Comparative study of redox characteristics and antioxidant activity of porphyrins with 2,6-dialkylphenol groups

Full text of DOI:10.1134/S0012500813060025

ISSN 0012ꢀ5008, Doklady Chemistry, 2013, Vol. 450, Part 2, pp. 152–155. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © V.Yu. Tyurin, Zhang Jingwei, A.A. Moiseeva, E.R. Milaeva, D.V. Belykh, E.V. Buravlev, T.K. Rocheva, I.Yu. Chukicheva, A.V. Kuchin, 2013, published in
Doklady Akademii Nauk, 2013, Vol. 450, No. 5, pp. 543–546.
CHEMISTRY
Comparative Study of Redox Characteristics and Antioxidant
Activity of Porphyrins with 2,6ꢀDialkylphenol Groups
V. Yu. Tyurina, Zhang Jingweia, A. A. Moiseevaa, E. R. Milaevaa, b,
D. V. Belykhc, E. V. Buravlevc, T. K. Rochevac, I. Yu. Chukichevac,
and Corresponding Member of the RAS A. V. Kuchinc
Received December 13, 2012
DOI: 10.1134/S0012500813060025
The oxidative stress of an organism is a result of the cophoric centers in the molecule, because such a comꢀ
acceleration of lipid peroxidation (LPO) in cells and
the formation of reactive oxygen species and free radꢀ
icals. This process leads to destruction of membranes,
the emergence of numerous pathologies, and premaꢀ
ture aging of the organism. The search for new antioxꢀ
idants, as well as for methods to assess the antioxidant
activity, is an important and interesting task [1]. Of
particular interest are synthesis and study of properties
bination is able not only to enhance the known physiꢀ
ological activity but also to cause the appearance
of new types of physiological activity [2–4]. Ionol
I
(2,6ꢀdiꢀtertꢀbutylꢀ4ꢀmethylphenol) is a known antiꢀ
oxidant used in the manufacture of foodstuffs (food
additive E321). 2,6ꢀDiisobornylꢀ4ꢀmethylphenol
(dibornol) IV is currently undergoing preclinical triꢀ
of polyfunctional compounds with several pharmaꢀ als as a promising drug [5].
4
с
×
10− , М
I
, mA
1.0
0.8
0.6
0.4
0.2
0.06
0.04
0.02
0
1
2
3
4
5
0
10
20
30
40
50
60
, min
t
−
0.02
2000
−
−
1000
0
1000
2000
, mV
Fig. 2. Kinetic curves of DPPH concentration vs. time in
the presence of additives: compound
([DPPH]/[additive] = 1 : 4), ( IV ([DPPH]/[additive] =
1 : 4), ( III ([DPPH]/[additive] = 1 : 1), (
([DPPH]/[additive] = 1 : 1), ( II ([DPPH]/[additive] =
1 : 1); DMF, Pt, 0.05 M ꢀBu NBF , Ag/AgCl/KCl,
0.1 mM. Reaction time, 60 min.
E
(1)
I
2)
3)
4) V
Fig. 1. Cyclic voltammogram of free base of porphyrin
DMF at a potential sweep rate of 100 mV/s (Pt, porphyrin
concentration 10 M, nꢀBu NBF , Ag/AgCl).
4 4
V in
5)
n
c =
0
4
4
–3
a Moscow State University, Moscow, 119992 Russia
b Institute of Physiologically Active Substances, Russian Academy of Sciences,
Severnyi proezd 1, Chernogolovka, Moscow oblast, 142432 Russia
c Institute of Chemistry, Komi Scientific Center, Ural Branch, Russian Academy of Sciences,
ul. Pervomaiskaya 48, Syktyvkar, 167982 Russia
152

COMPARATIVE STUDY OF REDOX CHARACTERISTICS AND ANTIOXIDANT ACTIVITY
153
OH
OH
I
IV
OH
HO
HO
OH
N
H
N
H
N
N
N
N
H
N
H
N
RO
OH
OH
HO
RO
R = H (II), C15H31C=O (III)
V
•
OH
O
O2N
O2N
R1
R1
R1
R1
Ph
Ph
Ph
•
+
+
N
N
NO2
N
N
NO2
H
Ph
O2N
DPPH
O2N
R2
R2
I–V
O2N
O2N
Ph
Ph
.
ꢀ
–
+ e
N
N
NO2
N
N
N
NO2
0.28 V
Ph
Ph
O2N
O2N
O2N
O2N
Ph
Ph
Ph
Ph
.
N
ꢁ
–
– e
N
NO2
N
NO2 0.78 V
O2N
O2N
Scheme 1.
Previously, it was shown that tetra(3,5ꢀdiꢀtert
ꢀ
in Wistar rat liver homogenates [6–8]. Tetra(3,5ꢀ
diisobornylꢀ4ꢀhydroxyphenyl)porphine ( ), containꢀ
ing bulky bicycloalkyl substituents on the phenyl ring,
has been recently synthesized [9].
V
butylꢀ4ꢀhydroxyphenyl)porphyrin (II), containing
ionol moieties, and its analogue with the palmitic acid
residue in the molecule (III) exhibit high antioxidant
activity in the model oxidation reaction of (Z)ꢀ9ꢀoctaꢀ
In this paper, we evaluated the antioxidant activity
decenoic (oleic) acid, as well as in the LPO processes of compounds I–V from the hydrogen atom transfer
DOKLADY CHEMISTRY Vol. 450
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2013

