2. DESIGNING NEW MEDICINAL DRUGS
The intermolecular bonds formed between the drug and its target molecule
involved:
Hydrogen bonding.
Ionic attraction.
Dipole-dipole force.
Van der waals force.
Molecular modelling: has greatly speeded up the process of designing new
medicines.
Molecular modelling on computer is used when designing medicine and other
compounds (e.g. pesticides and polymers).
Type of sesearch was used to make AIDS drugs in the late 1980s and 1990s.
3. Pharmaceutical industry: searching
for new drugs.
Most of the drugs contain at least one
chiral centre.
Using conventional organic reaction
to make desire product will yield a
50:50 mixture of the two enantiomers
( 2 non-superimposable mirror
images).
Benefits using pure enantiomers:
Reduces the patient’s dossage by
half.
Protects drug companies from
possible litigation.
Three ways to prepare pure
enantiomers:
Optical resolution.
Using optically active starting
materials.
Using a chiral catalyst.
CHIRALITY IN PHARMACEUTICAL SYNTHESIS
Optical resolution:
Following a traditional shynthetic
route to make the compound,
resulting in a racemic mixture, then
they separate the two enantiomers
in a process.
Using a chiral auxiliary that will
react with one of the isomer in the
mixture.
Separated by physical, e.g. the
solubility in a solven will differ, the
unwanted enantiomer and the new
product can be separated by
fractional crystallisation.
Large volume of organic solvents
are used in the process.
Chemistry are now using
supercritical carbon dioxide as a
solvent.
UsingOpticallyActive
Starting Materials:
Uses starting
materials that are
themselves optically
active and in the same
orientation as the
desired product.
These are often
naturally occuring
compounds such as
carbohydrates or L-
amino acids.
The synthetic route
is desinged to keep any
intermediates and the
final product formed in
the same enantiomeric
form.
4. Chiral catalyst
Ensure only one specific
enantiomer is formed in a
reaction.
The benefits:
Only small quantities are
needed.
They can be used over
and over again.
Enzyme are often immobilized: allow the reactants
to be passed over without the need to separate the
product from the enzyme after reaction.
Use an enzyme process might take a longer develop
than a conventional synthetic route
But.....the benefits will be generally outweigh the
disanvatages.
Pharmaceutical industry:
make pure enantiomer from optical resolution and chiral
synthesis.
Use enzymes to promote stereoselectivity and produce
single-enantiomer products.
The specific shape and the nature of the molecular is
interactions at the active site, only one enantiomer is formed.
5. DELIVERY OF DRUGS
Nano-cages of gold: using to deliver drugs to target sites in
the body.
The tiny gold particles can be selectivity absorbed by
tumours. It heated up, and destroys the tumour without
damaging healthy cells.
Coated by by a polyethylene glucol (PEG), this stops the
immune system from attacking the gold particles and ejecting
them from the blood stream.
6. Using liposomes:
Liposomes: tiny membrane bubbles, usually made of phospholipid.
Has water loving (hidrophilic) head.
Water hating (hidrophobic) tail.
Liposomes are using to the delivering drugs because a water-soluble drug can be carried in
aqueous inside the liposome.
A drug in the dissolves in fat can be transported in in the fatty layer of the wall made up of
the tails of the molecules.
Biodegradable and relatively non-toxic.
Works in cancer treatment in a smiliar way with nano cages of gold.
The liposomes are smiliar in size and can get throught the loosely packed walls of a tumour
blood vessels, without throught the walls of the healthy blood vessels.
Liposomes can fuse with cell membranes which have a smiliar structure and deliver contents
inside the cell.
Usage for skin treatment.
7. Designing polymers
PEG is made from monomers of epoxyethane(is a reactive
cyclic molecule,CH2CH2O) reacted with 1,2-ethanodiol.
PEG often used as liquids or low melting point solids.
Solubility in water.
Non-polar solvents.
The water in the timbers is replaced by PEG and the
remains of the ship can then be slowy dried out without
crumbling away.
Inspired by natural polymeric material:
Neoprene was made from the polymerisation of the monomer
2-chloro-1,3-butadiene in an addition reaction.
