IB Chemistry: Option D Medicinal Chemistry Exam Review: Important Techniques, Tests and Procedures
Therapeutic Index/Window
Purpose of Technique
To analyze the risk of toxicity of different
drugs/medications based on population statistics.
Important Information
Therapeutic window - Range of dosages between the minimum
amounts of the drug that produce the desired effect and a
medically unacceptable adverse effect.
Therapeutic Index (TI) – ratio of dose that produces toxicity to
the dose that produces a clinically effective response in a
population. Measure of drug’s safety.
Purpose of Test/Technique/Procedure:
Determine the dosing regime (specific quantity of drug to be taken
at a time and the frequency of administration.
Steps to Carry out Test/Technique/Procedure:
Minimum effect dose, ED50, dose that produces therapeutic effect
in 50% of the population.
Lethal dose, LD50, dose that is lethal to 50% of population, animal
trials
Toxic, TD50, dose that is toxic to 50% of the population, human
studies.
Animals TI= LD50/ED50
Humans TI= TD50/ED50
High therapeutic index: safe if taken in higher doses
than that required for therapeutic effect
Low therapeutic index: low margin of safety - related to
how bioavailability affect therapeutic effects
Important Reminders:
Remember that taking a high dosage of a particular drug
may not lead to an overdose because of increased
1. Synthesis, yield and crystallization Polarimetry
of aspirin from salicylic acid.
2. Characterization using IR and melting point.
Purpose of Technique Purpose of Technique
To create aspirin from salicylic acid, using laboratory techniques. Then to test the To identify enantiomers.
purity of the product. To determine the optical rotation of an optically active
compound (a measure of quality of an extract/synthetic
preparation). To identify racemic mixtures (racemate).
Steps to Carry out Procedure Steps to Carry out Procedure
1.Synthesis of Aspirin -A sample of the solution is placed into the analyser.
Step #1 Salicylic acid is converted into Aspirin through esterification reaction. -Light (rotating in all directions) is filtered by the polarizer
to produce plane-polarized light (PL), which rotates in one
direction.
-PL passes through the tube (containing sample solution).
-PL is rotated either clockwise or anticlockwise by
enantiomers.
-The angle of rotation is analyzed by the analyzer
Step #2: Isolation of Aspirin
Mixture is cooled to formed crystals. At low temperature, ethanoic acid is insoluble but Aspirin
is soluble, which enable ethanoic acid to be removed.
Step 3#: Purification of Aspirin
Recrystallization impure aspirin is dissolved in minimum volume of hot ethanol. Ethanol is
considered to be a more effective solvent for dissolving the impurities present, rather than the
Aspirin itself. This process produces a saturated solution of Aspirin. The solution is then
cooled, which allows the Aspirin to recrystallize. The recrystallized Aspirin can then be
separated from the solution by filtration. This leaves the remaining unreacted salicylic acid and
impurities in the solution.
Testing the Product
1. Infrared Spectroscopy can be used in the characterization of Aspirin and other related
compounds. Since Aspirin contains specific functional groups, when it is exposed to IR
radiation, the specific wave number of IR radiation absorbed provides us with an indication
what groups are present.
Similarities
Strong peaks from 1050 -1410 cm-1 , C-O in alcohol/ester
- Strong peaks from 1700 -1750 cm-1 , C=O in carboxylic acid
- Broad peaks from 2500 - 3000 cm-1, OH in carboxylic acid
- Peaks from 2850 - 3090 cm-1, C-H (which overlaps the broad OH peak
Differences No Rotation: Either optically active or a racemic mixture!
A second peak from 1700 -1750 cm-1 ,ester group in Aspirin Important Reminders:
- Peak from 3200 – 3600 cm-1 in salicylic acid, OH (hydroxyl) group which is absent in The polarized light rays are ROTATED (nothing else)
Aspirin If there is no rotation, this is a racemic mixture/racemate
(equal amounts of both enantiomers, hence cancelling out
tolerance, but it will most likely have a toxic effect on the rotation of each enantiomer) or the mixture is not
organ tissues (which could lead to death). optically active.
Remember to draw all chiral (asymmetric compounds) with
a stereochemical formula. Use an asterisk * to denote the
chiral centre. Always represent enantiomers relative to a
Steroid Detection: GC and MS mirror to show non-superimposable nature.

Purpose of Technique
A combination of gas (liquid) chromatography and mass
spectroscopy are used to detect for steroids in the body
(blood/urine). This is applicable to anti-doping initiatives where
athletes might be taking anabolic steroids (performance
enhancing drugs).