154
TYURIN et al.
Oxidation and reduction potentials (Eox
dant efficiency values (AE*) for compounds I–V
,
E
red) and antioxiꢀ
deterꢀ
mined from the rate of hydrogen elimination from DPPH
by the rotating disc electrode method
of the reaction by monitoring the change in the CV
peak current [10–13] or from the limiting diffusion
current in the polarization curve obtained by the rotatꢀ
ing disk electrode (RDE) method.
Compound
Eox
Ered
AE, %
The use of the electrochemical DPPH test requires
the absence of overlap of the oxidation–reduction
peaks of DPPH and compounds under consideration.
In this context, we studied the behavior of compounds
I
1.28
–
25.37
77.36
II
0.908
1.182
–1.167
I
–
V
in DMF by cyclic voltammetry (the choice of a
medium is due to the extremely low solubility of in
CH3CN). The cyclic voltammograms of phenols and
III
IV
V
0.961
1.246
–1.16
52.55
30.98
65.38
V
I
1.23
–0.681
–1.782
IV in the anodic range show a wave of the irreversible
twoꢀelectron oxidation localized on the hydroxyl
group of the sterically hindered phenol moiety to give
the phenoxylium cation (table).
0.912
1.247
–1.162
* The DPPH concentration is 0.1 mM. The additiveꢀtoꢀDPPH conꢀ
centration ratio is 1 : 1 (compounds II, III, and V) and 4 : 1 (comꢀ
The voltammograms of porphyrins II, III, and V in
pounds I and IV). Reaction time 60 min, Pt, 0.05 M nꢀBu NBF ,
4
4
DMF, Ag/AgCl.
the anodic range are similar: there are two irreversible
oneꢀelectron oxidation peaks (Fig. 1). The first peak is
apparently due to the oxidation of the porphyrin ring
to the radical cation, followed by its rapid reduction
via intramolecular electron transfer (IET) from the
phenol group (Scheme 2). The irreversible character
of the peak is caused by the rapid chemical stage of
proton elimination (the EC mechanism). The second
peak corresponds to oneꢀelectron oxidation of the
phenoxyl radical thus formed to the corresponding
cation [13]. The oxidation peak of phenol groups are
not observed because of the shift to the discharge
rate in the reaction with the stable radical 2,2'ꢀdipheꢀ
nylꢀ1ꢀpicrylhydrazyl (DPPH), Scheme 1. Since one
of the absorption bands of porphyrins (λmax, is
522.0 (II), 521.0 (III), and 522.5 (V) nm) is close to
the absorption band of DPPH (517 nm), the reaction
course was monitored using our proposed electroꢀ
chemical DPPH test. The cyclic voltammogram (CV)
of DPPH in the anode region shows two reversible
waves corresponding to the reduction and oxidation of
the DPPH radical. This allows us to study the kinetics region of the supporting electrolyte molecules.
•
ꢁ
ꢁ
OH
OH
OH
OH
R1
R1
R1
R1
R1
R1
R1
R1
–
–
– e
– e
IET
– H+
P
P
P
P
II, III, V
Scheme 2.
III, and For fixed values and the electrode area and rotation
Since the oxidation of porphyrins II
,
V
proceeds at more anodic potentials than the DPPH velocity, the ratio of the current at the beginning of the
reduction wave potential (table) [14], it is possible to reaction (no additives) and in the end is determined by
use the RDE method for estimating their antioxidant the DPPH concentration ratio:
activity. The limiting diffusion current of the polarizaꢀ
I/I0 = c/c0,
tion curve on the rotating disk electrode is determined
by the Levich equation [15]
where I0 is the limiting current at the initial DPPH
concentration c0 is the current at a DPPH concenꢀ
tration at a given moment of time.
,
I
1/2
I
d = 0.62nSFD2/3ω ν–1/6c0
,
where
electrode area (cm2),
diffusion coefficient (cm2/s),
n
is the number of transferred electrons,
S
is the
is the
As the reaction with DPPH proceeds, the limiting
diffusion current decreases. Knowing the values I, I0,
and c0 values, we construct kinetic curves of the DPPH
concentration versus reaction time (Fig. 2). The antiꢀ
oxidant activity was quantified by determining the
F
is Faraday’s constant,
D
ω
is the angular velocity
of electrode rotation (rad/s), is the kinematic viscosꢀ
ν
ity of a solution (cm2/s), and c0 is the depolarizer conꢀ
centration (mol/cm3).
DOKLADY CHEMISTRY Vol. 450
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COMPARATIVE STUDY OF REDOX CHARACTERISTICS AND ANTIOXIDANT ACTIVITY
155
antioxidant efficiency (AE) factor, which characterꢀ
izes the content of the unreacted DPPH: AE =
ACKNOWLEDGMENTS
This work was supported by the Division of Chemꢀ
istry and Materials Science of the RAS (program no. 9
“Medicinal and Biomolecular Chemistry,” project
no. 12ꢀTꢀ3–1020) and the Russian Foundation for
Basic Research (project nos. 12–03–00937 and 12–
03–00776).
(c0
⎯ cfin)/c0 × 100%, where c0 is the initial concentraꢀ
tion and cfin is the final concentration of DPPH (reacꢀ
tion time, 60 min). The AE values for compounds
are presented in the table.
I–V
It can be seen that the activity of porphyrins with
2,6ꢀdialkylphenol substituents changes along the
series III < V < II. The decrease in antioxidant activity
upon the introduction of the palmitic acid moiety is
presumably associated with aggregation processes that
occur due to hydrophobic interactions involving this
substituent. It should also be noted that the antioxiꢀ
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