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Brown's Chemistry Clinic
My unofficial
support for Salters
A2 Advanced Chemistry
Salters A2 Chemistry - 'exam
bashing' thoughts for
Unit MD
"Medicines by Design"
- part of module 2854
MD unit
map- learning
objectives * My revision index
* extra MD stuff *
My Salters A2 homepage *
Email
At the moment the AS/A2 links
are for the old syllabus *
My NEW
Salters AS Chemistry page
http://www.york.ac.uk/org/seg/salters/chemistry/word/Organicexercise1.doc
(a useful 1 page matching structure and organic functional group exercise)
http://www.york.ac.uk/org/seg/salters/chemistry/word/MDrevision.doc
(an excellent massive 36 page WORD organic synthesis exercise 761 Kb)
Summary
of organic functional groups * Summary of
chemical tests * Functional
group quiz
PLEASE REMEMBER, THESE ARE NOT 'STAND
ALONE' NOTES, and were designed for my classes for use alongside the Salters
resources - Chemical Ideas, Chemical Storylines, Practical
Activities-Investigations and the AS-A2 Revision guides all published by
Heinemann Secondary Series, to reduce the reading workload and offer a study
strategy. From your teacher (not
me!), its handy to have the answers to the Chemical Ideas, Storylines
Assignments and Activities Questions side by side with the texts and these
strategy pages. You haven't time to redo the Q's but a quick read of the Q's and
connecting with the official answers is valuable revision - there is too much
hit and miss revision from doing past papers in my opinion.
 There is a
problem with trying to do shortcuts with MD. Not only is it part of the
synoptic module, but in itself, it is the 'synoptic' organic unit, SO don't
skimp on unit MD! and it is
particularly important to keep CI, CS and Activities in strict PARALLEL!
Chemical Storylines MD1 Alcohol in the Body
-
Xenobiotics are substances
which the body doesn't contain but affect it. There are three types: foods, drugs (including medicines)
and poisons.
-
The metabolism of alcohol:
Exothermic oxidation to water and carbon dioxide
and water.
-
The de-stressing
short-term effect of alcohol have to be balanced against the negative effects of alcohol eg impairment of reaction
and judgement, cause of depression?
-
The blood alcohol
concentration (BAC) varies with age, sex, body weight, speed and amount of drinking etc.
-
A 'unit’ of alcohol as a convenient measure,
legal limit on BAC.
-
Ethanol is one of few
easily vaporised ‘drug’ molecules in blood,
-
The best original ‘breathalyser’ is based on oxidation of ethanol to ethanal
or ethanoic acid by potassium dichromate(VI) giving orange => green colour change(Cr3+)
-
The oxidation of ethanol is a redox reaction and can be used as a half-cell in an electrode
cell system.
-
The ‘Lion Alcolmeter’ system (phosphoric acid electrolyte, oxygen
reduced to water at one electrode, ethanol oxidised to ethanoic acid at the other).
-
Practical design parameters for the ‘Alcolmeter’.
-
Blood samples analysed by
gas-liquid chromatography (g.l.c.).
-
The most recent BAC method is via infra-red absorption
instrument.
-
Note the 'alcolmeter' design
criteria on p265.
-
Assignments 1 to 4 all useful
revision.
Chemical Ideas 13.7 Aldehydes and ketones
-
The structure and naming of
aldehydes and ketones and comparing them with the 'parent' alkane and
alcohol (p326-327).
-
Preparation from oxidising
alcohols with acidified [H2SO4(aq)] potassium
dichromate(VI).
-
primary alcohol =(i)=>
aldehyde (if distilled off) =(ii)=> carboxylic acid (if heated under
reflux)
-
secondary alcohol
=(iii)=> ketone ==> not readily oxidised further due to strong C-C
bonds of chain
-
tertiary alcohol ==> not
readily oxidised further due to strong C-C bonds of chain
-
Writing out the redox
equations, a bit tricky, but given the half-cells, it should be ok
-
In terms of colour change:
its orange to green for Cr2O72-(aq)
==> Cr3+(aq)
-
In terms of oxidation sate
changes: its 2 e's worth per alcohol => aldehyde/ketone or aldehyde
=> acid, or 4 e's worth from alcohol => acid, and 6 e's worth for
dichromate(VI) => chromium(III), so its usually 3 organic molecule to 1 of Cr2O72-(aq)
!
