1. Hydrolysis of ions Buffer solutions Protolytic reactions II Medical Chemistry Lecture 2 2007 (J.S.) Liquid colloid dispersions Tensides
2. Hydrolysis of ions Hydrolysis of ions occurs in solutions of salts that contain an anion of a weak acid or a cation of a weak base. All types of soluble salts are strong electrolytes – they dissociate completely in aqueous solution. The salts of strong acids and strong hydroxides dissociate into "strong" (spectator) ions, which do not take part in protolytic reactions being only hydrated. Those solutions are neutral. When a salt of a weak acid or a weak base is dissolves , high amounts of anions of a weak acid or cations of a weak base are passing into the solution. Those ion can exist only in equilibrium concentrations that comply with the ionization constants of particular acids or bases. The equilibria are reached by means of hydrolysis – the reaction of those ions with water. is the reaction of anions of weak acids and cations of weak bases with water .
3. Sodium acetate CH 3 COONa can serve as an example. CH 3 COO – Na + ( s ) CH 3 COO – + Na + Hydrolysis of the salt of a weak acid (and a strong hydroxide) Complete dissociation during dissolving: (a spectator cation) Hydrolysis of acetate anion is running parallel to dissolution: CH 3 COO – + H 2 O CH 3 COOH + OH – The solution is not neutral but slightly alkaline . Acetate (a strong conjugate base) tears off protons from water till the concentrations of CH 3 COO – , H + , and CH 3 COOH molecules will reach those that comply with K A of the weak acetic acid.
4. NH 4 + Cl – ( s ) NH 4 + + Cl – Hydrolysis of the salt of a weak base (and a strong acid) Ammonium chloride NH 4 Cl could be an example: Complete dissociation during dissolving: (a spectator cation) Hydrolysis of ammonium cation is running parallel to dissolution: Ammonium (a strong conjugate acid) releases protons till the concentrations of NH 4 + , OH – , and unionized molecules NH 3 will reach those that comply with K B of the weak base ammonia. The solution is not neutral but slightly acidic . NH 4 + + H 2 O NH 3 + H 3 O +
5. Hydrolysis of the salt derived from a weak hydroxide of a metal (and a strong acid) For example: copper (II) chloride CuCl 2 Cu 2+ Cl – 2 ( s ) Cu 2+ + 2 Cl – Complete dissociation during dissolving: The solution is not neutral but slightly acidic . Cu 2+ + 4 H 2 O [ Cu (H 2 O) 4 ] 2+ Cation of the metal is hydrated by forming a defined aquacomplex and takes part in hydrolysis: [ Cu ( H 2 O ) 4 ] 2+ + H 2 O [ Cu ( H 2 O ) 3 OH ] + + H 3 O +
6. NH 4 + NO 2 – ( s ) NH 4 + + NO 2 – Hydrolysis of the salt derived from both a weak base and a weak acid Example: Ammonium nitrite NH 4 NO 2 Complete dissociation during dissolving: Independent hydrolysis of both ions: Both ions H + and OH – occur as the products of hydrolysis, but they give water. The resulting pH value of the solution depends on p K B of the weak base and p K A of the weak acid. Mostly is the pH close to 7.0 . NH 4 + + H 2 O NH 3 + H 3 O + NO 2 – + H 2 O HNO 2 + OH –
7. Buffer solutions A small amount of an acid added to water results in large drop in pH. If a buffer is present, the decrease in pH will be much smaller. Simple buffer solutions are mixtures of a weak acid and the conjugate base of that or a weak base and its conjugate acid Both components should be present at approximately equal (at least at comparable) concentrations. Examples: acetic acid / sodium acetate ammonia / ammonium chloride sodium dihydrogen phosphate / hydrogen phosphate A buffer solution (a buffer) – resists a change in pH on addition of small amounts of an acid or a base, it absorbs the change in acidity, – serves to maintain a fairly constant pH value.