Steps to Carry out Procedure
1) Standard sample could be used first for comparative purposes
2) Obtain blood and urine samples for testing
3) In gas-liquid chromatography:
Mobile-phase: Vaporize sample and inject to a stream of inert
gas like Helium
Stationary phase: Expose to non-volatile liquid.
4) The components of the sample move at different rates
depending on their boiling points/solubility in the phases).
5) Gas chromatograph produced: passage of each component is
detected and recorded as a peak. Area under the peak represents
the amount of the compound.
6) Ethanol in the urine or blood sample or a steroid could be
identified by comparing the standard retention times.
7) Alternatively sample could be passed to a mass spectrometer
to undergo Vaporization, Ionization, Acceleration, Deflection,
and Detection. Fragments of cations are detected.
8) The produced mass spectrum is compared to an extensive
range of known banned substances.
9) Comparing the results of both chromatography and mass
spectroscopy is the most effective and the combination might
detect abusers who took the steroids weeks before the test.

Important reminders:
* A common steroid structure is provided in section 34 in the
data booklet.
*Anabolic steroids are mainly non-polar in nature; Each type of
steroid will produce a unique mass spectrum
* In summary: Chromatography ---- allows pure chemicals to be
isolated from mixtures (e.g. blood or urine). Mass Spectroscopy
---- allows for identification of chemical based on the fragments
detected.

3. Melting point Determination

Differences between the theoretical melting point of Aspirin and the experimental product
suggest the presence of impurities. Pure Aspirin has a melting point of 138-140°C. Salicylic acid
has a melting point of 159°C. A mixture would have a lower melting point than 138°C
 The Breathalyser Test:
Detection of Alcohol
Purpose of Technique
A sample of breath is analyzed for its ethanol content based on a redox reaction
involving acidified dichromate. Blood alcohol concentration is approximated
based on content in one’s breath.
Steps to Carry out Procedure
-Since ethanol is a volatile liquid, at body temperature it establishes an
equilibrium in the lungs where some is dissolved in the blood and some is
released into the air as part of an exhaled breath.
-Since this equilibrium has a steady equilibrium constant (Kc) at a given
temperature, it is possible to determine blood alcohol concentration based on the
amount of ethanol in one’s breath.
-The common breathalyzer test involves a portable breathalyzer which is used
by law enforcement officers.
-The breathalyzer test involves redox chemistry. The breathalyzer contains
crystals of potassium dichromate (VI) K2Cr2O7 - which is an oxidation agent.
These crystals are orange, but they change to green chromium (III) ions as they
oxidize ethanol to ethanal and ethanoic acid.
Important Reminders: There is a very good chance that you will be asked to
deduce the half-equations and even the complete equation. Typically, students
struggle with this because it integrates Topic 9/19 into an Option D question.
Analysis of Blood and Urine by Gas – The Use of a Fuel Cell in an
Liquid Chromatography Intoximeter
Detection of Alcohol Detection of Alcohol
Purpose of Technique Purpose of Technique
Gas-liquid chromatography is the most accurate way of measuring the A fuel cell can also be used in an Intoximeter. Electric
concentration of ethanol (alcohol) one’s sample of blood or urine. voltage is used to measure the ethanol concentration in a
breath.
Steps to Carry out Procedure Steps to Carry out Procedure
-The blood or urine sample is vaporized and injected into a stream of an inert 1.Electrochemical processes in the fuel cell (composed of
gas. The stream of the inert gas is considered to be the mobile phase. There is two platinum electrodes and porous acid electrolyte)
also a stationary phase made up of a non-volatile liquid. 2. When exhaled air passes through the fuel cell, ethanol is
-The components of the sample vapour (including ethanol gas and other oxidized to ethanoic acid at the anode.
gases) move at different rates depending on their boiling points (and 3. Half equations:
solubility in the phases).Therefore, the components move through the column Oxidation:
at differing speeds and exit after different time intervals. This is known as C2H5OH(g) + H2O(l) → CH3COOH(l) + 4H+(aq) + 4e-
their retention time. Reduction:
-The components of the gas are detected and recorded as a peak on a gas O2(g) + 4H+(aq) + 4e- → 2H2O(l)
liquid chromatograph. 4. Overall equation:
-It is important to note that before the sample being tested goes through this C2H5OH(g) + O2(g) → CH3COOH(l) + H2O(l)
apparatus, a standard ethanol sample is first passed through the column under 5. Electric current produced by the fuel cell is proportional
similar conditions (same carrier gas at same flow rate, the same stationary to the concentration of ethanol in the breath. Therefore,
phase and a set temperature) to determine its retention time. BAC can be calculated with the help of computer software.
