Studies of adsorbed phenothiazine antidotes by temperature-programmed desorption with mass-spectrometric analysis
By spectrophotometric and kinetic methods of analysis a study has been made of adsorption of three antidotes of the phenothiazine series on the surface of fumed silica from water solutions. Physical and chemical parameters of adsorption have been calculated. Thermal decomposition of bulk antidotes h...
Збережено в:
| Опубліковано в: : | Поверхность |
|---|---|
| Дата: | 2002 |
| Автори: | , , , |
| Формат: | Стаття |
| Мова: | English |
| Опубліковано: |
Інститут хімії поверхні ім. О.О. Чуйка НАН України
2002
|
| Теми: | |
| Онлайн доступ: | https://nasplib.isofts.kiev.ua/handle/123456789/126351 |
| Теги: |
Додати тег
Немає тегів, Будьте першим, хто поставить тег для цього запису!
|
| Назва журналу: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Цитувати: | Studies of adsorbed phenothiazine antidotes by temperature-programmed desorption with mass-spectrometric analysis / T.V. Kulik, N.P. Galagan, V.A. Pokrovskiy, V.V. Khrapak // Поверхность. — 2002. — Вип. 7-8. — С. 46-56. — Бібліогр.: 8 назв. — англ. |
Репозитарії
Digital Library of Periodicals of National Academy of Sciences of Ukraine| id |
nasplib_isofts_kiev_ua-123456789-126351 |
|---|---|
| record_format |
dspace |
| spelling |
Kulik, T.V. Galagan, N.P. Pokrovskiy, V.A. Khrapak, V.V. 2017-11-20T18:25:35Z 2017-11-20T18:25:35Z 2002 Studies of adsorbed phenothiazine antidotes by temperature-programmed desorption with mass-spectrometric analysis / T.V. Kulik, N.P. Galagan, V.A. Pokrovskiy, V.V. Khrapak // Поверхность. — 2002. — Вип. 7-8. — С. 46-56. — Бібліогр.: 8 назв. — англ. XXXX-0106 https://nasplib.isofts.kiev.ua/handle/123456789/126351 By spectrophotometric and kinetic methods of analysis a study has been made of adsorption of three antidotes of the phenothiazine series on the surface of fumed silica from water solutions. Physical and chemical parameters of adsorption have been calculated. Thermal decomposition of bulk antidotes has been investigated by the temperatureprogrammed desorption technique with the mass-spectrometric registration of volatile constituents (TPD MS) and the results achieved were compared with data for adsorbed samples. For all the samples at the first stage the maximum of HCl evolution is observed at 180°C. For methylene blue and toluidinee dark blue the first stage is accompanied by evolution of CH3Cl (m/z 50). Then the decomposition proceeds through the rupture of thiazine rings. At this stage, at the temperature of maximum 240°C and higher in mass spectra there appear lines at m/z 93, 66, 51 corresponding to molecular decomposition of aniline. Besides, sulfur-containing fragments originating from rupture of thiazine rings (lines at m/z 32, 34, 107, 121, 135) are observed among the lines attributed to products of thermal decomposition of methylene blue and toluidinee dark blue at high temperatures. Comparison of TPD MS experimental data about thermal decomposition of the antidotes in the condensed and adsorbed states has shown that adsorption on highly dispersed silica surface changed dramatically the mechanism of thermal transformations and increased thermal stability of antidote molecules in comparison to that in the condensed state. en Інститут хімії поверхні ім. О.О. Чуйка НАН України Поверхность Surface chemistry of silica and related sorbents Studies of adsorbed phenothiazine antidotes by temperature-programmed desorption with mass-spectrometric analysis Article published earlier |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| title |
Studies of adsorbed phenothiazine antidotes by temperature-programmed desorption with mass-spectrometric analysis |
| spellingShingle |
Studies of adsorbed phenothiazine antidotes by temperature-programmed desorption with mass-spectrometric analysis Kulik, T.V. Galagan, N.P. Pokrovskiy, V.A. Khrapak, V.V. Surface chemistry of silica and related sorbents |
| title_short |
Studies of adsorbed phenothiazine antidotes by temperature-programmed desorption with mass-spectrometric analysis |
| title_full |
