HL1 Medicinal Chemistry

Mr. Steiner
 D7 - Taxol - HL

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Objectives

▶ Explanation of how Taxol (Paclitaxel) is obtained and used as

a chemotherapeutic agent.

▶ Description of the use of chiral auxiliaries to form the desired

enantiomer.

▶ Explanation of the use of a polarimeter to identify

enantiomers.

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Taxol

▶ Taxol is sometimes known as Paclitaxel, and is one of a

group of related compounds known as taxoids.

▶ It is used primarily in the treatment of breast and

ovarian cancers.

▶ Taxol’s anti-cancer properties are a result of its ability to

bind to a protein called tubulin in cells.

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Chiral Molecules

▶ Biological molecules have very specific 3D shapes

▶ Since drugs act on biological molecules, their 3D shape

(as determined by stereoisomerism) is very important.

▶ Thalidomide – one enantiomer (optical isomer) is highly

effective, the other causes horrific birth defects

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 Chiral Auxiliaries
▶ A chiral auxiliary is like a template that allows us to selectively make
one optical isomer (enantiomer) over another (rather than the usual
50:50 mix).

▶ A chiral-molecule (the auxiliary, X) temporarily binds to our substrate

(S) in such a way as when the substrate reacts with a reactant ®, it can
only form one of the two possible optical isomers
X + S → X-S
X-S-R enantiomer A
X-S + R X
X-S-R enantiomer B
X-S-R → X + S-R (isomer A)

▶ Techniques like this were used in the synthesis of the highly chiral
anti-cancer drug taxol (left)
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D8 – Nuclear medicine - HL

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 Objectives
▶ Discuss common side effects from radiotherapy.

▶ Explain why technetium-99m is the most common radioisotope

used in nuclear medicine based on its half-life, emission type and
chemistry.

▶ Explain why lutetium-177 and yttrium-90 are common isotopes

used for radiotherapy based on the type of radiation emitted.

▶ Balance nuclear equations involving alpha and beta particles.

▶ Calculate the percentage and amount of radioactive material

decayed and remaining after a certain period of time using the
nuclear half-life equation.

▶ Explain TAT and how it might be used to treat diseases that have
spread throughout the body. Main
 Nuclear medicine
▶ The stability of an atom’s nucleus depends on the number
and type of nuclear particles present, the so-called nucleons,
which vary in different isotopes of the same element.

▶ Stable nuclei have balanced forces among the nucleons and

so are not reactive.

▶ Unstable nuclei have unbalanced forces and an excess of

internal energy, and so they spontaneously decay to form
more stable nuclei, in a process known as radioactivity.
These unstable nuclei are known as radionuclides.

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 Radionuclide decay
▶ When radionuclides decay into a more stable form, one or more
of the following events occurs in the nucleus:
• the ejection of a neutron
• the ejection of a proton
• the conversion of a neutron to a proton with the ejection of an
electron, known as a beta particle
• the conversion of a proton to a neutron with the ejection of a
positron
• the release of additional energy by the emission of photons,
known as gamma rays.

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Alpha and Beta Decay

Emission of an alpha particle causes the mass number of a

radionuclide to decrease by 4 units and the atomic number to
decrease by 2 units.
An example of beta decay is when thorium is converted into
protactinium:

Beta radiation is the ejection of electrons from the nucleus.

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Gamma Radiation page 908
▶ Gamma radiation is the emission of energy as
electromagnetic waves (or photons).

▶ The photons are denoted as γ.

▶ Gamma radiation results from energy changes in the

nucleus and does not alter the atomic number or the
mass number.

▶ It often accompanies alpha or beta radiation as the

energy of the radionuclide is lowered during radioactive
decay.

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▶ v

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Ionization density

▶ Ionization density refers to the average energy released

along a unit length of their track.

▶ Alpha particles with their +2 charge and relatively large

mass, have a high ionization density.

▶ X-rays and γ-rays have a lower ionization density.

