of phenolic ligands to energy
transfer in the Sn(IV) porphyrin complexes depends on the presence of
electron-donating and electron-acceptor substituents in the phenols. In
the Sn(IV) ([(TpTP)Sn(OH)2]) 5,10,15,20-tetra-(4-methylphenyl)por-
phyrin diaxial complexes with 3,4-dimethylphenol, p-cresol, phenol, 4-
(2,4-dinitrophenoxy)phenol or p-nitrophenol, quenching of the fluor-
escence intensity of the diaxial Sn-porphyrin complexes with phenol
and phenolic derivatives with electron-donor substituents is observed in
comparison with the intensity of [(TpTP)Sn(OH)2], while in the case
nitrophenol axial ligands, quenching of the fluorescence intensity of Sn-
porphyrin is insignificant.
Discussing the dependence of quenching of the fluorescence of the
diphenolic Sn-porphyrin complexes on the electron-acceptor properties
of the corresponding substituents on the phenyl rings, the authors of [9]
correlate φ with the first electrochemical reduction potential of this
porphyrin. If the first one-electron addition to complex Sn-porphyrin
which bears no substituents on the axial aryloxo ligand occurs at
−0.91 V, for Sn- porphyrin complex with aryloxo ligand with methyl
substituents it is −0.99 V, and for Sn-porhyrin with nitrophenyl ligands
it is −0.84 V.
To confirm our fluorimetry results we calculate the HOMO and
LUMO energies of the studied complexes.
In the Table S1 the calculated energies of the highest occupied and
inferior vacant orbitals for the sulfonated tetraphenylporphyrin, its
dihydroxy-Sn(IV)-porphyrin, and its diaxial complexes with anti-
oxidants are presented. Their values depend on the used basis, espe-
cially for the complexes with Sn. The quantum yield of fluorescence
should increase upon transition to systems having a smaller difference
in the energies of these MO with the obtained values of the difference in
the energies of the higher occupied and inferior vacant orbitals. Due to
the discrepancy between the change in the quantum yield and the en-
ergy of the electronic transition of the HOMO-LUMO, it was suggested
that the electronic transition occurs from lower orbitals in energy. To
confirm this assumption, the type of MO bindings was analyzed (Fig.
S4).
The data analysis of the of [9] showed that the φ value of the SnP
(L) 2 series with phenols free in orthoposition is well correlated with
the basicity constants of these phenols (pKa) (Fig. S4). Overall, the
higher the acidity ligand, the stronger donor-acceptor interactions be-
tween porphyrin and phenolic fragments and, apparently, the prob-
ability of migration of energy (electron) from one fragment to another
when excited above. By the analogy with the data of [9] (Fig. S4), for a
series of our SnP(L1-4)2 complexes one would expect a decrease in the
quantum yield in the SnP(L3) > SnP(L4) > SnP(L1) > SnP(L2) series
(Fig. 6a).
3.5. Photochemical stability of SnP(L)2 complexes
The most important property of any chemical compound is its re-
sistance to degradation (thermal, chemical and photochemical stabi-
lity), especially when it comes to substances with photosensitizing
However, as our studies shown, the above dependence is not ob-
served. The SnP(L2)2 and SnP(L4)2 complexes are left out of this series.
a
b
Fig. 6. Assumed dependence of the quantum yield of fluorescence of the diphenol complexes Sn(IV)-porphyrins on the pKa phenol (a); dependence of the quantum
yield for SnP(L1-4)2 on the nature of phenol in phosphate buffer pH 7.4 (298 K). Blue indicates how much the quenching of fluorescence is inhibited due to the
presence of alkyl substituents in the ortho-positions of the phenols. (For interpretation of the references to colour in this figure legend, the reader is referred to the
web version of this article.)
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G.M. Mamardashvili et al.