Studies of adsorbed phenothiazine antidotes by temperature-programmed desorption with mass-spectrometric analysis |
| title_fullStr |
Studies of adsorbed phenothiazine antidotes by temperature-programmed desorption with mass-spectrometric analysis |
| title_full_unstemmed |
Studies of adsorbed phenothiazine antidotes by temperature-programmed desorption with mass-spectrometric analysis |
| title_sort |
studies of adsorbed phenothiazine antidotes by temperature-programmed desorption with mass-spectrometric analysis |
| author |
Kulik, T.V. Galagan, N.P. Pokrovskiy, V.A. Khrapak, V.V. |
| author_facet |
Kulik, T.V. Galagan, N.P. Pokrovskiy, V.A. Khrapak, V.V. |
| topic |
Surface chemistry of silica and related sorbents |
| topic_facet |
Surface chemistry of silica and related sorbents |
| publishDate |
2002 |
| language |
English |
| container_title |
Поверхность |
| publisher |
Інститут хімії поверхні ім. О.О. Чуйка НАН України |
| format |
Article |
| description |
By spectrophotometric and kinetic methods of analysis a study has been made of adsorption of three antidotes of the phenothiazine series on the surface of fumed silica from water solutions. Physical and chemical parameters of adsorption have been calculated. Thermal decomposition of bulk antidotes has been investigated by the temperatureprogrammed desorption technique with the mass-spectrometric registration of volatile constituents (TPD MS) and the results achieved were compared with data for adsorbed samples. For all the samples at the first stage the maximum of HCl evolution is observed at 180°C. For methylene blue and toluidinee dark blue the first stage is accompanied by evolution of CH3Cl (m/z 50). Then the decomposition proceeds through the rupture of thiazine rings. At this stage, at the temperature of maximum 240°C and higher in mass spectra there appear lines at m/z 93, 66, 51 corresponding to molecular decomposition of aniline. Besides, sulfur-containing fragments originating from rupture of thiazine rings (lines at m/z 32, 34, 107, 121, 135) are observed among the lines attributed to products of thermal decomposition of methylene blue and toluidinee dark blue at high temperatures. Comparison of TPD MS experimental data about thermal decomposition of the antidotes in the condensed and adsorbed states has shown that adsorption on highly dispersed silica surface changed dramatically the mechanism of thermal transformations and increased thermal stability of antidote molecules in comparison to that in the condensed state.
|
| issn |
XXXX-0106 |
| url |
https://nasplib.isofts.kiev.ua/handle/123456789/126351 |
| citation_txt |
Studies of adsorbed phenothiazine antidotes by temperature-programmed desorption with mass-spectrometric analysis / T.V. Kulik, N.P. Galagan, V.A. Pokrovskiy, V.V. Khrapak // Поверхность. — 2002. — Вип. 7-8. — С. 46-56. — Бібліогр.: 8 назв. — англ. |
| work_keys_str_mv |
AT kuliktv studiesofadsorbedphenothiazineantidotesbytemperatureprogrammeddesorptionwithmassspectrometricanalysis AT galagannp studiesofadsorbedphenothiazineantidotesbytemperatureprogrammeddesorptionwithmassspectrometricanalysis AT pokrovskiyva studiesofadsorbedphenothiazineantidotesbytemperatureprogrammeddesorptionwithmassspectrometricanalysis AT khrapakvv studiesofadsorbedphenothiazineantidotesbytemperatureprogrammeddesorptionwithmassspectrometricanalysis |
| first_indexed |
2025-11-26T23:39:14Z |
| last_indexed |
2025-11-26T23:39:14Z |
| _version_ |
1850781694043357184 |
| fulltext |
46
46
STUDIES OF ADSORBED PHENOTHIAZINE ANTIDOTES
BY TEMPERATURE-PROGRAMMED DESORPTION
WITH MASS-SPECTROMETRIC ANALYSIS
T.V. Kulik1, N.P. Galagan1, V.A. Pokrovskiy1, and V.V. Khrapak2
1 Institute of Surface Chemistry, National Academy of Sciences
Gen. Naumov Str. 17, 03680 Kyiv-164, UKRAINE
2Institute of Farmacology and Toxicology, E. Potiet Str. 14, 03057 Kyiv, UKRAINE
Abstract
By spectrophotometric and kinetic methods of analysis a study has been made of
adsorption of three antidotes of the phenothiazine series on the surface of fumed silica from
water solutions. Physical and chemical parameters of adsorption have been calculated.
