DESIGN AND MATERIALS

A.Medicinal Chemistry and Drug Delivery

a) Challenges of Drug Design The main aim of drug design is to produce drugs molecules that achieve their desired effect with minimal undesirable side-effects; thus the two major challenges of drug design are; i. Designing drugs with maximum positive (desirable) effects: Drug molecules act by binding to receptors such as enzymes and must have the correct shape (to fit in the active site) and the functional group(s) to interact with the receptor molecule by means of hydrogen bonds, ionic bonds or dipole-dipole interactions. ii. Drugs with minimal undesirable side-effects: Undesirable side-effects may be caused by: Interactions/binding of the drug molecule with other receptors not initially intended. Presence of an isomer of the drug. Many drug molecules are chiral and it is important that only the enantiomer (isomer) with the desired effect is used. e.g the drug thalidomide prescribed to pregnant women (to treat morning sickness) in the 1960s was a mixture of two isomers one of which was a sedative and an antinausea and the other isomer had disastrous side-effects on the unborn babies who were born with deformed limbs. Overcoming the challenges Computational methods are used both in designing new medicines and in understanding how drugs act. Computer simulations are used to model how the drugs will fit into the receptors active site and the use of databases to predict if the drug will interact with other enzymes to get an idea of possible side effects. Asymmetric synthesis involves the synthesis of only the active isomer with the desirable effect. This saves on resources and the costs besides reducing possible side-effects. Identification and development of drug molecules: Natural products (molecules synthesised by a plant or other organisms) are often a good starting point for drug design. e.g the anticancer drug Taxol found in yew trees leaves.

The structure of such a large and complex molecule with many functional groups is worked out by the NMR and X-ray techniques among other techniques. b) Challenges of Drug Delivery Drug delivery is the process of getting the drug molecule to reach its target cell in the body. A drug such as the Taxol if swallowed orally in form of a pill will encounter the acid pH (which may degrade it through acid hydrolysis of ester and/or amide bonds in the taxol) and the enzymes (which may break it down) in the stomach hence the risks of it not being delivered to the target cell in one piece. For maximum effect it is important to deliver a drug safely to the target site at which it acts as a whole. Advantages of safe drug delivery include; Reduction of side-effects and the quantities of the drug needed. The two main methods of drug delivery: 1) Using Liposomes These are artificial microscopic vesicles consisting of an aqueous core enclosed in one or more phospholipid layers. A phospholipid is a molecule which have an ionic phosphate head i.e hydrophilic (waterloving) at one end and two long hydrocarbon tails i.e. hydrophobic (water-hating) at the other end. Hence, in water-based solutions such as blood, lipids group together to form double layers with their hydrophilic groups on the outside, forming polar interactions with the water, and their hydrophobic groups on the inside, away from the water. These bilayers can wrap into spherical vesicles.

Liposomes are biodegradable and non-toxic and can be used to carry vaccines, drugs, enzymes, or other substances to target cells or organs. They can carry both hydrophilic

molecules (polar molecules that form hydrogen bonds with water and hence dissolve) and hydrophobic molecules (non-polar molecules that do not dissolve in water) 2) Using polymers This involves carrying the drug molecule in the bloodstream by attaching them by a chemical bond to a polymer e.g. polyethylene glycol, PEG, i.e. HO-(CH2-CH2-O)n-H. The drug is attached to the OH groups in the polymer. When the polymer chain is quite short i.e. n is a relatively small number, PEG is soluble in water. The disadvantages of PEG compared with a liposome is that; It can only carry one or two drug molecules at a time unlike in the liposome in which the volume of the sphere can be large enough to carry many drug molecules. PEG can only carry one type of drug molecule (only those that form a chemical bond with the OH groups) unlike liposomes that can carry different types of drugs. Advantages of delivering a drug by injection rather than by oral delivery: to speed delivery of drug to target organ hence a faster response. to avoid the drug being hydrolysed/reacted/decomposed in the stomach due to the strong acid conditions of the stomach and the enzyme activities of pepsin. to allow a smaller dose to be used or greater accuracy of dosage The patient does not have to be conscious unlike in the case of oral delivery. Better-targeted delivery of drugs allows smaller amounts of drug doses to be used, this has advantages of economical in drug use, less chances of side-effects of the drug and reducing the risks of overdose. The delivery of cancer-destroying drugs has, in the past, been by injection of the relevant drug into the bloodstream, allowing it to be carried around the body to the tumour. New techniques have been developed which rely on binding the relevant drug molecule to an enzyme. Suggest the advantages of this new technique, both in economic terms and in terms of the effect on the patient.

B.

Properties of Polymers

Addition polymerisation
Addition polymers are formed from monomers with carbon-carbon double bonds and incorporate all of the atoms of the monomer into the polymer. Is used to form simple hydrocarbon polymers which tend to deform easily and once deformed do not return to their original shape. Their properties are primarily dependent on chain length and van der Waals forces between chains and can be modified by the number and nature of side chains.

