Lesson № 6. 1.   The properties of macromolecules (HMC – high molecular compounds)

Polymer Synthesis

The study of polymer science begins with understanding the methods in which these materials are synthesized. Polymer synthesis is a complex procedure and can take place in a variety of ways. Addition polymerization describes the method where monomers are added one by one to an active site on the growing chain.

Addition Polymerization

The most common type of addition polymerization is free radical polymerization. A free radical is simply a molecule with an unpaired electron. The tendency for this free radical to gain an additional electron in order to form a pair makes it highly reactive so that it breaks the bond on another molecule by stealing an electron, learing that molecule with an unpaired election (which is another free radical). Free radicals are often created by the division of a molecule (known as an initiator) into two fragments along a single bond. The following diagram shows the formation of a radical from its initiator, in this case benzoyl peroxide.

The stability of a radical refers to the molecule’s tendency to react with other compounds. An unstable radical will readily combine with many different molecules. However a stable radical will not easily interact with other chemical substances. The stability of free radicals can vary widely depending on the properties of the molecule. The active center is the location of the unpaired electron on the radical because this is where the reaction takes place. In free radical polymerization, the radical attacks one monomer, and the electron migrates to another part of the molecule. This newly formed radical attacks another monomer and the process is repeated. Thus the active center moves down the chain as the polymerization occurs.

There are three significant reactions that take place in addition polymerization: initiation (birth), propagation (growth), and termination (death). These separate steps are explained below.

Initiation Reaction

The first step in producing polymers by free radical polymerization is initiation. This step begins when an initiator decomposes into free radicals in the presence of monomers. The instability of carbon-carbon double bonds in the monomer makes them susceptible to reaction with the unpaired electrons in the radical. In this reaction, the active center of the radical “grabs” one of the electrons from the double bond of the monomer, leaving an unpaired electron to appear as a new active center at the end of the chain. Addition can occur at either end of the monomer. This process is illustrated in the following animation in which a chlorine atom possessing an unpaired electron (often indicated as cl-) initiates the reaction. As it collides with an ethylene molecule, it attracts one of the ethylene’s pair of pi bonded electrons in forming a bond with one of the carbons. The other pi electron becomes the active center able to repeat this process with another ethylene molecule. The sigma bond between the carbons of the ethylene is not disturbed. (Note that a molecular orbital model is employed here in describing this process. See any introductory college chemistry text for further discussion)

In a typical synthesis, between 60% and 100% of the free radicals undergo an initiation reaction with a monomer. The remaining radicals may join with each other or with an impurity instead of with a monomer. “Self destruction” of free radicals is a major hindrance to the initiation reaction. By controlling the monomer to radical ratio, this problem can be reduced.

Propagation Reaction

After a synthesis reaction has been initiated, the propagation reaction takes over. In the propagation stage, the process of electron transfer and consequent motion of the active center down the chain proceeds. In this diagram, (chain) refers to a chain of connected monomers, and X refers to a substituent group (a molecular fragment) specific to the monomer. For example, if X were a methyl group, the monomer would be propylene and the polymer, polypropylene.

In free radical polymerization, the entire propagation reaction usually takes place within a fraction of a second. Thousands of monomers are added to the chain within this time. The entire process stops when the termination reaction occurs.

Termination Reaction

In theory, the propagation reaction could continue until the supply of monomers is exhausted. However, this outcome is very unlikely. Most often the growth of a polymer chain is halted by the termination reaction. Termination typically occurs in two ways:combination and disproportionation.

Combination occurs when the polymer’s growth is stopped by free electrons from two growing chains that join and form a single chain. The following diagram depicts combination, with the symbol (R) representing the rest of the chain.

Disproportionation halts the propagation reaction when a free radical strips a hydrogen atom from an active chain. A carbon-carbon double bond takes the place of the missing hydrogen. Termination by disproportionation is shown in the diagram.

Disproportionation can also occur when the radical reacts with an impurity. This is why it is so important that polymerization be carried out under very clean conditions.

Living Polymerization

There exists a type of addition polymerization that does not undergo a termination reaction. This so-called “living polymerization” continues until the monomer supply has been exhausted. When this happens, the free radicals become less active due to interactions with solvent molecules. If more monomers are added to the solution, the polymerization will resume.

Uniform molecular weights (low polydispersity) are characteristic of living polymerization. Because the supply of monomers is controlled, the chain length can be manipulated to serve the needs of a specific application. This assumes that the initiator is 100% efficient.

Statistical Analysis of Polymers

When dealing with millions of molecules in a tiny droplet, statistical methods must be employed to make generalizations about the characteristics of the polymer. It can be assumed in polymer synthesis, each chain reacts independently.

Therefore, the bulk polymer is characterized by a wide distribution of molecular weights and chain lengths. The degree of polymerization (DP) refers to the number of repeat units in the chain, and gives a measure of molecular weight. Many important properties of the final result are determined primarily from the distribution of lengths and the degree of polymerization. The following simulation allows you to examine the distribution of chain lengths under varying conditions.

In order to characterize the distribution of polymer lengths in a sample, two parameters are defined: number average and weight average molecular weight. The number average is just the sum of individual molecular weights divided by the number of polymers. The weight average is proportional to the square of the molecular weight. Therefore, the weight average is always larger than the number average. The following graph shows a typical distribution of polymers including the weight and number average molecular weights.

The molecular weight of a polymer can also be represented by the viscosity average molecular weight. This form of the molecular weight is found as a function of the viscosity of the polymer in solution (viscosity determines the rate at which the solution flows – the slower a solution moves, the more viscous it is said to be – and the polymer molecular weight influences the viscosity). The following simulation allows you to calculate the viscosity of a polymer solution, and use the data you find to produce the viscosity average molecular weight.

The degree of polymerization has a dramatic effect on the mechanical properties of a polymer. As chain length increases, mechanical properties such as ductility, tensile strength, and hardness rise sharply and eventually level off. This is schematically illustrated by the blue curve in the figure below.

However, in polymer melts, for example, the flow viscosity at a given temperature rises rapidly with increasing DP for all polymers, as shown by the red curve in the diagram.

 

Polymer Structure

Although the fundamental property of bulk polymers is the degree of polymerization, the physical structure of the chain is also an important factor that determines the macroscopic properties.

The terms configuration and conformation are used to describe the geometric structure of a polymer and are often confused. Configuration refers to the order that is determined by chemical bonds. The configuration of a polymer cannot be altered unless chemical bonds are broken and reformed. Conformation refers to order that arises from the rotation of molecules about the single bonds. These two structures are studied below.

Configuration

The two types of polymer configurations are cis and trans. These structures caot be changed by physical means (e.g. rotation). The cis configuration arises when substituent groups are on the same side of a carbon-carbon double bond. Trans refers to the substituents on opposite sides of the double bond.

Stereoregularity is the term used to describe the configuration of polymer chains. Three distinct structures can be obtained. Isotactic is an arrangement where all substituents are on the same side of the polymer chain. A syndiotactic polymer chain is composed of alternating groups and atactic is a random combination of the groups. The following diagram shows two of the three stereoisomers of polymer chain.

 

Conformation

If two atoms are joined by a single bond then rotation about that bond is possible since, unlike a double bond, it does not require breaking the bond.

The ability of an atom to rotate this way relative to the atoms which it joins is known as an adjustment of the torsional angle. If the two atoms have other atoms or groups attached to them then configurations which vary in torsional angle are known as conformations. Since different conformations represent varying distances between the atoms or groups rotating about the bond, and these distances determine the amount and type of interaction between adjacent atoms or groups, different conformation may represent different potential energies of the molecule. There several possible generalized conformations: Anti (Trans), Eclipsed (Cis), and Gauche (+ or -). The following animation illustrates the differences between them.

Conformation Lattice Simulation

Like the polymer growth simulation, the conformation lattice simulation takes a statistical approach to the study of polymers. Probabilities of the different conformations are assigned which produces a polymer chain with many possible shapes. Click the icon to enter the virtual laboratory.

Other Chain Structures

The geometric arrangement of the bonds is not the only way the structure of a polymer can vary. A branched polymer is formed when there are “side chains” attached to a main chain. A simple example of a branched polymer is shown in the following diagram.

There are, however, many ways a branched polymer can be arranged. One of these types is called “star-branching“. Star branching results when a polymerization starts with a single monomer and has branches radially outward from this point. Polymers with a high degree of branching are called dendrimers Often in these molecules, branches themselves have branches. This tends to give the molecule an overall spherical shape in three dimensions.

A separate kind of chain structure arises when more that one type of monomer is involved in the synthesis reaction. These polymers that incorporate more than one kind of monomer into their chain are called copolymers. There are three important types of copolymers. A random copolymer contains a random arrangement of the multiple monomers. A block copolymer contains blocks of monomers of the same type. Finally, a graft copolymer contains a main chain polymer consisting of one type of monomer with branches made up of other monomers. The following diagram displays the different types of copolymers.

 

An example of a common copolymer is Nylon. Nylon is an alternating copolymer with 2 monomers, a 6 carbon diacid and a 6 carbon diamine. The following picture shows one monomer of the diacid combined with one monomer of the diamine:

Cross-Linking

In addition to the bonds which hold monomers together in a polymer chain, many polymers form bonds betweeeighboring chains. These bonds can be formed directly between the neighboring chains, or two chains may bond to a third common molecule. Though not as strong or rigid as the bonds within the chain, thesecross-links have an important effect on the polymer. Polymers with a high enough degree of cross-linking have “memory.” When the polymer is stretched, the cross-links prevent the individual chains from sliding past each other. The chains may straighten out, but once the stress is removed they return to their original position and the object returns to its original shape.

One example of cross-linking is vulcanization . In vulcanization, a series of cross-links are introduced into an elastomer to give it strength. This technique is commonly used to strengthen rubber.

Classes of Polymers

Polymer science is a broad field that includes many types of materials which incorporate long chain structure of many repeat units as discussed above. The two major polymer classes are described here.