Thermal decomposition of bulk antidotes has been investigated by the temperature-
programmed desorption technique with the mass-spectrometric registration of volatile
constituents (TPD MS) and the results achieved were compared with data for adsorbed
samples. For all the samples at the first stage the maximum of HCl evolution is observed at
180°C. For methylene blue and toluidinee dark blue the first stage is accompanied by
evolution of CH3Cl (m/z 50). Then the decomposition proceeds through the rupture of thiazine
rings. At this stage, at the temperature of maximum 240°C and higher in mass spectra there
appear lines at m/z 93, 66, 51 corresponding to molecular decomposition of aniline. Besides,
sulfur-containing fragments originating from rupture of thiazine rings (lines at m/z 32, 34,
107, 121, 135) are observed among the lines attributed to products of thermal decomposition
of methylene blue and toluidinee dark blue at high temperatures. Comparison of TPD MS
experimental data about thermal decomposition of the antidotes in the condensed and
adsorbed states has shown that adsorption on highly dispersed silica surface changed
dramatically the mechanism of thermal transformations and increased thermal stability of
antidote molecules in comparison to that in the condensed state.
Introduction
By the TPD MS technique a study has been made of the following three dyes of
phenothiazine series: Gen. Naumov Str. 17 chloride (Lauth’s violet) (I), methylene blue
(methylthionine chloride) (II), toluidine dark blue O (Textra) (III):
N
S N N
+
Cl -
R 1
R 2
R 3
R 4
R 5
I - R 1 =R 2 =R 3 =R 4 =R 5 =H;
II - R 1 =R 2 =R 4 =R 5 =CH 3 , R 4 =H;
III - R 1 =R 2 =R 3 =CH 3 , R 4 =R 5 =H; ´ZnCl2.
47
47
They are widely used in medicine as antidotes to provide treatment for toxic
methemoglobinemia and cyanide poisoning, [1-6]. They belong to a biochemical (metabolic)
class of antidotes because their use changes mechanisms of cell detoxication and enhances
activity of enzymatic systems. Adsorption immobilization of these antidotes is a way to new
medicinal compositions, which will differ from existing antidotes by a prolonged action,
higher sorption capacity, and longer term of storage. These characteristics will allow
preventive medicine practitioners to employ such compositions as multifunctional
noninjection sorption antidotes in extreme situations.
Experimental
The temperature-programmed mass spectrometry was used for analysis of volatile
products of thermal decomposition of antidotes in the condensed state and in the state set up
during their adsorption on the surface of fumed silica [7]. Weighed samples (of about 1 mg
each) of antidotes adsorbed on the surface of aerosil A-300 were placed in a
quartz-molybdenum tube, evacuated at 10–1 Pa, and then attached to the inlet system of a
MX 7304 monopole analyzer (Sumy, Ukraine). The reactor-to-mass spectrometer interface
included a high-vacuum valve (with an orifice 5 mm in diameter and an inlet tube 20 cm in
length), its temperature was kept at 150°C. The reaction space was open in the ion source
direction.
Adsorption of the dyes was effected from a water phase in steady-state conditions at a
temperature 21–23°C. The preliminary thermal treatment of an adsorbent at 400°C for 2 h and
proved to be sufficient to eliminate organic substances that could be adsorbed on its surface.
The adsorbate concentration interval was 1–1000 mmol L-1. An aqueous solution of a dye
10 mL in volume was mixed with 0.1 g of highly dispersed silica (S=300 m2 g-1), and the
mixture obtained was let to stand for 2 h. The suspensions prepared were centrifuged, washed
with water, and dried at room temperature. Adsorption values were determined by the
spectrophotometry method (at a wave length of l=540 nm for thionine and toluidine dark blue
and of l=670 nm for methylene blue) in terms of differences of concentrations in a solution in
question before and after adsorption. The adsorption isotherms recorded were linearized on
the Langmuir coordinates, with coefficients of determination R2 being equal to 0.979–0.998.
The samples used for the mass-spectrometric studies possessed surface concentrations of dyes
of about 20 mmol g-1. Desorption from aqueous solutions was effected under steady-state
conditions.