The intermolecular forces between natural rubber polymers
areVan derWall’s forces.
Vulcanisation process was invented to make rubber tyres more
resilient and hard wearing.
8. Kevlar (founded in 1970): synthetic polyamide
with strong intermolecular forces.
Use of kevlar:
1. Bullet-proof vests.
2. Racing leathers for motorbike riders.
3. Strength arises from the hydrogen bond
between its polymer chains.
4. Linear polymer chains.
The role of side chains:
LDPE: low density poly(ethene), produced in 1930s, softened plastic
at relatively low temperature.
HDPE: high density poly(ethene), produced in 1950s
Carl Zeigler discovered a catalyst that resulted in straight polymer
chains
HDPE is stronger than LDPE.
9. Poly(lactic acid), PLA.
Is a polyester.
Becoming increasingly popular because the starting material used to produce it comes
from plant starch.
Biodegrability.
Reduces greenhouse gas emission by around 30-50% compared with the manufacture
and use of traditional oil-based plastics.
The lactic acid molecules can undergo esterification (a condensation reaction) forming
water as well as the polymer.
Lactic acid (2-hydroxypropanoic acid) molecule has an alcohol and carboxylic group
within each molecule.
10. NANOTECHNOLOGY
Nanotechnology: design and creation of machines that are so small to measure them in
nanometers. 1nm = 10-9 m
Aim: making machines that are less than 100nm in size.
Two approaches to making the molecular machine:
1. Sculpt at material until left with the molecules or atoms on the surface. Microelectronis
at the molecular level uses this technique.
2. Developments involve building machine up from individual atoms or molecules, and do
this by physically moving the molecules using atomic force microscopes.
Special polymers called conjugate polymers that expand and contract when involved in
transferring electrons.
11. Buckyballs
The discovery of a form of carbon first
triggered interest in nano-particles and
the field of nanoscience. Sir Harry and 2
other scientist have discovered it, and get
noble prize in 1996s.
Fullerenes: a close relative is the ball shaped
molecule (C70).
Bucky tubes
Bucky tubes have also been made called
nanotubes, consist of a single rolled up
sheet of carbon atoms in the graphite
structure an are incredibly strong.
Fibres of tube can reinforce materials,
such as those used in bullet-proof vests.
The tubes have free electrons, can be use
in electrical equipment.
Benefits:
Lighting.
Molecular electronic
Hydrogen fuel in transportations.
12. FIGHTING POLLUTION
Problem:CFCs (chlorofluorocarbons)
CFCs are unreactive ande non toxic compound in normal conditions.
CFCs are reactive in the atmosphere.
The problems might appears if more UV light reaches:
Increase risk of sunburn.
Faster ageing of skin.
More skin cancer.
Damage eyes, such as cataracts.
Reduced restitance to some diseases.
Disruption of plant photosynthesis, and food chains.
13. In the stratosphere, the UV light from the sun breaks up their
molecules, high reactive chlorine atom splits off. Forming a
chlorine free radical.
Adding 2 propagation reaction together gives the overall
reaction:
Cl* acting as a catalyst because it is constantly regenerated by the
reaction of the ClO* free radical with an oxygen atom formed
when an O3 molecule is broken down bu absorbed UV light.
14. GREEN CHEMISTRY
6 important principles of a greener chemical industry:
1. design of processes to maximize the amount of raw material
that’s converted into product. E.g. synthesis of ibuprofen, this
principle improved the atom economy to 77.4% making more
efficient use of the raw materials and creating less waste.
2.The use of raw material or feed stock
that are rewenable rather than finite. E.g.
biofuels, such as biodiesel and ethanol.
3.The use of safe, enviromentally friendly solvents, or no
solvents at all where possibles.The use of auxiliary
substances (e.g. solvents , separation agents, etc.) should
be made unnecessary wherever possible.
4.The substances used in a
chemical process should be
selected to minimise the potential
risk of chemical accidents.
5.The design of energy-efficient processes, the energy
requirements of chemical process should be minimised to
reduce their impact on the enviroment and the costs.
6.The consideration of waste reduction in
the production process and at the end of a
product’s lifecycle, aiming not to create
waste in the 1st place.