Elastomers,or rubbery materials, have a loose cross-linked structure. This type of chain structure causes elastomers to possess memory. Typically, about 1 in 100 molecules are cross-linked on average. When the average number of cross-links rises to about 1 in 30 the material becomes more rigid and brittle. Natural and synthetic rubbers are both common examples of elastomers. Plastics are polymers which, under appropriate conditions of temperature and pressure, can be molded or shaped (such as blowing to form a film). In contrast to elastomers, plastics have a greater stiffness and lack reversible elasticity. All plastics are polymers but not all polymers are plastics. Cellulose is an example of a polymeric material which must be substantially modified before processing with the usual methods used for plastics. Some plastics, such as nylon and cellulose acetate, are formed into fibers (which are regarded by some as a separate class of polymers in spite of a considerable overlap with plastics). As we shall see in the section on liquid crystals, some of the main chain polymer liquid crystals also are the constituents of important fibers. Every day plastics such as polyethylene and poly(vinyl chloride) have replaced traditional materials like paper and copper for a wide variety of applications.

Polymer Morphology

Molecular shape and the way molecules are arranged in a solid are important factors in determining the properties of polymers. From polymers that crumble to the touch to those used in bullet proof vests, the molecular structure, conformation and orientation of the polymers can have a major effect on the macroscopic properties of the material. The general concept of self-assembly enters into the organization of molecules on the micro and macroscopic scale as they aggregate into more ordered structures. Crystallization, discussed below, is an example of the self-assembly process as is the orientational organization of liquid crystals to be discussed later.

Crystallinity

We need to distinguish here, between crystalline and amorphous materials and then show how these forms coexist in polymers. Consider a comparison between glass, an amorphous material, and ice which is crystalline. Despite their common appearance as hard, clear material, capable of being melted, a difference is apparent when viewed between crossed polarizers, as illustrated below:

The highly ordered crystalline structure of ice changes the apparent properties of the polarized light, and the ice appears bright. Glass and water, lacking that highly ordered structure, both appear dark.

The amorphous morphology of glass leads to very different properties from crystalline solids. This is illustrated in the heating process where the application of heat to glass turns it from a brittle solid-like material at room temperature to a viscous liquid, as discussed later in more detail under Thermal Properties of Polymers. In contrast, the application of heat to ice turns it from solid to liquid. Crystalline melting leads to striking changes in optical properties during the melting process when observed through crossed polarizers. This is illustrated in the following movie of the melting of an organic crystalline material. Note that while the temperatures are not recorded, the entire process occurs over a very narrow temperature range.

The reasons for the differing behaviors lie mainly in the structure of the solids. Crystalline materials have their molecules arranged in repeating patterns. Table salt has one of the simplest atomic structures with its component atoms, Na⁺ and Cl^–, arranged in alternating rows and the structure of a small cube. Salt, sugar, ice and most metals are crystalline materials. As such, they all tend to have highly ordered and regular structures. Amorphous materials, by contrast, have their molecules arranged randomly and in long chains which twist and curve around one-another, making large regions of highly structured morphology unlikely.

The morphology of most polymers is semi-crystalline. That is, they form mixtures of small crystals and amorphous material and melt over a range of temperature instead of at a single melting point. The crystalline material shows a high degree of order formed by folding and stacking of the polymer chains. The amorphous or glass-like structure shows no long range order, and the chains are tangled as illustrated below.

 

There are some polymers that are completely amorphous, but most are a combination with the tangled and disordered regions surrounding the crystalline areas. Such a combination is shown in the following diagram.

An amorphous solid is formed when the chains have little orientation throughout the bulk polymer. The glass transition temperature is the point at which the polymer hardens into an amorphous solid. This term is used because the amorphous solid has properties similar to glass.

In the crystallization process, it has been observed that relatively short chains organize themselves into crystalline structures more readily than longer molecules. Therefore, the degree of polymerization (DP) is an important factor in determining the crystallinity of a polymer. Polymers with a high DP have difficulty organizing into layers because they tend to become tangled.

The cooling rate also influences the amount of crystallinity. Slow cooling provides time for greater amounts of crystallization to occur. Fast rates, on the other hand, such as rapid quenches, yield highly amorphous materials. For a more complete discussion, see the section on thermal properties. Subsequent annealing (heating and holding at an appropriate temperature below the crystalline melting point, followed by slow cooling) will produce a significant increase in crystallinity in most polymers, as well as relieving stresses.

Low molecular weight polymers (short chains) are generally weaker in strength. Although they are crystalline, only weak Van der Waals forces hold the lattice together. This allows the crystalline layers to slip past one another causing a break in the material. High DP (amorphous) polymers, however, have greater strength because the molecules become tangled between layers. For uses and examples of high and low DP polymers, see the section on Polymer Applications. In the case of fibers, stretching to 3 or more times their original length when in a semi-crystalline state produces increased chain alignment, crystallinity and strength.

In most polymers, the combination of crystalline and amorphous structures forms a material with advantageous properties of strength and stiffness.

Also influencing the polymer morphology is the size and shape of the monomers’ substituent groups. If the monomers are large and irregular, it is difficult for the polymer chains to arrange themselves in an ordered manner, resulting in a more amorphous solid. Likewise, smaller monomers, and monomers that have a very regular structure (e.g. rod-like) will form more crystalline polymers.

 

 

The Macromolecules

        The four major classes of macromolecules are carbohydrates, lipids, proteins, and nucleic acids.

Most macromolecules are polymers, built from monomers

        Three of the four classes of macromolecules—carbohydrates, proteins, and nucleic acids—form chainlike molecules called polymers.

         A polymer is a long molecule consisting of many similar or identical building blocks linked by covalent bonds.

Illustration of a polypeptide macromolecule

A macromolecule is a very large molecule commonly created by polymerization of smaller subunits. In biochemistry, the term is applied to the three conventional biopolymers (nucleic acids, proteins and carbohydrates), as well as non-polymeric molecules with large molecular mass such as lipids and macrocycles. The individual constituent molecules of macromolecules are called monomers (mono=single, meros=part).

Usage

The term macromolecule was coined by Nobel laureate Hermann Staudinger in the 1920s, although his first relevant publication on this field only mentions high molecular compounds (in excess of 1,000 atoms). At that time the phrase polymer, as introduced by Berzelius in 1833, had a different meaning from that of today: it simply was another form of isomerism for example with benzene and acetylene and had little to do with size.

Usage of the term to describe large molecules varies among the disciplines. For example, while biology refers to macromolecules as the four large molecules comprising living things, in chemistry, the term may refer to aggregates of two or more molecules held together by intermolecular forces rather than covalent bonds but which do not readily dissociate.

According to the standard IUPAC definition, the term macromolecule as used in polymer science refers only to a single molecule. For example,a single polymeric molecule is appropriately described as a “macromolecule” or “polymer molecule” rather than a “polymer”, which suggests a substance composed of macromolecules.

 

Structure of a polyphenylene dendrimer macromolecule reported by Müllen, et al.

Because of their size, macromolecules are not conveniently described in terms of stoichiometry alone. The structure of simple macromolecules, such as homopolymers, may be described in terms of the individual monomer subunit and total molecular mass. Complicated biomacromolecules, on the other hand, require multi-faceted structural description such as the hierarchy of structures used to describe proteins.

Properties

Macromolecules often have unusual physical properties. For example, individual pieces of DNA in a solution can be broken in two simply by sucking the solution through an ordinary straw. This is not true of smaller molecules. The 1964 edition of Linus Pauling‘s College Chemistry asserted that DNA iature is never longer than about 5,000 base pairs. This error arose because biochemists were inadvertently and consistently breaking their samples into pieces. In fact, the DNA of chromosomes can be hundreds of millions of base pairs long.

Another common macromolecular property that does not characterize smaller molecules is their relative insolubility in water and similar solvents. Many require salts or particular ions to dissolve in water. Similarly, many proteins will denature if the solute concentration of their solution is too high or too low.

High concentrations of macromolecules in a solution can alter the rates and equilibrium constants of the reactions of other macromolecules, through an effect known as macromolecular crowding. This comes from macromolecules excluding other molecules from a large part of the volume of the solution, thereby increasing these molecules’ effective concentration.

         The repeated units are small molecules called monomers.

         Some of the molecules that serve as monomers have other functions of their own.

        The chemical mechanisms that cells use to make and break polymers are similar for all classes of macromolecules.

        Monomers are connected by covalent bonds that form through the loss of a water molecule. This reaction is called a condensation reaction or dehydration reaction.

         When a bond forms between two monomers, each monomer contributes part of the water molecule that is lost. One monomer provides a hydroxyl group (—OH), while the other provides a hydrogen (—H).

         Cells invest energy to carry out dehydration reactions.

         The process is aided by enzymes.

        The covalent bonds connecting monomers in a polymer are disassembled by hydrolysis, a reaction that is effectively the reverse of dehydration.

         In hydrolysis, bonds are broken by the addition of water molecules. A hydrogen atom attaches to one monomer, and a hydroxyl group attaches to the adjacent monomer.

         Our food is taken in as organic polymers that are too large for our cells to absorb. Within the digestive tract, various enzymes direct hydrolysis of specific polymers. The resulting monomers are absorbed by the cells lining the gut and transported to the bloodstream for distribution to body cells.

         The body cells then use dehydration reaction to assemble the monomers into new polymers that carry out functions specific to the particular cell type.

 An immense variety of polymers can be built from a small set of monomers.

        Each cell has thousands of different kinds of macromolecules.

         These molecules vary among cells of the same individual. They vary more among unrelated individuals of a species, and even more between species.

        This diversity comes from various combinations of the 40–50 common monomers and some others that occur rarely.

         These monomers can be connected in a great many combinations, just as the 26 letters in the alphabet can be used to create a great diversity of words.

Carbohydrates serve as fuel and building material

        Carbohydrates include sugars and their polymers.

        The simplest carbohydrates are monosaccharides, or simple sugars.

        Disaccharides, or double sugars, consist of two monosaccharides joined by a condensation reaction.

        Polysaccharides are polymers of many monosaccharides.

 Sugars, the smallest carbohydrates, serve as fuel and a source of carbon.

        Monosaccharides generally have molecular formulas that are some multiple of the unit CH₂O.

         For example, glucose has the formula C₆H₁₂O₆.

        Monosaccharides have a carbonyl group (>C=O) and multiple hydroxyl groups (—OH).

         Depending on the location of the carbonyl group, the sugar is an aldose or a ketose.

         Most names for sugars end in –ose.