Results and Discussion
By the temperature-programmed desorption and mass-spectrometric analysis of
volatile products (TPD MA) a study was made of adsorption and thermal stability of a number
of phenothiazine dyes in the condensed state and in the state set up as a result of adsorption on
the surface of highly dispersed silica (HDS).
The thermal decomposition of the dyes under investigation was distinguished for
having two stages of release of hydrogen chloride (Fig. 1). The low-temperature stage starts at
a temperature above 100°C and reaches its maximum yield at about 160°C. Besides, in the
case of methylene blue and toluidine dark blue one can also observe a release of CH3Cl
(50 m/z), with the line intensity being equal to about 5% of that for the 38 m/z line. The
high-temperature stage of the release of HCl for toluidine dark blue and thionine exhibits a
peak at about 400°C.
In the situation with free thionine in the temperature region between the peak
temperatures for the release of hydrogen chloride there is a maximum (at 290°C) of aniline
release in the molecular form (93, 66, 51 m/z) (Figs. 1, 2).
48
48
Fig. 1. Thermograms of fragments m/z: 93, 66, 38, 34, 27; decomposition
of thionine chloride in the condensed state.
Fig. 2. Electron impact mass-spectrum of thionine chloride in the condensed state at 302°C.
This maximum is not related to the thermal desorption curve characteristic of
hydrogen sulfide (35, 34, 33, 32 m/z). The onset of the hydrogen sulfide release coincides
with the maximum thermal release of aniline, and the maximum yield of the hydrogen sulfide
release is attained at about 440°C. This observation is attributed to the fact that aniline is
formed as a result of the phenothiazine ring rupture which proceeds in such a way that
sulfur-containing fragments continue to be retained in the solid phase and undergo
polymerization with a release of hydrogen sulfide and formation of a nitrogen-containing
polymer (analogous to polyaniline). With increasing temperature, one can observe destruction
49
49
of this polymer, which is corroborated by the fact that beginning from 290°C (aniline release
maximum and sulfur release onset) there takes place a monotonous enhancement of the 14 m/z
signal intensity as well as considerable increase in the 27 m/z signal intensity (Fig. 1). It is
known that thermal decomposition of polymers based on aromatic amines leads to formation
of hydrogen cyanide HCN (27 m/z). The thermolysis process can be represented by the
following scheme 1:
Scheme 1
Fig. 3. Electron impact mass-spectrum of thermolysis of condensed methylene blue at 444°C.
0160 C
0
rupture
-
-PhNH2
290 C
II stage -94, 93, 67, 66, 51 m/z
asymmetric
HH2
N
S NN
N
S NN2H
+ H
H
Cl
-HCl I stage - 35, 36, 37, 38 m/z
(4)
Polymeric
0
0
Destruction
-H2C2
-HCN 700 C
IV stage - 26, 27, 28 m/ z
n
N
N
-H2S
440 C
III stage - 32, 33, 34, 35 m/ z
N
S N
N
S N
N
S N
H
H
50
50
Fig. 4. Thermograms of fragments m/z: 150, 135, 121, 107, 93, 32; decomposition of toluidine
dark blue in the condensed state.
Elucidation of mechanism of adsorption of antidotes on the HDS surface can furnish
an explanation for adsorption mechanisms of bonding of antidote molecules with erythrocyte
membranes. Therefore, a research has been made into adsorption of antidotes from aqueous
solutions on the HDS surface. Adsorption methods and spectrophotometric technique of
analysis allow us to determine physicochemical parameters of adsorption of molecules of
these substances on the HDS surface and to obtain their adsorption isotherms (Fig. 5). These
isotherms can be linearized on the Langmuir coordinates with high correlation coefficients.
Thus, it becomes possible to determine such main physicochemical parameters of adsorption
of dyes as limiting adsorption value, adsorption equilibrium constant, variation of the Gibbs
free energy during adsorption, surface concentration of an adsorbate, surface area occupied by
an adsorbate molecule, surface coverage. A study has also been made of the ability of these
biomolecules to desorb from the HDS in a water solution. The physicochemical parameters
attained are presented in Table. The limiting adsorption values are underestimated in view of
the absence of saturation.
Table 1. Physicochemical parameters of adsorption of phenothiazine dyes on the surface of highly
dispersed silica.
