HL CHEMISTRY NOTES

Justin Kim
Table of Contents
STOICHIOMETRY 2
ATOMIC STRUCTURE 4
HL ATOMIC STRUCTURE 6

PERIODICITY 8
HL PERIODICITY 10

CHEMICAL BONDING AND STRUCTURE 16

HL CHEMICAL BONDING AND STRUCTURE 18

ENERGETICS 23
HL ENERGETICS 25

KINETICS 28
HL KINETICS 32

EQUILIBRIUM 36
HL EQUILIBRIUM 38

ACIDS AND BASES 41

HL ACIDS AND BASES 46

REDOX 49
ORGANIC CHEMISTRY 60
HL ORGANIC CHEM 77

ANALYTICS 86
MEDICINAL CHEMISTRY 90
PHARMACEUTICAL PRODUCTS AND DRUG ACTION, D.1 90
ASPIRINS AND PENICILLIN, D.2 97
OPIATES, D.3 102
PH REGULATION OF THE STOMACH, D.4 104
ANTIVIRAL MEDICATIONS, D.5 107
ENVIRONMENTAL CHEMISTRY, D.6 114
TAXOL: A CHIRAL AUXILIARY CASE STUDY, D.7 116
NUCLEAR MEDICINE, D.8 119
DRUG DETECTION AND ANALYSIS, D.9 128
Stoichiometry
 Determination of the amount of a substance using formulae and equations
 Relative atomic mass
o Absolute value is difficult to measure
o Mass of atom is measured as relative to another atom
 This is Carbon-12, agreed to by the IUPAC
 1 atom of Carbon-12 weights 1.99x10^-23 grams
 Therefore 12 g of Carbon-12 has approx. 6.02x10^23 atoms
 Avogadro’s number (Mole)
o A number of entities or particles
o A mass
 (M) Molar mass of a compound = Abs. mass(g)/moles(n)
o Relative atomic mass (A(r) )
 Mass relative to 1 atom of Carbon-12
o Relative molecular mass (M(r) )
 Mass relative to 1 atom of Carbon-12
o Atomic mass
 Mass of 1 mole of atoms (g/mol.)
o Molecular Mass
 Mass of 1 mole of molecules (g/mol.)
o Formula mass
 Sum of all atomic masses (g/mol.)
o Number of moles(n) = (M) Mass of substance (g) / (m) molar mass (g)
o Number of particles = number of moles (n) x Avogadro’s number
 Law of conservation of mass (Lavoisier)
o Matter can neither be created nor destroyed during a chemical reaction
o Law of definite proportions (Proust)
 Elements combine to form compounds in certain well-defined
proportions (by mass)
 Law of multiple proportions (Dalton’s Law)
 If two elements form more than one compound between
them, then the ratios of the masses of the second elements
which combine with a fixed mass of the first element will be
ratios of small whole numbers
 Gases – 1Pa = 1N/m^2
o Boyle’s Law
 Volume and pressure are inversely proportional ,V
o Charles’ Law
 Volume is directly proportional to temperature at constant pressure
and number of moles,
 V=kT, where k
 V1 = kT, V2 = kT
 Therefore k = V1/T1 = V2/T2
o Pressure Law
 Pressure in directly proportional to temperature at constant pressure
and no. of moles,
 o Avogadro’s Law

 PV = nRT
o P = Pascals (when V is in cubic metres) or Kilopascals (when V is in dm^3
o V = Cubic metres (when P is in Pascals) or decimeters cubed (when P is in
kilopascals)
o n = number of moles
o R is gas constant (8.31 J/K/mol.)
o T = Kelvin
 An ideal gas
o Volume of particle is ignored
o Particles mass is ignored
o Kinetic energy Temperature
o These assumptions hold at low P and high T, but they break down at High P
and low T
 Molar Volumes
o STP
 0°C/273.15°K, 100kPa, = 22.7 dm^3/22.7L per mole
o SATP
 25°C/298.15°K, 100kPa = 24.79 dm^3/24.79L per mole
 Molarity
o Concentration = n(moles of solute) / dm^3 of solution
o When n is the same, C1/V1 = C2/V2
Atomic Structure
 The nuclear atom
o Each kind of atom is different element
o 92 naturally occurring
o Atoms make up matter
 Cannot be created or destroyed
o Atoms make up
 Compounds
 Elements
 Structure of an atom
o Energy and spectra
 Emission spectra are formed when excited particle drop to a lower
energy state and emit a particular radiation frequency
 Absorption spectra are formed when particles absorb a particular
frequency to move to a higher energy state
 Energy is quantized (Bohr’s atom)
 Electrons
o The electrons of an atom are thought of as being in shells
 2n^2 electrons in each shell
 0  n-1
 l=0 (s), Group 1 and 2
 l=1 (p), Group 13 – 18
 l=2 (d), Group 3 – 12
 l=3 (f), Lanthanides and Actinides
 Definitions
o Atomic radius (r) is measured as half the distance between neighbouring
nuclei (measured in angstroms = 10^-10m)
o Ionic radius is half the distance between two ions that are barely toughing
eachother (measured in angstroms = 10^-10m)
o First ionization energy of an element is the energy required to remove one
mole of electrons from one mole of gaseous atoms in their ground state
o The electron affinity of an atom is the energy change that occurs when one
mole of electrons is added to one mole of gaseous atoms (kJ/mol.)
o Electronegativity is the ability of an atom to attract electrons in a covalent
bond
o Melting point is the temperature at which the solid and liquid phases of a
substance are in equilibrium at a specified pressure
  History of the periodic table
Name Contribution to knowledge of the Elements/Periodic Table
Aristotle (330 BCE) Four element theory of air, water, fire and earth (and later on,
ether, making up 5. He theorized that ether made up the stars,
moon and planets) He determined which objects were made
up of which of the four/five elements due to their physical
Characteristics
Antoine Lavoisier (1770 – 1789 Detailed list of 33 elements. First to distinguish between
CE) metals and non-metals, alluding to the idea of groups we have
in the modern periodic table
Jöns Jakob Berzelius (1828 CE) Developed a system of ordering elements by atomic weights,
first to use letters to symbolise elements.
Johann Döbereiner (1829 CE) Developed triads of elements with similar physical properties
and reactions
Li, Na, K
Ca, Sr, Ba
Cl, Br, I
First material theory of groups.
John Newlands (1863 CE) Formed a basic periodic table with a periodicity of 7, as the
Halogens had not been fully discovered yet. Was not taken
seriously as this theory of “Octaves” was not followed past the
first 2 periods.
Lothar Meyer (1864 CE) Published “the Modern theory of Chemistry”, using atomic
weights to categorise elements in the periodic table. However,
did not leave gaps in the table for missing atomic weights of
elements not yet discovered.
Dmitri Mendeleev (1869 CE) “Father of the modern periodic table”, used atomic weights as
well as similar characteristic to categorise elements and left
spaces for undiscovered elements, and was able to predict
their structure and physical attributes using the table.
Element named after him as ‘mendelevium’
Lord Rayleigh + William Ramsey Discoverers of the Noble Gases, filling up the major missing
(1894 CE) chunk of Mendeleev’s periodic table.
Henry Moseley (1913-1914 CE) Used x-ray emissions of atoms to show that atomic number
(no. of protons/electrons) of an atom was the way to arrange
rather than atomic weight. This solved the issues with
Mendeleev’s periodic table.
Glenn Seaborg (1944 CE) Synthesized transuranic (elements after no. 92, Uranium)
elements, as well as characterizing the heavy elements
including Actinides and Lanthanides.
Element named after him as “Seaborgium”
HL Atomic Structure
 In an emission spectrum, the limit of convergence at higher frequency corresponds
to the first ionization energy.

o Thus, the y-intercept is the ionization energy.

o Through , it is possible to determine the frequency, and thus, the wavelength
of the limit of convergence .

 Trends in first ionization energy across periods account for the existence of main
energy levels and sub-levels in atoms.

 Successive ionization energy data for an element give information that shows
relations to electron configurations.