The chain length; The longer the polymer chain, the stronger the van der Waals forces. The number of side chains; unbranched chains can closely pack together better than polymers with lots of side chains; low density poly(ethene) (LDPE), which has lots of side chains and is relatively weak and easy to deform. The type of bag that rustles is made from high density poly(ethene) which has fewer side chains. The types of bonding, e.g. the presence of chlorine atoms in poly(chloroethene) results in permanent dipole interactions between carbon and chlorine because of the polarity of the carbon-chlorine bond. Addition polymers do not show a wide range of properties like condensation polymers because they; have a limited range of bonds/monomers. Are mostly non-polar hence have fewer or no hydrogen bonds.

Condensation polymerisation
Requires two different molecules that can react together to form a bond such as an ester or amide bond with the elimination of a small molecule such as water e.g synthetic polymers like polyesters and polyamides, and natural ones like peptides and proteins. Can result in polymers with a variety of properties, e.g. elasticity, that depend on their functional groups and side chains. Condensation polymers such as proteins, polyesters and polyamides show a wide range of properties than addition polymerisation because they; have a range of combinations of monomers which give a wide range of properties. have monomers with many functional groups and/or sidechains. different sequences the monomers e.g in the different amino acid sequences in the protein results in different 2/3 structure.

The Spider Silk

A spider produces a dragline silk (a dragline connects a spider to its web and it is the strongest form of spider silk) made from a protein called fibroin. The silk is a condensation polymer. Based on weight, spider silk is five times stronger than steel of the same diameter and a strand of spider silk as thick as a pencil would stop a jumbo jet in flight! Fibroin consist of mainly two amino acids; glycine and alanine The spider silk is elastic/flexible and insoluble in water/has hydrophobic nature due to the regions that are rich in glycine and it also has a lower density. The properties of spider silk are very valuable and chemists are researching man-made polymers that have similar properties.

Kevlar is a very tough polymer similar in strength to spider silk. Kevlar is used for bulletproof vests; re enforcing Kevlar with spider silk would make these vests even stronger. Kevlar has replaced steel in rubber tyres, with the weight reduction leading to a small reduction in fuel consumption.

C. Enviroment and Energy

Applying chemistry problems
a) Oil Spillage/Slicks
Occurs when oil is spilled from oil tankers whilst at sea due accidents either by collisions with other ships or in rough seas. Effects; Kills birds/fish populations and negatively affects the tourism and the fishing industries. Remedy; Use of a porous fibreglass sorbent boom that repels water and allows oil to be absorbed. The secret is to trap fluorinated molecules in the structure of the fibreglass sorbent. The fluorine has hydrophobic properties and so repels water but allows oil in.

to

overcome

environmental

b) Cleaning contaminated soils

Knowledge of the physical and chemical properties of the pollutant is crucial here.

Physical properties include;

Solubility; suitable solvent must be chosen that will solvate/dissolve the contaminant. Volatility; highly volatile chemicals pollutants can be flushed out of soil simply by pumping air through it or simply vapourise it by heating the soil with warm air and heating coils. Electrical conductivity; Is achieved by inserting electrodes into soil, any charged or polar contaminants can be made to move towards one electrode, depending on whether they are positively or negatively charged. It works with the same principle as the electrophoresis.

Chemical properties;

(Natural) bacterial decay in the soil break down complex chemicals into CO 2. Addition of oxygen and nutrient to the soil for the bacterial speeds up this breakdown. Addition of chemicals to breakdown the contaminants e.g. the carcinogenic polyaromatic hydrocarbons (PAHs) which results from the incomplete burning of carbon-containing compounds can be broken down by ozone.

c) Ground-water contamination
Major cause; arsenic from the porous rocks surrounding the ground water. Long term consequences of arsenic poisoning include skin cancer, damage to the nervous system and miscarriages. Treatment of arsenic contaminated water is by using powdered dried roots (or whole plants) of the water hyacinth.

d) Chlorofluorocarbons (CFCs)
They were introduced in the 1920s to replace the toxic ammonia and the SO 2 as refrigerants. Two major effects;

Ozone destruction
Ozone is the Earths protective sunscreen that shields us from high-energy ultraviolet rays that cause skin cancer. CFCs are very stable and do not break down until they get to the stratosphere. In the stratosphere CFCs absorb ultraviolet light that causes a photodissociation of carbon-chlorine bonds as shown below for CF2Cl2. CF2Cl2(g) CF2Cl(g) + Cl(g) These radicals catalyse the breakdown of ozone to oxygen. Remedy; some alternatives to CFCs include hydrofluorocarbons e.g CH2FCF3 and some alkanes are used. The presence of the CH bonds is important because this enables the compound to break down before it reaches the stratosphere. And if it does reach the stratosphere, it cant produce the damaging chlorine free-radicals.