8. The buffer solution contains: cations Na + of the salt (sodium acetate) that are not taken into account because they are spectator ions; molecules CH 3 COOH at concentration equal to c acid because dissociation of the dissolved acetic acid is suppressed in the presence of acetate anions from the sodium acetate; anions CH 3 COO – at concentration equal to c salt because hydrolysis of the dissolved acetate is suppressed in the presence of undissociated CH 3 COOH of the second buffer component; ions H + at concentration that must comply with both equilibrium constants of acetic acid K A and water K w . The equilibria in buffer solutions Example: The buffer solution of acetic acid and sodium acetate was prepared to contain acetic acid at concentration c acid and sodium acetate at concentration c salt (i.e. c conj. base ). The equilibrium concentrations of the components must comply with the dissociation constant of acetic acid K A [H + ] [CH 3 COO – ] [CH 3 COOH]
9. takes the form , from which The concentration of H + ions in the buffer and its pH value depends on the K A value (i.e. on the type of the weak acid or base used) as well as on the ratio of the acidic and basic component concentrations . The logarithmic form of that relation is known as Henderson-Hasselbalch equation: c base in buffer solution with an weak acid is c salt (concentration of the conjugate base), c acid in buffers with a weak base means concentration of the conjugate acid ( c salt ). For the equilibrium in an acetate buffer, K A [ H + ] [ CH 3 COO – ] [ CH 3 COOH ] K A = c acid [H + ] c salt c salt [ H + ] = K A c acid c base pH = p K A + log c acid
10. An addition of acid to a buffer Concentration of H + increases that upsets the equilibrium. New equilibrium will settle, the buffer base binds most of the added H + ions which results in increase of the acidic buffer component. The result - [ H + ] increases proportionally to the increase of c acid / c base, , pH decreases proportionally to the decrease of the log c base / c acid . An addition of a strong hydroxide to a buffer Increase in OH – concentration withdraws H + from the buffer acid that transforms into its conjugate base. The result - [H + ] decreases proportionally to the decrease of c acid / c base , pH increases proportionally to the increase of the log c base / c acid . Buffer capacity β express the effectiveness of buffers. It is defined as the ratio of the amount of a strong acid or a strong base that have to be added to one litre of the buffer solution to change its pH by 0.1 . β = n (H + or OH – added) / l Δ pH
11. Buffer capacity depends – on the ratio of buffer components concentration pH = p K A + log c base c acid The highest buffer capacity (at a given total concentration c base + c acid ) occurs, if c base / c acid = 1 , i.e. at pH = p K A . In sufficient buffer solutions, the ratio c base / c acid should take values from 1:10 to 10:1, i.e. in the range p K A ± 1. – on the total buffer concentration ( c acid + c base )
12. Determination of the p K A value of a weak acid: A solution of a weak acid is titrated with a solution of hydroxide and the pH measured in the course of titration. The titration curve is plotted. Acetic acid ( c = 0,1 mol/l) serves as an example: It can be deduced from Henderson- Hasselbalch equation that pH of weak acid or base solution equals p K A just when the ratio c base / c acid equals 1. The pH value of the titrated solution equals p K A at the point when just one half of the weak acid or base is neutralized. n ( OH – ) / n ( acid ) 0 0.2 0.4 0.6 0.8 1.0 12 10 8 6 4 2 0 pH p K A
13. The dependence of buffer capacity on buffer components ration can be viewed on titration curves Weak acid ( acetic acid, c HA = 0.1 mol/l) Area in which the buffer is effective The highest effectiveness at pH = p K A . The slopes of tangents to the curve are indirectly proportional to the buffer capacity. n ( OH – ) / n ( acid ) 0 0.2 0.4 0.6 0.8 1.0 12 10 8 6 4 2 0 pH p K A p K A + 1 p K A – 1
14. Diprotic or triprotic weak acids (e.g. H 2 CO 3 , H 3 PO 4 ) act as buffers in two or three pH ranges CO 2 + H 2 CO 3 CO 3 2– HCO 3 – Percentage of particles present 100 % 50 % 0 pH of the solution 0 2 4 6 8 10 12 14 p K A 1 p K A 2 Buffer ( CO 2 + H 2 CO 3 ) / HCO 3 – Buffer HCO 3 – / CO 3 2–
15. Buffer systems in human body The pH value of blood is 7.40 ± 0.04 . Most biological happenings occur in the pH range 6 to 8. Blood buffer bases: Buffer: Hydrogen carbonate HCO 3 – / (H 2 CO 3 +CO 2 ) Plasma proteins protein / protein-H + Haemoglobin of red blood cells haemoglobin / haemoglobin-H + Hydrogen phosphate HPO 4 2– / H 2 PO 4 – All those buffer systems cooperate – a surplus of H + is accepted by all buffer bases but distributed proportionally to their concentration in blood. Each of those four buffer systems has its own p K A .
