Lyotropic liquid crystals- Anisotropic Solutions

1. Lyotropic liquid crystals-Anisotropic Solutions CHM3T1 Lecture - 6 M. Manickam School of Chemistry The University of Birmingham M.Manickam@bham.ac.uk

2. Out line of This Lecture • Aims and Objects • Introduction • Structures of lyotropic liquid crystal phases • Phase diagram of soap • Lyotropic liquid crystal polymers • Biological significance of liquid crystals • Applications lyotroic liquid crystals • Final comments

3. Learning Objectives • After completing this lecture you should have an understanding of, and be • able to demonstrate, the following terms, ideas and methods. • What is meant by amphiphilic molecules, • What is meant by micelles are, • Understand the types and meaning of lyotropic liquid crystals, • Understand the phase diagram of soap, • Understand the liquid crystalline structure of biological membranes and their function, • Understand how lyotropic liquid crystals has been used in our daily life, • Final comments

4. Types of Liquid Crystals

5. Lyotropic Liquid Crystals (LLCs) LLCs are two-component systems where an amphiphile is dissolved in a solvent. Thus, lyotropic mesophases are concentration and solvent dependent. The amphiphilic compounds are characterised by two distinct moieties, a hydrophilic polar “head” and a hydrophobic “tail”. Examples of these kinds of molecules are soaps (Figure-1a ) and various phospholipids like those present in cell membranes (Figure-1b). Figure-1a: Sodium dodecylsulfate (soap) forming micelles Figure-1b: Phospholipid (lecitine), present in cell membranes, in a bilayer lyotropic liquid crystal arrangement

6. Amphiphilic Molecules: Anionic Surfactants The types of molecular structure that generate lyotropic liquid crystal phases are amphiphilic (loving both kinds). Amphiphilic molecules possess both polar and non-polar regions in the same molecule. Surfactants are amphiphilic materials whose constituent molecules have a molecular structure that includes a polar head group and a non-polar chain. Soaps such a sodium separate (1) have a polar head group made up of a carboxylate salt and non-polar unit that is simply a long hydrocarbon chain. Synthetic detergents such as alkyl sulphates (2) and aromatic sulfonate (3) are analogous in nature to compound (1). Materials such as 1, 2, and 3 are known as anionic surfactants because the polar head groups are anionic moieties. (1) (3) (2) Anionic surfactants

7. Cationic Surfactants (4) (6) (5) Cationic surfactants also exist and these, not surprisingly, also exhibit lyotropic liquid crystal phases. Compound (4) is a simple example of a cationic surfactant that consists of an amine with a long terminal chain that has been converted into the ammonium chloride salt. The ammonium cation constitutes the polar head group, and as usual, the long terminal alkyl chain completes the amphiphilic molecule in the capacity of hydrophobic unit. Compounds 5 and 6 are more elaborate cationic surfactants. Compound 6 has two long hydrophobic alkyl chains and analogues of compound 6 are used as antistatic fabric softeners.

8. Non-ionic Surfactants 7 8 9 Amphiphilic molecules are also generated by non-ionic species. Such non-ionic surfactants have, for example, a long alkyl chains as the hydrophobic section and the hydrophilic polar head group is constructed of several ethylene glycol units. Compound 7 is a typical example of this type of poly(oxyethylene) alkyl ether system with a reasonably large polar head group. Amphiphilic molecules have also been prepared where the polar, hydrophilic head group is made up of a long perfluoroalkyl chain which is directly connected to a long hydrocarbon chain as the hydrophopic section.

9. Structure of micelles formed by amphiphilic molecules Figure -2 Amphiphilic molecules are usually depicted as circles (polar head group) with an attached chain (non-polar unit) as shown in figure-2, and often have more than one non-polar unit. These amphiphilic materials are either insoluble or the molecules dissolve to form a miccellar solution. Micelles are aggregates of molecules that form such that the non-polar chains aggregate together and are effectively removed from the water solvent by the surrounding polar head groups. Such micelles occur when the solution is relatively dilute and the solution behaves as an isotropic fluid. Micelles are stable in water provided that the concentration of surfactant is above the critical micelle concentration. micelle micelle cross- section

10. Structure of micelles formed by amphiphilic molecules Figure-3 Reverse micelles can also form where the non-polar chains radiate away from centrally aggregated head groups that surround the water solvent. Such reversed micelle formation usually occurs in oil- water mixtures where the amount of water is small and fills the void surround by the polar head groups. This phase in which the amphiphilic molecule separates the water from the oil is stable. In the case of micelles, the water surrounds the micelles, whereas, in the case of reverse micelles water resides inside the micelle. The structure of micelles and reverse micelles are shown in Figure-3 Reverse micelle Reverse micelle Cross-section

11. Structures of Lyotropic Liquid Crystals Just as there are many different types of the thermotropic liquid crystal phase there are also several different types of lyotropic liquid crystals phases. In general, the lyotropic liquid crystals phases of surfactant systems have been extensively investigated over the whole concentration range. This intensive research parallels the commercial importance of soap and detergent products. Three different classes of lyotropic liquid crystal phases structures are widely recognised. These are the • Lamellar • Hexagonal • Cubic phases Their structures have been classified by X-ray diffraction techniques.