-Therefore, ethanol in the urine or blood sample can be identified by
comparing the retention times.
-The area under the peak represents the amount of the compound. Therefore,
gas liquid chromatography can be used to determine whether ethanol is
present in a sample and how much is present.
Important Reminder: Do not confuse this with paper chromatography- used
in amino acid analysis. Also, keep in mind that Gas Chromatography can be
used to detect many different compounds, therefore the technique is not only
for ethanol.
 Infrared Spectroscopy
Purpose of Technique
Infrared Spectroscopy is the analysis of infrared light interacting
with a molecule. This can be analyzed in three ways by measuring
absorption, emission and reflection. It is used by chemists to
determine functional groups in molecules. IR Spectroscopy
measures the vibrations of atoms, and based on this it is possible to
determine the functional groups. Generally, stronger bonds and
light atoms will vibrate at a high stretching frequency
(wavenumber). Functional groups in compounds show
characteristic absorption peaks in infrared spectroscopy.
Steps to Carry out Procedure
Infrared radiation can be absorbed by certain chemical bonds,
causing them to stretch or bend. The frequency of IR radiation
absorbed is usually measured as the number of waves formally
known as wavenumbers. Absorption spectrum of a specific bond
can vary depending on the environment of the bond. Place few
drops of solution onto KBr or NaCl disk and apply high pressure
on the device to obtain the spectrum with peaks.
Important Reminders: remember to look out for the bonds that
are not in the diagram in addition to the bonds present in the
diagram.
The above IR spectrum describes butanoic acid.
Important Reminders: Remember the units for cm-
1
(wavenumber). Practice navigating the data booklet to
familiarize yourself with the relevant stretches.
Mass Spectrometry
Purpose of Technique
More basic: Determine the relative atomic mass of an element from its
isotopic composition
More complex: Identify compounds and determine their structure based on
fragmentation patterns.
Steps to Carry out Procedure
More basic: Isotopic Abundance
Vaporization, ionization, acceleration, deflection, detection (in mass
spectrometer)
Ionization→ Formation of cations: Bombardment of atoms with high
energy electrons
Deflection → Due to electromagnet. The higher the mass/charge ratio, the
greater the deflection.
Important Reminders:
-Only cations will be detected (free radicals not detected)
-Mass spectral fragment (section 28 in data booklet)
-You must be aware of the possibility of 2+ (etc.) ions, but the vast majority
of IB questions will give you mass spectra which only involve 1+ ions.
Unless there is some hint in the question, you can reasonably assume that
the ions you are talking about will have a charge of 1+.
More Complex: Mass Spectrometry and Fragmentation
-When a high energy electron from the electron gun in a mass spectrometer
hits the sample species the process of ionization occurs with the removal of
an electron:
X(g) + e- → X+(g) + 2e-
-This collision is often energetic enough that it causes the sample molecule
to break into different fragments. When chemists analyze the mass
spectrum to look at the fragmentation pattern they can make predictions
about the structure of the compound.
Proton NMR
Purpose of Technique
To determine shape and structure of molecules based on proton spin upon
exposure to a magnetic field.
Steps to Carry out Procedure
Detection:
-Place unknown compound (UC) in magnetic field.
-The hydrogen nuclei (H) within the compound each have their own spin,
either aligned with (lower) or against (higher energy) the magnetic field.
-Energy within the radio frequency range of EM spectrum used to change
the spin of H nuclei relative to the magnetic field.
-When the H nuclei returns to its relaxed state, the same amount of energy
(E) absorbed is released.
-This E is detected and shown as a signal on the NMR spectra.
-This is relative to the reference standard, tetramethylsilane (TMS) -
0.00ppm.
-The NMR signal of H nuclei of UC relative to the position of H nuclei in
TMS is called chemical shift of proton.
-Different H nuclei in different chemical environments = different chemical
shifts
Analysis of NMR spectra
I) Number of Different Absorption Signals
= No. of different chemical environments containing protons in compound
II) Area Under Each Signal
= Relative number of protons in each chemical environment
= Usually represented as integration trace
III) Chemical Shift
= Type of chemical environment (refer Data Booklet, Sec, 27) - in ppm
IV) Splitting pattern
= the number of neighbouring protons, which can be deduced based on
the splitting pattern of the signals--splitting caused by spin-spin
coupling.
