Modulation of bisquaternary ammonium agents effect on model biomembranes by complex formation with an organic anion
Aim. To study membranotropic activity modulation of bisquaternary ammonium compounds (BQAC) decamethoxinum and aethonium determined by their interaction with dihydroxybenzoic acid (DHB) organic anion. Methods. Differential scanning calorimetry, mass spectrometry. Results. Doping phospholipid membran...
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Інститут молекулярної біології і генетики НАН України
2010
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| Zitieren: | Modulation of bisquaternary ammonium agents effect on model biomembranes by complex formation with an organic anion / O.V. Vashchenko, V.A. Pashynska, M.V. Kosevich, V.D. Panikarskaya, L.N. Lisetski // Вiopolymers and Cell. — 2010. — Т. 26, № 6. — С. 472-477. — Бібліогр.: 8 назв. — англ, рос. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1859620108029132800 |
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| author | Vashchenko, O.V. Pashynska, V.A. Kosevich, Kosevich M.V. Panikarskaya, V.D. Lisetski, L.N. |
| author_facet | Vashchenko, O.V. Pashynska, V.A. Kosevich, Kosevich M.V. Panikarskaya, V.D. Lisetski, L.N. |
| citation_txt | Modulation of bisquaternary ammonium agents effect on model biomembranes by complex formation with an organic anion / O.V. Vashchenko, V.A. Pashynska, M.V. Kosevich, V.D. Panikarskaya, L.N. Lisetski // Вiopolymers and Cell. — 2010. — Т. 26, № 6. — С. 472-477. — Бібліогр.: 8 назв. — англ, рос. |
| collection | DSpace DC |
| container_title | Вiopolymers and Cell |
| description | Aim. To study membranotropic activity modulation of bisquaternary ammonium compounds (BQAC) decamethoxinum and aethonium determined by their interaction with dihydroxybenzoic acid (DHB) organic anion. Methods. Differential scanning calorimetry, mass spectrometry. Results. Doping phospholipid membranes with individual BQAC or DHB leads to a considerable decrease in the membrane melting temperature. At the same time, when BQAC and DHB are introduced together, a certain increase in the membrane melting temperature is observed, implying non-additivity of their action and incorporation of their complexes into the membranes. Conclusions. DHB decreases the efficiency of BQAC destabilizing action on the membranes, i. e. DHB is a modulator of their membranotropic activity. A possible molecular mechanism of the modulation consists in the compensation of charges of the BQAC dications by organic DHB anions on the complex formation; parameters of the complex interaction with the membrane structures differ from those of individual ionic compounds.
Мета. Вивчити модуляцію мембранотропної активності бісчетвертинних амонієвих сполук (БЧАС) декаметоксину та етонію, зумовлену їхньою взаємодією з органічнім аніоном дигідроксибензойної кислоти (DHB). Методи. Диференційна скануюча калориметрія, мас-спектрометрія. Результати. Виявлено, що додавання індивідуальних БЧАС або DHB до фосфоліпідних мембран значно знижує температуру фазового переходу «гель–рідкий кристал». При одночасному введенні БЧАС і DHB температура фазового переходу мембрани дещо підвищується, що свідчить про відсутність адитивності дії цих речовин та інкорпорацію у мембрани утворених ними комплексів. Висновки. DHB зменшує ефективність дестабілізувальної дії БЧАС на мембрани, тобто слугує модулятором їхньої активності. Ймовірний молекулярний механізм модуляції полягає у компенсації зарядів дикатіона БЧАС та органічних аніонів DHB при утворенні їхнього комплексу, взаємодія якого з мембранними структурами є відмінною від такої іонних форм індивідуальних сполук.
Цель. Изучить модуляцию мембранотропной активности бисчетвертичных аммониевых соединений (БЧАС) декаметоксина и этония, обусловленную их взаимодействием с органическим анионом дигидроксибензойной кислоты (DHB). Методы. Дифференциальная сканирующая калориметрия, масс-спектрометрия. Результаты. Обнаружено, что добавление индивидуальных БЧАС или DHB к фосфолипидным мембранам значительно снижает температуру перехода «гель–жидкий кристалл». При совместном введении БЧАС и DHB температура фазового перехода мембраны несколько повышается, что свидетельствует об отсутствии аддитивности действия этих веществ и встраивании в мембраны их комплексов. Выводы. DHB уменьшаает эффективность дестабилизирующего эффекта БЧАС на мембраны, то есть является модулятором их активности. Возможный молекулярный механизм модуляции заключается в компенсации зарядов дикатиона БЧАС и органических анионов DHB при образовании их комплекса, взаимодействие которого с мембранными структурами отличается от такового ионных форм индивидуальных соединений.
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STRUCTURE AND FUNCTION OF BIOPOLYMERS
Modulation of bisquaternary ammonium agents effect on
model biomembranes by complex formation with an
organic anion
O. V. Vashchenko, V. A. Pashynska1, M. V. Kosevich1, V. D. Panikarskaya,
L. N. Lisetski
Institute for Scintillation Materials NAS of Ukraine
60, Prospekt Lenina, Kharkiv, Ukraine, 61085
1Institute for Low Temperature Physics and Engineering NAS of Ukraine
47, Prospekt Lenina, Kharkiv, Ukraine, 61103
olga_v@isma.kharkov.ua
Aim. To study membranotropic activity modulation of bisquaternary ammonium compounds (BQAC)
decamethoxinum and aethonium determined by their interaction with dihydroxybenzoic acid (DHB)
organic anion. Methods. Differential scanning calorimetry, mass spectrometry. Results. Doping
phospholipid membranes with individual BQAC or DHB leads to a considerable decrease in the membrane
melting temperature. At the same time, when BQAC and DHB are introduced together, a certain increase in
the membrane melting temperature is observed, implying non-additivity of their action and incorporation of
their complexes into the membranes. Conclusions. DHB decreases the efficiency of BQAC destabilizing
action on the membranes, i. e. DHB is a modulator of their membranotropic activity. A possible molecular
mechanism of the modulation consists in the compensation of charges of the BQAC dications by organic
DHB anions on the complex formation; parameters of the complex interaction with the membrane structures
differ from those of individual ionic compounds.
Key words: membranotropic agents, phospholipid membranes, bisquaternary ammonium compounds,
dihydroxybenzoic acid, activity modulation, differential scanning calorimetry.
Introduction. It is known that the efficiency of
pharmacological preparations is determined by their
main active compound and the modulation of activity
by other substances present in the pharmaceutical form.
The present investigation was aimed at modulating
influence of antimicrobial preparations based on
bisquarternary ammonium compounds (BQAC) by
their binding to organic anions. One of the main
mechanisms of activity of membranotropic BQAC,
which are the cation surface active compounds
(surfactants), is believed to be their binding to the
cytoplasmic membranes of microorganisms, resulting
in their malfunction [1]. In the series of our previous
publications [2–4], dedicated to systematic study on
the molecular mechanisms of activity of the
BQAC-based antimicrobial preparations,
decamethoxinum and aethonium (Fig.1, a, b), we
showed that these preparations interacted with model
phospholipid membranes and formed stable
non-covalent complexes with phospholipids. The
472
ISSN 1993-6842. Biopolymers and cell. 2010. vol. 26. N 6.P. 472-477. Translated from Ukrainian
Ó Institute of Molecular Biology and Genetics NAS of Ukraine, 2010
further mass-spectrometry experiments revealed that
an anion of organic 2, 5-dihydroxybenzoic acid (DHB)
is able to replace a counter-ion of chloride, thus
forming a stable complex with decamethoxinum
dication. This fact allowed us to suppose a possibility
of formation of such complexes as a result of joint
action of these two substances on phospholipid
membranes, as well as to assume an effect of binding
BQAC dications to DHB organic anions on their
membranotropic activity. To check this assumption, a
model system was selected as water dispersions of
dipalmitoylphosphatidylcholine (DPPC) ? multilayer
lamellar structures consisting of phospholipid bilayers
separated by water layers, which imitate phospholipid
membranes. BQAC decamethoxinum and aethonium
were introduced separately or in combination with
DHB. It should be noted that DHB was chosen as a
compound modelling the acid and aromatic groups
present in a number of amino acids [5]. The main
method of investigation was differential scanning
calorimetry (DSC) allowing determining changes in
the calorimetric parameters of phase transitions in the
model membranes when they are affected by
membranotropic agents (MTA).
Materials and Methods. The DSC studies were
carried out using the Mettler TA 3000 thermoanalytic
system (Switzerland). Samples of 15–25 mg were
placed into aluminium crucibles with half-closed lids.
Programmed scheme of temperature scanning
consisted of consecutive cycles of heating and cooling
with the rate of 2 K/min.
Crystalline DPPC and BQAC were mixed and
water dispersions of this composition with mass ratio
DPPC: water of 50:50 [were prepared] using the
standard method, described in [6]. While introducing
BQAC and DHB simultaneously, we chose the
concentrations to ensure the ratio between quaternary
groups and DHB as 2:1, 1:1, and 1:2, corresponding to
the molar ratios of 1:1, 1:2, and 1:4. The investigation
of all the systems was performed at pH 7, the total
amount of MTA, introduced into phospholipid matrix,
was 5% (mass).
The investigation by matrix-assisted laser
desorption/ionization (MALDI) mass-spectrometry
was performed using a time-of-flight mass
spectrometer MALDI-TOF AutoFlex (Bruker
Daltonics, Germany). In these experiments, one of the
components of investigated systems, namely, DHB,
functioned also as a UV-absorbing matrix for MALDI.
Preparations of DPPC (5.45% humidity) of Alexis
Biochemicals (Switzerland) and 2,
5-dihydroxybenzoic acid of Sigma (Germany) were
473
MODULATION OF BISQUATERNARY AMMONIUM AGENTS EFFECT ON BIOMEMBRANES
O C C H2
O
N
CH 3
CH
3
(C H2)1 0 N
C H3
C H
3
C H2 C
O
O
. 2C l–
. 2Cl–(CH2)9 O C CH2
O
N
CH3
CH
3
(CH2)2 N
C H3
C H
3
C H2 C
O
OC H3 (CH2)9 C H3
OH
C
O
OH
OH
à
b
c
Fig. 1. Structural formulas of dichlorides of
BQAC of decamethoxinum (a), aethonium (b),
and 2.5-dihydroxybenzoic acid (c)
used in the work. Decamethoxinum and aethonium
were synthesized in the Institute of Organic Chemistry,
NAS of Ukraine.
Results and Discussion. The formation of stable
non-covalent complex of BQAC decamethoxinum
dication with DHB anion was registered in the
conditions of MALDI mass-spectrometry experiment
using solid samples obtained from dried water solution
of decamethoxinum and DHB (Fig.2). Along with the
dication associate with one chloride anion Cat+2•Cl-,
m/z 657, characteristic ion in mass-spectra of pure
decamethoxinum [2], the dication associate with DHB
anion Cat2+•(DHB–H)-, m/z 775 is formed. At
equimolar ratio of components in initial solution, the
intensity of associate Cat2+•(DHB–H) in MALDI
mass-spectra is considerably higher than that of
associate Cat2+•Cl-, which indicates the competition
between anions and predominate binding of organic
anion to dication (DHB–H)-.
DSC method was used to determine the
calorimetric parameters of phase transitions in model
membranes in the range of physiological temperatures,
namely, transition from gel phase into liquid crystalline
state. The study was performed on water dispersions of
DPPC alone, DPPC with addition of BQAC of
decamethoxinum, aethonium, and DHB, and mixtures
of BQAC: and DHB .Table 1 presents the data of DSC:
temperature (Tm) and enthalpy (DHm) of the main phase
transition, determined in the regimes of heating and
cooling, as well as hysteresis (DT).
To solve the question about stoichiometry of
possible complexes, we analyzed the initial data using
the method of quasibinary systems [7, 8]. In this
method, the phospholipid medium is considered as a
matrix, in which two dissolved components interact. In
the absence of interaction, any thermodynamic feature
of the system, expressed in corresponding units, is
additive with respect to the relative concentrations of
components and vice versa, specific interaction results
in a deviation from the additivity.
Fig.3 presents quasibinary phase diagrams for the
systems containing hydrated DPPC with additions of
BQAC of decamethoxinum and aethonium, as well as
DHB acids. The straight line connecting two extreme
points corresponding to Tm of BQAC and DHB relates
to the diagram in case of Tm additivity. The length of the
perpendicular dropped from the maximum of the
experimental curve on this line characterizes the
deviation from additivity; the location of the curve
474
VASHCHENKO O. V. ET AL.
Composition of
membranotropic agents
Heating Cooling
Hyste-
resis
Tm, °Ñ
DH,
J/g
Tm, °Ñ
DHm,
J/g
DT, °Ñ
no MTA 41,5 23,4 41,4 40,3 0,1
DHB 37,1 20,3 36,1 23,9 1,0
Decamethoxinum 35,7 15,8 35,2 24,5 0,5
Decamethoxinum:DHB
1:1
37,9 15,3 35,0 26,0 2,9
Decamethoxinum:DHB
1:2
41,8 15,8 40,5 17,7 1,3
Decamethoxinum:DHB
1:4
41,7 24,5 41,5 5,0 0,2
Aethonium 39,8 17,8 39,7 18,5 0,1
Aethonium:DHB 1:1 40,0 13,7 39,5 16,6 0,5
Aethonium:DHB 1:2 41,6 17,8 40,2 21,7 1,4
Aethonium:DHB 1:4 41,6 18,8 40,9 30,8 0,7
Parameters of phase transitions for systems of hydrated DPPC +
MTA
I, a. e.