Antidotes G¥ K ´ 102 -DG w a Q R2 Desorption
mmol g-1 L mol-1 kJ mol-1 nm2 mmol m-2 % %
Thionine chloride 29.7 25.41 19.44 16.81 0.099 3 0.979 18
Toluidine dark blue 112.4 5.34 15.58 4.43 0.375 11 0.997 3
Methylene blue 206.3 3.93 14.82 2.42 0.688 21 0.998 1
51
51
0
5
10
15
20
25
30
35
40
45
50
0 200 400 600 800 1000
С, mmol/l
Г,
m
m
ol
/g
- thionin chloride
- toluidin dark blue
- methylene blue
Fig. 5. Isotherms of thionine chloride, toluidine dark blue and methylene blue adsorption on
fumed silica surface.
The phenothiazine dyes in the state set up in the course of their adsorption on the HDS
surface have been studied by the TPD MS technique. The adsorbed samples are distinguished
for the fact that during their thermolysis there is not a stage of release of hydrogen chloride in
a high-temperature region (Figs. 6–8).
Fig. 6. Thermograms of fragments m/z: 93, 38, 34, 27; decomposition of toluidine dark blue
in adsorbed on fumed silica surface.
52
52
Fig. 7. Thermograms of fragments m/z: 93, 38, 34, 27; decomposition of methylene blue in
adsorbed on fumed silica surface.
Fig. 8. Thermograms of fragments m/z: 93, 38, 34, 27; decomposition of thionine chloride in
adsorbed on fumed silica surface.
In the case of adsorbed thionine there is not a stage of formation of aniline, what is also
undoubtedly related to the dye adsorption on the surface (Fig. 9). It is possible that active sites
of the silica surface stabilize phenothiazine rings, and their decomposition accompanied by the
hydrogen sulfide release begins at a temperature above 500°C and leads to formation of a
nitrogen-containing polymer which becomes chemically bonded with the silica surface so that
its decomposition with the release of 27 m/z fragments (HCN) starts at a temperature over 560°C,
i.e. its decomposition onset is shifted towards the high-temperature region by 100°C in comparison
with the condensed state.
53
53
Fig. 9. Electron impact mass-spectrum of thermolysis of methylene blue adsorbed
on fumed silica surface at 473 °C.
Further, it should be mentioned that the thermal decomposition of methylene blue and
toluidine dark blue in the adsorbed state is analogous with the decomposition of thionine in the
adsorbed state (see Figs. 6–8). The both processes do not have a stage with the release of sulfur- and
nitrogen-containing fragments, which is corroborated by the mass spectrum of volatile products of
the adsorbed methylene blue thermolysis (Fig. 9). The difference in their chemical structure as
compared to that of thionine (in particular, the presence of methyl groups in molecules of methylene
blue and toluidine dark blue) exerts a weak effect on the mechanism of thermolysis of these dyes in
the adsorbed state. There are differences only in the temperature intervals, positions of maxima on
the temperature scale, and relative ionic current intensities while the main reaction products and
sequence of stages do not vary. This fact indicates that the mechanism of adsorption for these three
compounds is the same and, moreover, the bonding proceeds through species common for
molecules of these compounds. The common and invariable species for all the three dyes under
investigation is a thiazine fragment whereas their condensed benzene rings have different
substituents (amine groups, dimethylamine groups, methyl groups) at different positions. Therefore,
if the bonding to the silica surface had proceeded only through interactions with amine or
dimethylamine groups, it would undoubtedly had manifested itself in the thermolysis mechanism
and, as a result, in some differences between the thermolysis products for the three studied dyes.