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Half-life page 909
▶ The half-life, t1⁄2, is the time taken for the concentration
of a reactant to decrease to one half its original value

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 99m
Technetium-99m, 43
Tc

▶ The tracers used in radiopharmaceuticals must emit

gamma rays with enough energy to escape from the
body and must have a half-life just long enough for the
scan to be complete before its decay.

▶ The radiopharmaceutical most widely used in diagnosis

99m
is technetium-99m, 43Tc. This isotope is used in about
80% of all nuclear imaging procedures.

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 99m
Technetium-99m, 43
Tc
▶ Its half-life is 6 hours.

▶ Biological half-life of 24hrs.

▶ Technetium is chemically versatile, so acts as a tracer by

bonding to a range of biologically active substances.
These are chosen according to the organ to be studied.

▶ Its decay involves the release of gamma rays and

low-energy electrons. Without high- energy beta
emission, the radiation dose is low. Low-energy gamma
rays escape the body and are accurately detected by the
gamma camera.

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Radioactive Decay Calculations
Data Booklet Equations

▶ (C.3) N = N0e-λt

▶ (C.3 & D.8) t1/2 = ln2

λ
t
t1/2
▶ (D.8) N(t) = N0(½)

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MRI
▶ MRI is an application of nuclear magnetic resonance
(NMR).

▶ MRI does not use ionizing radiation, so is considered

relatively non-invasive.

▶ Radio waves are low-energy waves and there are no

known hazards of the exposure of the body to the
strength of magnetic fields applied.

▶ MRI scans give detailed images of almost any part of

the body and are used in cancer detection, the diagnosis
of soft tissue injuries, and in monitoring degenerative
diseases. Main
Alpha, beta and gamma rays
▶ If the radioactive source is inside the body:
▶ Alpha radiation is the most dangerous because it is easily absorbed by
cells.
▶ Beta and gamma radiation are not as dangerous because they are less
likely to be absorbed by a cell and will usually just pass right through it

▶ If the radioactive source is outside the body:

▶ Alpha radiation is not as dangerous because it is unlikely to reach living

cells inside the body.
▶ Beta and gamma radiation are the most dangerous sources because
they can penetrate the skin and damage the cells inside.

▶ Notice that these effects are opposites and make sure you get them the
right way around.
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 Radionuclide therapy
▶ Cancer cells arise when normal cells lose their regulatory
mechanisms for the control of growth and division, and are
characterized as rapidly growing abnormal cells, often known as a
tumour.
▶ The fact that they are rapidly dividing can make cancerous cells
particularly sensitive to damage by radiation.
▶ This is because its ionizing effect primarily affects DNA that
controls cell division.
▶ Radionuclides used in therapy are ideally strong beta-emitters
that also emit gamma radiation to enable imaging. Lutetium-177
and yttrium-90 are widely used on the basis of their emissions.
Yttrium-90 is increasingly also being used in arthritis treatment.

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 TAT (targeted alpha therapy)
▶ Controlled amounts of lead-212 or actinium – 225 are
delivered by a drug or protein to the cancer cells.

▶ Alpha-emitting nuclides are emitted.

▶ Alpha particles cause more damage to cellular tissue than

the other types of radiation

▶ However it has a very short range and healthy cells are less
likely to be irradiated.

What is the nuclear equation for Pb-212?

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Boron Neutron Capture Therapy (BNCT)

▶ Used mainly brain and neck tumours.

▶ High dose of non-radioactive boron-10 is given to the

patient and this accumulates in the malignant tumour.

▶ The tumour is radiated with neutrons which is absorbed

by the boron. (BNC)

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 Side-effects of radiotherapy
▶ External radiotherapy tends to cause more general
side-effects than internal therapy.

▶ The ionizing effects of radiation cause changes in the DNA

of healthy as well as cancerous cells, particularly in those
that divide rapidly, such as hair follicle cells.

▶ Most common side-effects are:

▶ fatigue – rest and regular hydration are important during treatment
▶ nausea – more common when the treatment is in the area of the digestive
system
▶ hair-loss – this occurs within the treatment area and is usually temporary
▶ sterility – more likely if treatment is close to ovaries or testes
▶ skin reaction – skin may become red, sore, or itchy in local area of irradiation.

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