= if n adjacent protons in a chemical environment, n+1 signals in
splitting pattern
= E.g. 4 adjacent protons in same chemical environment, quintet
splitting pattern
-The parent ion (also known as the molecular ion) is formed is formed in a
mass spectrometer when a molecule loses one electron, but otherwise
remains unchanged.
-Since the loss of only 1 electron corresponds to a negligible loss of mass,
the parent ion should have a mass/charge ratio that is consistent with the
original mass of the compound that entered the spectrometer in the first
place.
H H
+
H C C H molecular ion (M ) m/z = 30
H H

H H H H
-
H C C H + e + H
H C C
H H H H
m/z = 29

H H
H C + C H (not detected by MS)
H H
- Only cations are detected.
- Radicals are “invisible” in MS. For each fragmentation, one of the
products keeps the positive charge. The other becomes a radical.
- Generally, the fragment that gives the more stable ion is formed.
The amount of deflection observed depends on the mass to charge ratio
(m/z).
- Most cations formed have a charge of +1 so the amount of deflection
observed is usually dependent on the mass of the ion.

Why TMS is used as standard?

Important Reminders: Know exactly where to look in the data booklet for
the values. Watch out for isomers and their effect on the parent
ion/molecular ion mass! Some fragments won’t be detected if they’re not
stable enough to form. For example, sometimes OH+ is not detected because
placing a formal charge of +1 on an electronegative species such as oxygen
is destabilizing. Therefore, it tends not to be formed or detected.
a) all of the 12 protons have the same chemical environment--strong
single signal
b) non-toxic and unreactive
c) volatility allows easy removal of TMS from sample
d) soluble in most organic solvents
e) no interference between sample and standard as majority of
compounds absorb downfield of the TMS signal
(HL parts bolded and underlined)
 Targeted Alpha Therapy (TAT)
Purpose of Technique
To treat cancer cells that has spread to different areas of the body.
Steps to Carry out Procedure
1) The radiation emitted from alpha particles is in direct range of the
cancerous cells, therefore reducing the harmful irradiation of normal
functioning cells near the cancer cells.
2) The radiation emitted from alpha particles has high ionization density,
therefore it is often strong enough to kill the targeted cancerous cells when
they are exposed to it.
Important Reminders: Lead-212 and actinium-225 are often used for
targeted alpha therapy (TAT), therefore they are both ‘alpha emitters’.
Boron Neutron Capture Therapy (BNCT) Magnetic Resonance Imaging
(MRI)
Purpose of Technique Purpose of Technique
Strategically creating an unstable form of boron to release Diagnosing issues with living tissues
radiation to treat brain and neck tumours. (E.g. cancerous tumours)
Steps to Carry out Procedure Steps to Carry out Procedure
1) The patient first gets a high dose of non-radioactive boron-10 often by
intravenous injection of organic compounds containing boron, such as 1) The odd number of protons in their nucleus enables hydrogen
boronophenylalanine. Boron-10 concentrates in malignant brain tumours. atoms to form a magnetic moment when exposed to powerful
2) The stable Boron-10 is then exposed to high intensity neutron beams. magnets.
3) After capturing a neutron the nucleus of boron-10 is converted to boron-11 2) Strong magnet radio waves are utilized to eventually generate
which immediately releases high energy alpha particles. an electronic signal which is converted in a computer to 2D and
4) The high energy alpha particles can then kill the neighbouring cancer cells. 3D images.
Important Reminders:
The human body is made of 70% water, which explains why
MRI is effective for living tissue. Lots of hydrogen in H2O.
Characteristics of radio waves: low energy, no known hazards of
the exposure to body.
***Take note that fraction lines should not be included in your half-life
equations. They are only included above due to the computer software
used.
Important Reminders:
Explain the characteristics of Alpha particles:
a- High density: strong enough to kill the targeted cancerous cells
b- Short range: reduces the harmful irradiation of normal functioning cells
near the cancer cells.
Half-Life and Radioactive Decay Calcs.
Purpose of Technique
To calculate the percentage and amount of radioactive material decayed
and remaining after a certain period of time using the nuclear half-life
equation. To determine how much substance has decayed over time and
how much remains.