         Glucose, an aldose, and fructose, a ketose, are structural isomers.

        Monosaccharides are also classified by the number of carbons in the carbon skeleton.

         Glucose and other six-carbon sugars are hexoses.

         Five-carbon backbones are pentoses; three-carbon sugars are trioses.

        Monosaccharides may also exist as enantiomers.

         For example, glucose and galactose, both six-carbon aldoses, differ in the spatial arrangement of their parts around asymmetrical carbons.

        Monosaccharides, particularly glucose, are a major fuel for cellular work.

        They also function as the raw material for the synthesis of other monomers, such as amino acids and fatty acids.

        While often drawn as a linear skeleton, monosaccharides in aqueous solutions form rings.

        Two monosaccharides can join with a glycosidic linkage to form a disaccharide via dehydration.

         Maltose, malt sugar, is formed by joining two glucose molecules.

         Sucrose, table sugar, is formed by joining glucose and fructose. Sucrose is the major transport form of sugars in plants.

         Lactose, milk sugar, is formed by joining glucose and galactose.

 Polysaccharides, the polymers of sugars, have storage and structural roles.

        Polysaccharides are polymers of hundreds to thousands of monosaccharides joined by glycosidic linkages.

        Some polysaccharides serve for storage and are hydrolyzed as sugars are needed.

        Other polysaccharides serve as building materials for the cell or the whole organism.

        Starch is a storage polysaccharide composed entirely of glucose monomers.

         Most of these monomers are joined by 1–4 linkages (number 1 carbon to number 4 carbon) between the glucose molecules.

         The simplest form of starch, amylose, is unbranched and forms a helix.

         Branched forms such as amylopectin are more complex.

        Plants store surplus glucose as starch granules within plastids, including chloroplasts, and withdraw it as needed for energy or carbon.

         Animals that feed on plants, especially parts rich in starch, have digestive enzymes that can hydrolyze starch to glucose.

        Animals store glucose in a polysaccharide called glycogen.

         Glycogen is highly branched like amylopectin.

         Humans and other vertebrates store a day’s supply of glycogen in the liver and muscles.

        Cellulose is a major component of the tough wall of plant cells.

         Plants produce almost one hundred billion tons of cellulose per year. It is the most abundant organic compound on Earth.

        Like starch, cellulose is a polymer of glucose. However, the glycosidic linkages in these two polymers differ.

         The difference is based on the fact that there are actually two slightly different ring structures for glucose.

         These two ring forms differ in whether the hydroxyl group attached to the number 1 carbon is fixed above (beta glucose) or below (alpha glucose) the plane of the ring.

        Starch is a polysaccharide of alpha glucose monomers.

        Cellulose is a polysaccharide of beta glucose monomers, making every other glucose monomer upside down with respect to its neighbors.

        The differing glycosidic links in starch and cellulose give the two molecules distinct three-dimensional shapes.

         While polymers built with alpha glucose form helical structures, polymers built with beta glucose form straight structures.

         The straight structures built with beta glucose allow H atoms on one strand to form hydrogen bonds with OH groups on other strands.

         In plant cell walls, parallel cellulose molecules held together in this way are grouped into units called microfibrils, which form strong building materials for plants (and for humans, as lumber).

        The enzymes that digest starch by hydrolyzing its alpha linkages cannot hydrolyze the beta linkages in cellulose.

         Cellulose in human food passes through the digestive tract and is eliminated in feces as “insoluble fiber.”

         As it travels through the digestive tract, cellulose abrades the intestinal walls and stimulates the secretion of mucus, aiding in the passage of food.

        Some microbes can digest cellulose to its glucose monomers through the use of cellulase enzymes.

        Many eukaryotic herbivores, from cows to termites, have symbiotic relationships with cellulolytic microbes, providing the microbe and the host animal access to a rich source of energy.

         Some fungi can also digest cellulose.

        Another important structural polysaccharide is chitin, used in the exoskeletons of arthropods (including insects, spiders, and crustaceans).

         Chitin is similar to cellulose, except that it contains a nitrogen-containing appendage on each glucose monomer.

         Pure chitin is leathery but can be hardened by the addition of calcium carbonate.

        Chitin also provides structural support for the cell walls of many fungi.

Lipids are a diverse group of hydrophobic molecules

        Unlike other macromolecules, lipids do not form polymers.

        The unifying feature of lipids is that they all have little or no affinity for water.

        This is because they consist mostly of hydrocarbons, which form nonpolar covalent bonds.

        Lipids are highly diverse in form and function.

 Fats store large amounts of energy.

        Although fats are not strictly polymers, they are large molecules assembled from smaller molecules by dehydration reactions.

        A fat is constructed from two kinds of smaller molecules: glycerol and fatty acids.

         Glycerol is a three-carbon alcohol with a hydroxyl group attached to each carbon.

         A fatty acid consists of a carboxyl group attached to a long carbon skeleton, often 16 to 18 carbons long.

         The many nonpolar C—H bonds in the long hydrocarbon skeleton make fats hydrophobic.

         Fats separate from water because the water molecules hydrogen bond to one another and exclude the fats.

        In a fat, three fatty acids are joined to glycerol by an ester linkage, creating a triacylglycerol, or triglyceride.

        The three fatty acids in a fat can be the same or different.

        Fatty acids may vary in length (number of carbons) and in the number and locations of double bonds.

         If the fatty acid has no carbon-carbon double bonds, then the molecule is a saturated fatty acid, saturated with hydrogens at every possible position.

         If the fatty acid has one or more carbon-carbon double bonds formed by the removal of hydrogen atoms from the carbon skeleton, then the molecule is an unsaturated fatty acid.

        A saturated fatty acid is a straight chain, but an unsaturated fatty acid has a kink wherever there is a double bond.

        Fats made from saturated fatty acids are saturated fats.

         Most animal fats are saturated.

         Saturated fats are solid at room temperature.

        Fats made from unsaturated fatty acids are unsaturated fats.

         Plant and fish fats are liquid at room temperature and are known as oils.

         The kinks caused by the double bonds prevent the molecules from packing tightly enough to solidify at room temperature.

         The phrase “hydrogenated vegetable oils” on food labels means that unsaturated fats have been synthetically converted to saturated fats by the addition of hydrogen.

         Peanut butter and margarine are hydrogenated to prevent lipids from separating out as oil.

         A diet rich in saturated fats may contribute to cardiovascular disease (atherosclerosis) through plaque deposits.

         The process of hydrogenating vegetable oils produces saturated fats and also unsaturated fats with trans double bonds. These trans fat molecules contribute more than saturated fats to atherosclerosis.

        The major function of fats is energy storage.

         A gram of fat stores more than twice as much energy as a gram of a polysaccharide such as starch.

         Because plants are immobile, they can function with bulky energy storage in the form of starch. Plants use oils when dispersal and compact storage is important, as in seeds.

         Animals must carry their energy stores with them and benefit from having a more compact fuel reservoir of fat.

         Humans and other mammals store fats as long-term energy reserves in adipose cells that swell and shrink as fat is deposited or withdrawn from storage.

        Adipose tissue also functions to cushion vital organs, such as the kidneys.

        A layer of fat can also function as insulation.

         This subcutaneous layer is especially thick in whales, seals, and most other marine mammals.

 Phospholipids are major components of cell membranes.

        Phospholipids have two fatty acids attached to glycerol and a phosphate group at the third position.

         The phosphate group carries a negative charge.

         Additional smaller groups may be attached to the phosphate group to form a variety of phospholipids.

        The interaction of phospholipids with water is complex.

         The fatty acid tails are hydrophobic, but the phosphate group and its attachments form a hydrophilic head.

        When phospholipids are added to water, they self-assemble into assemblages with the hydrophobic tails pointing toward the interior.

         This type of structure is called a micelle.

        Phospholipids are arranged as a bilayer at the surface of a cell.

         Again, the hydrophilic heads are on the outside of the bilayer, in contact with the aqueous solution, and the hydrophobic tails point toward the interior of the bilayer.

         The phospholipid bilayer forms a barrier between the cell and the external environment.

         Phospholipids are the major component of all cell membranes.

 Steroids include cholesterol and certain hormones.

        Steroids are lipids with a carbon skeleton consisting of four fused rings.

        Different steroids are created by varying functional groups attached to the rings.

        Cholesterol, an important steroid, is a component in animal cell membranes.

        Cholesterol is also the precursor from which all other steroids are synthesized.

         Many of these other steroids are hormones, including the vertebrate sex hormones.

        While cholesterol is an essential molecule in animals, high levels of cholesterol in the blood may contribute to cardiovascular disease.

        Both saturated fats and trans fats exert their negative impact on health by affecting cholesterol levels.

Proteins have many structures, resulting in a wide range of functions

        Proteins account for more than 50% of the dry mass of most cells. They are instrumental in almost everything that an organism does.

         Protein functions include structural support, storage, transport, cellular signaling, movement, and defense against foreign substances.

         Most important, protein enzymes function as catalysts in cells, regulating metabolism by selectively accelerating chemical reactions without being consumed.

        Humans have tens of thousands of different proteins, each with a specific structure and function.

        Proteins are the most structurally complex molecules known.

         Each type of protein has a complex three-dimensional shape or conformation.

        All protein polymers are constructed from the same set of 20 amino acid monomers.

        Polymers of proteins are called polypeptides.

        A protein consists of one or more polypeptides folded and coiled into a specific conformation.

 Amino acids are the monomers from which proteins are constructed.

        Amino acids are organic molecules with both carboxyl and amino groups.

        At the center of an amino acid is an asymmetric carbon atom called the alpha carbon.

        Four components are attached to the alpha carbon: a hydrogen atom, a carboxyl group, an amino group, and a variable R group (or side chain).

         Different R groups characterize the 20 different amino acids.

        R groups may be as simple as a hydrogen atom (as in the amino acid glycine), or it may be a carbon skeleton with various functional groups attached (as in glutamine).

        The physical and chemical properties of the R group determine the unique characteristics of a particular amino acid.

         One group of amino acids has hydrophobic R groups.

         Another group of amino acids has polar R groups that are hydrophilic.

         A third group of amino acids includes those with functional groups that are charged (ionized) at cellular pH.

