Kharkiv National Medical University Department of Medical and B ioorganic chemistry

1. KharkivNational Medical University Department of Medical and Bioorganic chemistry «Medical Chemistry» Lecture№ 9 Colloidal solutions Coarsely dispersed systems Lecturer: As. Professor, Department of Medical and Bioorganic Chemistry,, Ph.D. LukianovaL.V.

2. Plan of lecture 1. Dispersed systems: general aspects, classification. 2. Methods of preparation of colloidal solutions. 3. Methods of colloidal solutions purification. 4. Properties of colloidal solutions. 5. Structure of micelles. 6. Stability and coagulation of the dispersed systems. 7. Coagulation by means of electrolytes. 8. Coagulation in the biological systems. 9. Coarsely dispersed systems.

3. The most important biological liquids such as blood, urine and spinal fluid contain slightly soluble substances in colloid state: cholesterol, carbonate, phosphate, urate, and salts of other acids. Break of their stability causes their precipitation resulting in arteriosclerosis, holelithiasis, urolithiasis, etc. Knowledge of coagulation and stability of the dispersed, systems is necessary to understand processes taking place in the human organism, because a large number of biological fluids in the organism are colloidal systems. One of the most important characteristics of blood is red corpuscles sedimentation rate (RCSR) which increases if some kind of pathology takes place. Coagulation phenomena become clearly seen in the process of blood coagulation. The nature of blood coagulation must be taken into account during the blood conservation as well as in the process of creation of new medicinal materials possessing antithrombotic properties.

4. Colloid chemistry – the science of surface phenomena and disperse systems. Surface phenomena – a set of phenomena associated with the physical characteristics of the interfaces between contiguous phases. Disperse Systems – heterogeneous system in which one phase is dispersed in the (fragmented state). Colloid chemistry

5. Colloidal solution Dispersed phase (fractured part dispersed system) Dispersed phase Dispersion medium Dispersion medium (continuous part of the dispersion system)

6. Dispersed system – is a system consisting of dispersed particles and the medium in which these are suspended. • Dispersedsystemsareclassifiedaccordingto: • theirdispersity; • thestateofaggregationofthedispersedphaseandthedispersionmedium; • theintensityoftheinteractionbetweenthem; • theabsenceorformationofstructuresinthedispersedsystems.

7. Classification of dispersed systems • on the base of particles size • True solutions– size of particles is < 10-9 m, particles of solute are molecules or ions • Colloids – size of particles is10-7 - 10-9 m, particles of intermediate size • Coarsely dispersed systems– size of particles is > 10-7 m, particles of solute are insoluble in a given solvent (suspensions, emulsions).

8. Classification of the state of aggregation of the dispersed phase and the dispersion medium

9. Depending upon the nature of interactions between dispersed phase and dispersion medium, the colloidal solutions can be classified into two types as: lyophilic and lyophobic sols. 1. Lyophilic colloids– the colloidal solutions, in which the particles of the dispersed phase have a great affinity for the dispersionmedium. These solutions are easily formedand they are reversible in nature (after evaporation of these colloidssolutions and the addition of a new portion of solvent, the dry residueagain passes into the solution). They include natural and synthetichigh-molecular substances having a molecular mass from ten thousand to several millions. The molecules of these substances have the size ofcolloidal particles, therefore such molecules are called macromolecules(glue, gelatin, starch, proteins, rubber, etc.) 2.Lyophobiccolloids–thecolloidalsolutionsinwhichthereisnoaffinitybetweenparticlesofthedispersedphaseandthedispersionmedium. Suchsolutionsareformedwithdifficulty. Theseareirreversibleinnature (theprecipitatesremainingaftertheevaporationdonotform a solagainuponcontactwithdis­persionmedium) (solutionsofmetalslikeAgandAu, A1(OH)3,Fe(OH)3 etc).