From the data presented in Table it is evident that the difference between the chemical
structures of the three compounds under study affects the nature of their adsorption from water
solution on the HDS surface. In the investigated interval of concentrations the adsorption value
increases with increasing number of methyl groups in molecules of the dyes, which seems to be
related to an additional contribution of Van der Waals interactions to the bonding with the surface,
as well as with increasing basicity of amine groups. At the same time, the fact that the largest
change in the Gibbs free energy during adsorption is observed for thionine indicates that
among the studied series of compounds it is thionine molecules that form the most strong
bonds with the silica surface, which is corroborated by the most considerable increase (by
200°C in comparison with the condensed state) in the thermal stability of thiazine rings of
thionine. In compliance with the Giles classification the adsorption isotherms of the dyes
54
54
Si
H
Cl
+
N
0
0
0
r u p t u r e
sy m m e t r i c
H N NH
N
n
De st r u c t i o n
- H2C2
- H CN
76 0 C
I I I st a g e - 2 6 , 2 7, 2 8 m / zPo l y m er i c
6 0 0 C
I I s t ag e - 3 2 , 3 4 m / z- H2S
- HCl
2 2 0 C
I s t ag e - 3 6 , 3 8 m / z
H
H
H
H
S
N
N N
+
O-
Si
OO
Si
O
Si
O--O
Si
O
Si
OOO O
Si
O
Si
O- -O
Si
O O O
Si
O-
-
+
NSN
H
H
H
H
under investigation are L-type isotherms (Fig. 5) and, consequently, during adsorption the
principal plane of such a molecule should be in parallel to the silica surface. At this
orientation of a molecule its bonding with the surface may involve both its amine groups and
central thiazine ring. In the condensed state the positive charge of the corresponding cation
will be delocalized on 16 atoms of the heteroaromatic system, with the largest part of the
charge being delocalized on the sulfur atom of the thiazine ring (which is due to a larger atomic
radius and lower electronegativity of sulfur in comparison with nitrogen). Besides, in the condensed
state the delocalization of this charge may involve atoms and groups of atoms of the silica surface. It
leads to stabilization of phenothiazine cations on the SiO2 surface, and so the destruction of the
phenothiazine heterosystem proceeds at substantially higher temperatures in comparison to the
condensed state and begins with the release of hydrogen sulfide (i.e. of the fragment which makes
the greatest contribution to the bonding with the surface), and it is this phenomenon that was more
than once observed by us during thermolysis of a number of adsorbed biomolecules.
Bonding of a dye cation with the silica surface leads to a higher degree of delocalization of
the charge and symmetry of its distribution so that phenothiazine system in the adsorbed state
acquires a higher degree of symmetry in comparison with the condensed state. This manifests itself
in the identical ‘symmetric’ mechanism of the thermal decomposition of the three dyes, which
proceeds through rupture of chemical bonds symmetric about the center of a thiazine ring and
involves abstraction of sulfur (Scheme 2). The compound formed as a result of this process
undergoes polymerization at nitrogen atoms. The destruction of this polymer is evidenced for by the
mass spectrum lines at 28, 27, 26 m/z (H2CN+, HCN+, HCºCH+). In this case the structural
differences among these dyes are smoothed out. In the mass spectra of volatile products of
thermolysis of adsorbed samples for the whole studied interval of temperatures (up to 800 °C) there
are no lines which would correspond to nitrogen- and sulfur-containing fragments and which would
be observed in the situation with an asymmetrical rupture of chemical bonds. It is this asymmetric
mechanism that is characteristic of the condensed dye thermolysis (Fig. 8).
Scheme 2
The above-described observations are related to the fact that during the first stage of the
thermolysis of the samples in the condensed state HCl is released as a result of abstraction of
protons from dye molecules so that this process leads, in all probability, to formation of imine
(stage I), i.e. uncharged asymmetric molecules. As a result, the subsequent thermolysis involves an
asymmetric rupture of a phenothiazine molecule and release of sulfur- and nitrogen-containing
fragments. In the situation with adsorbed forms of phenothiazines the release of HCl during stage I
55
55
proceeds at the expense of abstraction of protons of silanol groups on the silica surface. The
phenothiazine cation remains unchanged and is stabilized due to a more symmetric delocalization of
the charge. The methyl groups that are contained in molecules of methylene blue and toluidine dark
blue create conformational hindrances to this stabilization, which seems to be related to the greater
adsorption equilibrium constant and higher thermal stability of thiazine rings for thionine. That is,
one can say that the difference in the chemical structure manifests itself in that the studied dyes in
the condensed state require different mechanisms of their thermolysis while in the case of the
adsorbed state the difference does not manifest itself. But this statement is inconsistent with a
long-established fact that the difference in the structure does not affect the high antidotal action of
these three compounds, i.e. does not affect their bonding with receptors in vivo. Thus, it is thiazine
rings that perform a determining role in the process of bonding and detoxication. This inference is
corroborated by the absence of any antidotal activity of compounds of the phenoxazine series
(where sulfur atoms are replaced with oxygen atoms). Another support for the inference is that in
the case of methemoglobinemia the function of antidotes is performed by such sulfur-containing
compounds as aminosulfides (e.g. cystamine). Besides, it has been shown that methylene blue exerts
a profound antidotal effect in the case of acute intoxications with hydrogen sulfide, which is likely
to be related to its ability to block the toxic action through bonding with receptors of sulfhydryl
groups that contain metal cations.