Global warming
The new replacements for CFCs may be better in terms of the ozone layer but they are still greenhouse gases. However, they are present in the atmosphere in much smaller quantities than other greenhouse gases such as carbon dioxide. Overcoming Energy Challenges Alternative sources of energy. a) Biofuels: diesel and ethanol fuels The use of ethanol as a potential alternative source of fuel to oil-based fuels like diesel/petrol, makes use of local resources and is less polluting. Brazil and Columbia have

powered their cars from ethanol made from sugar cane. Biodiesel refers to fuels that can be used in place of diesel and that are usually made from vegetable oils or animal fats. b) Fuel cells For example, hydrogen/oxygen fuel cells for powering car engines. Here the reactants are hydrogen and oxygen gases, the only by-product is water hence its environment friendly compared to the oil-based fuels. Challenges/disadvantages of using H2/O2 fuel cells; i. Storage of Hydrogen gas; Hydrogen gas must be compressed in order for it to be stored at a small enough volume on a vehicle. This results in a big risk of explosion when the H 2 is ignited with O2. ii. Source of hydrogen gas; Processes used to produce hydrogen are not environment friendly e.g. Electrolysis of water, requires large amounts of electricity which still comes primarily from power stations that burn fossil fuels. Another source of hydrogen is from methane in natural gas, but this process uses up natural resources and generates greenhouse gases. c) Nuclear Power There are arguments, both environmental and economic, for and against nuclear power: i. Nuclear fuel is viewed as a clean source of energy with zero emissions of greenhouse gases i.e. it is an environmentally friendly option compared to coal or gas fired power stations that release carbon dioxide, sulphur dioxide and oxides of nitrogen which contribute to global warming. ii. Nuclear power stations generate radioactive waste products and the cost of cleaning up and securing nuclear waste is prohibitive. iii. An accident at or a terrorist attack on a nuclear plant would have much more devastating and long-term consequences than an accident at or a terrorist attack on a gas or oil-fired power station or pipeline. N/B: Chemists have a role both in optimising the process and in investigating waste disposal. Recycling of materials Materials may be recycled if they are valuable or if they require large amounts of energy to produce. In doing so, this may help to save on energy or/and resources, thus extending the life of the existing scarce resources; Examples: i. Glass: Saves on energy as making glass is energy-intensive but the raw materials are easily accessible and cheap ii. Steel:

iii. iv.

Saves energy extracting iron from its ore and mining the ore is energy-intensive. It also saves on the resource as the iron ore is becoming a scarce resource. Plastics: Saves on a valuable and a scarce resource i.e. the crude oil / petroleum from which it is made from.

D. Nanotechnology
Is the science which involves the study and application of extremely small-sized (microscopic) but very powerful machines/devices. Nano- is a billionth part of a unit. One nanometre = 1.0 x 10-9 m. Atoms and molecules are nano-metre sized. Science involving nano-sized particles is called nanoscience. Nano-sized particles have many useful properties that can be different from bulk materials, due to for example, different surface area to size ratios.

1. Buckminsterfullerene or a buckyball (C60)

Is the third allotrope of carbon (besides graphite and diamond) with a total of 60 carbon atoms that forms a sphere consisting of 5-carbon and 6-carbon atom rings arranged in the same pattern as a modern soccer ball. It is just less than a nanometer in size.

Buckyballs have unusual properties which led to a lot of excitement about their potential. They; i. may be harder than diamond! ii. may be more slippery than Teflon(a plastic with non-stick properties that is used as a coating .e.g. for the cookware). iii. may be insulators or conductors. iv. may be soluble e.g. C60 is pink and C70 is red in solution. It can enclose a highly reactive atom (e.g. lanthanum atom) of another element or a molecule inside itself despite its small size; while enclosed inside the trapped element or molecule cannot react, but as soon as it is removed it can then react.

2. Carbon nanotubes

They are cylindrical in structure and they resemble a rolled-up sheet of graphite, with the carbon molecules arranged in repeating hexagons. (N/B: The discovery of buckyballs led to the discovery of other forms of carbon that are structurally related and from which carbon nanotubes are made). They have a diameter of a few nanometers and can be open at both ends, sealed at one end or sealed at both ends.

Properties;
i. They are many times stronger than steel. This mechanical property (stiffness, strength, toughness) is due to the huge network the strong covalent bonds in its structure. Good thermal and electrical conductors;- due to the delocalised electrons as one electron per carbon atom is not used for bonding.

ii.

Applications;
The above properties of the nanotubes has found a multitude of applications, from batteries of laptop computers and fuel cells to fibres and cables to pharmaceuticals and biomedical materials. N/B: The worlds smallest test tube was made from a carbon nanotube and has been accepted for the Guinness Book of World Records. The tube has a volume of 10 -24 dm3.