10. Dispersed systems are very widely spread in nature! Soils, clays, natural water, air, clouds, dust, minerals (including precious stones), bread, milk, butter – are colloidal systems. Cells, genes, viruses – are colloidal particles. Biological liquids – blood, lymph, urine, cerebrospinal fluid – are colloidal dispersions. In these liquids substances, e.g. proteins, cholesterine, glycogen and others are present being in colloidal state. Finely dispersed substances easily penetrate through the pores of skin. Medicines in the form of colloids (emulsions, ointments, pastes, aerosols) are widely used in medicine.

11. 1.Heterogeneity (multiphase). 2.Dispersibility (fragmentation). Signs facilities colloid chemistry

12. Obtaining of colloidal solution 1. By the dispersion, i.e. comminution of large bodies. Comminution by crushing, grinding, or attrition yields comparatively coarsely dispersed powders (over 60 mm size). Finer comminution is achieved with the aid of special equipment named colloid mills, or by employing ultrasound. 2. By the condensation of substances forming molecular or ionic solutions. The condensation method consists in the obtaining of insoluble compounds by reactions of exchange, hydrolysis, reduction, or oxidation.

13. The methods are based on the formation of insoluble compounds as a result of chemical reactions. 1. Reduction reaction (obtaining sols Au, Ag, Pt). Restoring aurate sodium formaldehyde. 2NaAuO2 + 3HCOH + Na2CO3 = 2Au + 3HCOONa +NaHCO3 + H2O The structure of the micelle: Chemical condensation methods The condensation method consists in the obtaining of by reactions of exchange, hydrolysis, reduction, or oxidation

14. 2.ReactionsofexchangePreparation of silver iodide sol. AgNO3 + KJ(exess) = AgJ↓ + KNO3 The structure of the micelle:

15. 3. Oxidation reactions Formation sol sulfur. 2H2S(l) + O2 = 2S ↓+ 2H2O The structure of the micelle:

16. 4. Hydrolysis reactions Obtaining sol of iron hydroxide. FeCl3 + 3H2O = Fe(OH)3 ↓ + 3HCl The structure of the micelle:

17. 3. Methods of colloidal solutions purification 1. Dialysis – the process of separating the particles of colloids fromimpurities by means of diffusion through a suitable membrane. Its principle is based upon the fact that colloidalparticles cannot pass through a parchment or cellophane membranewhile the ions of the electrolyte can pass through it. The colloidalsolution is taken in a bag made of cellophane or parchment. The bag is suspended in fresh water. The impurities slowly diffuse out of the bag leaving behind pure colloidal solution. The ordinary process of dialysis is slow. To increase the process of purification, the dialysis is carried out by applying electric field. This process is called electrodialysis. 2. Ultra-filtration. It is the process of removing the impurities fromthe colloidal solution by passing it through graded filter papers calledultra-filter papers. These filter papers are made from ordinary filterpapers by impregnating them with colloidal solutions. As a result, thesize of the pores gets reduced. These filter papers allow the ions and molecules of the impurities to pass but retain colloidal particles. Ordinary filter papers cannot be used for the purpose since the colloidal particles can easily pass through the pores of these papers.

18. Solutions vs Colloids Solution: • solute particles are of ionic or molecular size (a few nm across); • transparent to ordinary light; • stable unless solvent evaporated; • may pass through dialytic, but not true osmotic, membranes. Colloids: • solute (called “dispersed phase”) typically 1000 nm or more per particle; • giant molecules (or “clumps” of smaller ones); • not totally transparent – Tyndall Effect; • dispersed phase may separate out (similar to separation of mayonnaise); • particles too large to pass through most membranes

19. Properties of colloidal solutions • Colligative properties are negligible small. • Optical properties. Colloidal systems scatter the light (Tyndall effect). • Molecular-Kinetic properties: • a) Brownian movement; • b) diffusion; • c) sedimentation • 4. Electrical properties: • a) electrophoresis; • b) electroosmosis

20. Solutions vs Colloids The Tyndall Effect True Solution Colloidal Mixture

21. Solutions vs Colloids The Tyndall Effect True Solution Colloidal Mixture

22. Transmembrane Diffusion Solution (H2O + Solutes) Pure H2O Semipermeable membrane Only water passes through osmotic membranes and faster from the side on which water is more concentrated.