-
(i) 3RCH2OH(aq)
+ Cr2O72-(aq) + 8H+(aq)
==> 3RCHO(aq) + 2Cr3+(aq) + 7H2O(l)
-
(ii) 3RCHO(aq) +
Cr2O72-(aq) + 8H+(aq)
==> 3RCOOH(aq) + 2Cr3+(aq) + 4H2O(l)
-
(iii) 3R2CHOH(aq)
+ Cr2O72-(aq) + 8H+(aq)
==> 3R2C=O(aq) + 2Cr3+(aq)
+ 4H2O(l)
-
Simple test for aldehydes: warm
a few drops with Fehlings solution, the blue Cu2+(aq)
complex solution forms a brown precipitate of copper(I) oxide Cu2O(s).
The aldehyde reduces the copper ion and in the process gets oxidised to a
carboxylic acid.
-
Aldehydes and ketones can be
reduced to the corresponding alcohol by NaBH4.
-
The nucleophilic addition of
hydrogen cyanide to aldehydes and ketones:
-
sample equations on page
328
-
must know the mechanism
too, doesn't the equation need a + OH- on the end to
balance at the bottom of p328?
-
you need to be able to
compare and contrast this with the electrophilic addition reaction of
alkenes (CI 12.2).
Chemical Ideas 14.1 Planning a synthesis
-
Why
make organic compounds?, rather useful chemicals!, but understanding their behaviour is linked to functional groups.
-
Revise
structure of functional groups, many a synthesis is often multi-stepped,
this usually means several changes of functional group.
-
Organic synthesis involves 3 main procedures
[good summary box p341]
-
Planning
a synthesis from the starting materials to the target molecule:
-
The required compound is
called the target molecule.
-
You need suitable starting
materials.
-
Intermediates en
route' may have to be prepared.
-
Need to know how to work out the yield
of a reaction (for a step or overall, examples p342-343), must base on one that is NOT
in excess! and remember most organic reactions do not give 100% yield (losses due to side reactions,
processing losses etc.)
-
Problems with isomers, may need to select conditions to
maximise desired isomer or separate them in the purification procedures eg fractional
crystallisation or chromatography (optical isomers are particularly difficult to separate)
-
Choosing the reagent from the ‘tool-kit’ of functional group chemistry
to achieve any particular synthesis step.
-
There can be several different pathways available,
one may be superior to another BUT
you need to know all the main reactions of the functional groups* to make
an informed choice which can often come down to which is the most economic! *
see CI 14.2
Chemical Ideas 14.2 Summary of organic
reactions
these
are given in the exam
-
All of CI 14.2 contains many useful summary diagrams of
the products and reaction conditions to achieve a particular synthesis step. These
are your revision summaries with odd notes in between AND references to detailed
CI sections if necessary.
Mechanistic detail, or at least the reaction type descriptors are needed (choose
from elimination, or electrophilic/nucleophilic/free radical PLUS addition or
substitution). Sometimes different reactivities of compounds are
discussed which affect reaction conditions needed or choice of reagent.
-
Alkenes :
Reaction with hydrogen (then alkane + chlorine,
free radical substitution), conc. HBr to bromoalkane, polymerisation to
poly(alkene), water via acid catalyst to alcohol, bromine (direct/organic
solvent) to dibromoalkane, bromine water to bromoalcohol[note all addition reactions via ionic electrophilic mechanism or free
radicals, know which applies]
-
Halogenoalkanes: reaction
with water to alcohol, sodium hydroxide faster to alcohol, ammonia to form
amine(and cyanide to form nitrile, not shown in text but given in exam).
-
Alcohols: Oxidation
with acidified potassium dichromate(VI) to aldehydes, ketones or carboxylic
acids, reaction with acyl (acid) chlorides or acid anhydrides to give
esters (reversal is hydrolysis), dehydration to give alkenes, reaction with
HBr/HCl,
condensation of diols with dicarboxylic acids to give polyesters.
-
Aldehydes and ketones: Oxidation of
aldehydes with acidified potassium dichromate(VI) to carboxylic acids, reduction
with NaBH4 to alcohols, addition of hydrogen cyanide to form
hydroxynitriles.