4000
3000
2000
1000
0
600 650 700 750 m/z
775
657
621
Cat2+ · (DHB-H)–
Cat2+ · Cl–
[Cat2+-H]+•
Fig. 2. Part of MALDI mass-spectrum of decamethoxinum sample
in DHB matrix containing dication associates of decamethoxinum
with chloride anion Cat+2•Cl- and anion of deprotonated DHB
Cat2+•(DHB–H)-
maximum points to the most advantageous
stoichiometry of the complexes incorporated into the
membrane.
The analysis of the data obtained gives grounds for
the following conclusions. The change in
thermodynamic parameters of model membranes at
introducing individual MTA into the water dispersion
of DPPC proves the interaction of all investigated
MTA with phospholipid bilayers. The introduction of
MTA considerably decreases the temperature of the
main phase transition, i.e. it results in disorder of
phospholipid bilayers. As quaternary ammonium
compounds and DHB acid dissociate in water solution,
it is possible to suppose that these MTA are built into
the membrane in the form of ions: dications of
decamethoxinum and aethonium Cat2+ and anion
(DHB–H)-.
Simultaneous introduction of BQAC and DHB into
DPPC dispersion also changes its thermodynamic
parameters, but there is no observed additivity of
BQAC and DHB effects related to the concentration of
introduced components. A considerable deviation from
additivity in systems (DPPC + BQAC + DHB) is an
evidence of specific interaction between the additives
introduced into phospholipid matrix. The complexes of
BQAC and DHB are likely to be formed similarly to the
complexes of Cat2+• (DHB–H) - registered in the
mass-spectrometry experiment ([see] Fig.2) due to
Coulomb interaction between corresponding cations
and anions.
Plotting of quasibinary diagrams allowed
determining the stoichiometry of complexes BQAC:
DHB 1:2, which is notable for the maximal deviation
from additivity ([see] Fig.3). In these complexes one
DHB anion corresponds to each ammonium group in
the composition of BQAC.
The degree of effect of simultaneously introduced
BQAC and DHB on the system calorimetric parameters
significantly depends on the ratio between
components. If molar ratio BQAC to DHB is 1:1, Tm
values for the three-component system (DPPC +
BQAC + DHB) do not differ much from those for the
binary system (DPPC + BQAC). If BQAC ratio to
DHB is 1:2 and 1:4, there are qualitative changes: a
shift of the main transition temperature changes the
sign with respect to Tm of non-doped DPPC; however,
an increase in Tm absolute value is insignificant. This
effect may be considered as elimination of disordering
influence of BQAC on membranes in the presence of
475
MODULATION OF BISQUATERNARY AMMONIUM AGENTS EFFECT ON BIOMEMBRANES
42
40
38
36
42
40
38
36
0 20 40 60 80 100
<CDHB>, mol%
1:2
1:1
1:4
T
m
, °CT
m
, °C
42
40
38
36
42
40
38
36
0 20 40 60 80 100
<CDHB>, mol%
1:2 1:4
1:1
T
m
, °C T
m
, °C
Fig. 3. Phase diagrams of quasibinary systems:
decamethoxinum–DHB (a), aethonium–DHB (b) in the medium of
hydrated DPPC (total MTA concentration in all the systems is 5
mass. %). Corresponding molar ratios of MTA are indicated in
markings of experimental points
definite DHB concentrations. Therefore, it is possible
to regard DHB as a modulator of BQAC activity. On
the other hand, complex formation with BQAC
decreases the DHB activity.
Neutralization of the charge of BQAC dication
while forming its complex with DHB seems to be the
most probable molecular mechanism of the
abovementioned effect of modulation of the BQAC
activity. This assumption is based on the fact that the
transition from decrease to increase in melting
temperature Tm in the system (DPPC + BQAC + DHB)
occurs at the DHB content that either equals or exceeds
the amount of positively charged ammonium groups
(two groups per one BQAC molecule), which is
sufficient for their neutralization at the complex
formation. If molecular ratio BQAC to DHB is 1:1, one
of the dication positive centres on average is not
“compensated” by DHB anion and the calorimetric
parameters still change in accordance with the effect of
ion MTA on the membrane.