To sum up, it is possible to suggest the following mechanism of the biological effect. At the
first stage on the erythrocyte membrane surface there proceeds bonding of a dye cations with
receptors of sulfhydryl groups (these dyes are known to find use as metallochrome indicators for
ions of such metals as Mg, Ca, Cd, Co(II), Ni, Zn (methylene blue) and Fe(II), Al, Pb, Hg(II)
(thionine) [8]). At the second stage the metal that is present in a receptor reduces a dye cation to a
leuco-derivative which is uncharged and, therefore, is capable of penetrating into an erythrocyte
through its membrane. During the third stage the leuco-derivative reduces methemoglobin to
hemoglobin.
Conclusions
Because of the asymmetric charge distribution in a phenothiazine cation (the charge is
predominantly localized on one of amine groups) it is possible to observe an asymmetric rupture of
molecules with release of sulfur- and nitrogen-containing fragments in the case of condensed
samples. In the case of adsorbed dyes due to the symmetric charge distribution among two amine
groups and sulfur atom of a thiazine ring one can observe a symmetric rupture of a molecule, with
the thiazine ring center being on the rupture plane. The cation adsorption observed takes place
through bonding with deprotonated silanol groups of the silica surface so that bonding of an
erythrocyte with the surface involves, in all probability, negatively charged oxygen and nitrogen
atoms on the membrane surface. Adsorption of phenothiazine cations on the highly dispersed silica
surface and, possibly, on the receptor surface favours stabilization of the cations owing to the charge
delocalization, which facilitates the charge transfer and reduction of the cations to leuco-derivatives,
with the reducing agent function being performed by a metal present in the receptor.
References
1. Pronczuk de Jarbino J. Evaluation of antidotes: international activities // IPCS INTOX
Workshop on Poisons Control in Eastern European Countries // Erfurt., 11-15 November,
1996. – Germany. - P.30-35.
2. Kouides P.A., Abboud C.N., and Fairbanks V.F. Flutamide-induced cyanosis refractory to
methylene blue therapy // Br. J. Haematol. – 1996. – V.94 (1) – P.73-75.
3. Sadeghi-Hashjin G., Folkerts G., Henricks P.A.J., Van de Loo P.G.F., Dik I.E.M., and
Nijkamp F.P. Relaxation of guinea-pig trachea by sodium nitroprusside: cyclic GMP and nitric
oxide not involved // Br. J. Pharmacol. – 1996. – V.118 (3). – P.466-470.
56
56
4. Brown G., Frankl D., and Phang T. Continuous infusion of methylene blue for septic shock //
Postgrad. Med. J. – 1996. – V.72 (852). – P.612-614.
5. Oksengendler G.I. Poisons and Counterpoisons // Nauka. – Leningrad. – 1982 – 192 p. (in
Russian).
6. Khrapak V.V. and Kulik T.V. Toxic military substances as a cause of chemical catastrophes //
Suchasni Problemy Toksikologii. - 2000. - V.2 - P. 3-19.
7. Kulik T.V., Galagan N.P., and Pokrovskiy V.A. TPD MS studies on adsorption immobilization
of phenothiazine antidotes // 49th ASMS Conference on Mass Spectrometry and Allied
Topics. - Chicago. - Illinois. - May 27-31. – 2001. - Book Abstr. (CD ROM).
8. Bishop E. (Ed.), Indicators, Pergamon Press, Oxford. New York. Toronto. Sydney.
Braunschweig, 1972.
1 Institute of Surface Chemistry, National Academy of Sciences
1 Institute of Surface Chemistry, National Academy of Sciences
1 Institute of Surface Chemistry, National Academy of Sciences
1 Institute of Surface Chemistry, National Academy of Sciences
1 Institute of Surface Chemistry, National Academy of Sciences
Abstract
Introduction
Experimental
Experimental
Experimental
Experimental
Experimental
Scheme 1
Table 1. Physicochemical parameters of adsorption of phenothiazine dyes on the surface of highly dispersed silica.
Desorption
Desorption
Scheme 2
Conclusions
|