Periodicity

 Diatomic molecules
o Have No Fear Of Ice Cold Beer
o Hydrogen
o Nitrogen
o Fluorine
o Oxygen
o Iodine
o Chlorine
o Bromine
 Alkali metals (group 1)
o Reactivity increases as you go down periods
o All solids
 Halogens
o Reactivity decreases as you go down periods
o F and Cl are gases, Br is a liquid, I is a solid
 Properties of Metals
o Lustrous
o Conductors of heat and electricity
o Malleable
o Ductile
o Solid at room temperature (except Hg)
 Semi-metals
o Can conduct electricity (semi-conductors)
o Used in organic chemistry usually
HL Periodicity
 D-block elements
o 4s Shells filled before the 3d shell
o Oxidation states tell us the change on the monatomic metal ion
 Indication of how many electrons have been “lost”
o The transition metals are those metals that have partly filled d-subshells in
one of its common oxidation states
 Electron configuration of the period 4 elements

o
 o

o Stability of half-filled and filled orbitals

o Similar atomic radii and ionization energies, hence similar physical and
chemical properties
o 4s electrons shielded by 3d electrons

 Formation of alloys
o Similar sized atoms fit into the lattice more easily with less disruption
o Variable oxidation states
 All have +2 (removal of the 4s electrons)
 All have +3, but higher oxidation states harder for the later elements
due to increased nuclear charge
 Increasing oxidation states moving across to Mn then decreases
 Oxidation states above +3 show covalent character
 Higher charge density, polarizes anion, increased covalent
character
 Higher oxidation states tend to be oxidizing agents
 Distinguishing properties
o Multiple valencies or oxidation states
o Forms complex ions
o Frequently highly coloured compounds
o Display catalytic properties
o Display magnetic properties
 Variable oxidation states
o Loss of the 2 4s electrons means that the 2+ oxidation state is commonly
found amongst the transition metals
o Stability of 2+ increases across as nuclear charge increases
o Due to the closeness in energies of the 3d and 4s, multiple valencies are
possible
 Complex ion formation
o Unfilled orbitals of transition metals (also elements in lower half of “p” block)
can accept a long pair of electrons to form a molecule and form complex ions
o Molecules that donate electrons pairs and form a coordinate covalent
(dative) bond in this way are called ligands
 E.g. Cl-, NH3, CN-, H2O, H2NCH2NH2, C5H5N (Pyridine), PPh3, EDTA
 o Ligands can donate a single pair of electrons (monodentate) or multiple pairs
(polydentate)
o Coordinate number
 Number of ligands in covalent coordinate bonds around the central
ion
 Commonly tetrahedral and octahedral
 Highly coloured compounds
o Ligand will affect the colour of the metal ion complex by altering the energy
difference between d-orbitals
 Empty or full ‘d’ orbitals have no colour
o Absorption of energy to move electrons between d orbitals to higher
energies results in colour
o Isomerism
 Same molecular formula, different structural formula
 PtCl2(NH3)2, CIS Platin, biologically active

 Catalysis
o Transition metals used as catalysts
 Can accept a lone pair of electrons (close contact between metal and
ligand)
 Wide variety of stable oxidation states means it has an ability to be
involved in redox reactions (loss and gain of electrons)
 Examples of heterogeneous catalysis
o H2O2 decomposition using MnO2
 Contact process (V2O5)
 Haber process (Fe)
 Hydrogenation of alkenes (Ni)
o Fe in hemoglobin, O2 transport
2+

o CO3+ in Vitamin B12, 5 sites, 6th available for biochemical reactions

 Magnetic properties of transition metals

o Diamagnetism
 Property of all materials
 Weak opposing magnetic field to an applied magnetic field
o Paramagnetism
 Stronger than diamagnetism
 Only materials with unpaired electrons
 Produces a magnetic field similar to/same as an applied magnetic
field
o Ferromagnetism
 Largest effect
 Produces field much greater than applied
 Long range effect due to long range of ordering of unpaired electrons
 Unpaired d-orbitals in large numbers of atoms in ‘domains’
 These domains arrange in a order when magnetic field is applied
  The effect lasts after magnetic field is removed, as domains remain
aligned due to the long range interactions
 E.g. Fe, Ni, Co
 How to tell the difference between Ferromagnetism and Diamagnetism
o Paramagnetic
 One or more unpaired electrons
 Pulled into an external magnetic field
o Diamagnetic
 All electrons are paired
 Repelled by an external magnetic field
o Carbon is paramagnetic – 1s2 2s2 2p2
o Helium is diamagnetic – 1s2
o Sodium is paramagnetic – 1s2 2s2 2p6 3s1
o Na+ is diamagnetic – 1s2 2s2 2p6
 Coloured complexes
o Complex ions of transition metals are coloured
 Therefore, certain frequencies have been absorbed
o Colour is the non-absorbed colour wavelength
o Some colours are absorbed, we observe the colours that aren’t
o If d-orbital is full or empty, no electrons promotion can take place, so the
complex appears white or colourless
o D-orbitals at the same energy are degenerate
o However, the energies of the d-orbitals can change
o In the presence of an electric field, their energies change and are split
o Ligands provide these electric fields which causes the d-orbital to split in
energy
o EMR in visible region will match the energy gap at some
o Colour is affected by
 Ligand
 Metal ion (central, oxidation state)
 Charge density of ligand
 Geometry of ligand (electric field)
 No. of d-electrons
o Consider Mn2+ and Fe3+
 Both are [Ar] 3d5
 Higher nuclear charge of Fe3+ means that the ligand is attracted more
 Therefore;
 Mn(H2O)6 is pale pink, (absorbs green light)
 Fe(H2O)6 is yellow brown (absorbs blue light)
o Charge density of ligand
 As charge density increases, the split in the d-orbital energy increases
 Spectrochemical series
 E.g. Cu(H2O)62+ vs. Cu(NH3)62+
 Blue vs. Deep blue respectively
 Deep blue absorbs more in the shorter yellow region
 I < Br- < S2- < Cl- < F- < OH- < H2O < SCN < NH3 < CN- CO
-

 Number/geometry of ligands
o Co(H2O)62+ = pale pink, CoCl42- = dark blue
o Orientation of ligand with respect to d-orbital geometry
o being absorbed
o Tetrahedral arrangement creating greater split
 Number of d-electrons and oxidation state
o Ions of an element will have the same nuclear charge
o Different oxidation states will have different d-electrons
o As oxidation state increases, d-orbital split increases

o
Chemical Bonding and structure
 Chemical bonds
o A chemical bond is the force of attraction that acts strongly enough to hold
particles together
o If no forces between particles of a substance  gas
 Ionic bonds
o High melting and boiling points due to electronegative attraction between
the ions in a lattice being very hard to break through just heat energy
 NaCl – 800°C (Melting point)
 Na2O – 1132°C (Melting point)
 MgO – 2800°C (Melting point)
o The higher the electrostatic charges between the two ions, the higher the
melting and boiling point
 Giant Covalent structures
o Very high melting and boiling points as all covalent bonds within the
structure need to be broken through just heat
 Diamond – 4000°C (Melting point)
 Graphite – 3600°C (Melting point)
 Molecular Covalent
o Very low boiling and melting points as intermolecular forces are very weak
and break down easily
 Metallic bonds
o High melting and boiling point, as it is a lattice of positively charged particles
within a “sea” of electrons
 Bonding in Carbon
o Single bonds
 0.154nm
 Bond energy – 346 kJ/mol.
o Double bonds
 0.134nm
 Bond energy – 598 kJ/mol.
o Triple bonds
 0.129nm
 Bond energy – 837kJ/mol.
 Allotropes  Different forms of the same element
o Graphite, Graphene, Bucky balls, Carbon nanotubes, Diamond, Coal
 Isomers  Same molecular formula, different structural formula
o C5H12
 Pentane
 Methylbutane
 Dimethylpropane
 Intermolecular bonds (Van der Waal’s forces)
o Dipole-dipole bonds
o Hydrogen bonds (between Hydrogen and Oxygen, Fluorine and Nitrogen)
o Dispersion forces (temporary)
HL Chemical Bonding and Structure
 Expanded Octet
o Occurs for elements after period 3
o Due to the similarity in energy levels of the electrons in the d orbitals and the
p orbitals
o Promotions of electrons, for example from the 3p to the 3d orbital, allows
additional electron pairs to form
 Species with 5 electron domains
o Electron domains arrange in triangular bipyramidal structure
o Bond angles of 120, 180 and 90
o Non-bonding pairs prefer to be in the equatorial plane, so that they have a
maximum distance between them
o One non-bonding pair gives a see-saw shape molecule
 Bond angles of 90, 117 and 180
 
o Two non-bonding pairs give a T shaped molecule
 Bond angles of 90 and 180


o Three non-bonding pairs give a liner shape
 Bond angle of 180


 Species with 6 electron domains
o Electron domains arrange in a square bipyramidal structure/octahedral
structure
o Bond angles are 90
o All electron domains are equally apart from each other
o One non-bonding pair results in a square pyramidal molecule
 Bond angles of 90 and 180


o Two non-bonding pairs results in a square planar molecule
 VSEPR Theory, non-bonding pairs repel from each other most
 Bond angles of 90 and 180


 Shapes and Molecules predicted from VSEPR Theory
 Molecular Geometry and Molecular Polarity
o Geometry determines polarity
o Polarity of a molecule can be determined from the orientations of its polar
bonds, and whether the bond dipoles cancel or not
o If no lone pairs and everything attached to the central atom is the same, then
no polarity
 E.g. PCl5, SF6


o If there are no lone pairs but not everything attached to the central atom is
the same, there may or may not be a net dipole depending on symmetry