It should be noted that previously we described the
dependence of membranotropic activity of the
BQAC-based surfactants on their structure, i.e. the
nature of hydrophobic “tail” and a distance between
positively charged atoms of quaternary nitrogen, on the
example of decamethoxinum and aethonium [2, 3]. The
structure of aethonium dication, including a polar
“head” of two closely located ammonium groups and
two hydrophobic carbohydrate chains, is generally
similar to the structure of DPPC molecules, which
provides the building of aethonium dication into the
membrane due to the substitution of DPPC molecule. A
more complicated structure of hydrophobic “tails” of
decamethoxinum, containing methyl residues, as well
as rather large distance between positively charged
ammonium groups result in greater destabilizing effect
of decamethoxinum on the membranes in comparison
to aethonium.
As for enthalpy val ues of the main phase tran si tion
in model mem branes de ter mined in the re gime of sam -
ple heat ing, they dem on strate a gen eral ten dency to
de creas ing when MTA is in tro duced into the sys tem.
At first sight, this fact shows that dis or der ing of mem -
branes re quires much less en ergy in the pres ence of
destabilizing agents in their com po si tion. The pro -
cesses oc cur ring dur ing cool ing of the sys tem are re -
lated to the pe cu liar i ties of MTA in clu sion into the liq -
uid crys tal struc ture of mem branes, which is a sub ject
of fur ther studies beyond the framework of this review.
Conclusions. The possibility of modulation of the
activity of MTA, based on BQAC salts, was considered
for the case of their simultaneous with organic acid
DHB introduction into the model phospholipid
membranes.
The data of DSC research demonstrated the
absence of additivity of calorimetric parameters, which
is a characteristic of the model membranes containing
individual MTA, in the case of simultaneous
introduction of the mixture of DHB with BQAC
decamethoxinum and aethonium into the water
dispersion of hydrated DPPC. This experimental fact
evidences the insertion of MTA complexes instead of
individual MTA into the membranes.
The data of mass-spectrometry showed the
possibility of formation of stable complexes of cations
of quaternary ammonium compounds with DHB anion.
The analysis of calorimetric parameters of the
systems investigated revealed that the insertion of
dissociated in solution individual components in ionic
state into the membranes, results in a decrease in the
temperature of main transition and corresponding
disordering of the membrane structure. The similar
effect of decrease in the membrane melting
temperature is observed if components of the MTA
mixtures added are in the ratio sustaining a charged
state of their complexes. In case of the formation of
neutral complexes of BQAC dications with DHB
anion, an increase in the temperature of main transition
is revealed along with ordering the membrane
structure. This effect may be considered as BQAC
deactivation, i.e. modulation of the BQAC activity by
organic acid. Neutralization of ionic MTA due to the
formation of cation-anion complexes was suggested as
a molecular mechanism of such modulation.
The possibility of weakening membranotropic
activity of the BQAC-based antimicrobial agents,
revealed at their introduction together with organic
acid, should be taken into account while developing
polycomponent drugs of antimicrobial activity. The
approach proposed in this work may be used on a
broader scale for testing the combined activity of MTA
of various nature.
476
VASHCHENKO O. V. ET AL.
Î. Â. Âà ùåí êî, Â. À. Ïà øèí ñêàÿ1, Ì. Â. Êî ñå âè÷1,
Â. Ä. Ïà íè êàð ñêàÿ, Ë. Í. Ëè ñåö êèé
Ìî äó ëÿ öèÿ âîç äå éñòâèÿ ÷åò âåð òè÷ íûõ àì ìî íè å âûõ ñî å äè íå -
íèé íà ìî äåëü íûå áè î ìåì áðà íû ïî ñðå äñòâîì êîì ïëåê ñî îá ðà -
çî âà íèÿ ñ îðãà íè ÷åñ êèì àíè î íîì
Èíñòè òóò ñöèí òèë ëÿ öè îí íûõ ìà òå ðè à ëîâ ÍÒÊ «Èíñòè òóò ìî -
íîê ðèñ òàë ëîâ» ÍÀÍ Óêðà è íû
Ïðîñ ïåêò Ëå íè íà, 60, Õàðü êîâ, Óêðà è íà, 61001
1Ôè çè êî-òåõ íè ÷åñ êèé èí ñòè òóò íèç êèõ òåì ïå ðà òóð
èì. Á. È. Âåð êè íà ÍÀÍ Óêðà è íû
Ïðîñ ïåêò Ëå íè íà, 47, Õàðü êîâ, Óêðà è íà, 61103
Ðå çþ ìå
Öåëü. Èçó ÷èòü ìî äó ëÿ öèþ ìåì áðà íîò ðîï íîé àê òèâ íîñ òè áèñ -
÷åò âåð òè÷ íûõ àì ìî íè å âûõ ñî å äè íå íèé (Á×ÀÑ) äå êà ìå òîê ñè -
íà è ýòî íèÿ, îá óñëîâ ëåí íóþ èõ âçà è ìî äå éñòâè åì ñ
îðãà íè ÷åñ êèì àíè î íîì äè ãèä ðîê ñè áåí çîé íîé êèñ ëî òû (DHB).