InorganicaChimicaActa486(2019)468–475
methine bridges of the tetrapyrrole macrocycle and the formation of
noncyclic tetrapyrrole (Scheme 1). The mechanism of the stage pre-
ceding the breaking of cyclic tetrapyrrole is debatable problem. The
strong dependence of the photochemical destruction of aromatic tet-
rapyrroles on the nature of the metal cation in the coordination center
of the macrocycle and its axial ligands [33–35] indicates that the first
stage of the interaction of macrocycles with peroxides is the co-
ordination of the peroxide molecule at the central coordination center.
The availability of a free coordination site near the metal cation in
porphyrin for a peroxide molecule is also one of the most important
factors contributing to the process of destruction macrocycle.
The substitution of hydroxyl groups in SnP(OH)2 for phenol mole-
cules partially shields the coordination center of the macrocycle,
making it less accessible to peroxide molecules. The greatest screening,
obviously, is observed in the case of the most stable diionol complex.
In conclusion, we synthesized the Sn(IV)-tetra(4-sulfophenyl) por-
phyrin complexes with drugs (methoxydol and ionol), and their pre-
cursors (para-cresol and 3-hydroxypyridine) of 1: 2 composition –
preimages of Sn-based sensitizers (IV) – porphyrins with antioxidant
molecules axially coordinated on them. The mass and NMR spectro-
scopy studies confirmed the complex formation. The fluorescence
spectroscopy studies indicate that the possibility of electron/energy
transfer among the constituted components in the investigated triads
depends on the nature of the drug. The energy migration occurs in the
case of methoxidol complexes, and in the case of ionol complexes it is
almost completely absent. Sn-Porphyrin complexes with methoxydol
and ionol are more resistant to photochemical oxidation in the presence
of reactive oxygen species that can be formed as a result of photo-
sensitized conversion of ordinary molecular oxygen.
Fig. 7. Diagram of the dependence of the rate constants of the SnP(L)2 de-
composition under light irradiation (irradiation wavelength range is
380–800 nm, and the intensity is 13,000 Lux) in the presence of H2O2 (phos-
phate buffer pH 7.4, 298 K).
%
properties. The variety of active forms of oxygen (H2O2, O2−, ROO ,
%
%
HOO , OH , etc.), formed as a result of photosensitized conversion of
ordinary molecular oxygen, leads to processes of oxidative destruction,
both structural elements of the tumor tissue, and the photosensitizers
themselves in photodynamic therapy.
Despite the fact that the porphyrin molecules, due to the presence of
the extended aromatic conjugated π-system, are extremely resistant, in
the presence of, H2O2 and other redox reagents, they can also undergo
destruction processes, the rate of which increases with increasing
temperature.
Acknowledgements
This research was funded by the Russian Scientific Foundation
(project № 14-23-00204-P), the Russian Foundation for Basic Research
(project №18-03-00048_a) and performed with the use of equipment of
the Shared Facility Center, the Upper Volga Regional Center of
Physicochemical Studies. The authors are grateful to Dr. Simanova O.R.
(ISC RAS) for help in photochemical stability experiment.
Earlier in [34], we investigated the features of the interaction of Co-
tetraphenylporphyrins with organic peroxides in benzene in light, the
kinetic parameters of the reactions of the destruction of the porphyrin
macrocycle depending on the nature of the peroxide, the valence of the
cobalt cation, the presence and nature of the axial ligands on the por-
phyrinate.
The Sn(IV) porphyrins in buffer solutions in the presence of both
organic and inorganic peroxides undergo to dissociation processes. In
Fig. S5, as an example, changes in the UV–vis spectra of a solution of
SnP(L4)2 in the presence of the strongest peroxide – H2O2 are shown.
With a concentration ratio of peroxide and porphyrin (100:1), the
macrocycle completely dissociates in 8 h. Analysis of the mass spectra
of the reaction products of SnP(OH)2 and SnP(L1-L4)2 with HOOH in
the middle of the degradation process indicates the successive de-
struction of tetrapyrroles to monopyrroles, showing peaks corre-
sponding to tetra-, di- and monopyrroles (Fig. S6). The peak in the mass
spectra of the products of the final decomposition of all the porphyrins
studied is the peak corresponding to the unsubstituted pyrrole (m/z 66)
(Fig. S7).
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.ica.2018.11.003.
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