12. Lamellar Lyotropic Liquid Crystal Phase Figure- 4: Structure of the Lamellar Lyotropic Liquid Crystal Phase

13. Lamellar Lyotropic Liquid Crystal Phase The lamellar (Lα)lyotropic liquid crystals phase structure is illustrated in Figure-4 and as can be seen this particular phase consists of a layered arrangement of amphiphilic molecules. The amphiphilic nature of the molecules means that the self-assembly is bilayer in nature with two layers being made up of intertwining non-polar chains form oppositely directed molecules. Where the polar head groups meet is separated by a layer of water. The bilayer thickness is 10-30% less than twice the length of an ‘all-trans’ non-polar chain and the water layer thickness is between 1 and 10 nm if the water content is between 10 and 50% by weight. Usually, lamellar lyotropic liquid crystals phase only exist down to 50% surfactant. Below 50% surfactant, the lamellar phase gives way to hexagonal lyotropic liquid crystal phases or an isotropic miceller solution. However, in some cases the lyotropic lamellar phase is exhibited in extremely dilute solutions. LLLCPs are less viscous than the hexagonal LLCPs despite the fact that they contain less water. This is because the parallel layers slide over each other with relative ease during shear and this is quite easy to visualise (Figure-4).

14. Hexagonal Lyotropic Liquid Crystal Phase Figure- 5: Structure of the Hexagonal Lyotropic Liquid Crystal Phase

15. Hexagonal Lyotropic Liquid Crystal Phase The hexagonal lyotropic liquid crystal phases have a molecular aggregate ordering which corresponds to a hexagonal arrangement Figure- 5 and 6 These phases give similar birefringent texures when examined by optical polarising microscopy to the thermotropic hexagonal liquid crystal phases. There are two types of hexagonal lyotropic liquid crystal phases, the hexagonal phase (H1) and the reversed hexagonal phase (H2). The hexagonal phase consists of micellar cylinders of indefinite length packed in a hexagonal arrangement (Figure-5). The diameter of the miceller cylinders in typically 10 to 30% less than twice the length of an ‘all-trans’ non-polar chain.

16. Reversed Hexagonal Lyotropic Liquid Crystal Phase Figure-6: Structure of the Reversed Hexagonal Lyotropic Liquid Crystal Phase

17. Hexagonal Lyotropic Liquid Crystal Phase The spacing between cylinders varies enormously between 1 and 5 nm depending upon the relative amounts of water and surfactant. Hexagonal lyotropic liquid crystals phases typically contain 30 to 60% water by weight and despite this high water content the phase is very viscous. The viscosity of the hexagonal phase means that it is best avoided in the practical, industrial handling of surfactants. The reversed hexagonal phase is basically the same as the hexagonal phase except that the micellar cylinder are reversed with the non-polar chains radiating outwards from the cylinders (Figure-6)

18. Cubic Lyotropic Liquid Crystal Phase Figure-7: Structure of the cubic lyotropic liquid crystal phase

19. Cubic Lyotropic Liquid Crystal Phase Cubic lyotropic liquid crystal phase are not as common as the lamellar or hexagonal phase This phases are not as well characterised as the lamellar or hexagonal phases. Two types of cubic lyotropic liquid crystals phases have been established and each can be generated in the ‘ normal’ manner (water continuous ) or in the ‘reversed’ manner (non-polar chain continuous), which makes for a total of four different phase types. The most well-known cubic phase consists of a cubic arrangement of molecular aggregates. The molecular aggregates are similar to micelles (I1 phase) or reversed micelles (I2 phase) micelles Reversed micelles

20. Cubic Lyotropic Liquid Crystal Phase The structure of the ‘normal’ (I1) CLLC phase is shown in the Figure-7. Some reports suggest that the molecular aggregates are spherical but others claim that they are cylindrical or ellipsoidal. The second type of CLLC phases is found to lie between the hexagonal (H1) and lamellar (Lα) phases. CLLC phases are extremely viscous and are even more viscous than the hexagonal phases. Cubic phases are often called viscous isotropic phases. The isotropic nature of the cubic phases often makes them difficult to detect by OPM and so they sometimes undetected.

21. Phase Diagram of Soap (1) The best way to illustrate the behaviour of an amphiphilic material in water is to show a phase diagram. Phase diagram are constructed with amphiphilic concentration along the horizontal axis and temperature along the vertical axis. Such phase diagrams are often used to show the liquid crystal phase behaviour of a mixture of two thermotropic LCs. Figure-8: Phase diagram for a typical soap (1) in water

22. Phase Diagram of Soap (1) A typical phase diagram (Figure-8) for a soap, such as compound 1, in water clearly shows the critical micelle concentration (below which micelles do not form) and the Krafft point at each temperature (below which the crystal is insoluble in water). Above the Krafft pint, LLC phases are generated. At relatively low concentrations the hexagonal phase is generated up to certain temperatures when it gives way to a micellar solution. At relatively high concentrations the lamellar is formed which exists up to a higher temperature than the hexagonal phase but eventually, at even higher temperature, a micellar solution is formed. At extremely high concentrations of amphiphile, reversed or inverted LLC phases are generated which, on cooling, give way to crystalline phase. Soap (1) Krafft Point Surfactants dissolved in water have a Krafft point, defined as the temperature (TK) below which micelles are insoluble. Above the Krafft point LLC phases are generated.

23. Lyotropic Liquid Crystal Polymers If a polymer is to be lyotropic LC polymer, it must firstly be fairly rigid and secondly it must dissolve in a solvent. These two requirements are often mutually exclusive in the rigid structure are usually not soluble. Accordingly, drastic solvents such as sulfuric acid are often required. A famous and technologically significant LLC is a LLCP called Kevlar. Kevlar (10) is a synthetic polyamide of rather simple structure. However, when Kevlar is dissolved in high concentrations in sulfuric acid, a liquid crystalline phase is generated. LCPs acquire extremely high strength. Compared with nylon, Kevlar is 30 times stronger despite being only slightly more dense. In fact steel is 5 times more dense then Kevlar which, pound for pound, makes Kevlar stronger than steel. Kevlar (10)

24. The Liquid Crystalline Structure of Biological Membranes Plasma membranes of cells, are constructed of phospholipids. Phospholipids all have a structure that closely resembles the structure of the soaps and detergent surfactants discussed above in that the constituent molecules have an amphiphilic nature. This nature arises from the presence of both polar and non-polar regions within the same molecule. Polar region is hydrophilic (lipophobic) and the non-polar region is hydrophobic (lipophilic). Phospholipids are composed of glycerol where two adjacent hydroxyl functions are esterified with large, long chain fatty acid units. Remaining terminal hydroxyl function is esterified with a phosphoric acid unit that has an attached amino-alcohol moiety. Polar region Non-polar region Phospholipid (11)

25. The Liquid Crystalline Structure of Biological Membranes (Fluid mosaic model) Compound (11) is a typical example of a phospholipid, where one fatty acid is partially unsaturated and choline is employed as the nitrogenous phase. Accordingly, phospholipid materials have two non-polar chains in their structure and the polar head group is composed of the glycerol ester unit, the phosphate ester unit, and the amino-alcohol unit. Figure- 9; The Liquid Crystalline Structure of the cell membrane (fluid mosaic model)

26. The Liquid Crystalline Structure of Biological Membranes The structure of the cell plasma membrane is illustrated in Figure-9 . The phospholipids molecules aggregate into a bilayer which serves to remove the hydrophobic chains from the aqueous environment and place a polar, hydrophilic head group at each side of the bilayer which is exposed to water. The bilayer aggregate is liquid crystalline in nature, in that the head groups do not have any periodic ordering and the hydrocarbon chains are not rigid. The liquidity of the structure allows the movement of phospholipids molecules about the cell membrane. Of course, the associated proteins can also move within the cell membrane but they do so more slowly. This liquid crystalline structure of the cell membrane provides form and allows the selective movement of materials in and out of the cells. Also clear from Figure- 9 is the presence of two types of protein associated with the cell membrane.

27. The Liquid Crystalline Structure of Biological Membranes The peripheral proteins are weakly bound and can be readily displaced. The integral proteins are tightly bound to the phospholipids bilayer. The proteins serve a wide range of different functions; for example, they act as transport carriers, drug and hormone receptor sites, and enzymes. Proteins correctly perform their particular functions by folding up their amino acid sequences, in a specific way and so the phospholipids bilayer is important in the correct functioning of proteins. For example, the interactions between the proteins and the phospholipids molecules determine how the sequence of amino acids in a protein is folded, which in turn affects the functioning of the protein. Accordingly, the functioning of proteins is extremely sensitive to the interaction between the phospholipids membrane and proteins.

28. The Change of structure at the Gel to Liquid Crystal Transition Figure - 10: The change of structure at the gel to liquid crystal transition

29. The Change of structure at the Gel to Liquid Crystal Transition The liquid crystalline membrane has a phase transition temperature, just like a thermotropic liquid crystalline compounds. In this case the phase transition is called a gel point and the structural change at this phase transition is illustrated in Figure-10 On cooling the environment of the cell membrane to just below the normal ambient temperature, the head groups become arranged in a more ordered hexagonal manner and the hydrocarbon chains become more straight. The temperature of the LC phase to gel phase transition depends upon the environment of the organism concerned.

30. Application of Amphiphile/Water/Oil Mixtures Soaps and Detergents. The oldest (3000 years) use of lyotropic LCs has been as soaps and detergents for cleaning. However, knowledge of how they work has been very recent. In general high temperatures (40-60°C) and high concentrations are required to form the lyotropic LC phase for detergents to operate effectively. Of course, this results in washing being a relatively expensive business! Thus, if an amphiphile could be developed that formed a lyotropic LC phase at low temperatures and/or low concentrations, then somebody could make a lot of money! Crude Oil Industry. When an oil well ‘dries-up’ it still contains up to 50% of the original oil, but is trapped in porous rocks. The oil industry is trying to develop lyotropic LC that could flood the “dry” wells in order to release the oil from the porous rocks. Food Industry. Lyotropic LCs are used as food emulsifiers to make the ingredients mix. In particular, food products such as mayonnaise, salad dressing, marshmallows, whipped cream, beer, cheese, bread, ice cream, and jelly, rely on food emulsifiers to maintain texture, colour, flavour and viscosity. Some grains used for making bread already have natural amphiphiles which serve as food emulsifiers, other grains do not and synthetic ones are added.

31. Applications Lyotropic LCs Medicine Some drugs are insoluble in blood, and, therefore, are not very active the addition of a small quantity of amphiphile can help solubilise the drug molecules. Other drugs which are taken orally are attacked by the gastric acids and, therefore, become inactive. The incorporation of these drugs in liposomes, shields the drugs from the acids and delivers a higher effective dose of the drug. The use of liposomes in this manner has been termed stealth liposomes. Lyotropic LCs and Disease From our discussion above it is evident that any disruption of the biological lyotropic LCs will have disastrous consequences. Such disruption has been traced back to many diseases. Multiple Sclerosis This disease is characterized by the local disintegration of the myelin sheath around nerve axons, which results in the electrical signals being impeded as they travel along the axons. The myelin sheath is a phospholipids bilayer structure which acts as an insulator around the nerve axons.

32. Applications Lyotropic LCs Sickle-Cell Anemia Normal red blood cells are disc-shaped which allows efficient transfer of gases between the extra cellular and intracellular compartments of the cell membrane. In sickle-cell red blood cells the membrane has been effected such that it is now sickle-shaped and is very inefficient at transferring gases, and the blood is more viscous. Atherosclerosis This disease is a result of the local thickening of the arterial cell walls which supplies blood to the heart, brain and other vital organs. Cholesterol is the main component of the thickening material. However, it is also found that LC cholesterol esters are present which ‘dissolve’ the cholesterol and stop it crystallizing. Thus, the LC acts as a defense mechanism The liquid crystalline structure of biological membranes. The biological significance of liquid crystals

33. Final Comments Lyotropic liquid crystals were the first liquid crystals to be discovered (1850). Much research has been carried out on LLCs because of their commercial potential in household products and foods. However, the importance of LLCs has been completely overshadowed by thermotropic LCs. Thermotropic LCs caught the imagination of researchers at the right time and are tremendously successful in display devices from simple watch and calculator displays to very large, intricate colour television displays. LLCs, however, are connected with things that are taken for granted and not seen as technologically important. This is a pity because research into LLCs still has much potential. For example, very little work has gone into the design and synthesis of novel lyotropic materials. Accordingly, potential uses have not been extensively investigated. There will always be a need for better, more effective detergents that, for example, act at much lower temperatures and cause less damage to delicate items. Most importantly, life itself is based on LLCs systems, and it seems certain that future biomedical research will include studies into lyotropic liquid crystalline structure of life systems. Overall, LLs look to have a very significant future; after all, we all know how important life is.