         Some acidic R groups are negative in charge due to the presence of a carboxyl group.

         Basic R groups have amino groups that are positive in charge.

         Note that all amino acids have carboxyl and amino groups. The terms acidic and basic in this context refer only to these groups in the R groups.

        Amino acids are joined together when a dehydration reaction removes a hydroxyl group from the carboxyl end of one amino acid and a hydrogen from the amino group of another.

         The resulting covalent bond is called a peptide bond.

        Repeating the process over and over creates a polypeptide chain.

         At one end is an amino acid with a free amino group (the N-terminus) and at the other is an amino acid with a free carboxyl group (the C-terminus).

        Polypeptides range in size from a few monomers to thousands.

        Each polypeptide has a unique linear sequence of amino acids.

 The amino acid sequence of a polypeptide can be determined.

        Frederick Sanger and his colleagues at Cambridge University determined the amino acid sequence of insulin in the 1950s.

         Sanger used protein-digesting enzymes and other catalysts to hydrolyze the insulin at specific places.

         The fragments were then separated by a technique called chromatography.

         Hydrolysis by another agent broke the polypeptide at different sites, yielding a second group of fragments.

         Sanger used chemical methods to determine the sequence of amino acids in the small fragments.

         He then searched for overlapping regions among the pieces obtained by hydrolyzing with the different agents.

         After years of effort, Sanger was able to reconstruct the complete primary structure of insulin.

         Most of the steps in sequencing a polypeptide have since been automated.

 Protein conformation determines protein function.

        A functional protein consists of one or more polypeptides that have been twisted, folded, and coiled into a unique shape.

        It is the order of amino acids that determines what the three-dimensional conformation of the protein will be.

        A protein’s specific conformation determines its function.

        When a cell synthesizes a polypeptide, the chain generally folds spontaneously to assume the functional conformation for that protein.

        The folding is reinforced by a variety of bonds between parts of the chain, which in turn depend on the sequence of amino acids.

         Many proteins are globular, while others are fibrous in shape.

        In almost every case, the function of a protein depends on its ability to recognize and bind to some other molecule.

         For example, an antibody binds to a particular foreign substance.

         An enzyme recognizes and binds to a specific substrate, facilitating a chemical reaction.

         Natural signal molecules called endorphins bind to specific receptor proteins on the surface of brain cells in humans, producing euphoria and relieving pain.

         Morphine, heroin, and other opiate drugs mimic endorphins because they are similar in shape and can bind to the brain’s endorphin receptors.

        The function of a protein is an emergent property resulting from its specific molecular order.

        Three levels of structure—primary, secondary, and tertiary structures—organize the folding within a single polypeptide.

        Quaternary structure arises when two or more polypeptides join to form a protein.

        The primary structure of a protein is its unique sequence of amino acids.

         Lysozyme, an enzyme that attacks bacteria, consists of 129 amino acids.

         The precise primary structure of a protein is determined by inherited genetic information.

        Even a slight change in primary structure can affect a protein’s conformation and ability to function.

         The substitution of one amino acid (valine) for the normal one (glutamic acid) at a particular position in the primary structure of hemoglobin, the protein that carries oxygen in red blood cells, can cause sickle-cell disease, an inherited blood disorder.

         The abnormal hemoglobins crystallize, deforming the red blood cells into a sickle shape and clogging capillaries.

        Most proteins have segments of their polypeptide chains repeatedly coiled or folded.

        These coils and folds are referred to as secondary structure and result from hydrogen bonds between the repeating constituents of the polypeptide backbone.

         The weakly positive hydrogen atom attached to the nitrogen atom has an affinity for the oxygen atom of a nearby peptide bond.

         Each hydrogen bond is weak, but the sum of many hydrogen bonds stabilizes the structure of part of the protein.

        Typical secondary structures are coils (an alpha helix) or folds (beta pleated sheets).

        The structural properties of silk are due to beta pleated sheets.

         The presence of so many hydrogen bonds makes each silk fiber stronger than a steel strand of the same weight.

        Tertiary structure is determined by interactions among various R groups.

         These interactions include hydrogen bonds between polar and/or charged areas, ionic bonds between charged R groups, and hydrophobic interactions and van der Waals interactions among hydrophobic R groups.

         While these three interactions are relatively weak, strong covalent bonds called disulfide bridges that form between the sulfhydryl groups (SH) of two cysteine monomers act to rivet parts of the protein together.

        Quaternary structure results from the aggregation of two or more polypeptide subunits.

         Collagen is a fibrous protein of three polypeptides that are supercoiled like a rope.

         This provides structural strength for collagen’s role in connective tissue.

         Hemoglobin is a globular protein with quaternary structure.

         It consists of four polypeptide subunits: two alpha and two beta chains.

         Both types of subunits consist primarily of alpha-helical secondary structure.

         Each subunit has a nonpeptide heme component with an iron atom that binds oxygen.

        What are the key factors determining protein conformation?

        A polypeptide chain of a given amino acid sequence can spontaneously arrange itself into a 3D shape determined and maintained by the interactions responsible for secondary and tertiary structure.

         The folding occurs as the protein is being synthesized within the cell.

        However, protein conformation also depends on the physical and chemical conditions of the protein’s environment.

         Alterations in pH, salt concentration, temperature, or other factors can unravel or denature a protein.

         These forces disrupt the hydrogen bonds, ionic bonds, and disulfide bridges that maintain the protein’s shape.

        Most proteins become denatured if the are transferred to an organic solvent. The polypeptide chain refolds so that its hydrophobic regions face outward, toward the solvent.

        Denaturation can also be caused by heat, which disrupts the weak interactions that stabilize conformation.

         This explains why extremely high fevers can be fatal. Proteins in the blood become denatured by the high body temperatures.

        Some proteins can return to their functional shape after denaturation, but others cannot, especially in the crowded environment of the cell.

        Biochemists now know the amino acid sequences of more than 875,000 proteins and the 3D shapes of about 7,000.

         Nevertheless, it is still difficult to predict the conformation of a protein from its primary structure alone.

        Most proteins appear to undergo several intermediate stages before reaching their “mature” configuration.

        The folding of many proteins is assisted by chaperonins or chaperone proteins.

         Chaperonins do not specify the final structure of a polypeptide but rather work to segregate and protect the polypeptide while it folds spontaneously.

        At present, scientists use X-ray crystallography to determine protein conformation.

        This technique requires the formation of a crystal of the protein being studied.

        The pattern of diffraction of an X-ray by the atoms of the crystal can be used to determine the location of the atoms and to build a computer model of its structure.

        Nuclear magnetic resonance (NMR) spectroscopy has recently been applied to this problem.

         This method does not require protein crystallization.

Nucleic acids store and transmit hereditary information

        The amino acid sequence of a polypeptide is programmed by a unit of inheritance known as a gene.

        A gene consists of DNA, a polymer known as a nucleic acid.

 There are two types of nucleic acids: RNA and DNA.

        There are two types of nucleic acids: ribonucleic acid (RNA) and deoxyribonucleic acid (DNA).

         These are the molecules that allow living organisms to reproduce their complex components from generation to generation.

        DNA provides directions for its own replication.

        DNA also directs RNA synthesis and, through RNA, controls protein synthesis.

        Organisms inherit DNA from their parents.

         Each DNA molecule is very long, consisting of hundreds to thousands of genes.

         Before a cell reproduces itself by dividing, its DNA is copied. The copies are then passed to the next generation of cells.

        While DNA encodes the information that programs all the cell’s activities, it is not directly involved in the day-to-day operations of the cell.

         Proteins are responsible for implementing the instructions contained in DNA.

        Each gene along a DNA molecule directs the synthesis of a specific type of messenger RNA molecule (mRNA).

        The mRNA molecule interacts with the cell’s protein-synthesizing machinery to direct the ordering of amino acids in a polypeptide.

        The flow of genetic information is from DNA -> RNA -> protein.

        Protein synthesis occurs on cellular structures called ribosomes.

        In eukaryotes, DNA is located in the nucleus, but most ribosomes are in the cytoplasm. mRNA functions as an intermediary, moving information and directions from the nucleus to the cytoplasm.

        Prokaryotes lack nuclei but still use RNA as an intermediary to carry a message from DNA to the ribosomes.

 A nucleic acid strand is a polymer of nucleotides.

        Nucleic acids are polymers made of nucleotide monomers.

        Each nucleotide consists of three parts: a nitrogenous base, a pentose sugar, and a phosphate group.

        The nitrogen bases are rings of carbon and nitrogen that come in two types: purines and pyrimidines.

         Pyrimidines have a single six-membered ring.

         There are three different pyrimidines: cytosine (C), thymine (T), and uracil (U).

         Purines have a six-membered ring joined to a five-membered ring.

         The two purines are adenine (A) and guanine (G).

        The pentose joined to the nitrogen base is ribose in nucleotides of RNA and deoxyribose in DNA.

         The only difference between the sugars is the lack of an oxygen atom on carbon two in deoxyribose.

         Because the atoms in both the nitrogenous base and the sugar are numbered, the sugar atoms have a prime after the number to distinguish them.

         Thus, the second carbon in the sugar ring is the 2’ (2 prime) carbon and the carbon that sticks up from the ring is the 5’ carbon.

         The combination of a pentose and a nitrogenous base is a nucleoside.

        The addition of a phosphate group creates a nucleoside monophosphate or nucleotide.

        Polynucleotides are synthesized when adjacent nucleotides are joined by covalent bonds called phosphodiester linkages that form between the —OH group on the 3’ of one nucleotide and the phosphate on the 5’ carbon of the next.

         This creates a repeating backbone of sugar-phosphate units, with appendages consisting of the nitrogenous bases.

        The two free ends of the polymer are distinct.

         One end has a phosphate attached to a 5’ carbon; this is the 5’ end.

         The other end has a hydroxyl group on a 3’ carbon; this is the 3’ end.

        The sequence of bases along a DNA or mRNA polymer is unique for each gene.

         Because genes are normally hundreds to thousands of nucleotides long, the number of possible base combinations is virtually limitless.

        The linear order of bases in a gene specifies the order of amino acids—the primary structure—of a protein, which in turn determines three-dimensional conformation and function.

 Inheritance is based on replication of the DNA double helix.

        An RNA molecule is a single polynucleotide chain.

        DNA molecules have two polynucleotide strands that spiral around an imaginary axis to form a double helix.

         The double helix was first proposed as the structure of DNA in 1953 by James Watson and Francis Crick.

        The sugar-phosphate backbones of the two polynucleotides are on the outside of the helix.

         The two backbones run in opposite 5’ -> 3’ directions from each other, an arrangement referred to as antiparallel.

        Pairs of nitrogenous bases, one from each strand, connect the polynucleotide chains with hydrogen bonds.

        Most DNA molecules have thousands to millions of base pairs.

        Because of their shapes, only some bases are compatible with each other.

         Adenine (A) always pairs with thymine (T) and guanine (G) with cytosine (C).

        With these base-pairing rules, if we know the sequence of bases on one strand, we know the sequence on the opposite strand.

         The two strands are complementary.

        Prior to cell division, each of the strands serves as a template to order nucleotides into a new complementary strand.

         This results in two identical copies of the original double-stranded DNA molecule, which are then distributed to the daughter cells.

        This mechanism ensures that a full set of genetic information is transmitted whenever a cell reproduces.

 

Stress-Strain Behavior

The description of stress-strain behavior is similar to that of metals, but a very important consideration for polymers is that the mechanical properties depend on the strain rate, temperature, and environmental conditions.

The stress-strain behavior can be brittle, plastic and highly elastic (elastomeric or rubber-like). Tensile modulus (modulus) and tensile strengths are orders of magnitude smaller than those of metals, but elongation can be up to 1000 % in some cases. The tensile strength is defined at the fracture point and can be lower than the yield strength.

Mechanical properties change dramatically with temperature, going from glass-like brittle behavior at low temperatures (like in the liquid-nitrogen demonstration) to a rubber-like behavior at high temperatures.

In general, decreasing the strain rate has the same influence on the strain-strength characteristics as increasing the temperature: the material becomes softer and more ductile.

Deformation of Semicrystalline Polymers

Many semicrystalline polymers have the spherulitic structure and deform in the following steps:

·      elongation of amorphous tie chains

·      tilting of lamellar chain folds towards the tensile direction

·      separation of crystalline block segments

·      orientation of segments and tie chains in the tensile direction

The macroscopic deformation involves an upper and lower yield point and necking. Unlike the case of metals, the neck gets stronger since the deformation aligns the chains so increasing the tensile stress leads to the growth of the neck.

Factors that Influence the Mechanical Properties of Polymers

The tensile modulus decreases with increasing temperature or diminishing strain rate. 

Obstacles to the steps mentioned in 16.4 strengthen the polymer. Examples are cross-linking (aligned chains have more van der Waals inter-chain bonds) and a large mass (longer molecules have more inter-chain bonds). Crystallinity increases strength as the secondary bonding is enhanced when the molecular chains are closely packed and parallel. Pre-deformation by drawing, analogous to strain hardening in metals, increases strength by orienting the molecular chains.  For undrawn polymers, heating increases the tensile modulus and yield strength, and reduces the ductility – opposite of what happens in metals. 

Crystallization, Melting, and Glass Transition Phenomena

Crystallization rates are governed by the same type of S-curves we saw in the case of metals. Nucleation becomes slower at higher temperatures.

The melting behavior of semicrystalline polymers is intermediate between that of crystalline materials (sharp density change at a melting temperature) and that of a pure amorphous material (slight change in slope of density at the glass-transition temperature). The glass transition temperature is between 0.5 and 0.8 of the melting temperature.

The melting temperature increases with the rate of heating, thickness of the lamellae, and depends on the temperature at which the polymer was crystallized.

Melting involves breaking of the inter-chain bonds, so the glass and melting temperatures depend on:

·      chain stiffness (e.g., single vs. double bonds)

·      size, shape of side groups

·      size of molecule

·      side branches, defects

·      cross-linking

Rigid chains have higher melting temperatures.

Thermal Properties of Polymers

Polymer Glass Transition

In the study of polymers and their applications, it is important to understand the concept of the glass transition temperature, T_g. As the temperature of a polymer drops below T_g, it behaves in an increasingly brittle manner. As the temperature rises above the T_g, the polymer becomes more rubber-like. Thus, knowledge of T_gis essential in the selection of materials for various applications. In general, values of T_g well below room temperature define the domain of elastomers and values above room temperature define rigid, structural polymers.

This behavior can be understood in terms of the structure of glassy materials which are formed typically by substances containing long chains, networks of linked atoms or those that possess a complex molecular structure. Normally such materials have a high viscosity in the liquid state. When rapid cooling occurs to a temperature at which the crystalline state is expected to be the more stable, molecular movement is too sluggish or the geometry too awkward to take up acrystalline conformation. Therefore the random arrangement characteristic of the liquid persists down to temperatures at which the viscosity is so high that the material is considered to be solid. The term glassy has come to be synonymous with a persistent non-equilibrium state. In fact, a path to the state of lowest energy might not be available.

To become more quantitative about the characterization of the liquid-glass transition phenomenon and T_g, we note that in cooling an amorphous material from the liquid state, there is no abrupt change in volume such as occurs in the case of cooling of a crystalline material through its freezing point, T_f. Instead, at the glass transition temperature, T_g, there is a change in slope of the curve of specific volume vs. temperature, moving from a low value in the glassy state to a higher value in the rubbery state over a range of temperatures. This comparison between a crystalline material (1) and an amorphous material (2) is illustrated in the figure below. Note that the intersections of the two straight line segments of curve (2) defines the quantity T_g.

The specific volume measurements shown here, made on an amorphous polymer (2), are carried out in a dilatometer at a slow heating rate. In this apparatus, a sample is placed in a glass bulb and a confining liquid, usually mercury, is introduced into the bulb so that the liquid surrounds the sample and extends partway up a narrow bore glass capillary tube. A capillary tube is used so that relatively small changes in polymer volume caused by changing the temperature produce easily measured changes in the height of the mercury in the capillary.

The determination of T_g for amorphous materials, including polymers as mentioned above, by dilatometric methods (as well as by other methods) are found to be rate dependent. This is schematically illustrated in the figure below, again representing an amorphous polymer, where the higher value, T_g2, is obtained with a substantially higher cooling rate than for T_g1.

We can understand this rate dependence in terms of intermolecular relaxation processes. Since a glass is not an equilibrium phase, its properties will exhibit a time dependence, or physical aging. The primary portion of the relaxation behavior governing the glass transition in polymers can be related to their tangled chain structure where cooperative molecular motion is required for internal readjustments. At temperatures well above T_g, 10 to 50 repeat units of the polymer backbone are relatively free to move in cooperative thermal motion to provide conformational rearrangement of the backbone. Below T_g, the motion of these individual chains segments becomes frozen with only small scale molecular motion remaining, involving individual or small groups of atoms. Thus a rapid cooling rate or “quench” takes rubbery material into glassy behavior at higher temperatures (higher T_g).

While the dilatometer method is the more precise method of determining the glass transition temperature, it is a rather tedious experimental procedure and measurements of Tg are often made in a differential scanning calorimeter (DSC). In this instrument, the heat flow into or out of a small (10 – 20 mg) sample is measured as the sample is subjected to a programmed linear temperature change. This will be discussed in the next section. There are other methods of measurement such as density, dielectric constant and elastic modulus which are treated in texts on polymers. These methods are, of course, also rate dependent.

T_g and Mechanical Properties

Another important property of polymers, also strongly dependent on their temperatures, is their response to the application of a force, as indicated by two main types of behavior: elastic and plastic. Elastic materials will return to their original shape once the force is removed. Plastic materials will not regain their shape. In plastic materials, flow is occurring, much like a highly viscous liquid. Most materials demonstrate a combination of elastic and plastic behavior, showing plastic behavior after the elastic limit has been exceeded.

Glass is one of the few completely elastic materials while it is below its T_g. It will remain elastic until it reaches its breaking point. The T_g of glass occurs between 510 and 560 degrees C, meaning that it will always be a brittle solid at room temperature. In comparison, polyvinyl chloride (PVC) has a T_g of 83 degrees C, making it good, for example, for cold water pipes, but unsuitable for hot water. PVC also will always be a brittle solid at room temperature.

Adding a small amount of plasticizer to PVC can lower the T_g to – 40 degrees C. This addition renders the PVC a soft, flexible material at room temperature, ideal for applications such as garden hoses. A plasticized PVC hose can, however, become stiff and brittle in winter. In this case, as in any other, the relation of the T_g to the ambient temperature is what determines the choice of a given material in a particular application.

A striking example of the rate dependence of these viscoelastic properties is furnished by Silly Putty. Slowly pulling on two parts of the Silly Putty stretches it apart until it very slowly separates. Placing the Silly Putty on a table and hitting it with a hammer will shatter it.

The above images are representative of the behavior of a material above and below its glass transition temperature. The image on the (left) is Silly Putty that has been slowly stretched. The image on the (right) is Silly Putty which has been hit with a hammer. The speed of the hammer raised the rate of the application of the force and in turn raised the T_g. This caused the Silly Putty to react as if it were below its T_g and to shatter. Even though both reactions took place at the same ambient temperature, one reaction appeared to be above the effective T_g and the other appeared to be below.

Our focus has been on amorphous polymers in the preceding discussion but we have hardly touched on their mechanical properties. A further complication arises in dealing with general polymers from their semi-crystalline morphology in which amorphous regions and crystalline regions are intermingled. This gives rise to a mixed behavior depending on the percent crystallinity and on their temperature, relative to T_g of the amorphous regions. You are referred to texts on polymer science for basic discussion of these topic but the inhomogeneity of the material and its characteristics presents interesting analytical challenges.

Differential Scanning Calorimetry

In differential scanning calorimetry (DSC), the thermal properties of a sample are compared against a standard reference material which has no transition in the temperature range of interest, such as powdered alumina. Each is contained in a small holder within an adiabatic enclosure as illustrated below.

The temperature of each holder is monitored by a thermocouple and heat can be supplied electrically to each holder to keep the temperature of the two equal. A plot of the difference in energy supplied to the sample against the average temperature, as the latter is slowly increased through one or more thermal transitions of the sample yields important information about the transition, such as latent heat or a relatively abrupt change in heat capacity.

The glass transition process is illustrated in the figure below for a glassy polymer which does not crystallize and is being slowly heated from below T_g.

 

Here, the drop marked T_g at its midpoint represents the increase in energy supplied to the sample to maintain it at the same temperature as the reference material, due to the relatively rapid increase in the heat capacity of the sample as its temperature is raised through T_g. The addition of heat energy corresponds to this endothermal direction.

A melting process is also illustrated below for the case of a highly crystalline polymer which is slowly heated through its melting temperature:

Again, as the melting temperature is reached, an endothermal peak appears because heat must be preferentially added to the sample to continue this essentially constant temperature process. The peak breadth is primarily related to the size and degree of perfection of the polymer crystals.

Note that if the process were reversed so that the sample were being cooled from the melt, the plot would be inverted. In that case, as both are being cooled by ambient conditions, even less heat would need to be supplied to the sample than to the reference material, in order that crystals can form. This corresponds to an exothermal process.

Use of the DSC will be illustrated again in the section on liquid crystals in connection with the identification of their phase transitions. An interesting exercise for the reader would be to predict the general form of a DSC plot for a semicrystalline polymer which has been rapidly quenched from the melt to a temperature below T_g. In the DSC plot, assume the temperature is slowly increased from this value below T_g to a value well above, thus allowing for significant increases in the chain mobility as temperatures above T_g are reached so that some crystallization can begin, well before the melting point is reached.

 

Thermoplastic and Thermosetting Polymers

Thermoplastic polymers (thermoplasts) soften reversibly when heated (harden when cooled back)

Thermosetting polymers (thermosets) harden permanently when heated, as cross-linking hinder bending and rotations. Thermosets are harder, more dimensionally stable, and more brittle than thermoplasts.

Viscoelasticity

At low temperatures, amorphous polymers deform elastically, like glass, at small elongation. At high temperatures the behavior is viscous, like liquids. At intermediate temperatures, the behavior, like a rubbery solid, is termed viscoelastic.

Viscoelasticity is characterized by the viscoelastic relaxation modulus

    E_r = s(t)/e₀.

If the material is strained to a value e_0.it is found that the stress needs to be reduced with time to maintain this constant value of strain (see figs. 16.11 and 16.12).

In viscoelastic creep, the stress is kept constant at s₀ and the change of deformation with time e(t) is measured. The time-dependent creep modulus is given by

    E_c = s₀/e(t).

16.8 Deformation and Elastomers

Elastomers can be deformed to very large strains and the spring back elastically to the original length, a behavior first observed iatural rubber. Elastic elongation is due to uncoiling, untwisting and straightening of chains in the stress direction.

To be elastomeric, the polymer needs to meet several criteria:

·      must not crystallize easily

·      have relatively free chain rotations

·      delayed plastic deformation by cross-linking (achieved by vulcanization).

·      be above the glass transition temperature

16.9 Fracture of Polymers

As other mechanical properties, the fracture strength of polymers is much lower than that of metals. Fracture also starts with cracks at flaws, scratches, etc. Fracture involves breaking of covalent bonds in the chains. Thermoplasts can have both brittle and ductile fracture behaviors. Glassy thermosets have brittle fracture at low temperatures and ductile fracture at high temperatures.

Glassy thremoplasts often suffer grazing before brittle fracture. Crazes are associated with regions of highly localized yielding which leads to the formation of interconnected microvoids (Fig. 16.15). Crazing absorbs energy thus increasing the fracture strength of the polymer.

16.10 Miscellaneous Characteristics

Polymers are brittle at low temperatures and have low impact strengths (Izod or Charpy tests), and a brittle to ductile transition over a narrow temperature range.

Fatigue is similar to the case of metals but at reduced loads and is more sensitive to frequency due to heating which leads to softening.

16.11 Polymerization

Polymerization is the synthesis of high polymers from raw materials like oil or coal. It may occur by:

·      addition (chain-reaction) polymerization, where monomer units are attached one at a time

·      condensation polymerization, by stepwise intermolecular chemical reactions that produce the mer units.

16.12 – 16.14 – not covered

16.15 Elastomers

In vulcanization, crosslinking of the elastomeric polymer is achieved by an irreversible chemical reaction usually at high temperatures (hence ‘vulcan’), and usually involving the addition of sulfur compounds. The S atoms are the ones that form the bridge cross-links. Elastomers are thermosetting due to the cross-linking.

Rubbers become harder and extend less with increasing sulfur content. For automobile applications, synthetic rubbers are strengthened by adding carbon black.

In silicone rubbers, the backbone C atoms are replaced by a chain of alternating silicon and oxygen atoms. These elastomers are also cross-linked and are stable to higher temperatures than C-based elastomers.

 Superabsorbent polymer

Superabsorbent polymers (SAP) (also called slush powder) are polymers that can absorb and retain extremely large amounts of a liquid relative to their own mass.

Water absorbing polymers, which are classified as hydrogels when cross-linked, absorb aqueous solutions through hydrogen bonding with water molecules. A SAP’s ability to absorb water is a factor of the ionic concentration of the aqueous solution. In deionized and distilled water, a SAP may absorb 500 times its weight (from 30–60 times its own volume) and can become up to 99.9% liquid, but when put into a 0.9% saline solution, the absorbency drops to maybe 50 times its weight. The presence of valence cations in the solution will impede the polymer’s ability to bond with the water molecule.

The total absorbency and swelling capacity are controlled by the type and degree of cross-linkers used to make the gel. Low density cross-linked SAP generally have a higher absorbent capacity and swell to a larger degree. These types of SAPs also have a softer and more sticky gel formation. High cross-link density polymers exhibit lower absorbent capacity and swell, but the gel strength is firmer and can maintain particle shape even under modest pressure.

The largest use of SAP is found in personal disposable hygiene products, such as baby diapers, adult protective underwear and sanitary napkins. SAP was discontinued from use in tampons due to 1980s concern over a link with toxic shock syndrome. SAP is also used for blocking water penetration in underground power or communications cable, horticultural water retention agents, control of spill and waste aqueous fluid, artificial snow for motion picture and stage production. The first commercial use was in 1978 for use in feminine napkins in Japan and disposable bed liners for nursing home patients in the USA.

History

Until the 1980s, water absorbing materials were cellulosic or fiber-based products. Choices were tissue paper, cotton, sponge, and fluff pulp. The water absorbent capacity of these types of materials is only up to 11 times their weight, but most of it is lost under moderate pressure.

In the early 1960s, the United States Department of Agriculture (USDA) was conducting work on materials to improve water conservation in soils. They developed a resin based on the grafting of acrylonitrile polymer onto the backbone of starch molecules (i.e. starch-grafting). The hydrolyzed product of the hydrolysis of this starch-acrylonitrile co-polymer gave water absorption greater than 400 times its weight. Also, the gel did not release liquid water the way that fiber-based absorbents do.

The polymer came to be known as “Super Slurper”. The USDA gave the technical know-how to several USA companies for further development of the basic technology. A wide range of grafting combinations were attempted including work with acrylic acid, acrylamide and polyvinyl alcohol (PVA).^[4]

Polyacrylate/polyacrylamide copolymers were originally designed for use in conditions with high electrolyte/mineral content and a need for long term stability including numerous wet/dry cycles. Uses include agricultural and horticultural. With the added strength of the acrylamide monomer, used as medical spill control, wire & cable water blocking

Current synthesis

Copolymer chemistry

Superabsorbent polymers are now commonly made from the polymerization of acrylic acid blended with sodium hydroxide in the presence of an initiator to form a poly-acrylic acid sodium salt (sometimes referred to as sodium polyacrylate). This polymer is the most common type of SAP made in the world today.

Other materials are also used to make a superabsorbent polymer, such as polyacrylamide copolymer, ethylene maleic anhydride copolymer, cross-linked carboxymethylcellulose, polyvinyl alcohol copolymers, cross-linked polyethylene oxide, and starch grafted copolymer of polyacrylonitrile to name a few. The latter is one of the oldest SAP forms created.

Today superabsorbent polymers are made using one of three primary methods; gel polymerization, suspension polymerization or solution polymerization. Each of the processes have their respective advantages but all yield a consistent quality of product.

Gel polymerization

A mixture of frozen acrylic acid, water, cross-linking agents and UV initiator chemicals are blended and placed either on a moving belt or in large tubs. The liquid mixture then goes into a “reactor” which is a long chamber with a series of strong UV lights. The UV radiation drives the polymerization and cross-linking reactions. The resulting “logs” are sticky gels containing 60-70% water. The logs are shredded or ground and placed in various sorts of driers. Additional cross-linking agent may be sprayed on the particles’ surface; this “surface cross-linking” increases the product’s ability to swell under pressure — a property measured as Absorbency Under Load (AUL) or Absorbency Against Pressure (AAP). The dried polymer particles are then screened for proper particle size distribution and packaging. The gel polymerization (GP) method is currently the most popular method for making the sodium polyacrylate superabsorbent polymers now used in baby diapers and other disposable hygienic articles.

Solution polymerization

Solution polymers offer the absorbency of a granular polymer supplied in solution form. Solutions can be diluted with water prior to application. Can coat most substrates or used to saturated. After drying at a specific temperature for a specific time, the result is a coated substrate with superabsorbent functionality. For example, this chemistry can be applied directly onto wires & cables, though it is especially optimized for use on components such as rolled goods or sheeted substrates.

Solution based polymerization is commonly used today for SAP manufacture of co-polymers — particularly those with the toxic acrylamide monomer. This process is efficient and generally has a lower capital cost base. The solution process uses a water based monomer solution to produce a mass of reactant polymerized gel. The polymerization’s own reaction energy (exothermic) is used to drive much of the process, helping reduce manufacturing cost. The reactant polymer gel is then chopped, dried and ground to its final granule size. Any treatments to enhance performance characteristics of the SAP are usually accomplished after the final granule size is created.

Suspension polymerization

The suspension process is practiced by only a few companies because it requires a higher degree of production control and product engineering during the polymerization step. This process suspends the water-based reactant in a hydrocarbon-based solvent. The net result is that the suspension polymerization creates the primary polymer particle in the reactor rather than mechanically in post-reaction stages. Performance enhancements can also be made during, or just after, the reaction stage.

Composition

Gels consist of a solid three-dimensional network that spans the volume of a liquid medium and ensnares it through surface tension effects. This internal network structure may result from physical bonds (physical gels) or chemical bonds (chemical gels), as well as crystallites or other junctions that remain intact within the extending fluid. Virtually any fluid can be used as an extender including water (hydrogels), oil, and air (aerogel). Both by weight and volume, gels are mostly fluid in composition and thus exhibit densities similar to those of their constituent liquids. Edible jelly is a common example of a hydrogel and has approximately the density of water.

Cationic polymers

Cationic polymers are positively charged polymers. Their positive charges prevent the formation of coiled polymers. This allows them to contribute more to viscosity in their stretched state, because the stretched-out polymer takes up more space. Gel is a colloid solution of dispersion phase as liquid and dispersion medium as solid.

Types of gels

Hydrogels

Hydrogel is a network of polymer chains that are hydrophilic, sometimes found as a colloidal gel in which water is the dispersion medium. Hydrogels are highly absorbent (they can contain over 99.9% water) natural or synthetic polymers. Hydrogels also possess a degree of flexibility very similar to natural tissue, due to their significant water content. Common uses for hydrogels include

·      currently used as scaffolds in tissue engineering. When used as scaffolds, hydrogels may contain human cells to repair tissue.

·      hydrogel-coated wells have been used for cell culture

·      environmentally sensitive hydrogels which are also known as ‘Smart Gels’ or ‘Intelligent Gels’. These hydrogels have the ability to sense changes of pH, temperature, or the concentration of metabolite and release their load as result of such a change.

·      as sustained-release drug delivery systems.

·      provide absorption, desloughing and debriding of necrotic and fibrotic tissue.

·      hydrogels that are responsive to specific molecules, such as glucose or antigens, can be used as biosensors, as well as in DDS.

·      used in disposable diapers where they absorb urine, or in sanitary napkins

·      contact lenses (silicone hydrogels, polyacrylamides)

·      EEG and ECG medical electrodes using hydrogels composed of cross-linked polymers (polyethylene oxide, polyAMPS and polyvinylpyrrolidone)

·      water gel explosives

·      rectal drug delivery and diagnosis

Other, less common uses include

·      breast implants

·      now used in glue.

·      granules for holding soil moisture in arid areas

·      dressings for healing of burn or other hard-to-heal wounds. Wound gels are excellent for helping to create or maintain a moist environment.

·      reservoirs in topical drug delivery; particularly ionic drugs, delivered by iontophoresis (see ion exchange resin)

Common ingredients are e.g. polyvinyl alcohol, sodium polyacrylate, acrylate polymers and copolymers with an abundance of hydrophilic groups.

Natural hydrogel materials are being investigated for tissue engineering; these materials include agarose, methylcellulose, hyaluronan, and other naturally derived polymers.

Organogels

An organogel is a non-crystalline, non-glassy thermoreversible (thermoplastic) solid material composed of a liquid organic phase entrapped in a three-dimensionally cross-linked network. The liquid can be, for example, an organic solvent, mineral oil, or vegetable oil. The solubility and particle dimensions of the structurant are important characteristics for the elastic properties and firmness of the organogel. Often, these systems are based on self-assembly of the structurant molecules.

Organogels have potential for use in a number of applications, such as in pharmaceuticals, cosmetics, art conservation, and food. An example of formation of an undesired thermoreversible network is the occurrence of wax crystallization in petroleum.

Xerogels

A xerogel is a solid formed from a gel by drying with unhindered shrinkage. Xerogels usually retain high porosity (15-50%) and enormous surface area (150–900 m²/g), along with very small pore size (1-10 nm). When solvent removal occurs under hypercritical (supercritical) conditions, the network does not shrink and a highly porous, low-density material known as an aerogel is produced. Heat treatment of a xerogel at elevated temperature produces viscous sintering (shrinkage of the xerogel due to a small amount of viscous flow) and effectively transforms the porous gel into a dense glass.

Properties

Many gels display thixotropy – they become fluid when agitated, but resolidify when resting. In general, gels are apparently solid, jelly-like materials. By replacing the liquid with gas it is possible to prepare aerogels, materials with exceptional properties including very low density, high specific surface areas, and excellent thermal insulation properties.

Naturally occurring gels in the animal kingdom

Some species secrete gels that are effective in parasite control. For example, the long-finned pilot whale secretes an enzymatic gel that rests on the outer surface of this animal and helps prevent other organisms from establishing colonies on the surface of these whales’ bodies.

Applications

Many substances can form gels when a suitable thickener or gelling agent is added to their formula. This approach is common in manufacture of wide range of products, from foods to paints and adhesives.

In fiber optics communications, a soft gel resembling “hair gel” in viscosity is used to fill the plastic tubes containing the fibers. The main purpose of the gel is to prevent water intrusion if the buffer tube is breached, but the gel also buffers the fibers against mechanical damage when the tube is bent around corners during installation, or flexed. Additionally, the gel acts as a processing aid when the cable is being constructed, keeping the fibers central whilst the tube material is extruded around it.

Hydrogels existing naturally in the body include mucus, the vitreous humor of the eye, cartilage, tendons and blood clots. Their viscoelastic nature results in the soft tissue component of the body, disparate from the mineral-based hard tissue of the skeletal system. Researchers are actively developing synthetically derived tissue replacement technologies derived from hydrogels, for both temporary implants (degradable) and permanent implants (non-degradable). A review article on the subject discusses the use of hydrogels for nucleus pulposus replacement, cartilage replacement, and synthetic tissue models.

Thixotropy is shear thinning property. Certain gels or fluids that are thick (viscous) under normal conditions flow (become thin, less viscous) over time when shaken, agitated, or otherwise stressed. They then take a fixed time to return to a more viscous state. In more technical language: some non-Newtonian pseudoplastic fluids show a time-dependent change in viscosity; the longer the fluid undergoes shear stress, the lower its viscosity. A thixotropic fluid is a fluid which takes a finite time to attain equilibrium viscosity when introduced to a step change in shear rate. Some thixotropic fluids return to a gel state almost instantly, such as ketchup, and are called pseudoplastic fluids. Others such as yogurt take much longer and can become nearly solid. Many gels and colloids are thixotropic materials, exhibiting a stable form at rest but becoming fluid when agitated.

Some fluids are anti-thixotropic: constant shear stress for a time causes an increase in viscosity or even solidification. Constant shear stress can be applied by shaking or mixing. Fluids which exhibit this property are usually called rheopectic. They are much less common.

Natural examples

Some clays are thixotropic, with their behavior of great importance in structural and geotechnical engineering. Landslides, such as those common in the cliffs around Lyme Regis, Dorset and in the Aberfan spoil tip disaster in Wales are evidence of this phenomenon. Similarly, a lahar is a mass of earth liquefied by a volcanic event, which rapidly solidifies once coming to rest.

Drilling muds used in geotechnical applications can be thixotropic. Honey from honey bees may also exhibit this property under certain conditions.(heather honey).

Another example of a thixotropic fluid is the synovial fluid found in joints between some bones. The ground substance in the human body is thixotropic, as is semen.

Some clay deposits found in the process of exploring caves exhibit thixotropism: an initially solid-seeming mudbank will turn soupy and yield up moisture when dug into or otherwise disturbed. These clays were deposited in the past by low-velocity streams which tend to deposit fine-grained sediment.

A thixotropic fluid is best visualised by an oar blade embedded in mud. Pressure on the oar often results in a highly viscous (more solid) thixotropic mud on the high pressure side of the blade, and low viscosity (very fluid) thixotropic mud on the low pressure side of the oar blade. Flow from the high pressure side to the low pressure side of the oar blade is non-Newtonian. (i.e.: fluid velocity is not proportional to the square root of the pressure differential over the oar blade).

Applications

Thread-locking fluid is a thixotropic adhesive that cures anaerobically.

Thixotropy has been proposed as a scientific explanation of blood liquefaction miracles such as that of Saint Januarius in Naples.

Semi-solid casting processes such as thixomoulding use the thixotropic property of some alloys (mostly light metals) (bismuth). Within certain temperature ranges, with appropriate preparation, an alloy can be put into a semi-solid state, which can be injected with less shrinkage and better overall properties than by normal injection molding.

Solder pastes used in electronics manufacturing printing processes are thixotropic.

Many kinds of inks—used in silkscreen textile printing—made from plastisol, exhibit thixotropic qualities. Some, such as those used in CMYK-type process printing, are designed to quickly regain viscosity once they are applied to protect the structure of the dots for accurate color reproduction.

The swelling capacity of a polymer is determined by the amount of liquid material that can be absorbed. This test can done by two methods:

1.  Beaker test method

2.  Tea bag test method

Beaker test method

In this method

·      A small amount of superabsorbent polymer material is taken (0.1g) and it is placed in the beaker.

·      100 ml of doionised water is poured into the beaker.

·      After 20 min the swollen polymer was separated by using filter paper

·      By weighing the polymer, one can find the swollen capacity of the SAP material.

Tea bag test method

·      In this method, Take 0.1g of SAP material and put the bag suspended over the excess watered beaker.

·      Note the time 20 min. And weigh the bag and we calculate the percentage of swelling through the following formula:

(w2-w1)/(w1)  %

w1= weight of the polymer (Before swelling)

w2= weight of the polymer (After swelling)

·      Note: Filter paper only for removing water.

Suspension is a heterogeneous mixture containing solid particles that are sufficiently large for sedimentation. Usually they must be larger than 1 micrometer.  The internal phase (solid) is dispersed throughout the external phase (fluid) through mechanical agitation, with the use of certain excipients or suspending agents. Unlike colloids, suspensions will eventually settle. An example of a suspension would be sand in water. The suspended particles are visible under a microscope and will settle over time if left undisturbed. This distinguishes a suspension from a colloid, in which the suspended particles are smaller and do not settle.^[2] Colloids and suspensions are different from solutions, in which the dissolved substance (solute) does not exist as a solid, and solvent and solute are homogeneously mixed.

A suspension of liquid droplets or fine solid particles in a gas is called an aerosol or particulate. In the atmosphere these consist of fine dust and soot particles, sea salt, biogenic and volcanogenic sulfates, nitrates, and cloud droplets.