Ìå òî äû. Äèô ôå ðåí öè àëü íàÿ ñêà íè ðó þ ùàÿ êà ëî ðè ìåò ðèÿ,
ìàññ-ñïåê òðî ìåò ðèÿ. Ðå çóëü òà òû. Îáíà ðó æå íî, ÷òî äî áàâ -
ëå íèå èí äè âè äó àëü íûõ Á×ÀÑ èëè DHB ê ôîñ ôî ëè ïèä íûì ìåì -
áðà íàì çíà ÷è òåëü íî ñíè æà åò òåì ïå ðà òó ðó ïå ðå õî äà
«ãåëü–æèä êèé êðèñ òàëë». Ïðè ñî âìåñ òíîì ââå äå íèè Á×ÀÑ è
DHB òåì ïå ðà òó ðà ôà çî âî ãî ïå ðå õî äà ìåì áðà íû íå ñêîëü êî ïî -
âû øà åò ñÿ, ÷òî ñâè äå ò åëüñòâó åò îá îò ñó òñòâèè àä äè òèâ íîñ -
òè äå éñòâèÿ ýòèõ âå ùåñòâ è âñòðà è âà íèè â ìåì áðà íû èõ
êîì ïëåê ñîâ. Âû âî äû. DHB óìåíü øà à åò ýô ôåê òèâ íîñòü äåñ -
òà áè ëè çè ðó þ ùå ãî ýô ôåê òà Á×ÀÑ íà ìåì áðà íû, òî åñòü ÿâ ëÿ -
åò ñÿ ìî äó ëÿ òî ðîì èõ àê òèâ íîñ òè. Âîç ìîæ íûé ìî ëå êó ëÿð íûé
ìå õà íèçì ìî äó ëÿ öèè çà êëþ ÷à åò ñÿ â êîì ïåí ñà öèè çà ðÿ äîâ äè êà -
òè î íà Á×ÀÑ è îðãà íè ÷åñ êèõ àíè î íîâ DHB ïðè îá ðà çî âà íèè èõ
êîì ïëåê ñà, âçà è ìî äå éñòâèå êî òî ðî ãî ñ ìåì áðàí íû ìè ñòðóê -
òó ðà ìè îò ëè ÷à åò ñÿ îò òà êî âî ãî èîí íûõ ôîðì èí äè âè äó àëü -
íûõ ñî å äè íå íèé.
Êëþ ÷å âûå ñëî âà: ìåì áðà íîò ðîï íûå àãåí òû, ôîñ ôî ëè ïèä -
íûå ìåì áðà íû, áèñ ÷åò âåð òè÷ íûå àì ìî íè å âûå ñî å äè íå íèÿ, äè -
ãèä ðîê ñè áåí çîé íàÿ êèñ ëî òà, ìî äó ëÿ öèÿ àê òèâ íîñ òè,
äèô ôå ðåí öè àëü íàÿ ñêà íè ðó þ ùàÿ êà ëî ðè ìåò ðèÿ.
