Investigation on combined effect of quaternary ammonium compounds and an organic acid on model phospholipid membranes
Abstract
Effects caused by combined inclusion of two membranotropic agents (MTA) of different nature into model
phospholipid membranes have been examined. An effect of significant change in activity of individual MTA based on quaternary and bisquaternary ammonium compounds (QAC, BQAC) – decamethoxinum, aethonium, tetramethylammonium – and organic 2,5-dihydroxybenzoic acid (DHB) on their combined incorporation into model multibilayer structures of hydrated dipalmitoylphosphatidycholine (DPPC) is revealed. Differential scanning calorimetry (DSC) data have shown that, when both types of MTA are jointly present in the system, significant deviations from additivity values are noted for the measured calorimetry parameters. This shows that it is the MTA complexes, rather than individual MTAs, affect the model membrane properties. Mass-spectrometric and quantum chemistry calculations data have demonstrated a possibility of formation of stable noncovalent complexes including (di)cations of quaternary ammonium bases and anions of organic DHB acid. Plotting of “membrane melting temperature (Tm) vs. MTA composition” quasi-binary diagrams permitted us to determine the optimal stoichiometry of the BQAC-DHB membrane-incorporated complexes. It was revealed by means of DSC that incorporation into membranes of individual ionic BQAC and DHB as well as their complexes with stoichiometry providing preservation of the ionic (charged) state of the MTAs causes decrease of Tm and, correspondingly, disordering of the membrane structure. At the same time, under MTA concentrations providing neutral complexes of BQAC and DHB, some increase in Tm is observed, corresponding to an ordering of membrane structure, which can be interpreted as deactivation of BQAC, i.e. modulation of their activity in the presence of the organic acid. The ascertained possibility of suppression of membranotropic activity of antimicrobial BQAC on their combined use with an organic acid is to be taken into account in design of multi-component antimicrobial drugs.
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2. Євстигнєєв М.П. Міжмолекулярні взаємодії біологічно активних ароматичних речовин і ДНК у водному розчині. – Автореф. дисс. … докт. физ.-мат. наук. – Харьков, 2006.
3. Виевский А.Н. Механизмы биологического влияния катионных поверхностно-активных веществ. - М.: Б.И.,1991. 250 с.
4. Vievsky A. // Tenside, Surfactants, Detergents. 1997.V. 34, N. 1. P. 18-21.
5. Суходуб Л.Ф., Косевич М.В., Шелковский В.С., Волянский Ю.Л. // Антибиотики и химиотерапия. 1989. Т. 34, № 11. C. 823-827.
6. Косевич М.В., Пашинская В.А., Шилаги З., Векей К., Шелковский В.С., Благой Ю.П. // Вісн. Харк. ун-ту, Біофізичний вісник. 1998. Т. 422, № 2. C. 15-23.
7. Kosevich M.V., Pashinskaya V.A., Stepanian S.G., Shelkovsky V.S., Orlov V.V., Blagoy Yu.P. // Proc. Kharkov State Univ., Biophysical Bulletin. 1999. V. 434, N. 1. P. 31-38.
8. Пашинская В.А., Косевич М.В., Степанян С.Г. // Вісник проблем біології і медицини. 1999. Вип. 9. С. 118-125.
9. Korzovskaya O.V., Pashinskaya V.A., Kosevich M.V., Lisetski L.N. // Biophysical Bulletin 1999. V.450, Nо 2. P. 35-39.
10. Пашинская В.А., Косевич М.В., Гомори А., Векей К., Корзовская О.В., Лисецкий Л.Н., Благой Ю.П. // Вісн. Харк. ун-ту., Біофізичний вісник. 1999. Т. 450, №. 2. С. 59-62.
11. Pashynskaya V.A., Kosevich M.V., Gomory A., Vashchenko O.V., Lisetski L.N. // Rapid Commun. Mass Spectrom. 2002. V. 16. N. 18. P. 1706-1713.
12. Pashynska V.A., Kosevich M.V., Van den Heuvel H., Cuyckens F., Claeys M. // Proc. Kharkov State Univ., Biophysical Bulletin. 2004. V. 637, N. 1-2(14). P. 123-130.
13. Pashynska V.A., Kosevich M.V., Gomory A., Szilagyu Z., Vekey K., Stepanian S.G. // Rapid Commun. Mass Spectrom. 2005. V. 19, N. 6 . P. 785-797.
14. Pokrovsky V.A., Kosevich M.V., Osaulenko V.L., Chagovets V.V., Pashynska V.A., Shelkovsky V.S., Karachevtsev V.A., Naumov A.Yu. // Масс-спектрометрия. 2005. Т. 2, N. 3. С. 183-192.
15. Pashynska V.A., Kosevich M.V., Van den Heuvel H., Claeys M. // Rapid Commun. Mass Spectrom. 2006. V. 20, N 5. P. 755-763.
16. Pahynska V., Kosevich M., Stepanian S., Adamowicz L. // J. Mol. Struct.: THEOCHEM. 2007. V. 815, N. 1-3, P. 55-62.
17. Kosevich M.V., Boryak O.A., Chagovets V.V., Pashynska V.A., Orlov V.V., Stepanian S.G., Shelkovsky V.S. // Rapid Commun. Mass Spectrom. 2007. V. 21, N. 11. P. 1813-1819.
