N. Melnikova, I. Ioffe, A. Volkov, M. Kulikov.

1. The artificial membranes as a model of interaction of medicine with biosystems at the presence metal ions • Introduction. The principles of the representation of polar (ionic channel) and lipofile fragment of membrane. The role of ion-metals of active life of membrane. • The Interaction of medicine with palmitic acid monolayers on the water subphase at the presence Ca2+, Mg2+, Cu2+, Zn2+, Fe2+ ions. • The study of different kinds of layers (Langmuir monolayers on water subphase, vesicles type ( MUV, SUV, LUV, LOV) by action medicine at presence ion-metals. N. Melnikova, I. Ioffe, A. Volkov, M. Kulikov.

2. Ionic Channel in Plasmatic Membranes  water P P hydrophobic surface (lipid layers) water porous (ionic channel) hydrophilic surface P – protein part of ionic channel Polyglucoside chains

3. Self-organizing of Amphiphilic Compounds Membrane of oncology cell or soap bubble Surface film Clathrates Micelle Vesicle Normal membrane

4. Study of Langmuir Monolayers IR – irradiationcontrol system interface IR torsion spring teflon plate movable barrier teflon trough electric drive water subphase antivibrational table

5. Langmuir-Blodgett Technique of Transfer of Layers (Horizontal Lifting Method) Movable clamp Pressing roller

6. Compounds The medicine having cromonyl groups γ-pyron [4H-pyranone-4] Chromone [benzo-4H-pyranone-4] Sodium nedochroglycate Dihydroquersetin Anthraqunoneantibiotic Sodium chromoglicate doxorubicine

7. The Interaction of Medicine with PalmiticAcidMonolayers on the Water Subphase π, mN/m π, mN/m palmitic acid Mg2+ 40 NaCrg 40 complex with Mg2+ or «micelle» ? Mg2+ & NaCrg 20 20 water water 20 25 30 20 25 30 A, Å2/mol A, Å2/mol

8. Properties of C15H31COOH Monolayers on the Subphase at the Presence of Mg2+ & Ca2+ A0, Å2/mol π, mN/m

9. Isotherms of Monolayers of Palmitic Acid at the Presence Cu(CH3COO)2 and Medicine π, mN/m π, mN/m π, mN/m Cu2+ Cu2+ Cu2+ & DOX 60 60 60 DHQ & Cu2+ (1:1) Cu2+ Cu2+ & NaCrg 40 40 40 DOX DHQ & Cu2+ (2:1) Cu2+ & NaNCr 20 20 20 25 30 25 30 25 30 A, Å2/mol A, Å2/mol A, Å2/mol initial monolayer of C15H31COOH

10. Properties of C15H31COOH Monolayers on the Subphase at the Presence of Cations A0, Å2/mol π, mN/m

11. Structure of Cu2+-content Compounds of Subphase, at pH 5.6 Cu(CH3COO)2, Cu2+, CuOH+, [Cu(H2O)6]2+, Cu2+(OH-)(CH3COO-), CH3COOH, complexes medicine with Cu2+, Cu(OH)2, Cu(C15H31COO)2 [Cu2+]>>[Cu(OH)]+ Copper (II) – chelated complexes of bioflaonoids I II Complexes of Cu(II) with chromyl compounds IV III

12. Absorption Spectra of the Reaction Products of Medicine With Cu(CH3COO)2 in Subphase of Palmitic Acid Monolayers D D D Cu(CH3COO)2 (τ = 0) NaCrg & Cu(CH3COO)2 DHQ & Cu2+ (τ = 0) NaCrg (τ = 0) DHQ (τ = 0) DHQ & Cu2+ (τ = ∞) NaCrg (τ = ∞) Cu(CH3COO)2 (τ = ∞) 260 300 340 650 750 850 200 250 300 A, Å2/mol A, Å2/mol A, Å2/mol

13. Decreasing of pH in Subphase of Palmitic Acid Monolayers -ΔpH ΔE, mV O + n H+ + n ē↔R ΔpH = - F / 2.3 RT∙ΔE ΔE – trans-membrane potential 20 10

14. Energetic properties of transferred layers by using wettability data

15. Isotherms of Lipid Layers at the Water Subphase - at the presence - at the absence of Ca2+ π, mN/m π, mN/m π, mN/m pH 11 60 60 60 pH 5.8 pH 2 Ca2+ Ca2+ Ca2+ 40 40 40 20 20 20 Neutral form Ca2+ & DHQ 40 70 100 40 80 120 40 80 120 A, Å2/mol A, Å2/mol A, Å2/mol zwitterionic interaction … … pH 5.8

16. Influence Ca2+-ions on Characteristic of Lipid Layers at the Presence of Medicine π, mN/m 60 DOX 40 40 DHQ 20 NaCrg 40 80 120 A, Å2/mol Isotherms of lipid layers on the water subfase pH=5.8

17. Specific Flavanoid Attachment to Artificial Membranes to Lipid-bound Copper (II) Surface pressure-area isotherms of pure lipid POGPC on buffered subphase* π, mN/m on buffered subphase, containing Cu(CH3COO)2 and DHQ on buffered subphase, containing Cu(CH3COO)2 lipid layer MMA, Å2/molecule * 20 mM MOPS, 10 mM NaCl, pH 7.5

18. Formation of Vesicles on Substrate Type Methods SUV 0.02-0.1 μm (small unilamellar vesicles) LUV 0.1-1 μm (large unilamellar vesicles) LOV 0.1-1 μm (large oligolamellar vesicles) GV up 50 μm (giant vesicles) MUV 0.1-100 μm (multilamellar vesicles) • Solution of lecitine in solvent • Deposit lecitine solution on solid substrate • Drying by vacuum • Addition of water solution to dried lipid layers on solid Wettability of lipid layers cos Θ n c, g/l Θ – contact angle (degree); n – number of transferred layers; c – lipid concentration

19. Polar components of Gibbs Surface Energy Hydrated Lipid Layers

20. The Permeability of Aqueous Solution Into Lipid Layers Placed on Quartz Plates Kinetic curves of liquid absorption into lecetin layers h, µm 3.28∙10-3M DHQ; 3.28∙10-3M DHQ and 7.4∙10-2M CaCl2; 3.28∙10-3M DHQ and 4.38∙10-2M MgSO4; 3.28∙10-3M DHQ and 3.28∙10-5M Cu(CH3COO)2. τ, min

21. The Characteristic of the Permeability of DHQ into Lipid Layers cos Θdinamic τ, min DHQ DHQ+Ca2+ DHQ+Mg2+ DHQ+Cu2+ [DHQ] = 3,28∙10-3 M

22. Micellar Mechanism of Formation of Ionic Channel palmitic acid Normal membrane complex (C15H31COO…H)2…Ca2+ Aggregation of membrane by action of salt or protein Pinch effect (compression) in membrane and modification of ionization surrounding Neuman R.D., J. Colloid Interface, 1975, 53, 161  Formation of ionic channel Bray D., Nature, 1975, 244, 93

23. The permeability of Medicine into small unilamellar vesicles (SUV) evaporation sol. • Formation multilamellar Vesicles (MUV) • Ultrasound treatment (44 kHz) & formation SUV • Purification US Dialysis I II II membranes Spectra of passing through in visible region T,% - transmission factor

24. Collaborators Slava Sokolov Ira Ioffe Sasha Volkov Nizhny Novgorod Technical State University Engineering physic-chemistry Faculty Lab of “Surface phenomena”