Î. Â. Âà ùåí êî, Â. À. Ïà øè íñüêà, Ì. Â. Êî ñå âè÷,
Â. Ä. Ïàí³êà ðñüêà, Ë. Ì. Ëè ñåöü êèé
Ìî äó ëÿö³ÿ âïëè âó á³ñ÷åò âåð òèí íèõ àìîí³ºâèõ ñïî ëóê íà
ìî äåëüí³ á³îìåì áðà íè âíàñë³äîê êîì ïëåê ñî óò âî ðåí íÿ
ç îðãàí³÷íèì àí³îíîì
Ðå çþ ìå
Ìåòà. Âèâ ÷è òè ìî äó ëÿö³þ ìåì áðà íîò ðîï íî¿ àê òèâ íîñò³ á³ñ-
÷åò âåð òèí íèõ àìîí³ºâèõ ñïî ëóê (Á×ÀÑ) äå êà ìå òîê ñè íó òà
åòîí³þ, çó ìîâ ëå íó ¿õíüîþ âçàºìî䳺þ ç îðãàí³÷í³ì àí³îíîì äè-
ã³äðîê ñè áåí çîé íî¿ êèñ ëî òè (DHB). Ìå òî äè. Äè ôå ðåíö³éíà ñêà-
íó þ ÷à êà ëî ðè ìåòð³ÿ, ìàñ-ñïåê òðî ìåòð³ÿ. Ðå çóëü òà òè. Âè ÿâ -
ëå íî, ùî äî äà âàí íÿ ³íäèâ³äó àëü íèõ Á×ÀÑ àáî DHB äî ôîñ ôî-
ë³ï³äíèõ ìåì áðàí çíà÷ íî çíè æóº òåì ïå ðà òó ðó ôà çî âî ãî ïå ðå -
õî äó «ãåëü–ð³äêèé êðèñ òàë». Ïðè îä íî ÷àñ íî ìó ââå äåíí³ Á×ÀÑ ³
DHB òåì ïå ðà òó ðà ôà çî âî ãî ïå ðå õî äó ìåì áðà íè äåùî
ï³äâè ùóºòüñÿ, ùî ñâ³ä÷èòü ïðî â³äñóòí³ñòü àäè òèâ íîñò³ 䳿
öèõ ðå ÷î âèí òà ³íêîð ïî ðàö³þ ó ìåì áðà íè óòâî ðå íèõ íèìè êîì -
ïëåêñ³â. Âèñ íîâ êè. DHB çìåíøóº åôåê òèâí³ñòü äåñ òàá³ë³çó -
âàëü íî¿ ä³¿ Á×ÀÑ íà ìåì áðà íè, òîá òî ñëóãóº ìî äó ëÿ òî ðîì
¿õíüî¿ àê òèâ íîñò³. Éìîâ³ðíèé ìî ëå êó ëÿð íèé ìå õàí³çì ìî äó -
ëÿö³¿ ïî ëÿ ãຠó êîìïåí ñàö³¿ çà ðÿä³â äè êàò³îíà Á×ÀÑ òà
îðãàí³÷íèõ àí³îí³â DHB ïðè óòâî ðåíí³ ¿õíüî ãî êîì ïëåê ñó,
âçàºìîä³ÿ ÿêî ãî ç ìåìá- ðàí íè ìè ñòðóê òó ðà ìè º â³äì³ííîþ â³ä
òà êî¿ ³îí íèõ ôîðì ³íäè- â³äó àëü íèõ ñïî ëóê.
Êëþ ÷îâ³ ñëî âà: ìåì áðà íîò ðîïí³ àãåí òè, ôîñ ôîë³ï³äí³ ìåì -
áðà íè, á³ñ÷åò âåð òèíí³ àìîí³ºâ³ ñïî ëó êè, äèã³äðîê ñè áåí çîé íà
êèñ ëî òà, ìî äó ëÿö³ÿ àê òèâ íîñò³, äè ôå ðåíö³éíà ñêà íó þ ÷à êà ëî -
ðè ìåòð³ÿ.
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UDC 577.352:615.2
Recåived 29.03.10
477
MODULATION OF BISQUATERNARY AMMONIUM AGENTS EFFECT ON BIOMEMBRANES
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| id | nasplib_isofts_kiev_ua-123456789-154213 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 0233-7657 |
| language | English |
| last_indexed | 2025-11-29T01:50:52Z |
| publishDate | 2010 |
| publisher | Інститут молекулярної біології і генетики НАН України |
| record_format | dspace |
| spelling | Vashchenko, O.V. Pashynska, V.A. Kosevich, Kosevich M.V. Panikarskaya, V.D. Lisetski, L.N. 2019-06-15T10:05:29Z 2019-06-15T10:05:29Z 2010 Modulation of bisquaternary ammonium agents effect on model biomembranes by complex formation with an organic anion / O.V. Vashchenko, V.A. Pashynska, M.V. Kosevich, V.D. Panikarskaya, L.N. Lisetski // Вiopolymers and Cell. — 2010. — Т. 26, № 6. — С. 472-477. — Бібліогр.: 8 назв. — англ, рос. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.000176 https://nasplib.isofts.kiev.ua/handle/123456789/154213 577.352:615.2 Aim. To study membranotropic activity modulation of bisquaternary ammonium compounds (BQAC) decamethoxinum and aethonium determined by their interaction with dihydroxybenzoic acid (DHB) organic anion. Methods. Differential scanning calorimetry, mass spectrometry. Results. Doping phospholipid membranes with individual BQAC or DHB leads to a considerable decrease in the membrane melting temperature. At the same time, when BQAC and DHB are introduced together, a certain increase in the membrane melting temperature is observed, implying non-additivity of their action and incorporation of their complexes into the membranes. Conclusions. DHB decreases the efficiency of BQAC destabilizing action on the membranes, i. e. DHB is a modulator of their membranotropic activity. A possible molecular mechanism of the modulation consists in the compensation of charges of the BQAC dications by organic DHB anions on the complex formation; parameters of the complex interaction with the membrane structures differ from those of individual ionic compounds. Мета. Вивчити модуляцію мембранотропної активності бісчетвертинних амонієвих сполук (БЧАС) декаметоксину та етонію, зумовлену їхньою взаємодією з органічнім аніоном дигідроксибензойної кислоти (DHB). Методи. Диференційна скануюча калориметрія, мас-спектрометрія. Результати. Виявлено, що додавання індивідуальних БЧАС або DHB до фосфоліпідних мембран значно знижує температуру фазового переходу «гель–рідкий кристал». При одночасному введенні БЧАС і DHB температура фазового переходу мембрани дещо підвищується, що свідчить про відсутність адитивності дії цих речовин та інкорпорацію у мембрани утворених ними комплексів. Висновки. DHB зменшує ефективність дестабілізувальної дії БЧАС на мембрани, тобто слугує модулятором їхньої активності. Ймовірний молекулярний механізм модуляції полягає у компенсації зарядів дикатіона БЧАС та органічних аніонів DHB при утворенні їхнього комплексу, взаємодія якого з мембранними структурами є відмінною від такої іонних форм індивідуальних сполук. Цель. Изучить модуляцию мембранотропной активности бисчетвертичных аммониевых соединений (БЧАС) декаметоксина и этония, обусловленную их взаимодействием с органическим анионом дигидроксибензойной кислоты (DHB). Методы. Дифференциальная сканирующая калориметрия, масс-спектрометрия. Результаты. Обнаружено, что добавление индивидуальных БЧАС или DHB к фосфолипидным мембранам значительно снижает температуру перехода «гель–жидкий кристалл». При совместном введении БЧАС и DHB температура фазового перехода мембраны несколько повышается, что свидетельствует об отсутствии аддитивности действия этих веществ и встраивании в мембраны их комплексов. Выводы. DHB уменьшаает эффективность дестабилизирующего эффекта БЧАС на мембраны, то есть является модулятором их активности. Возможный молекулярный механизм модуляции заключается в компенсации зарядов дикатиона БЧАС и органических анионов DHB при образовании их комплекса, взаимодействие которого с мембранными структурами отличается от такового ионных форм индивидуальных соединений. en Інститут молекулярної біології і генетики НАН України Вiopolymers and Cell Structure and Function of Biopolymers Modulation of bisquaternary ammonium agents effect on model biomembranes by complex formation with an organic anion Модуляція впливу бісчетвертинних амонієвих сполук на модельні біомембрани внаслідок комплексоутворення з органічним аніоном Модуляция воздействия четвертичных аммониевых соединений на модельные биомембраны посредством комплексообразования с органическим анионом Article published earlier |
| spellingShingle | Modulation of bisquaternary ammonium agents effect on model biomembranes by complex formation with an organic anion Vashchenko, O.V. Pashynska, V.A. Kosevich, Kosevich M.V. Panikarskaya, V.D. Lisetski, L.N. Structure and Function of Biopolymers |
| title | Modulation of bisquaternary ammonium agents effect on model biomembranes by complex formation with an organic anion |
| title_alt | Модуляція впливу бісчетвертинних амонієвих сполук на модельні біомембрани внаслідок комплексоутворення з органічним аніоном Модуляция воздействия четвертичных аммониевых соединений на модельные биомембраны посредством комплексообразования с органическим анионом |
| title_full | Modulation of bisquaternary ammonium agents effect on model biomembranes by complex formation with an organic anion |
| title_fullStr | Modulation of bisquaternary ammonium agents effect on model biomembranes by complex formation with an organic anion |
| title_full_unstemmed | Modulation of bisquaternary ammonium agents effect on model biomembranes by complex formation with an organic anion |
| title_short | Modulation of bisquaternary ammonium agents effect on model biomembranes by complex formation with an organic anion |
| title_sort | modulation of bisquaternary ammonium agents effect on model biomembranes by complex formation with an organic anion |
| topic | Structure and Function of Biopolymers |
| topic_facet | Structure and Function of Biopolymers |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/154213 |
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