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The artificial membranes as a model of interaction of medicine with biosystems at the presence metal ions 1.Introduction. The principles of the representation.

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Presentation on theme: "The artificial membranes as a model of interaction of medicine with biosystems at the presence metal ions 1.Introduction. The principles of the representation."— Presentation transcript:

1 The artificial membranes as a model of interaction of medicine with biosystems at the presence metal ions 1.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. 2.The Interaction of medicine with palmitic acid monolayers on the water subphase at the presence Ca 2+, Mg 2+, Cu 2+, Zn 2+, Fe 2+ ions. 3.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  hydrophobic surface (lipid layers) water porous (ionic channel) hydrophilic surface PP P – protein part of ionic channel Polyglucoside chains

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

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

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 Sodium chromoglicate Dihydroquersetin Anthraqunone antibiotic doxorubicine

7 The Interaction of Medicine with Palmitic Acid Monolayers on the Water Subphase π, mN/m complex with Mg 2+ or «micelle» ? palmitic acid Mg 2+ & NaCrg π, mN/m NaCrg Mg 2+ water A, Å 2 /mol

8 Properties of C 15 H 31 COOH Monolayers on the Subphase at the Presence of Mg 2+ & Ca 2+ A 0, Å 2 /molπ, mN/m

9 Isotherms of Monolayers of Palmitic Acid at the Presence Cu(CH 3 COO) 2 and Medicine π, mN/m A, Å 2 /mol π, mN/m A, Å 2 /mol π, mN/m A, Å 2 /mol 30 Cu 2+ Cu 2+ & NaCrg Cu 2+ & NaNCr DHQ & Cu 2+ (1:1) DHQ & Cu 2+ (2:1) Cu 2+ & DOX DOX initial monolayer of C 15 H 31 COOH

10 Properties of C 15 H 31 COOH Monolayers on the Subphase at the Presence of Cations A 0, Å 2 /molπ, mN/m

11 Structure of Cu 2+ -content Compounds of Subphase, at pH 5.6 Cu(CH 3 COO) 2, Cu 2+, CuOH +, [Cu(H 2 O) 6 ] 2+, Cu 2+ (OH - )(CH 3 COO - ), CH 3 COOH, complexes medicine with Cu 2+, Cu(OH) 2, Cu(C 15 H 31 COO) 2 [Cu 2+ ]>>[Cu(OH)] + Copper (II) – chelated complexes of bioflaonoids Complexes of Cu(II) with chromyl compounds I II III IV

12 Absorption Spectra of the Reaction Products of Medicine With Cu(CH 3 COO) 2 in Subphase of Palmitic Acid Monolayers DDD DHQ & Cu 2+ (τ = 0) DHQ & Cu 2+ (τ = ∞) DHQ (τ = 0) Cu(CH 3 COO) 2 (τ = 0) Cu(CH 3 COO) 2 (τ = ∞) NaCrg & Cu(CH 3 COO) 2 NaCrg (τ = 0) NaCrg (τ = ∞) A, Å 2 /mol

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

14 Energetic properties of transferred layers by using wettability data

15 Isotherms of Lipid Layers at the Water Subphase zwitterionic interaction π, mN/m π, mN/m π, mN/m Ca 2+ & DHQ Ca 2+ A, Å 2 /mol pH 2 pH at the absence- at the presenceof Ca 2+ pH 11 Ca 2+ … … pH 5.8 Neutral form

16 Influence Ca 2+ -ions on Characteristic of Lipid Layers at the Presence of Medicine π, mN/m DOX NaCrg DHQ Isotherms of lipid layers on the water subfase pH=5.8 A, Å 2 /mol

17 Specific Flavanoid Attachment to Artificial Membranes to Lipid-bound Copper (II) π, mN/m Surface pressure-area isotherms of pure lipid POGPC on buffered subphase* * 20 mM MOPS, 10 mM NaCl, pH 7.5 lipid layer on buffered subphase, containing Cu(CH 3 COO) 2 and DHQ on buffered subphase, containing Cu(CH 3 COO) 2 MMA, Å 2 /molecule

18 Formation of Vesicles on Substrate SUV μm (small unilamellar vesicles) LUV μm (large unilamellar vesicles) LOV μm (large oligolamellar vesicles) GV up 50 μm (giant vesicles) MUV μm (multilamellar vesicles) 1.Solution of lecitine in solvent 2.Deposit lecitine solution on solid substrate 3.Drying by vacuum 4.Addition of water solution to dried lipid layers on solid cos Θ c, g/l n Wettability of lipid layers Θ – contact angle (degree); n – number of transferred layers; c – lipid concentration Type Methods

19 Polar components of Gibbs Surface Energy Hydrated Lipid Layers

20 The Permeability of Aqueous Solution Into Lipid Layers Placed on Quartz Plates 3.28∙10 -3 M DHQ; 3.28∙10 -3 M DHQ and 7.4∙10 -2 M CaCl 2 ; 3.28∙10 -3 M DHQ and 4.38∙10 -2 M MgSO 4 ; 3.28∙10 -3 M DHQ and 3.28∙10 -5 M Cu(CH 3 COO) 2. Kinetic curves of liquid absorption into lecetin layers h, µm τ, min

21 The Characteristic of the Permeability of DHQ into Lipid Layers DHQ DHQ+Ca 2+ DHQ+Mg 2+ DHQ+Cu 2+ [DHQ] = 3,28∙10 -3 M cos Θ dinamic τ, min

22 Micellar Mechanism of Formation of Ionic Channel Normal membrane Aggregation of membrane by action of salt or protein Pinch effect (compression) in membrane and modification of ionization surrounding Formation of ionic channel  Bray D., Nature, 1975, 244, 93 Neuman R.D., J. Colloid Interface, 1975, 53, 161 palmitic acid complex (C 15 H 31 COO…H) 2 …Ca 2+ 

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

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


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