-
Carboxylic acids and related compounds:
-
Acyl (acid) chlorides: reaction with water = hydrolysis back to acid, alcohols and
phenols to form esters, ammonia and amines to form amides and N-substituted
amides (secondary amides) *
-
Acid anhydrides: reaction with water = hydrolysis back to acid, alcohols and
phenols to form esters, ammonia and amines to form amides and N-substituted
amides (secondary amides) *
-
*
apart from water, the reaction is reversed by refluxing
with NaOH(aq) to give the free alcohol/ammonia/amine and the sodium salt of the phenol or
acid
-
Arenes (aromatic hydrocarbons): apart from reduction with hydrogen/Ni
catalyst, rest via electrophilic substitution reactions: Cl2/AlCl3
to give chloroarene,
conc. HNO3/H2SO4 to give nitroarene ,RCl/AlCl3
to give alkylarene, RCOCl or (RCO)2O/AlCl3 to give
aromatic ketone, conc. H2SO4 to give sulphonic acid, Br2/Fe or
FeBr3 to give bromoarene
-
CI 14.2 problems p351-353:
problems on choosing
reagent for a step, deducing products of a reaction, type of reaction/mechanism involved,
working out multi-step synthesis routes, equations for synthesis reactions.
Chemical Ideas 7.6 Chromatography
(revision)
Chemical Ideas 6.4 Infrared spectroscopy
(revision)
Activity MD1.1 Aldehydes and ketones
Activity
MD1.2
BAC determination using gas-liquid chromatography
Chemical Storylines MD2 The Drug Action of
Ethanol
-
A touch of nerves as the exam is
gets closer!
-
The central nervous system (brain + spinal cord) and peripheral (the rest) nervous system.
-
The function of
CNS detectors and effectors
-
the very basic mechanism of nerve signal transmission
-
neuron cells, nerve impulse (electrical
signal), receptors on dendrites
-
neurotransmitters (crucial messenger
molecules acting at the synapse link sites)
-
Some
neuropharmacology:
-
basic mechanism of electrical signal of nerve impulse due to movement
of Na+, K+ and Cl- ions in/out of cells
-
potential difference across cell membranes,
ion
movement (triggered by neurotransmitter molecule) through membrane protein channels
changes potential across the membrane ‘firing’ the nerve cell,
-
Switching nerve cells on
and off is due to ion movement and the process uses lots of energy
-
nervous inhibition - the role of GABA, (a neurotransmitter) in
switching off nerve cell action,
-
GABA binds to receptor sites causing protein to change
shape and open Cl- channels (this Cl- movement inhibits rise in
Na+ and K+, restricting the potential to
‘fire’ nerve cell)
-
thought that ethanol molecules bind to nerve cells near to
GABA
receptors enhancing GABBA effect
-
neurons more inhibited if ethanol present
and other
molecules have a similar effect and are used to treat anxiety eg benzodiazepines like
Valium
-
BUT dangers if taken with alcohol, if ethanol + benzodiazepine molecules are
bound to nerve cells the effect is much greater than either singly and potentially fatal.
Chemical Ideas 13.9 Amino acids (revision)
Chemical Storylines MD3 Medicines that send
messages to nerves
-
To discovering/design a new medicine
you need a biological
understanding of the ‘disease’ and a ‘lead compound’ which shows some
promise ie some biological activity and gives some clues for a more effective molecule.
-
Knowledge of the neurotransmitter noradrenaline has lead to medicines to treat asthma and
heart disease
-
Some naturally occurring lead compounds found by accident eg penicillin
but often large scale molecule screening programs needed.
-
Noradrenaline is the
neurotransmitter in many of the synapses where nerves join organs in the body, release of
noradrenaline produces increased heart rate and sweating, bronchioles in lungs widen.
-
Noradrenaline potentially useful for asthma but too dangerous
because noradrenaline has
wide ranging effects with receptors of similar structure (too much can be fatal!).
-
However chemists are able to design and synthesise molecules which interact with more selectively with
receptors eg isoprenaline and salbutamol (compare their structures with noradrenaline on
p271).
-
Note in salbutamol, a good example of molecular modification, the –CH2OH
group slows rate at which active molecule is metabolised, effect lasts longer.
-
Agonists
and antagonists: Molecule activity depends on a structural fragment binding to the
receptor ie molecular recognition by precisely fitting into the shape of the receptor,
this crucial structural ‘fragment’ is called the pharmacophore ie the structural
section that confers activity on the molecule.