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17. Plasma proteins and haemoglobin as buffers In all proteins, only ionizable groups can take part in acid-base reactions. At physiological pH values, imidazol e groups of histidine residues alone act as effective buffer bases. Hydrogen phosphate buffer is of second-rate significance in the blood due to relatively low concentration. However, within the cells, phosphates with proteins are the major buffer bases. 3,9 4,3 6,0 8,3 10,1 10,5 12,5 -carboxyl (-COOH) -carboxyl (-COOH) imidazolium sulfanyl (-SH) phenolic hydroxyl -ammonium (-NH 3 + ) guanidinium –NH-C(NH 2 )=NH 2 + Aspartate Glutamate Histidine Cysteine Tyrosine Lysine Arginine p K A Ionizable group in the side chain Amino acid
19. Liquid colloid dispersions In this part, the aqueous colloid dispersions are discussed. In general, lyophobic particles are those without any interactions between their surface and molecules of the solvent; lyophilic particles are of similar polarity as the molecules of the solvent and are surrounded by a layer of solvent molecules attracted by weak intermolecular forces If water is the solvent, then the colloid particles of solutes are either hydrophobic or hydrophilic . The size of colloidal particles ranges from 1 nm to an upper limit of 500 (– 1000) nm. The colloid particles are able to pass through filter paper (not through cellophane or parchment paper), exhibit Brownian movement, Tyndall effect and opalescence; they do not settle out on standing spontaneously.
20. Aqueous colloid dispersions Examples: colloid dispersion of sulfur, silver, gold. Dispersed particles are HYDROPHOBIC COLLOID SOLS The dispersion is stabilized by electric charge only , more diphasic than homogenous, less stable . Flocculation occurs after addition of a small amount of electrolytes, unless a protective colloid is added. Dispersed particles are (at least partly) HYDROPHILIC COLLOID SOLUTIONS stabilized by both electric charge and solvation shell , more stable than hydrophobic sols, aggregation caused by change in pH,. alcohol, acetone, and by salting-out MOLECULAR colloid solutions of macromolecular polymers (starch, proteins, nucleic acids, etc.) of tensides that form micells because of their amphipathic molecules MICELLAR colloid solutions
21. Solubility of hydrophilic macromolecules (e.g. proteins) Solubility of a protein is enabled by interactions of polar groups on the molecular with surface with water dipoles (both type dipole-ion and hydrogen bonds). Several layers of orientated water molecules represent the solvation shell ( hydration shell ) of a protein molecule. When salts are present, their ions also interact with polar groups of the protein (ion-ion and ion-dipole interactions) so that an diffuse layer of ions – electric dilayer – intermingled with water molecules surrounds the macromolecule. . Molecular colloid solutions Cl – protein anion, e.g. Cl – cation, e.g. Na + molecules of water charged groups of the macromolecule
22. Stability of protein solutions – the dependence on salt concentration When the concentration of ions in the solution is low , the diffuse layer is large and the protein molecules exhibit maximum repulsion – the colloid dispersion is stable. Some protein sorts are soluble only in solutions with low concentrations of salts (the salting-in effect). When the concentration of ions is large , the electrostatic repulsion that prevents colloidal particles from coagulating becomes inefficient – protein molecules are coagulated by adding high amounts of electrolytes ( salting-out ). The competi ti on for water molecules that form the hydration shell also cannot be neglected. Salting-in occurs only when some sorts of proteins are dissolved Salting-out Salt concentration Solubility
23. Stability of aqueous molecular colloid solutions depends primarily on the existence of a hydration shell and on the net electric charge of dispersed molecules. The more concentrated molecular colloid solutions are less stable than those at low concentrations. Molecular colloid dispersions can be destabilized so that the solute aggregates and precipitates by means of – eliminating the charge of the solute, e.g. by a change of pH of the solution, – abstracting the solute from its solvation shell by addition of a solvent that binds water being easily hydrated (acetone, ethanol), – exclusion of both stabilizing factor by addition of large amount of a salt (increase of the ionic strength – salting-out).