 E.g.
o The presence of lone pairs often, but not always, dictates an overall polarity


 Formal Charge
o A tool for finding the most stable structure out of a molecule’s resonance
structures
o E.g. SO2


o Formal Charge (FC) is;
 No. of Valence electrons in unbonded atom (V) – No. of electrons
assigned to atom in Lewis dot structure
 No. of electrons assigned = ½ the electrons in bonded pairs (B)
+ no. of electrons in lone pairs (L)
 FC = V – (½B + L)


 FC = 0 is most stable
 Bond overlap
o Explains how orbitals shaped as spheres and cones can form bond angles
such as 109.5
o Simple way of describing the amalgamation of two atomic orbitals
o Sigma Bond
 When two atomic orbitals combine along the inter-nucleic axis, an
imaginary line between the two atoms’ nuclei


 Electron density is concentrated between the two atoms’ nuclei
o Pi Bond
 When two atomic orbitals combine perpendicular to the inter-nucleic
axis, an imaginary line between the two atoms’ nuclei


 Hybridisation
o Carbon, in an excited state, promotes one of the electrons in its 2s orbital to
the 2p orbital, so that there are 4 unbonded pairs of electrons to create
bonds with
o These four electrons, one from the s orbital and 3 from the p orbital,
combine to create hybrid bonds
o Sp3
 A hybridised bond with 75% p orbital character and 25 s orbital
character


 E.g. Methane, where there are 4 sp3 bonds formed out of carbon’s
valence electrons


o Sp2
 When carbon forms a double bond, it undergoes sp2 hybridisation,
where the s electron and two of the p electrons hybridise to create
three equal molecular bonds


 These are in a trigonal planar structure
 E.g. Ethene


 Double bond, with a sigma and a pi bond
o Sp
 When carbon forms a triple bond, it undergoes sp hybridisation,
where two equal bonds are formed


 E.g. Ethyne


 Hybridisation and predicting molecular shape


Energetics
 Enthalpy
o Heat is a form of energy
o Is the heat content or total energy of a system or substance (H)
o A standard enthalpy change refers to an enthalpy change under standard
conditions (100kPa, 1mol.1dm^3)
o We measure changes in enthalpy (∆H) Temp = 298K
 Not absolute enthalpy
o Through forming bonds, energy is released, therefore ∆H < 0
 Exothermic, ∆H < 0
o Through breaking bonds, energy is added to the system, therefore ∆H > 0
 Endothermic, ∆H > 0
o Change in enthalpy/heat should always be presented beside the reaction to
which it applies and should always have a sign (±)
 Heat and Temperature
o Temperature = kinetic energy of particles of a substance
 Measured in Kelvin (K)
 ∆T of a substance in a reaction depends on
 Mass
 Heat capacity (Joules/K/g)
o Heat energy/Change in heat energy = mc∆T
 m = mass (g)
 c = heat capacity (water is 4.18)
 ∆T = Change in temperature (°K)
 Hess’s Law
o First Law of thermodynamics
o Energy can neither be created or destroyed, but only converted from one
form to another
o The corollary of this is that for a given chemical process, the energy change
will be the same regardless of the reaction pathway, or even if a pathway is
possible.
o ∆H1 = (∆H2 + ∆H3) = (∆H4 + ∆H5 + ∆H6

 Heat of formation
o ∆Hf
o The enthalpy chance when one mole of a substance is formed form its
constituent elements, both in their standard states
o ∆H = ∑∆Hf (p) + ∑∆Hf (r)
HL Energetics
 Lattice Enthalpy :
o The amount of energy required to convert one mole of a substance into
gaseous ions.
o Lattice enthalpies are influenced by the charge and size of the ions.
o The greater the charge of the ion, the higher the lattice enthalpy.
o The greater the size of the ion, the lower the lattice enthalpy.
o
 Enthalpy of Solution :
o The energy change when one mole of an ionic compound dissolves in water
to give an infinitely dilute solution.
o
 Enthalpy of Hydration :
o The energy change when one mole of gaseous ions dissolve to give an
infinitely dilute solution.
o Enthalpy of a hydration is influenced by ionic radius and charge.
o The greater the charge, the greater the enthalpy of hydration.
o The greater the ionic radius, the lower the enthalpy of hydration.
o

o
 Enthalpy of Atomisation :
o The enthalpy change that occurs when one mole of gaseous atoms is formed
from the element in its standard state.
o
o
 Born-Haber Cycle:


o Enthalpy of lattice formation is the opposite of lattice enthalpy.

 Spontaneity:
o Spontaneous changes occur without the need to do work, aside from the
energy required to surpass the activation energy. The reversal of a
spontaneous change comes at the expense of energy.
 Entropy (S):
o Entropy refers to the distribution of available energy amongst the particles.
o The more ways the energy can be distributed, the higher the entropy.
o Enthalpy can also be thought of as the level of disorder of a substance.

o
o As everything tends to disorder, entropy increases with time.
o Increasing the number of particles increases the entropy.
o The entropy of a substance is highest in its gaseous state.
o The entropy of a substance is lowest in its solid state.
 o
o
 Gibbs Free Energy :
o
o , for spontaneous reactions.
o If is low, then only exothermic reactions are feasible.
o However, if is sufficiently high, any reaction can occur, given a favourable
entropy change.

o
 Gibbs Free Energy and Equilibrium:

o

Kinetics
 Rate of Reaction :
o The rate at which products are formed or reactants consumed.
o It is measured by change in concentration over change in time.
o
o

 Complex bonds take longer to break down than simpler bonds.

o Complex Bonds:

o Simple Bonds:

 The reaction rate at a certain moment in time during the reaction is found by
drawing a tangent to the curve.
 o

 Types of Rate of Reaction:

o Initial Rate:
 Found by drawing a tangent to the curve at It is the highest rate of
reaction. Minimises the effect of an endothermic or exothermic
reaction’s effect upon temperature, and consequently the rate of
reaction.
o Instantaneous Rate:
 Found by drawing a tangent to any point on the curve, to find the rate
of reaction at that particular moment.
o Average Rate of Reaction:
 Found by drawing a tangent to each endpoint and finding the mean of
their gradients.
o Values can also be summarised in a table, or otherwise graphically
represented.
 Methods of Experimentally Monitoring Rate of Reaction:
o Volume:
 Requires a gaseous product. Measured using a gas syringe or inverted
beaker of displaced water (provided the gas is insoluble in water).
o Mass:
 Continuous readings of mass. Requires gaseous product. Change in
mass is indicative of rate of reaction. If there is not a significant mass
change then this may prove an insufficient method.
o Colorimetry (Spectrophotometry):
 The change in a mixture’s absorbance of light. Measured using a
colorimeter.
 Kinetic Theory:
o Particles in a gas are:
  Continually in random motion. (Brownian motion)
 Straight-line motion.
 Point particles
 No inter-particle forces.
 All collisions are completely elastic.

 Particles will have higher or lower kinetic energy than
 Maxwell-Boltzmann Distribution Curve:
o The kinetic energy of a substance is not equally dispersed.

 Reaction Occurrence:
o Particles must have sufficient kinetic energy and correct geometry upon
collision, in order to successfully react.
o Particles must have kinetic energy greater than the necessary activation
energy to react during the collision.
o
 o

o Likewise, particles must collide with appropriate geometry in order to react.

o These two conditions are both necessary for particles to react upon collision.
 Influential Factors Upon Reaction Rate:
o Temperature:

 Therefore, temperature dictates both the frequency and kinetic
energy of collisions.
 An increase in temperature increases reaction rate.

o Concentration:
 Concentration dictates the frequency of collisions.
 A higher concentration increases the reaction rate.
o Particle Size:
 Particles size dictates surface area, therefore, the frequency of
collisions.
 A smaller particle size increases reaction rate.
o Catalyst:
 Catalysts lower the activation energy without chemically changing
themselves. Increases both the forward and reverse reaction rates. It
does not affect equilibrium position or yield.
 

 Q: What are the 3 characteristics of reactants particles which affect the rate of
reaction?
o A: Collision Geometry, Energy of Collision and Frequency of Collisions.
HL Kinetics


 Use potential energy level profiles to illustrate multi-step reactions; showing the
higher Ea in the rate- determining step in the diagram.
 Catalysts are involved in the rate-determining step.
 Any experiment which allows students to vary concentrations to see the effect upon
the rate and hence determine a rate equation is appropriate.
 Use energy level diagrams to illustrate multi-step reactions showing the RDS in the
diagram.
 Reactions where the rate-determining step is not the first step should be considered.
 Consider concentration–time and rate–concentration graphs.
 Overall Rate Expression:
o
o
o In respect to the reaction is x-order.
o In respect to the reaction is y-order.
o The entire rate is order.
o
o is specific to particular reactions.
o does not vary with concentration.
o varies with temperature.
o varies with particle size.