-
Salbutamol is an agonist, a molecule that
behaves like a body’s natural substance in the way it binds to a receptor, however
for some people, response like increased heart rate may be bad news!
-
What is needed are
molecules which compete with natural compounds for receptor sites but have no effect when
bound (ie don’t trigger electrical impulse), these are call antagonists.
-
They are
sufficiently similar to fit on the receptor site but produce no effect because they
don’t have the pharmacophore eg beta-blocker molecules like propranolol
which are used to treat people with heart disorders where over-activity could be fatal!
-
Assignments 6 to 8 are good
revision.
Chemical Ideas 6.5 Mass spectrometry
(revision)
Chemical Ideas 6.6 NMR (revision)
Chemical Ideas 6.8 uv and visible
spectroscopy (revision)
Activity MD3.1 Making a toolkit of organic
reactions
Activity MD3.2 Classifying reactions
Activity MD3.3 Using the toolkit to
synthesise medicines
Activity MD3.4 Manufacturing salbutamol
Chemical Storylines MD4 Enzyme inhibitors
as medicines
-
Enzyme inhibitors acting as medicines:
Similarity of 3D
protein of enzymes and receptors, so some molecules can lock onto enzyme site inhibiting its
action.
-
Angiotensin example described, called Captopril, works by inhibiting the
formation of protein known to be a factor in raising blood pressure - the ‘lead’
molecule for Captopril was obtained from a deadly snake venom which caused death by
lowering blood pressure (Fig 26), illustrate the key-lock (and staying
locked!) mechanism of enzyme inhibition.
-
So by knowing the 3D
stereochemistry of the
situation, it is possible to use computer simulations to design potential medicines.
-
Finding the best medicine based on the snake venom,
all active lead molecules had proline
at the –COOH end of the chain, various proline derivatives tested, eventually
leading to Captopril (p277).
-
Captopril is not a protein and is not broken down by
digestive enzymes and so can be taken orally.
-
Captopril is good example of development eg
starting with a natural source and observed effect! => lead molecule => derived molecule
=> successful medicine.
-
When reading this sort of
section concentrate on molecular ideas and checkout Assignments 9and
10.
Chemical Storylines MD5 Targeting Bacteria
-
Some medicines act by inhibiting the action of enzymes in
bacteria.
-
Penicillin is an example of such an enzyme inhibitor, the bacteria cells are
unable to grow, divide and multiply but this ‘miracle cure’ discovered by accident!
(serendipity again + 'mucky' working?).
-
Penicillin provided the basis for a whole range of antibiotics
though at first only moulds were used to
produce penicillin products.
-
Adding 'synthetic' methods
allows improvements on nature, by identifying the active
‘nucleus’ of the penicillin molecule (6-APA)
-
Then by changing the side chain
substituents you produce a range of biologically active derivatives eg derivatives made by
reacting 6-APA from penicillin G with reagents such as ethanoyl chloride (acylating agent).
-
Penicillin works by inhibiting the action of an enzyme involved in building the cell
wall of the bacteria because the shape of a penicillin molecule resembles the shape of crucial
amino acids needed in the cross-linking process producing rigid bacterium cell walls.
-
If this process is not completed,
the bacterium cell bursts open and dies.
-
BUT 1: Nature fights back, bacteria
can produce an enzyme that hydrolyses the lactam ring in the penicillin molecule
(‘deactivating it’).
-
Chemists have found a natural product (Clavulanic acid)
that is
recognised by the enzyme b-lactamase, so when mixed with penicillin previously rendered
inactive by the enzyme, the penicillin works well while the Clavulanic acid locks onto and
inhibits the potentially penicillin hydrolysing b-lactamase enzyme.
-
BUT 2: Constant
development on new ranges of antibiotics is needed as bacteria evolve into new strains!
Activity MD5.1 Making and testing a
penicillin
Activity MD5.2 A closer look at the
structure of penicillin's
Activity
MD6 Check your notes on Medicines by Design and Storylines MD6 Summary are
incorporated into the MD learning objectives and
don't forget the MD UNIT TEST
provides extra Q practice and note what you got wrong!
GENERAL
REVISION
NOTES
* Salters
Advanced Level Chemistry * Salters Advanced Level Chemistry * Salters
Advanced Level Chemistry * Salters Advanced Level Chemistry * Salters
Advanced Level Chemistry *
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C2H5OH(g) is 0.00044, so it can be detected in breath.