23. Transmembrane Diffusion Solution (H2O + Solutes) Pure H2O Semipermeable membrane Diffusion rates tend to equalize as flow continues.

25. H2O NaCl Transmembrane Diffusion Mixture (H2O, Na+Cl-, protein) NaCl more concen-trated here Pure H2O H2O more concentrated here Dialytic membrane Water and solutes pass down concentration gradient through dialytic membrane. Colloids do not cross membrane.

26. Pb(NO3)2 NaCl Structure of colloidal particle (micelle) Pb(NO3)2 + 2NaCl → PbCl2↓ + 2NaNO3 [PbCl2]m nucleus

27. Pb(NO3)2 NaCl Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Cl- Pb(NO3)2 + 2NaCl → PbCl2↓ + 2NaNO3 [PbCl2]m potential-determining ions

28. Na+ Pb(NO3)2 Na+ Na+ NaCl Cl- Cl- Cl- Cl- Na+ Cl- Cl- Na+ Cl- Cl- Na+ Cl- Cl- Cl- [PbCl2]m Pb(NO3)2 + 2NaCl → PbCl2↓ + 2NaNO3 gegenions

29. Na+ Na+ Na+ [PbCl2]m Na+ Na+ Na+ Cl- Cl- Cl- Cl- Cl- Na+ Cl- Cl- Na+ Na+ Cl- Cl- Na+ Na+ Cl- Cl- Nucleus, potential-determining ions and part of gegenions compose granule of micelle. Potential-determining ions and gegenions which are in the granule compose inner layer of ions. Remaining part of gegenions constitutes the diffuse layer of ions.

30. Na+ nucleus granule Na+ Na+ Na+ [PbCl2]m potential- determining ions Na+ Na+ Cl- Cl- Cl- Cl- Na+ Cl- Cl- Cl- gegenions Na+ Na+ Cl- Cl- Na+ Na+ Cl- Cl- inner layer of ions diffuse layer Micelle

31. gegenions Na+ granule Na+ Na+ Na+ [PbCl2]m Na+ Na+ nucleus Cl- Na+ Cl- inner layer of ions Cl- Cl- Na+ potential- determining ions Na+ granule Na+ Cl- Cl- diffuse layer of ions Na+ Cl- Cl- Cl- Cl- nucleus potential-determining ions gegenions diffuse layer of ions inner layer of ions {[PbCl2]mnCl-(n-x)Na+}-xxNa+

32. {[PbCl2]mnCl-(n-x)Na+}-x xNa+ ζ-potential (electrokinetic potential) ε-potential (electrothermodynamic potential) Electrical double layer Micelle has electrical double layer. ζ-potential determines the rate of movement of particles in the electric field. The granule of given micelle will move to the anode, while ions of diffuse layer will move to the cathode.

33. If all gegenions are in the inner layer, ζ-potential becomes equal zero and micelle is said to be in isoelectric state. {[PbCl2]mnCl-nNa+}0 The thickness of electrical double layer and the value of ζ-potential depend on concentration of solution. ζ-potential decreases with increase in concentration. In isoelectric state colloidal systems are unstable. The movement of dispersed phase particles in electric field is called electrophoresis. The rate of movement depends on ζ-potential value. Electrophoresis is widely used for aminoacids, antibiotics, enzymes, antibodies and other objects separation. It is also used for plasma proteins investigations with diagnostic purposes.