Half-Life Definition: time it takes for an initial quantity of substance to
decay to ½ of its amount.
There are three main equations which can be used to calculate:
1) t1/2 = ln2/k, where k is the rate constant and t1/2 is the half-life of the
radioactive substance.
This first equation is useful for calculating the half-life or the rate
constant of the substance if one of the factors are given in the question.
However it does not compute any information which involves the
concentration of the reactants.
2) lnNt/N0= -kt, where No is the concentration of reactants when time =
0/initial concentration, Nt is the concentration of reactant at time t, t is
the time elapsed and k is the rate constant.
3) Nt/No = (0.5)t/t1/2, where No is the concentration of reactants when
time = 0, Nt is the concentration of the reactant at time t, (N o/Nt is the
proportion of isotope remaining), t is the time elapsed and t1/2 is the half-
life of the isotope.
Formulas 2 and 3 can be used interchangeably depending on what
variables are given. Formulas 2 and 3 can also be used as an extension to
formula 1.
These formulas also yield the concentration of the radioisotope.
Nt is the concentration of the isotopes remaining. To find concentration
of isotope decayed, use concentration of initial isotope- concentration of
isotope remaining.
To find the percentage of isotope decayed, use decayed amount/ initial
amount x 100%.
To find the amount of isotope decayed, use mol x molar mass.
Important Reminders: remember the formula. Remember to check if
the question is asking for isotopes REMAINING or isotopes
DECAYED. Also check if they are asking for CONCENTRATION,
PERCENTAGE, or MASS. Remember to include your UNITS when
relevant (E.g., after an answer or on labels of a plot)
Also, remember that all first order reactions have constant half-lives.
You could see a connection between reaction kinetics and half-life on
paper 2.
Fractional Distillation
Purpose of Technique
To isolate drug products from liquid mixtures that focuses on the difference in
volatility (which is influenced by intermolecular forces of attraction).
Steps to Carry out Procedure
Fractional distillation is very similar to simple distillation, except that it uses a
fractionating column. The fractions created contain a mixture of liquids with
very similar boiling points.
How it works?
When boiling a mixture of substances, the more volatile compounds will exert
greater vapour pressure at the same temperature.
The vapour is collected and condensed back to form a solution it will be
enriched with the most volatile component of the original mixture.
This cycle of evaporation-collection-condensation is repeated then better
separation of the components is possible.
Fractionating column is used in fractional distillation. Surface area inside the
column contains glass beads to increase and maximize surface area inside.
Boil-condensation cycles occur in the column.
As solution boils, vapour rises within the column until it reaches a cool region
and then condenses and falls back down.
It will evaporate again once the vapour rising from below reaches it.
After many of these cycles have occurred, ideally the most volatile component
of the initial solution will exit the top of the column in the form of vapour. The
vapour is then cooled by a cold water condenser and the liquid is collected which
is primarily the most volatile component from the original sample solution used.
*The collected sampled can be distilled again and again to obtain the pure form.
Important Reminders: Fractional distillation is based Raoult’s Law. One must
understand mole fractions, vapour pressure and Raoult’s Law.
Solvent (Liquid-Liquid) Extraction
Purpose of Technique
To separate compounds (solutes) based on their relative
solubilities in two different immiscible liquids (solvents), usually
water and an organic solvent. It exploits the fact that solute used
will likely be more soluble in one of the solvents versus the other.
The solute becomes unevenly spread between the two solvents
when given the chance to dissolve in both solvents.
Steps to Carry out Procedure
1. A product mixture (aqueous solution that contains
required product) is added to a separating funnel.
2. An organic solvent is added.
3. The funnel is shaken and the contents are allowed to
settle.
4. The less dense solvent will form the upper layer while the
denser solvent forms the bottom layer.
5. The bottom layer is drained.
6. If the desired product is primarily in the top layer, once
the bottom layer is drained, the solvent in the top layer is
evaporated to isolate the desired product.
7. If the desired product is in the bottom layer, the drained
solvent in the bottom layer is evaporated to isolate the
desired product.
Important Reminders:
*Solvent extraction is used in the preparation of penicillin.
Trichloromethane is used as the organic solvent to extract
penicillin from its aqueous solution.
*The desired product/solute must have different solubilities in
the two immiscible solvents.
*The solute (or desired product) will dissolve in whichever layer
(solvent) that it can form the best interaction with (solute
dissolve in solvent that is it most soluble in).
Additional Study Notes and Reminders regarding techniques: