Molecular Self-Assembly Professor Jim F. Rathman, Department of Chemical Engineering

Molecular Self-Assembly Professor Jim F. Rathman, Department of Chemical Engineering Learning Objectives This module will introduce students to: Role of intermolecular forces in molecular self-assembly of amphiphilic molecules. Formation of 3-D structures by self-assembly in solution Surface tension and the formation of 2-D structures by self-assembly at interfaces Introduction Self-assembly is the process in which molecules or molecular aggregates spontaneously organize into 2- or 3-dimensional structures. The forces involved in self-assembly are much weaker than the relatively strong forces involved in covalent chemical bonds. The organization of a selfassembled structure is maintained by a balance of weaker intermolecular forces. These forces include hydrogen bonding, Coulombic (electrostatic) interactions, coordination bonding, and van der Waals interactions. For example, self-assembly of soap molecules in water involves both hydrophobic forces, which tend to promote aggregation, and hydrophilic interactions, which favor the dispersion of molecules. Since the majority of self-assembly processes involve nanometer-sized entities, external effects such as capillary forces, electric or magnetic fields, and flow can strongly influence the self-assembly process. Although scientific knowledge in this area has a long history, interest in molecular self-assembly has dramatically increased in recent years. Exciting new techniques have been developed that allow us to actually manipulate individual molecules or clusters of molecules. For this reason, selfassembly is key to bottom-up strategies in the nanomanufacturing of novel materials and devices. Biological systems provide numerous examples of self-assembled structures. Many essential life activities are strongly controlled and regulated by self-assembly. Due to the relatively weak interactions involved, a self-assembled structure is much more sensitive and responsive to its environment than a more rigid structure held together by covalent bonds. Self-assembly processes in biological systems are usually directional and functional, and often lead to the formation of extremely complex structures. For example, the three-dimensional structure adopted by a protein in solution is critical to the protein s function, and this structure is determined by both strong (covalent) and weak interactions. Thanks to the weaker interactions, the protein can respond dynamically to changes in its environment. The wide spectrum of self-assembly phenomena can be categorized in various ways. In this module, we will discuss the similarities and differences between 2- and 3-dimensional systems. We will also discuss applications of self-assembly processes. Fundamentals Intermolecular forces. In order to understand the process of self-assembly, we need to start by thinking about the types of interactions that may occur between two molecules. The strongest interaction is the special case in which a covalent bond forms between the molecules we call

this a chemical reaction and the result is that we no longer have two distinct molecules, but rather a new molecule. We are not interested in chemical reactions here because self-assembly generally involves much weaker types of interactions. Charge-charge (Coulombic) interactions are important when ionic molecules are involved: attractive interactions result when the molecules are oppositely-charged, and repulsive interactions occur when the molecules are either both positive or both negative. Coulombic interactions are also important when non-ionic polar molecules are involved. The electrons in a polar molecule are not uniformly distributed, so although the molecule has no net charge one portion of the molecule has a slight negative charge while another portion is slightly positive. When two polar molecules come into close proximity, an attractive interaction can develop as the positively-charged region in one molecule interacts with the negatively-charged region of the second molecule. Interestingly, attractive interactions also arise between molecules that are non-ionic and non-polar. On average, the electrons are distributed uniformly within these molecules; however, at any given instant the electrons may be non-uniformly distributed due to their random and chaotic movement. This effect is enhanced when another molecule comes close to the first molecule the dynamic fluctuations in electron distributions in one molecule are influenced by the fluctuations in the other molecule. The net result of all this chaos turns out to be an attractive interaction that we call van der Waals forces. Thanks to the van der Waals interactions, attractive interactions occur between any two molecules, even for example two molecules of an inert substance such as helium. Amphiphilic molecules. Molecules that are amphiphilic are especially important in selfassembly. An amphiphilic molecule is one in which part of the molecule is chemically similar to the solvent in which the molecule is placed while another part of the molecule is chemically incompatible with the solvent. Did you brush your teeth this morning? If so, then your toothpaste probably contained sodium dodecylsulfate, an amphiphilic molecule that has a hydrophilic ( water-loving ) head group and hydrophobic ( water-fearing ) hydrocarbon tail group. Throughout the day you use many products containing amphiphilic molecules, including surfactants ( surface-active agents ) and soaps used in cleaning products and as dispersing agents in foods. 3-D self-assembly of surfactants. Now let s consider what happens when we dissolve amphiphilic molecules in water. At low concentrations a solution will contain individual molecules of surfactant dispersed in the solvent (water). Since water is a polar solvent, the ionic headgroup of the surfactant interacts favorably with the surrounding water molecules; interactions between water molecules and the hydrophobic surfactant tail are also attractive, but are much weaker. Because the hydrophobic tail disrupts the hydrogen bonding between water molecules in this vicinity, the water molecule are packed in a highly ordered structure along the surfactant tail. Note that the term hydrophobic is really not a very good description of this interaction the surfactant tail does not fear water molecules in fact, van der Waals interactions result in a net attractive interaction, but this interaction is relatively weak and comes at the expense of breaking some of the stronger hydrogen bonds between water molecules. If the concentration of surfactant is increased, at hydrophilic head hydrophobic tail micelle 2 5 nm

some point the surfactant molecules get close enough to start interacting with each other instead of just interacting with water molecules. Although there is a repulsive interaction between surfactant head groups, there is a strong attractive interaction between the tails. As a result, surfactant molecules in solution will spontaneously self-assemble into aggregates (called micelles ) that allow for extensive interaction between their hydrophobic tails while allowing the hydrophilic heads to remain in contact with the solvent. The water molecules also like this process no longer confined to being packed in orderly fashion along the hydrophobic tail of the amphiphilic molecule, they are now free to move about the solution like normal water molecules. This phenomena, driven by attractive tail-tail interactions and the desire of the bound water molecules to go free, is called the hydrophobic effect. Depending on properties of the amphiphilic molecule and its concentration in solution, a rich variety of self-assembled structures can be formed. For example, rod-shaped micelles can be formed and, at higher concentrations, the micelles themselves aggregate to form a liquid crystalline phase. Other types of amphiphiles, such as the lipids that form cell membranes in biological systems, tend to form bilayer structures. hexagonal packing of rod-shaped micelles It s useful to think about why amphiphilic molecules are so important in the formation of self-assembled structures. What might happen for example, in a solution containing a simple hydrocarbon oil such as decane? Decane is not amphiphilic it is a purely bilayer structure hydrophobic compound. Since there is no hydrophilic group to interact strongly with water, it s very difficult to dissolve a decane molecule into water; nature doesn t like having to break the strong hydrogen bonds between water molecules when all it gets in return are the much weaker water-decane interactions. Decane molecules also don t like this they much rather prefer interacting with other decane molecules and will therefore do so very readily. Remember that the self-assembly of surfactant molecules is a balance between attractive tail-tail interactions and repulsive head-head interactions. In the case of decane, there are no repulsive interactions to counter the attractive decane-decane interactions, so an infinite number of decane molecules can come together. We all know that oil and water don t mix this is exactly the reason why! If we attempt to make a solution of decane in water, we end up with an essentially pure liquid decane floating on top of an essentially pure liquid water phase. The selfassembly of a surfactant is in many ways similar to a phase separation with one very important difference: because of the balance between hydrophilic and hydrophobic effects, the equilibrium size of the self-assembled structure is finite, consisting of a relatively small number of molecules. From an engineering standpoint, self-assembly of amphiphilic molecules is therefore an extremely attractive route towards creating materials and devices with nanoscale features that are of the same size and shape as these structures. Self-assembly in biological systems. In addition to the hydrophobic and electrostatic forces that are major factors in the self-assembly of surfactants and amphiphilic polymers, the formation of self-assembled biological structures also often involves the formation of covalent bonds, such as disulfide bonds for example. These rather strong forces provide additional driving forces for biological self-assembly, but in many cases they act as functional forces as well. A variety of vital life activities such as cell-cell interaction, intercellular aggregation, activation of the

cytoskeleton, transport through plasma membranes, cell fusion and lysis, focal adhesion, formation of collagen and fibronectin networks, and movement of certain cells on solid surface are largely due to biological self-assembly that can be understood as the hierarchical evolution of self-assembly in nature. Due to its diversity and complexity, biological self-assembly is more difficult to characterize than surfactant self-assembly. Self-assembly at larger length scales. Self-assembly is not limited to molecular-scale building blocks. Self-assembly of much larger entities is also possible, usually aided by external forces such as capillary effects, electric and magnetic field, and shear and elongational flows. These approaches rely on the careful design and modification of surface chemistry of the building block objects. For example, assembly of solid objects on the millimeter-to-centimeter size into an amazing level of hierarchy and architectural variety using lateral capillary forces has been demonstrated. Assembly and directional orientation of liquid crystals in a magnetic field provides another example of this category of self-assembly. Surface tension and 2-D self-assembly. Nature doesn t like surfaces. A water droplet falling through the air will tend to take on a spherical shape in order to minimize the water-air surface area. If two water droplets rolling around on a Teflon surface collide they readily coalesce to form a single drop, again because the single drop has less exposed area than the two drops. The tendency to minimize interfacial area is a consequence of surface tension, an important property of liquids and solids. Although surface tension is a complex phenomena, we can start to understand it by appreciating the fact that molecules at a surface or interface are in a different environment than molecules inside a homogeneous bulk phase. In pure liquid water, a water molecule in the bulk is surrounded by other water molecules, experiencing many attractive interactions due to the strong polar nature of water. A water molecule at the air-water surface is much less happy since there are far fewer molecules for this molecule to interact with and so water has a rather high surface tension. The surface tension of a liquid can be decreased significantly by the addition of amphiphilic molecules. In addition to their self-assembly to form 3-dimensional structures in solution, these molecules also do some very interesting things at interfaces. Surfactant molecules dissolved in water not only may form micelles within the solution but will adsorb at the air-water interface. Due to the favorable tail-tail interactions between adsorbed air surfactant molecules, surfactant molecules are much more comfortable at the interface than water molecules, so the surface tension of the solution is much lower than for pure water. The attractive tail-tail interactions also drive the selfassembly of surfactant molecules into structured aggregates on the surface. Since this process is confined to the interfacial water region, these aggregates are essentially 2-dimensional analogs of the 3-dimensional structures formed by selfassembly in bulk solution. Self-assembled structures formed on a liquid surface can be deposited onto a solid surface using a process known as Langmuir-Blodgett deposition. This technique allows for a high degree of control over the transfer process, so that the structure of extremely thin films can be preserved

during the transfer process. As discussed in the next section, these nanostructured thin films have a variety of possible applications. Examples and Applications of Molecular Self-Assembly Biomineralization and biomimetic materials. Diatoms, animal bone, abalone shell, spider silk, and eggshell are among the many examples of complex materials produced in nature by biomineralization. Understanding the process by which these materials are formed will therefore provide excellent insight for the development of new synthetic materials. The key to biomineralization, the process in which these materials are produced in nature, is the cooperative self-assembly between inorganic constituents and self-assembled bioorganics such as proteins, enzymes, and membrane lipids. These self-assembled structures act as templates on which the polymerization of reactive inorganics occurs to form the structured solid material. An important characteristic of this process is that the self-assembly usually proceeds multi-step wise, making the final structures highly hierarchical. Mimicking the biomineralization process in the laboratory is believed to be a very promising and efficient route towards the discovery of new materials with excellent mechanical, chemical, and/or electromagnetic properties. Advanced porous materials. Examples of advanced materials produced by exploiting molecular self-assembly include highly porous materials, magnetic fluids, and optomagnetic multilayered films. In the production of mesoporous silica, reactive silicate species are added to a concentrated surfactant solution. The 3-dimensional self-assembled surfactant structures act as templates the reaction of silicate ions to form silica occurs on the outer walls of the surfactant aggregates. At the end of the reaction, the surfactant is removed either by solvent extraction or calcination, leaving a remarkably porous silica product. This material can have a surface area of more than 1000 m 2 per gram, which is ideal for use as a catalyst support or adsorbent. Ultrathin films. Applications of ultrathin films containing 2-dimensional self-assembled structures include sensors and scaffolds for tissue engineering. This picture shows a 10 µm 10 µm image, obtained by atomic force microscopy, of a 2-dimensional network of collagen fibers grown on a self-assembled lipid monolayer at an air-water interface. Collagen is the most abundant protein present in animals and plays an important role in connective tissues and the adhesion of cells to surfaces. This is an example in which an extremely complex biological process, the polymerization of collagen monomers to form a fibrous network, has been successfully realized in an artificial environment. An Historical Perspective: The Amazing Agnes Pockels Some of the most important contributions in science come from the least expected places. Extraordinary people have accomplished remarkable things despite very limited means or

difficult circumstances. A prime example is the development of the technique first used to estimate the size of a molecule and still used today to investigate the self assembly of molecules on the surface of a liquid. This technique was developed by a woman who had only a high school education, working in her own home with common household wares for her experimental tools, and performed in the 1880 s, a time when many people did not even believe in the existence of molecules. Agnes Pockels was born in 1862 and, after completing high school in Brunswick, Germany, she dreamed of continuing her education at a university but unfortunately she was never able to do so: In high school, I had already developed a passionate interest in the natural sciences, especially in physics, and would have liked to become a student, but at that time women were not accepted for higher education and later on, when they started to be accepted, my parents nevertheless asked me not to do so. Pockels lived at home for all of her life, finding time for her experiments while not taking care of the house and her sickly parents. Her experiments were truly amazing! Agnes was interested in surface tension. She was especially interested in how the surface tension of water could be drastically changed by deposition of very tiny amounts of other materials (materials we now call surfactants ) onto the surface. Pockels devised a method that allowed her to deposit an extremely tiny amount of surfactant on the surface, so that initially the number of surfactant molecules per unit area of surface was very low. She then showed that, by sweeping a movable barrier across the surface, the confined molecules could be concentrated into a smaller area and that the surface tension decreased as the number of surfactants molecules per area increased. References for Further Study: Rajagopalan, R. Colloids and Interfaces, in The Expanding World of Chemical Engineering, Furusake, S.; Garside, J.; Fan, L.-S. (Eds.), 2 nd edition, Taylor and Francis, New York (2002) Whitesides, G. M. Self-Assembling Materials Scientific American, Sept 1995, 146-149. Gupta, V. K.; Abbott, N. L. Design of Surfaces for Patterned Alignment of Liquid Crystals on Planar and Curved Substrates Science 1997, 276, 1533-1536. Philp, D.; Stoddart, J. F. Self-Assembly in Natural and Unnatural Systems Angew. Chem. Int. Ed. Engl. 1996, 35, 1154-1196. Questions for Discussion: 1. Explain how various charges and forces at the molecular level contribute to 2-D and 3-D self-assembly processes at the nanoscale. 2. Surfactants are key ingredients in laundry detergents. Micelles greatly increase the amount of oily substances on fabric that can be dissolved into the wash solution. Explain

why a hydrophobic molecule, such as a triglyceride present in spaghetti sauce, would be more soluble in a solution containing surfactant micelles than in pure water. 3. More than two hundred years ago, Ben Franklin demonstrated that the evaporative loss of water from a lake could be greatly reduced by spreading a small amount of surfactant on the surface. Fatty acids are amphiphilic molecules found in many biological systems. When adsorbed at an air-water interface, a fatty acid molecule occupies an area of approximately 0.20 nm 2 (1 nm = 10-9 m). Calculate the volume (number of milliliters, ml) of a fatty acid that is needed to cover the surface of a lake that has a surface area of 2000 m 2. The fatty acid has a density of 0.8 g/ml and 1 g of material contains 2 10 21 molecules. Why does a self-assembled monolayer of fatty acid molecules reduce the rate of water evaporation? 4. Simple experiment to do at home: Add water to a wide pan; sprinkle a small amount of flour onto the surface of the water; then add one drop of a water solution into which you have dissolved some soap or detergent. What happens? Why?