34. γ α2 α1 β Albumins Globulins Electrophoresis of blood serum proteins

35. Electrophorogramme of patient with multiple myeloma Normal electrophorogramme

36. Pb(NO3)2 NaCl NaCl Pb(NO3)2 Micelles with different charges of granule can be obtained depending upon the substance which is present in surplus. Pb(NO3)2 + 2NaCl → PbCl2↓ + 2NaNO3 {[PbCl2]mnCl-(n-x)Na+}-xxNa+ Negatively charged sol surplus {[PbCl2]mnPb2+(2n-x)NO3-}+x xNO3- Positively charged sol surplus

37. NO3- NO3- NO3- NO3- Pb2+ NO3- Pb2+ NO3- NO3- Pb2+ Pb2+ NO3- NO3- Pb2+ Pb2+ NaCl Pb2+ NO3- NO3- NO3- NO3- Pb(NO3)2 NO3- Pb(NO3)2 + 2NaCl → PbCl2↓ + 2NaNO3 {[PbCl2]mnPb2+(2n-x)NO3-}+x xNO3- [PbCl2]m

38. Conditions for colloidal systems obtaining 1. An essential condition for colloidal systems obtaining is the mutual insolubility of the substance being dispersed and the dispersion medium. 2. One reagent (it is stabilizer) must be in a small surplus 3. Nucleus of a colloidal micelle – is an insoluble product 4. Potential-determining ions are common for the nucleus and for the stabilizer 5. Gegenions come from the stabilizer. FeSO4 + Na2S → FeS↓ + Na2SO4 surplus FeSO4 + Na2S → FeS↓ + Na2SO4 surplus {[FeS]mnFe2+(n-x)SO42-}+x xSO42- {[FeS]mnS2-(2n-x)Na+}-x x Na+

40. Emulsions The various pharmaceuticals widely used in medicine are colloidal or coarsely dispersed systems. These are: suspensions, ointments, aerosols, powders, emulsions, pastes. Emulsions are the coarsely dispersed systems of two immiscible liquids in which the liquid acts as the dispersed phase as well as the dispersion medium. They are obtained by mixing an oil with water. Since the two do not mix well, the emulsion is generally unstable and is stabilized by adding emulsifier or emulsifying agent (gum, soap, glass powder, etc). There are two types of emulsions: 1. Oil-in-water emulsion (aqueous emulsions) 2. Water-in-oil emulsion (oily emulsions)

41. Water droplets Oil Water Water in oil Oil in water Oil droplets In oil-in-water emulsion oil acts as dispersed phase and water as the dispersion medium. E.g. Milk is an emulsion of soluble fats in water and here casein acts as an emulsifier. In water-in-oil emulsions water acts as dispersed phase while oil behaves as the dispersion medium. E.g. butter, cod liver oil, etc. Emulsions are readily adsorbed in the intestine. Highly dispersed, concentrated, stable emulsions are used for intravenous injections to provide energy for starved or weakened organism. The colloidal medicines are quite effective on account of their easy assimilation and adsorption. A few important medicines are colloidal gold, silver, manganese, sulfur, antimony, etc.

42. Stability – constant in time the main parameters of the disperse system: the degree of dispersion and uniform distribution of the dispersed phase in the dispersion medium. Coagulation – the process of destruction of colloidal systems by sticking particles form larger aggregates and loss of stability, followed by separation. Stability and coagulation of dispersed systems

43. Rules electrolyte coagulation Coagulation of sols with electrolytes • All electrolytes at certain concentrations can cause coagulation of the sol. • The rule of sign of the charge: the coagulation of the sol causes the ion electrolyte, the sign of the charge which is opposite to the charge of the colloidal particles. This ion is called an ion-coagulator. • Each electrolyte relative to the colloidal solution has a threshold of coagulation (coagulating ability).

44. Coagulation threshold (γ, C) – the lowest concentration of the electrolyte sufficient to cause coagulation of the sol Coagulation ability (P) – the inverse of the threshold of coagulation • Effect of ion charge-coagulator (Schulze-Hardy rule): coagulation ability of the electrolyte increases with increasing ion charge-coagulator n = 2 ÷ 6

45. Thank you for your attention!