Suspensions are classified on the basis of the dispersed phase and the dispersion medium, where the former is essentially solid while the latter may either be a solid, a liquid, or a gas.

In modern chemical process industries, high shear mixing technology has been used to create many novel suspensions.

Suspensions are unstable from the thermodynamic point of view; however, they can be kinetically stable over a large period of time, which determines their shelf life. This time span needs to be measured to ensure the best product quality to the final consumer. “Dispersion stability refers to the ability of a dispersion to resist change in its properties over time.” D.J. McClements.

Technique monitoring physical stability

Multiple light scattering coupled with vertical scanning is the most widely used technique to monitor the dispersion state of a product, hence identifying and quantifying destabilization phenomena. It works on concentrated dispersions without dilution. When light is sent through the sample, it is back scattered by the particles. The backscattering intensity is directly proportional to the size and volume fraction of the dispersed phase. Therefore, local changes in concentration (sedimentation) and global changes in size (flocculation, aggregation) are detected and monitored.

Accelerating methods for shelf life prediction

The kinetic process of destabilisation can be rather long (up to several months or even years for some products) and it is often required for the formulator to use further accelerating methods in order to reach reasonable development time for new product design. Thermal methods are the most commonly used and consists in increasing temperature to accelerate destabilisation (below critical temperatures of phase inversion or chemical degradation). Temperature affects not only the viscosity, but also interfacial tension in the case of non-ionic surfactants or more generally interactions forces inside the system. Storing a dispersion at high temperatures enables simulation of real life conditions for a product (e.g. tube of sunscreen cream in a car in the summer), but also to accelerate destabilisation processes up to 200 times.

Mechanical acceleration including vibration, centrifugation and agitation are sometimes used. They subject the product to different forces that pushes the particles / droplets against one another, hence helping in the film drainage. However, some emulsions would never coalesce iormal gravity, while they do under artificial gravity.^[8] Moreover, segregation of different populations of particles have been highlighted when using centrifugation and vibration.

 

Pharmaceutical Suspension can improve chemical stability of certain drug.

Disadvantages

·         Physical stability,sedimentation and compaction can causes problems.

·         It is bulky sufficient care must be taken during handling and transport.

·         It is difficult to formulate

·         Uniform and accurate dose caot be achieved unless suspension are packed in
unit dosage form

·       1.4 Features Desired In Pharmaceutical Suspensions

·         The suspended particles should not settle rapidly and sediment produced, must be
easily re-suspended by the use of moderate amount of shaking.

·         It should be easy to pour yet not watery and no grittiness.

·         It should have pleasing odour, colour and palatability.

·         Good syringeability.

·       It should be physically, chemically and microbiologically stable.

·        Parenteral/Ophthalmic suspension should be sterilizable.

Applications

·         Suspension is usually applicable for drug which is insoluble or poorly soluble. E.g. Prednisolone suspension

·         To prevent degradation of drug or to improve stability of drug. E.g. Oxytetracycline suspension

·         To mask the taste of bitter of unpleasant drug. E.g. Chloramphenicol palmitate suspension

·         Suspension of drug can be formulated for topical application e.g. Calamine lotion

·         Suspension can be formulated for parentral application in order to control rate of drug absorption.

·         Vaccines as a immunizing agent are often formulated as suspension. E.g. Cholera vaccine

·         X-ray contrast agent are also formulated as suspension. E.g. Barium sulphate for examination of alimentary tract

Formulation Of Pharmaceutical Suspensions

Structured Vehicle

For the need of a stable suspension, the term ‘Structured vehicle’ is most important for formulation view and stability criteria. The main disadvantage of suspension dosage form that limits its use in the routine practice is its stability during storage for a long time. To overcome this problem or to reduce it to some extent, the term ‘Structured vehicle has got importance.

What do you mean by Structured Vehicle?

The structured vehicle is the vehicle in which viscosity of the preparation under the static condition of very low shear on storage approaches infinity. The vehicle behaves like a ‘false body’, which is able to maintain the particles suspended which is more or less stable.

Generally, concept of Structured vehicle is not useful for Parenteral suspension because they may create problem in syringeability due to high viscosity.

In addition, Structured vehicle should posses some degree of Thixotropic behaviour viz., the property of GEL-SOL-GEL transformation. Because during storage it should be remained in the form of GEL to overcome the shear stress and to prevent or reduce the formation of hard cake at the bottom which to some extent is beneficial for pourability and uniform dose at the time of administration.

Preparation Of Structured Vehicle

Structured vehicles are prepared with the help of Hydrocolloids. In a particular medium, they first hydrolyzed and swell to great degree and increase viscosity at the lower concentration. In addition, it can act as a ‘Protective colloid’ and stabilize charge.

Density of structured vehicle also can be increased by: Polyvinylpyrrolidone Sugars Polyethylene glycols Glycerin

The various components, which are used in suspension formulation, are as follows.

Components	Function
API	Active drug substances
Wetting agents	They are added to disperse solids in continuous liquid phase.
Flocculating agents	They are added to floc the drug particles
Thickeners	They are added to increase the viscosity of suspension.
Buffers and pH adjusting agents	They are added to stabilize the suspension to a desired pH range.
Osmotic agents	They are added to adjust osmotic pressure comparable to biological fluid.
Coloring agents	They are added to impart desired color to suspension and improve elegance.
Preservatives	They are added to prevent microbial growth.
External liquid vehicle	They are added to construct structure of the final suspension.

List Of Suspending Agents

Alginates Methylcellulose Carageenan Powdered cellulose Gelatin Hydroxyethylcellulose

Carboxymethylcellulose Sodium Carboxymethylcellulose Microcrystalline cellulose

Acacia Tragacanth Xanthan gum Bentonite Carbomer

Most suspending agents perform two functions i.e. besides acting as a suspending agent they also imparts viscosity to the solution. Suspending agents form film around particle and decrease interparticle attraction.

A good suspension should have well developed thixotropy. At rest the solution is sufficient viscous to prevent sedimentation and thus aggregation or caking of the particles. When agitation is applied the viscosity is reduced and provide good flow characteristic from the mouth of bottle.

For aqueous pharmaceutical compositions containing titanium dioxide as an opacifying agent, only Avicel RTM RC-591 microcrystalline cellulose is found to provide thixotropy to the solution, whereas other suspending agents failed to provide such characteristics to the product. Most of the suspending agents do not satisfactorily suspend titanium dioxide until excessive viscosities are reached. Also they do not providethixotropic gel formulation that is readily converted to a pourable liquid with moderate force for about five seconds.

The suspending agents/density modifying agents used in parenteral suspensions are PVP (polyvinylpyrrolidone), PEG (Polyethylene glycol) 3350 and PEG 4000.⁴

The polyethylene glycols, having molecular weight ranging from 300 to 6000 are suitable as suspending agents for parenteral suspension. However, PEG 3350 and PEG 4000 are most preferably used.

PVPs, having molecular weight ranging from 7000 to 54000 are suitable as suspending agents for parenteral suspension. Examples of these PVPs are PVP K 17, PVP K 12, PVP K 25, PVP K 30. Amongst these K 12 and K17 are most preferred.⁴

The selection of amount of suspending agent is dependent on the presence of other suspending agent, presence or absence of other ingredients which have an ability to act as a suspending agent or which contributes viscosity to the medium.

The stability of the suspensions depends on the types of suspending agents rather than the physical properties of the drugs. They formulated aqueous suspension of three drugs (Griseofulvin, Ibuprofen, Indomethacin). The suspending agents used were Na CMC, MCC/CMC mixer and jota carageenan (CJ). Evaluation of suspension was based on the physical and physico-chemical characteristics of the drugs, the rheological properties of the suspending medium, corresponding drug suspension and the physical and chemical stability of the suspension. They noted that the physical stability of
suspension was mainly dependent on the type of suspending agent rather than the physical characteristics of the drug. The suspending agents which gave highest stability were jota carageenan (having low-temperature gelation characteristics) and MC/CMC (having thixotropic flux).

Stability pH range and coentrations of most commonly used suspending agents.

Suspending agents	Stability pH range	Concentrations used as suspending agent
Sodium alginate	4-10	1 – 5 %
Methylcellulose	3-11	1 – 2 %
Hydroxyethylcellulose	2-12	1-2 %
Hydroxypropylcellulose	6-8	1-2 %
Hydroxypropylmethylcellulose	3-11	1-2 %
CMC	7-9	1-2 %
Na-CMC	5-10	0.1-5 %
Microcrystalline cellulose	1-11	0.6 – 1.5 %
Tragacanth	4-8	1-5%
Xanthangum	3-12	0.05-0.5 %
Bentonite	PH > 6	0.5 – 5.0 %
Carageenan	6-10	0.5 – 1 %
Guar gum	4-10.5	1-5%
Colloidal silicon dioxide	0-7.5	2 – 4 %

Suspending agents also act as thickening agents. They increase in viscosity of the solution, which is necessary to prevent sedimentation of the suspended particles as per Stoke’s’s law. The suspension having a viscosity within the range of 200 -1500 milipoise are readily pourable.

Use of combination of suspending agents may give beneficial action as compared to single suspending agent. For Glafenine, thecombination of 2 % veegum and 2 % sorbitol was best as compared to otherformulation of Glafenine. The physical stability of Mefenamic acid and Flufenamic acid was improved by combining 2 % veegum, 2 % sorbitol and 1 % Avicel. Excellent suspension for Ibuprofen and Azapropazone was observed by combining 1 % veegum, 1 % sorbitol, and 1 % alginate.

References:

 1.The abstract of the lecture.

2. intranet.tdmu.edu.ua/auth.php

3. Atkins P.W. Physical chemistry. – New York. – 1994. – P.299-307.

4. en.wikipedia.org/wiki

5.Girolami, G. S.; Rauchfuss, T. B. and Angelici, R. J., Synthesis and Technique in Inorganic Chemistry, University Science Books: Mill Valley, CA, 1999

6.John B.Russell. General chemistry. New York.1992. – P. 550-599

7. Lawrence D. Didona. Analytical chemistry. – 1992: New York. – P. 218 – 224.

8. http://www.pharmainfo.net/free–books/pharmaceutical–suspensionsa–review

Prepared by PhD Falfushynska H.