18. Almeida Paz F.A., Soares-Santos P.C.R., Nogueira H.I.S., Trindade T., Klinowski J. // Acta Cryst. 2003; E59: o506.
19. Singer S., Nicolson G. // Science 1972. V. 175, N. 4023. P. 720-731.
20. Булиган И. Жидкокристаллический порядок в биологических мембранах. В сб. Жидкокористалли-ческий порядок в полимерах. – М.: Мир, 1981.
21. Albertini G., Ponzi-Bossi M.G., Rustichelli F. Modification of the phase transitions of model membranes by exogenous molecules. In: Phase Transitions in Liquid Crystals. Ed. S. Martelucci, A.N. Chester. - New York: Plenum Press, 1992.
22. Minami H., Inoue T. // J. Coll. Interf. Sci.1998. V. 206. P. 338-341.
23. Albertini G., Bertoli E., Curatola G., Mariani P., Rustichelli F., Zolese G. // Chem. Phys. Lipids. 1989. V. 50. P. 143-153.
24. Kyrikou I., Hadjikakou S. K., Kovala-Demertzi D., Viras K., Mavromoustakos T. // Chem. Phys. Lipids. 2004. V. 132. P. 157-169.
25. Li S., Lin H. N., Wang G., Huang C. // Biophys. J. 1996. V. 70. P. 2784-2794.
26. Balasubramanian S. V., Straubinger R. M., Morris M. E. J. // Pharm. Sci. 1997. V. 86. P. 199-204.
27. Bedu-Addo F. K., Huang L. // J. Pharm. Sci. 1996. V. 85. P. 714-719.
28. Cannon B., Hermansson M., Gyorke S., Somerharju P., Virtanen J. A., Cheng K. H. // Biophys. J. 2003. V. 85. P. 933-942.
29. Carrer D. C., Maggio B. // J. Lipid Res. 1999. V. 40. P. 1978-1989.
30. Castelli F., Trombetta D., Tomaino A., Bonina F., Romeo G., Uccella N., Saija A. // J. Pharmacol. Toxicol. Methods. 1997. V. 37. P. 135-141.
31. Castelli F., Caruso S., Uccella N. // J. Agric. Food Chem. 2003. V. 51. P. 851-855.
32. Корзовская О.В., Лисецкий Л.Н., Паникарская В.Д. // Известия РАН 1998. Т. 62. № 8. С. 1695-1697.
33. Корзовская О.В., Лисецкий Л.Н., Паникарская В.Д. // Вісн. Харк. ун-ту, Біофізичний вісн. 1998. Т. 422, № 2. С. 85-89.
34. Вирник К. М., Корзовская О.В., Лисецкий Л.Н., Паникарская В.Д. // Укр. биохим. журн. 1998. Т. 70. № 6. С. 85-90.
35. Антонов В.Ф., Смирнова Е.Ю., Шевченко Е.В. Липидные мембраны при фазовых превращениях. - М.: Наука, 1992.
36. Kosevich M.V., Chagovets V.V, Shelkovsky V.S., Boryak O.A., Orlov V.V., Gomory A., Vegh P. // Rapid Commun. Mass Spectrom. 2007. V. 21. P. 466-478.
37. Lisetski L.N., O.V. Vashchenko, A.V. Tolmachev, K.B. Vodolazhskiy. Effect of membranotropic agents on mono-, multilayers of dipalmitoylphosphatidylcholine // Eur. Biophys. J. 2002. V. 31. P. 554-558.
38. Овчинников Ю.А. Биоорганическая химия. - М.: Просвещение, 1987.
39. Введение в биомембранологию / Под ред. А.А. Болдырева. - М.: Изд-во МГУ, 1990.
40. Гордієнко Е.О., Товстяк В.В. Фізика біомембран. - К.: Наук. думка, 2009.
41. Ивков В.Г., Берестовский Г.Н. Динамическая структура липидного бислоя. - М.: Наука, 1981.
42. Харакоз Д.П. // Успехи биол. химии. 2001. Т. 41. С. 333-364.
43. Геннис Р. Биомембраны: молекулярная структура и функции. - М.: Мир, 1997. - 624 с.
44. Фиалков Ю. Я., Житомирский А. Н., Тарасенко Ю. А. Физическая химия неводных растворов. - Л: Химия, 1973.
45. Растворы неэлектролитов в жидкостях / М. Ю. Никифоров, Г. А. Альпер, В. А. Дуров и др. - М.: Наука, 1989.
46. Ситникова Т. А., Рахнянская А. А., Ярославова Е. Г., Сергеев-Черенков А. Н., Хомутов Г. Б., Гринберг В. Я., Бурова Т. В.,. Ярославов А. А. // Высокомолек. соед. 2009. Т. 51. № 6. С. 954-961.
47. Pashynska V., Boryak O., Kosevich M.V., Stepanian S., Adamovicz L. // Eur. Phys. J. D. 2010. V. 58. P. 287-296.
48. Aitipamula S., Chow P.S., Tan R.B.N. // Acta Cryst. 2009. E65, o2126-o2127.
49. Ashidate K, Kawamura M., Mimura D., Tohda H., Miyazaki S., Teramoto T., Yamamoto Y., Hirata Y. // Eur. J. Pharmacology. 2005. V. 513. Iss. 3. P. 173-179.
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