24. Micellar colloid solutions A micelle are solutions of tensides - low-molecular compounds that have amphiphilic (diphilic) character. Their name is derived from the ability to diminish surface tension of liquids . Although tensides are low-molecular, they associate to form colloid particles – micelles : H 2 O H 2 O H 2 O H 2 O H 2 O H 2 O H 2 O H 2 O H 2 O H 2 O H 2 O H 2 O Hydrophobic parts Molecules of tenside Hydrophilic parts The molecules of tensides ( surfactants ) have two parts: – a long or voluminous hydrocarbon chain (hydrophobic part), and – a polar (hydrophilic) group.
25. At low concentration of a tenside, the molecules are adsorbed at the phase boundary; some free molecules are dispersed in the liquid (true solution). At concentrations higher than critical micellar concentration the molecules of tenside form micelles .
26. Classification of tensides according to the polar group: polyethylene glycol glycosides phospholipids quaternary ammonium cations (with s long aliphaticd chain) soaps alkyl sulfates (alkanesulfonates) bile acids Anionic tensides Cationic tensides Amphoteric tensides Non-ionogenic tensides negative electric charge positive electric charge both negative and positive charge polar group without any charge
27. Anionic tensides Soaps are produced by alkaline hydrolysis (saponification) of fats and vegetable oils (triacylglycerols). Washing powders (detergents) are mixtures of synthetic tensides and several additives. sodium alkyl sulfate sodium alkanesulfonate O S O O O N a S O O O N a C O N a O sodium stearate O stearate anion acts as a tenside
28. Cationic tensides Tetraalkylammonium salts (one or two lon-chain alkyls) Antiseptics and disinfectants with a considerable cleaning effect N + C l - R 1 R 2 X – N + R 2 R 1 R 3
29. Phospholipids are extremely important as constituents of lipidic dilayers of biomembranes. Natural tensides of the human body Bile acids Both phospholipids and bile acids enable dissolution of another bile constituent – cholesterol. Bile acids are excreted by the liver into the bile. They act as potent emulsifiers of lipids in the small intestine facilitating lipid digestion and absorption of all liposoluble compounds. Cholic acid C C H 2 C H C H 2 O O P O O O C H 2 C H 2 O N C H 3 C H 3 C H 3 C O O Phosphatidylcholine Phospholipids
30. Effect of tensides Micelles in solution of tensides are able to absorb limited amount of hydrophobic compounds into their hydrophobic inner. Micells keep their size in the range required for colloid dispersions (less than 500 nm). If the concentration of micelles remains constant and the amount of hydrophobic compounds is too large, the tenside molecules cover the surface of hydrophobic droplets and stabilize the resulting crude dispersion ( emulsion ).. Solubilizing effect Emulsifying effect
31. Liposomes are used for transport of hydrophilic pharmaceuticals (even nucleic acids) into cells; They enter cells by means of endocytosis. Liposomes Aqueous inner of the liposome Lipidic dilayer, a phospholipid membrane prepared arteficially by sonication of phospholipid colloid dispersion