 Rate of Reaction and  Double Conc.  Triple Conc.

 Concentration
 Zero-Order  No Change To Rate  No Change To Rate
 First-Order  
 Second-Order  

 The Initial Rate Method:

o To determine the order of a reaction:
o Measure the initial rate of reaction
o Change the concentration of one reactant
o Measure the initial rate of reaction.
 Reaction Mechanism:
o Reactions do not occur instantaneously. .
o The reaction mechanism is comprised of several elementary steps.
o The slowest elementary step is referred to as the rate determining step (RDS)
o The rate determining step has the highest activation energy of the
elementary steps.
o Thus, the rate determining step influences the reaction rate.
o Most chemical reactions make a series of steps, each step passing through a
transition/intermediate species.
o Therefore, the reaction mechanism is a series of steps; each step is called an
elementary step.
o Elementary steps are impossible to observe.
o The sum of the elementary steps will give the overall chemical reaction.
o The slowest step of a series determines the rate of a multi-step reaction.
 Rate expressions are determined experimentally.
o Rate expressions can be inferred from considering a reaction mechanism and
the rate determining step.
o Molecularity:
 The number of reactant molecules involved in an elementary step.
(Uni-, Bi-, Ter-)
 The molecularity of the complete reaction equation is equal to the
molecularity of the rate determining step.
o Kinetics data doesn’t provide a reaction mechanism as it is impossible to
observe given the speed at which these elementary steps occur.
o Kinetics can only support or provide evidence against the proposed
mechanism.
 The reactants involved must:
o Appear in the rate expression
o Be raised to its stoichiometric coefficient in the RDS, in the rate expression.

 Molecularity  RDS  Rate Expression

 Unimolecular

 Bimolecular  
 

 Termolecular  
 
 

 In a bimolecular step the species collide to give a transition state (activated

complex), which breaks down.
 This transition state/activated complex:
o Has an unstable bond arrangement
o Both breaks and forms bonds
o Occurs at the maximum point of a Potential Energy Diagram
o Cannot be isolated.
o The products produced by the elementary steps are called intermediates.
o The activated complex and intermediates do not appear in the overall
reaction.
o
o
o Therefore, it is not a one-step reaction.
o It is zero-order with respect to .
o It is second-order with respect to .
 Extrapolation of Reaction Mechanism:
o
o
o This reaction mechanism is plausible because:
 Adding the two steps gives the overall reaction.
 There is an activated complex .
 The rate determining step corresponds with the rate expression.
 Catalysts:
o A substance which lowers the activation energy of a reaction without being
chemically altered itself.
o The catalyst lowers the activation energy of the rate determining step.
 Reaction Constant:
o In every rate expression there a constant, denoted by .
o The reaction rate depends on .
 Arrhenius’ Equation:
o
o Where,

 Dependent upon collision geometry and energetic
requirements



 Therefore, absolute temperature affects .
o An increase in when is low has a smaller effect upon than when the is high.
o The Arrhenius constant is related to the correct orientations of the colliding
molecules (geometry of collision) and their energetic requirements.


o Therefore, the Arrhenius constant can be found by plotting against , as the

Equilibrium
 Reactions are reversible.
o Some reactions do not achieve completion.
o Once dynamic equilibrium is reached the rate of formation matches the rate
of depletion.
o No macroscopic changes can be observed, once at equilibrium.
o At equilibrium the concentration of reactants and products does not change.
o Therefore, we talk about an EQUILIBRIUM CONSTANT
o E.g.





 The equilibrium constant does not apply to liquids or solids.

o Therefore, liquid and solid substances are eliminated from the expression.
o Only temperature can affect .

 Action  Effect on
 Inversing the reaction 
 Doubling the coefficients 
 Tripling the coefficients 
 Halving the coefficients 
 Adding Reactions 

 Reaction Quotient
o
o When the system is at equilibrium.
o If the equilibrium position will move towards the reactants.
o If the equilibrium position will move towards the products.
 Le Chatelier’s Principle:
o The system readjusts to counteract the change made to the system. Only
temperature affects the equilibrium constant.
o “If a stress is applied to a system at equilibrium, the equilibrium condition is
upset, a net reaction occurs in that direction which tends to relieve the
‘stress’ and a new equilibrium is obtained.”
 Concentration:
o If the concentration of the products increases, the equilibrium position
moves towards the reactants to counteract it and vice-versa.
 Pressure:
o An increase in pressure triggers the shifting of the equilibrium position
towards the side with a smaller number of molecules and vice-versa.

 Temperature:
o Whether a reaction is exothermic or endothermic determines whether heat
is a product or a reactant.
 o The equilibrium constant is affected by the temperature.
o Increasing the temperature of an endothermic reaction moves the
equilibrium position towards the products, increasing .
o Increasing the temperature of an exothermic reaction moves the equilibrium
position towards the reactants, decreasing .
 Catalyst:
o A catalyst increases both the forward and backward reaction rates.
o It does not affect , equilibrium position or yield.
o However, it does cause the reaction to reach equilibrium sooner.
 HL Equilibrium
Make sure the overall equation and equilibrium constant expression are consistent.
 ICEbox:
o Initial conditions/concentrations
o Change applied to the system
o Equilibrium conditions/concentrations
o

Initial
Conditions
Change

Equilibrium
Conditions
Concentration

o
o
o

Initial Conditions
Change
Equilibrium
Conditions
Concentration

o
 Gibbs Free Energy and Equilibrium:
o indicates if the forwards or reverse reaction is spontaneous (favoured).
o magnitude indicates if the reactants or products are favoured at equilibrium.
o These quantities are also influenced by temperature and for a given system
are related by the following equation.
o
 is in Joules
 is in (gas constant)
o



o Therefore,
o When
 The equilibrium mixture is mainly products.
o When
 The equilibrium mixture is mainly reactants.
o When
 Appreciably similar concentrations.
o So why do reactions have different values?
 is influenced by .
 in turn is influenced by and
o At equilibrium:
 Gibbs Free Energy is at a minimum. whether one starts with the
products or reactants.
 Entropy is at a maximum. For all spontaneous processes: . Entropy
must have reached a maximum at equilibrium.
 


Acids and Bases
 Timeline
o Lavoisier (1776): acids based on Oxygen, non-metal and hydrogen
o Davy (1810): Acids contain hydrogen
o Liebig (1830’s): Acids contain hydrogen which can be displaced by a metal
o Svante Arrhenius (1887): Electrolyte dissociation
 Acids produce H+ to a solution (AH  A- + H+)
 Bases produce OH- to a solution (BOH  B+ + OH-
 When H+ in water, forms a dative bond with H2O to form H3O+
 Amphoteric: Reacts with acids and bases
 Amphiprotic: Can both accept and donate protons (H+ ions)
 Bronsted-Lowry acids and bases;
o Have conjugate bases and acids
 NH3 + H2O  NH4+ + OH-
 NH4+ is conjugate acid
 OH- is conjugate base
o A Bronsted-Lowry acid must be able to dissociate with and release H+
o A Bronsted Lowry base must be able to accept a H+ ion, and so must have a
lone pair of electrons to form a dative bond
 Ph Scale:

o
o pH is related to the number of H+ ions.
o
o Thus, each unit of pH is one order of magnitude of

o
o pH can be measured using universal indicator or a pH meter.
o The pH scale is founded on the ionic product of water.
o
 o
o
 Acids and bases can both be corrosive.
o Colour changes in indicators.
o Some conduct electricity, produce electrolytes in water
o Electrolyte: Substances, which when placed in water allow the solution to
conduct electricity.
 Acid-Base Definitions:
o Arrhenius’ Theory:
 Acids create hydrogen ions, bases create hydroxide ions in an
aqueous state. Does not explain acid-base neutralisation reactions
outside of water.
o Brønstead-Lowry Theory:
 Bases accept protons . Acids donate protons. Does not explain acid-
metal reactions.
o Lewis Theory:
 Bases donate an electron pair. Acids accept electron pairs.
o Conjugate Acid-Base Pairs:
 In a neutralisation reaction (exothermic), the acid becomes a base
and the base becomes an acid. These are referred to as conjugate
acid-base pairs.

o
o Amphiprotic:
 A substance which can act as both a proton donor and a proton
recipient.
o Amphoteric
 A substance which an both react with acids and bases
o Salt:
 A substance whose hydrogen has been replaced by a metal or another
cation.
o Alkali:
 Soluble bases, which release hydroxide ions in water.
 Complete and Net Ionic Equations:
o
o Note: As this is a neutralisation reaction it is exothermic and:
 and are a conjugate acid-base pair.
 and are a conjugate acid-base pair.
 Complete Ionic Equation:
o All aqueous substances are ionised.
o
 Spectator Ions:
o Ionic species that remain unchanged after the reaction.
 Net Ionic Equation:
o All spectator ions are removed.
o
 Ionic Product/Equilibrium Constant of Water:
o
o
o
 Strong and Weak Acids and Bases:
o Strong acids and bases completely disassociate in water.
o Their conjugate pairs are weak bases and acids.
o Weak acids and bases do not disassociate completely, thus, the reaction
tends not to go to completion, and reaches an equilibrium instead.

o
 Distinguishing Between Strong and Weak:
o pHECRRE
 pH. As a measure of acidity/alkalinity it can be used to distinguish
strong and weak acids/bases.
 Electrical Conductivity. Due to possessing a higher concentration of
mobile ions, stronger acids and bases possess higher electrical
conductivity.
 Rate of Reaction. Stronger acids react at a faster rate than weaker
acids.
 Equilibrium position. Stronger acids and bases tend to result in
reactions going to completion. Thus, the closer the equilibrium
position is to the products the stronger the reactants are.
 Acid Deposition:
o Dissolved in the atmosphere causes rain to have a natural pH of as carbonic
acid is formed .
 Acid Rain:
o Atmospheric precipitation with a pH less than
 Wet Acid Deposition:
o When acid rain is deposited as an aqueous precipitate.
 Dry Acid Deposition:
o When acidifying particles fall to the ground, dissolving in water, forming
acids.
 Primary Pollutants:
o Sulfur oxides are released through the burning of coal and heavy oil. (SOB-
CHO).
o Sulfur oxides can form sulfurous acid and sulfuric acid .
o
o Nitrogen oxide are released through internal combustion engines. (NOICE).
o Nitrogen oxides can form nitrous acid and nitric acid
o
o

 The Effects of Acid Deposition:

o Destruction of marble and limestone.
o Corrosion of metals.
o Leaching of vital minerals within the soil. and are washed away.
o Exposure of toxic substances to plants.
o Eutrophication: the over-fertilisation of the soil by nitrates.
o Damage to aquatic ecosystems. It acidifies the water, decreasing the pH.

  is toxic and acidic. It interferes with fish gills and reduces their ability
to intake oxygen. Most aquatic lifeforms cannot survive in water with
less than a pH of
o Human harm. Damage to the respiratory system from inhalation of nitrates
and sulfates.
 Reduction of Acid Deposition:
o Pre-Combustion:
 Hydrodesulfurisation (HDS) is the use of hydrogen as a catalyst to
remove sulfur from refined petroleum. Crushing and washing coal
also removes metal sulfides.
o Post-Combustion:
 Flue-gas desulfurisation is the use of and to remove up to 90% of in
Flue-gas.
HL Acids and Bases
 Lewis Acids and Bases:
o A base is an electron pair donor.
o An acid is an electron pair receptor.
o NB: A Lewis acid or base does not necessarily affect the acidity or alkalinity.
o Examples:
 Coordinate (Dative) Covalent bonds
 Complex ions – Ligands (Lewis bases) and Central ions (Lewis acids)
o Nucleophiles (Lewis Bases)
o Electrophiles (Lewis Acids)
 pH of Water
o
o
o The reaction is endothermic.
o Therefore, if heat is added would increase.
o pH would decrease.
o pOH would increase.
o Thus, despite pH decreasing it would remain a neutral substance, as
 E.g. HCL
o
o
o
 E.g. CH3COOH
o
o
 Acid Dissociation Constant:
o is the equilibrium constant of the disassociation of an acid in water.
o
o
o
 Base Dissociation Constant:
o is the equilibrium constant of the disassociation of an acid in water.
o
o
o

o
 Example:
o
o
o Find the
o
o
o Since is very small we can assume remains

o
o
 The use of quadratic equations will not be assessed.


 Indicators
o Indicators provide a way to determine the acidity of bacisity of a substance
o They do this because they exhibit different colours in either acidic or basic
solutions
o E.g.
 Methyl Orange
 Phenolphthalein
 Bromothymol blue
 Universal Indicator
o The substance (often an organic dye) is a weak acid or base in equilibrium
with its conjugate


o Colour of the solution depends on which form of the indicator predominates
o Most indicators change colour within a range of 2pH (100x conc. Of H+ ions)
o Indicator most useful in a titration when the colour change occurs rapidly at
the equivalence point of the titration
 Buffer
o Able to resist small changes in pH
o Related to the equilibrium of the weak acid or base

o
o Buffer works best when the conc. Of the buffer salt is greater than the strong
acid or base
o Approximately equal amounts of a weak acid and its conjugate base
 E.g. CH3CHOOH  CH3COO- + H+
 Add NaCH3COO as a buffer
o Le Chateliers principle??
 When other external factors affect pH, compromises the system
 E.g. Adding H+ reacts with the conjugate base of CH3COO-
 However, adding OH- reacts with H+, but as there is a lot of
reactant left (small K), Le Chateliers principle causes more
CH3COOH to dissociate, replacing the lost H+ ions
o Making Buffers
 Weak acid + salt of weak acid
 Weak base + salt of weak base
 Small amount of strong base added to a weak acid
 Small amount of strong acid added to a strong base
 NB: Significant concentration of the acid and conjugate base for good
buffering
 Solutions of salts
o Some solutions of salts are neutral
 E.g. NaCl
o Others are basic or acidic – influenced by which anions or cations are present
o Solution of NaCH3COO is basic, as the CH3COO- ion is a strong conjugate base
for a weak acid
o Neutral anions come from strong acids
 Cl-, NO3-
o Neutral cations are group I and II cations
 Na+, K+, Ca2+
o Basic anions come from weak acids
 CH3COO-, CO32-, ClO-, S2-, F-
o Polyprotic acids produce both acidic and basic anions
 Acidic  HSO4-, H2PO4-
 Basic  HCO3-, HPO42-
Redox – HL and SL
Understandings:
● Oxidation and reduction can be considered in terms of oxygen gain/hydrogen loss,
electron transfer, or change in oxidation number.
● An oxidizing agent is reduced and a reducing agent is oxidized.
● Variable oxidation numbers exist for transition metals and for most main-group non-
metals.
● The activity series ranks metals according to the ease with which they undergo oxidation.
● The Winkler method can be used to measure biochemical oxygen demand (BOD), used as
a measure of the degree of pollution in a water sample.

Voltaic (Galvanic) cells:

● Voltaic cells convert energy from spontaneous, exothermic chemical processes to
electrical energy.
● Oxidation occurs at the anode (negative electrode) and reduction occurs at the cathode
(positive electrode) in a voltaic cell.
● A voltaic cell generates an electromotive force (EMF) resulting in the movement of
electrons from the anode (negative electrode) to the cathode (positive electrode) via the
external circuit. The EMF
is termed the cell potential (E*).
● The standard hydrogen electrode (SHE) consists of an inert platinum electrode in contact
with
1 hydrogen ion and hydrogen gas at 100 kPa and 298 K. The standard electrode potential
(E*) is the potential (voltage) of the reduction half-equation under standard conditions
measured relative to the SHE. Solute concentration is 1 or 100 kPa for gases. E* of the SHE
is 0 V.
● G* = –nFE*. When E* is positive, ∆G* is negative indicative of a spontaneous process.
When E* is negative, ∆G* is positive indicative of a non-spontaneous process. When E* is 0,
then ∆G* 0.
Guidance
● ∆G* = –nFE* is given in the data booklet in section 1.
● Faraday’s constant = 96 500 C mol−1 is given in the data booklet in section 2.

Electrolytic cells
● Electrolytic cells convert electrical energy to chemical energy, by bringing about non-
spontaneous processes.
● Oxidation occurs at the anode (positive electrode) and reduction occurs at the cathode
(negative electrode) in an electrolytic cell.
● When aqueous solutions are electrolysed, water can be oxidized to oxygen at the anode
and reduced to hydrogen at the cathode.
● Current, duration of electrolysis, and charge on the ion affect the amount of product
formed at the electrodes during electrolysis.
● Electroplating involves the electrolytic coating of an object with a metallic thin layer.
Applications and skills:
● Deduction of the oxidation state of an atom in an ion or a compound.
● Deduction of the name of a transition metal compound from a given formula, applying
oxidation numbers represented by Roman numerals.
● Identification of the species oxidized and reduced and the oxidizing and reducing agents,
in redox reactions.
● Deduction of redox reactions using half-equations in acidic or neutral solutions.
● Deduction of the feasibility of a redox reaction from the activity series or reaction data.
● Solution of a range of redox titration problems.
● Application of the Winkler method to calculate BOD.
●Construction and annotation of both types of electrochemical cells.
●Explanation of how a redox reaction is used to produce electricity in a voltaic cell and how
current is conducted in an electrolytic cell.
●Distinction between electron and ion flow in both electrochemical cells.
●Performance of laboratory experiments involving a typical voltaic cell using two
metal/metal-ion
half-cells.
●Deduction of the products of the electrolysis of a molten salt.
●Calculation of cell potentials using standard electrode potentials.
●Prediction of whether a reaction is spontaneous or not using E* values.
●Determination of standard free-energy changes (∆G*) using standard electrode potentials.
●Explanation of the products formed during the electrolysis of aqueous solutions.
●Perform lab experiments that could include single replacement reactions in aqueous
solutions.
●Determination of the relative amounts of products formed during electrolytic processes.
●Explanation of the process of electroplating.

Oxidation states should be represented with the sign given before the number, e.g. +2 not
2+.
The oxidation state of hydrogen in metal hydrides (–1) and oxygen in peroxides (–1) should
be covered.
For voltaic cells, a cell diagram convention should be covered.
Explanations should refer to E* values, nature of the electrode, and concentration of the
electrolyte.
Electrolytic processes to be covered in theory should include the electrolysis of aqueous
solutions (e.g. sodium chloride, copper(II) sulfate, etc.) and water using both inert platinum
or graphite electrodes and copper electrodes.
The term cells in series should be understood.
 Since metals corrode, the study of the reaction of metals with oxygen was one of the
earliest reactions of interest to chemists.
 Oxidation:
o Originally regarded as the reaction with, or addition of oxygen.
o
o
 Reduction:
o Originally regarded as the removal of oxygen.
o
o
 Oxidation and reduction were redefined as the loss or gain (respectively) of
hydrogen.
o They are interdependent. If is a redox reaction, and if A is oxidised, B is
reduced.
o
o
 Oxidation and reduction were redefined as electron transfer processes.
o
o
o
o LEO-GER:

o
 Oxidation:
o The loss of electrons, is oxidation.
 Reduction:
o Gain of electrons, is reduction.



 Redox Reactions:
o Oxidation and reduction happen simultaneously.
o
 o
o A reaction that forms an ionic compound is a redox reaction.
 Valence and Oxidation State:
o Ionic:
o Oxidation State of ions.


o Oxidation State of ions.
o
o
o Covalent:
o Assume all bonds are broken.
o Electrons are retained by the most electronegative element.


o The oxidation state of an element is 0.
o
o
 Oxygen gained electrons
 Magnesium loses electrons
 Oxidation is the increase of the oxidation state.
 Reduction is the decrease of the oxidation state.

 Oxidation Number:
o


 – Phosphorous (III) Chloride

 – Phosphorous (V) Chloride

 – Dichromate (VI)

 – Manganate(VII)
o The sum of the oxidation states given the ionic charge of the compound or
atom.

 Oxidation State Rules:

o Oxidation State is an indication of the number of electrons under the control
of an atom.
o
 o
o
o
o Carbon, Nitrogen, Phosphorous and Sulfur and transition metals often
change their oxidation state.
 Half-Equations:
o Must be balanced in charge as well as number of atoms.
o A combination of half-equations, forms the net ionic equation.
o Oxidising agents are reduced.
o Reducing agents are oxidised.
o Balance oxygen using
o Balance Hydrogen using
o Balance charge using

o
o

o
o
o
o If the electrons do not balance, then they must be balanced with hydrogen
ions.
o The hydrogen ions are then balanced with water molecules

 Reactivity and Redox:

o The activity series ranks metals according to the ease with which they
undergo oxidation.
 o

o More reactive metals are stronger reducing agents than less reactive metals
and thus can reduce the ions of weaker metals.

o More reactive non-metals are stronger oxidising agents than less reactive
non-metals, and thus can oxidise the ions of weaker metals.

o
o
o
 The Winkler Method:
o Biological Oxygen Demand (BOD):
The quantity of oxygen needed to oxidise organic matter in a sample of water
over a five-day period at a specified temperature.
o The Winkler method is used to find the BOD, of a body of water.
o A high BOD, indicates a low level of dissolved oxygen, denoting a polluted
water source.
o A low BOD, indicates a high level of dissolved oxygen, denoting a healthy
water source.
o Method;
 Extract sample of water.
 Add a Manganese (II) salt. (
 Oxidation of Manganese:

 Oxidation of acidified Iodide ions:

 The iodide produced is then titrated against sodium thiosulfate. Thus,
for every one mole of four moles of sodium thiosulfate are
consumed.

 Electrochemical Cells
o Voltaic (Galvanic) Cells
 Cells that generate electricity from spontaneous exothermic redox
reactions.

o The more reactive the metal, the greater the negativity of its electrode
potential in its half-cell.
o Two half cells form one voltaic cell.
o

o Oxidation occurs at the anode.

o Reduction occurs at the cathode.
o AnOx, RedCat
o The function of the salt bridge is to maintain electrical neutrality within the
internal circuit.
o The ions in the salt bridge travel to opposite half-cells in order to balance the
charge.
o The salt chosen for the salt bridge must be soluble and not react with either
of the half-cells.
o Electrons flow from the anode to the cathode in the external circuit.
o Anions move to the anode. Anions are oxidised at the anode.
o Cations move to the cathode. Cations are reduced at the cathode.
o The anions in the salt bridge go to the negative anode because of the
surrounding positively charge cations. The cations in the salt bridge go to the
positive cathode to balance the flow of charge.
o The greater the difference between the reactivity of the metals, the greater
the voltage (EMF).
o
 o

o Cell Diagram Convention:

 Left side is oxidised.
 Right side is reduced.
 Written in the order that they are occurring.


 Electrolysis:
o Anions are attracted to the positive anode. Their electrons are taken and
they revert to their natural state.
o Cations are attracted to the negative cathode. They are given electrons and
revert to their natural state. Since the cations are usually metals, a metal is
usually formed at the cathode.
o The electrodes are made out of an inert metal which will not react. (e.g
Platinum, graphite)
o Liquid Electrolysis:
 Cations are reduced at the cathode:
 

 Anions are oxidised at the anode.


o How could pure water be electrolysed?
 It is done by adding a small amount of electrolytes.
o Dilute Aqueous Electrolysis:
 Cations are attracted to the cathode.
 Metal cations are reduced if
 Water is reduced to hydrogen gas
 Hydrogen cations are reduced.
 Anions are attracted to the anode.
 Anions are oxidised.
 Water to oxygen gas
 Oxidation of a reactive metal electrode and metal ions. (This is in the
case of reactive electrodes. E.g. copper electrodes ( at the negative
cathode. And
o Concentrated Aqueous Electrolysis:
 In this situation the cations and anions of the electrolyte are oxidised
and reduced as they are of a higher concentration than the water.
o Reactive Electrodes:
 The possibility of the oxidation and reduction of the electrodes must
also be considered.
 The electrolysis of metals is used to purify them. Impurities will collect
at the bottom of the beaker.
NaCL Product at Anode Product at Cathode
Conc. NaCl + inert Cl2 Gas, vales are very H2 Gas, H2O is
electrode similar and are preferentially reduced
dependent on
equilibrium 2Cl- /
Cl2 + 2e-
Dilute NaCl O2 Gas, vales favour H2 Gas, as H2O is
oxidation of H2O preferentially reduced
CuSO4 Product at Anode Product at Cathode
Inert (Graphite) O2 Gas, H2O is Cu solid, as Cu2+ is
electrodes preferentially oxidised preferentially reduced
Copper electrodes Reduction of electrode, Cu solid, as Cu2+ is
Copper anode is preferentially reduced
oxidised preferentially
o Electrolytic process
 Amount of product depends on
 Size of current
 Time used
 Equation: Q = It
 I = current
 T = time (s)
  Divide Q by 96500c (charge of 1mol of electrons) to get mol. Of
electrons used
 Standard Electrode Potential:
o The potential difference between the half-cell of a specified substance and a
hydrogen half-cell.
o The emf (Electromotive force) of a connected standard half-cell and another
half-cell gives the standard electrode potential of the half-cell.
o The emf of a galvanic cell is the maximum voltage.
o Any electrode is compared to a standard hydrogen electrode.
o This standard electrode is assigned an arbitrary electrode potential of 0.
o is NOT affected by stoichiometric coefficients.
o All solutions must have 1moldm-3
o All gases must have a pressure of 100kPa
o All substances must be pure
o Temperature must be 298K
o Platinum is used as the hydrogen electrode as it is inert.
o If > 0 then the metal has a greater tendency to be reduced than H+
o If <0 then the metal has less of a tendency to be reduced than H+
o is a measure of how favourable the reduction of a substance is, in
comparison to hydrogen. The higher the of a substance the stronger an
oxidising agent it is. The lower the value of the stronger a reducing agent it
is.

o The standard electrode potential is calculated with the oxidised species on

the left and the reduced species on the right.
o Thus are known also as standard reduction potentials.
o The stoichiometric coefficients have no effect, when comparing .
o The half-cell with the more positive standard electrode potential (greatest )
attracts more electrons.
o The standard electrode potentials are a measure of the spontaneity of
reduction. If a substance is being oxidising reverse the sign of
o The half-equation with the highest will be reduced.
o The half-equation with the highest will be oxidised.
 The Electric Cell Potential:
o In a voltaic cell the half-cell with the greater E theta will be reduced, whilst
the half-cell with the lower E theta value will be oxidised.
o Electric Cell Potential is positive for all spontaneous reactions.
o If the Electric Cell Potential is negative then the reverse of the reaction is
spontaneous.
o If the Electric Cell Potential =0, then the reaction is at equilibrium.
 Free Energy (G) [Joules]
o
o N= no. of moles
o F= Faraday Constant
o
o Reduction potentials must be used.
o for all spontaneous reactions.
Organic Chemistry
Understandings:

● A homologous series is a series of compounds of the same family, with the same general
formula, which differ from each other by a common structural unit.

● Structural formulas can be represented in full and condensed format.

● Structural isomers are compounds with the same molecular formula but different
arrangements of atoms.

● Functional groups are the reactive parts of molecules.

● Saturated compounds contain single bonds only and unsaturated compounds contain
double or triple bonds.

● Benzene is an aromatic, unsaturated hydrocarbon.

● Alkanes: have low reactivity and undergo free radical substitution reactions.

● Alkenes: are more reactive than alkanes and undergo addition reactions. Bromine water
can be used to distinguish between alkenes and alkanes.

● Alcohols: undergo nucleophilic substitution reactions with acids (also called esterification
or condensation) and some undergo oxidation reactions.

● Halogenoalkanes: are more reactive than alkanes. They can undergo (nucleophilic)
substitution reactions. A nucleophile is an electron-rich species containing a lone pair that it
donates to an electron-deficient carbon.

● Polymers: addition polymers consist of a wide range of monomers and form the basis of
the plastics industry.

● Benzene: does not readily undergo addition reactions but does undergo electrophilic
substitution reactions.

Applications and skills:

● Explanation of the trends in boiling points of members of a homologous series.

● Distinction between empirical, molecular, and structural formulas.

● Identification of different classes: alkenes, alkynes, halogenoalkanes, alcohols, ethers,

aldehydes, ketones, esters, carboxylic acids, amines, amides, nitriles, and arenes.

● Identification of typical functional groups in molecules, e.g. phenyl, hydroxyl, carbonyl,

carboxyl, carboxamide, aldehyde, ester, ether, amine, nitrile, alkyl, alkenyl, and alkynyl.

● Construction of 3D models (real or virtual) of organic molecules.

● Application of IUPAC rules in the nomenclature of straight-chain and branched-chain
isomers.

● Identification of primary, secondary, and tertiary carbon atoms in halogenoalkanes and

alcohols and primary, secondary, and tertiary nitrogen atoms in amines.

● Discussion of the structure of benzene using physical and chemical evidence.

● Alkanes: Writing equations for the complete and incomplete combustion of

hydrocarbons. Explanation of the reaction of methane and ethane with halogens in terms of
a free radical substitution mechanism involving photochemical homolytic fission.

● Alkenes: Writing equations for the reactions of alkenes with hydrogen and halogens and
of symmetrical alkenes with hydrogen halides and water. Outline of the addition
polymerization of alkenes. Relationship between the structure of the monomer to the
polymer and repeating unit.

● Alcohols: Writing equations for the complete combustion of alcohols. Writing equations
for the oxidation reactions of primary and secondary alcohols (using acidified potassium
dichromate(VI) or potassium manganate(VII) as oxidizing agents). Explanation of distillation
and reflux in the isolation of the aldehyde and carboxylic acid products. Writing the
equation for the condensation reaction of an alcohol with a carboxylic acid, in the presence
of a catalyst (e.g. concentrated sulfuric acid) to form an ester.

● Halogenoalkanes: Writing the equation for the substitution reactions of halogenoalkanes

with aqueous sodium hydroxide.

The general formulas (e.g. CnH2n 2) of alkanes, alkenes, alkynes, ketones, alcohols,
aldehydes, and carboxylic acids should be known.

● Skeletal formulas should be discussed in the course.

● The distinction between class names and functional group names needs to be made,
e.g. for OH, hydroxy is the functional group whereas alcohol is the class name.

● The following nomenclature should be covered:

○ non-cyclic alkanes and halogenoalkanes up to halohexanes

○ alkenes up to hexene and alkynes up to hexyne

○ compounds up to six carbon atoms (in the basic chain for nomenclature purposes)
containing only one of the classes of functional groups: alcohols, ethers, aldehydes,
halogenoalkanes, ketones, esters, and carboxylic acids.

● Reference should be made to initiation, propagation, and termination steps in free

radical substitution reactions. Free radicals should be represented by a single dot.

 Homologous Series:
 o Organic compounds of the same class, with identical functional groups and
general formula.
o Successive members of a homologous series differ only by a group.
o Successive members of a homologous series increase in boiling point, as
London Dispersion forces increase in strength with increasing numbers of
electrons.
o Members of a homologous series have similar chemical properties.
 Formulas:
o There are multiple ways to represent an organic compound.


o Stereochemical formula:
 An attempt to depict the relative positions of the atoms and groups
around the carbon in 3 dimensions.


  Nomenclature:
o Identify the longest chain of carbons.
o Meth- Single Bond – -ane
o Eth- Double Bond – -ene
o Prop- Triple Bond – -yne
o But-
o Pent-
o Hex-
o Hept-
o Oct-
o Non-
o Dec-

 Identify functional group.

Class Name Functional General Structural Formula (Example)

Group Formula
(Open
Chain, One
functional
group)
Alkanes Alkane Alkyl

Alkenes Alkene Alkenyl

Alkynes Alkyne Alkynyl

Alcohols Alkanol Hydroxyl

Carboxylic Alkyl Terminal

Acid Alkanoate Carboxyl

Aldehyde Alkanal Aldehyde

(Terminal
Carboxyl)
Ketone Alkanone Carbonyl

Ether Alkoxy Ether

Alkane
Ester Alkyl Ester
Alkanoate

Amide Alkanamide Terminal

Carboxyamid
e

Nitrile Alkanenitrile Nitrile

Amine Alkanamine Amine

Arene Alkyl Phenyl-
Benzene
 3. Identify side-chains or substituent groups.
o

o
o It is important to note that in the numbering of carbons, bond numbers are
prioritised over substituents.
 Structural Isomers:
o Molecules that have the same molecular formula but different arrangements
of atoms.
o

o Both have the molecular formula

 Index of Hydrogen Deficiency:
o A measure of an organic molecule level of hydrogen saturation.
o An IHD of 0, denotes a completely saturated organic molecule.
o
o Or:
o
o
o
o
o
o
o
 Primary, Secondary and Tertiary Molecules:
o A primary molecule is when the carbon attached to the functional group is
attached to at least two hydrogen atoms
o Or, when the carbon with the functional group is attached to one other
carbon


o A secondary molecule is when the carbon attached to the functional group is

attached to two alkyl groups and one hydrogen atom as well.
 

o A tertiary molecule is when the carbon is attached to the functional group,

but also to three alkyl groups.


o In amines, the nature of the molecule is determined by the nitrogen instead.



 Arenes:
o A family of molecules derived from benzene.
o They form a special branch of organic compounds known as the aromatics.
o Other organic compounds belong to the aliphatic group.
o Benzene does not behave like other unsaturated organic molecules, despite
its high degree of unsaturation. (
o The special stability of benzene is due to that fact that it is actually a
resonance hybrid.
o Empirical Evidence:
 X-ray Diffraction:
 Using x-ray diffraction, it was found that all of benzene
carbon-carbon bonds were equal, and were intermediate in
length between single and double bonds.

 Reactivity:
 It was found that benzene is more likely to undergo
substitution reactions, rather than addition reactions. Thus, it
does not have double bonds. An addition reaction would also
likely disturb the electron cloud.
  Enthalpy of Hydrogenation:

 The delocalised electrons minimise the repulsion between electrons,

giving benzene a more stable structure.
 Physical Properties of Hydrocarbons:
o Branched hydrocarbons have lower boiling points than their straight-chain
isomers.
o This is because the strength of London Dispersion Forces increases with
proximity.
o
 Alkanes:
o Saturated hydrocarbons.
o The carbon-carbon and carbon-hydrogen bonds are very strong and have a
weak polarity.
o All bonds are single and so the electron density is low
o Thus, alkanes are not very reactive.
o Alkanes are combustible.
o In cases of excess oxygen, carbon dioxide and water will be produced.
o In cases of limited oxygen, carbon monoxide ( and water will be produced.
o In cases of extremely limited oxygen, carbon and water will be produced.
o Alkanes are susceptible to substitution reactions.
o Substitution:
 When another reactant, such as a halogen takes the place of a
hydrogen atom, in the alkane.


 Free Radicals:
 Highly reactive atoms which contain an unpaired electron.
o Homolytic Fission:
 When the bond between two atoms is broken, by splitting the shared
pair of electrons, creating two free radicals.
o Process of Halogenation:
 Initiation:
 Photochemical homolytic fission creates free radicals.


o Propagation:
 Free radicals are both used and produced creating a chain reaction.


o Termination:
 Reactions which remove free radicals from the system by pairing their
electrons.


 Alkenes:
o Unsaturated carbons.
o Undergo addition reactions.
o Hydrogenation facilitated by a catalyst (nickel).


o Addition of a halogen.

o Addition of a halide.


o Hydration of an alkene facilitated by a catalyst (Sulfuric Acid).
 

 Polymerisation of Alkenes
o Monomers collide
 Double bond splits homolytically, shown by fishhook diagram
 1 electron moves to each end of chain
 Collisions must be carbon-carbon
o Polymer chains held together by dispersion forces
 Flexible
o Polymers stored as pellets
o Branched (Grid) form
 Low intermolecular forces
 Low melting point
o Unbranched
 High intermolecular forces
 High melting point
o Polypropene
 Strong, not flexible, high IMF
o More electrons in monomer = more IMF forces
o Vulcanisation
 Buta-di-ene – has double bonds as a polymer
o PVC (Polyvinylchloride) is made soft and flexible through plasticisers
 Plasticisers reduce IMF forces to increase flexibility
o In addition, monomers are added to other monomers
o Double bond is broken, and each carbon retains 1 electron from the bond
o These unpaired electrons pair up to form C-C

o
 Oxidising Alkanols
o Primary Alkanol


 Alkanol  Aldehyde/Alkanal  Alkanoic/Carboxylic acid
o Secondary Alkanol


 Alkanol  Ketone/Alkanone
o Tertiary Alkanol
 Not readily oxidised
 This would involve breaking the carbon skeleton of the molecule
which requires far greater energy


 Nucleophilic substitution
o Primary, secondary and tertiary halogenoalkanes
o Nucleophiles usually have a lone electron pair
 E.g. H2O, NH3, OH-, CN-
o When the nucleophile attacks the halogen-bearing carbon, the reaction
involves a substitution of the halogen by the nucleophile
o Hence called nucleophilic substitution

o
 Esterification
o Alkanoic Acid + Alkanol  Water + Ester/Alkyl Alkanoate
 Alkanol becomes the Alkyl
 Alkanoic Acid becomes the Alkanoate
 Condensation reaction
 Conc. H2SO4 as catalyst
o Must be performed at reflux, as products are often more volatile than
reactants
 Hydrogen bonds are stronger than dispersion forces
o Done at reflux allows the reaction to be performed at higher temperatures
than would be otherwise possible
o Acid catalysis lowers activation energy
o Esterification is often an equilibrium reaction
 Shifted towards products w/ higher concentration of reactants
o Examples
 Ethyl Ethanoate
 Paint and Lacquer solvent
 Butyl Ethanoate
 Nail and lacquers
 4-hydroxybenzoic acid esters
 Face Cream preservative
 Acetylsalicylic acid
 Aspirin
 Methyl salicylate
 Oil of wintergreen
 Pentyl Ethanoate
 Banana Fragrance
 2-Butyl Methanoate
 Raspberry Fragrance
 Benzene  Electrophilic substitution
o Stability of Benzene
o Resistant to Addition
o Will undergo substitution by electrophiles
 Electrophiles are electron deficient, positive/partial positive charge
o Ring is electron rich, so electrophiles substitute in
HL Organic Chem
 Isomerism
o Identical molecular formula
o Different structural formula
o Occurs when
 Functional groups are positioned differently
 Different spatial arrangement of several parts of the molecule
 E.g. But-2-ene

o
 Stereoisomers
o Conformational isomers (staggered)
 Rotated around sigma bond


 o Configurational isomers
 Formed by bond breaking/reformation
 E.g. But-2-ene


 When functional groups are on;
 Same side of the multiple bond, CIS isomer
 Different sides of the multiple bond, Trans isomer
o Ring puckering
 E.g. Cyclobutane
 Eclipsed = torsional strain
 Ring = angular strain
 Ring puckering reduced torsional strain but increases ring/angular
strain
 CIS Trans isomers occur in alkenes or cycloalkanes
o Differ in position of atoms (or groups) relative to a reference plane
 E-Z notation
o Identifying whether a molecule is trans or cis when the functional groups are
different
o Find the highest priority atom attached to each carbon, using the atomic
number of the atom attached to each carbon in the chain
o Identify whether they are opposite or same sided
o E = trans
o Z = cis
 Optical isomers
o Mirror images of each other
o Non-superimposable
o Mixture of 2 is called a racemate (ra-suh-mate)
o Causes polarised light to rotate in exactly opposite directions
o Regarded as optically active
o Enantiomers are
 Non-superimposable
 Mirror images
o Diastereomers are
 Non-superimposable
 NOT mirror images
 Nucleophilic substitutions
o Can occur through two mechanisms
 Sn1 – substitution nucleophilic unimolecular, First order
 Sn2 – substitution nucleophilic diamolecular, Second order
o Sn1 occurs in 2 steps
 Heterolytic fission of Carbon-Halogen bond and formation of carbo-
cation
 Nucleophilic attach of the carbo-cation to form final product
 Rate expression = k x [Halogenoalkane]
 Rate Determining Step is Heterolytic fission
 Tertiary halogenoalkanes react via Sn1
 Steric hindrance, as the other carbons attached to the one
with the functional group hinder the nucleophile from
colliding with the carbo-cation
 Greater stability  positive polarisation is induced over all the
carbons and becomes more stable (induction)
 Alkyl groups push electrons to carbon-halogen bond


o Sn2
 Occurs where the nucleophile attacks the polar Carbon-Halogen bond,
forming an intermediate transition state (activated complex)
 Primary halogenoalkanes react via Sn2
 Rate = k x [Halogenoalkane] x [Nucleophile]
 1 step reaction


 Nucleophile attacks the carbon on the opposite side of the Carbon-
Halogen bond/leaving group
 Causes an inversion of the functional groups around the
carbon
 Much like an umbrella blowing inside out
 
 Favoured by polar, aprotic solvents
 Aprotic solvents do not form hydrogen bonds
 May have strong dipoles
 Solvate the metal cation rather than the nucleophile
 The unsolvated nucleophile has a higher energy state and
increases the rate of reaction
o Secondary Halogenoalkanes react via either Sn1 or Sn2
 Comparison of the rates of nucleophilic substitutions
o The effect of the mechanism
 Experimental data shows that Sn1 proceeds quicker than Sn2
 Thus, tertiary alkanes undergo substitution faster than primary
alkanes, with secondary alkanes in between the two
 Tertiary (Sn1) > Secondary (Sn1 and Sn2) > Primary (Sn2)
o The influence of the leaving group/halogen
 Electronegativity of the halogens decrease from Fluorine to Iodine
 Thus, the Carbon in the Carbon-Halogen bond become progressively
less electron deficient as we go down the periodic table
 Thus, Fluoroalkane > Chloroalkane > Bromoalkane > Iodoalkane IN
TERMS OF ELECTRONEGATIVITY DIFFERENCE/POLARITY
 Bond energy data shows that the strength of carbon-halogen bonds
decrease going down
 Thus, Iodoalkane > Bromoalkane > Chloroalkane > Fluoroalkane IN
TERMS OF EASE WITH WHICH THE BOND IS BROKEN
 Rate of reaction data shows that the bond strength/ease with which
the bond is broken is the determining factor here
o Choice of solvent
 Sn1 prefers polar, protic solvents
 Sn2 prefers polar, aprotic solvents
 Thus, tertiary Iodoalkanes in polar, protic solvents have the fastest
reaction

 Electrophilic addition reactions – Alkenes
o Alkenes are unsaturated
o Double bond has high electron density
 Attracts electrophiles


o Carbons in the double bond are sp2 hybridised, and so are in a trigonal planar
structure
o Is very open for electrophiles to attack
o Pi bond is less closely associated with the nuclei and is weaker, and so is
more readily broken
o When this pi bond region is attacked by electrophiles, reactants attach at
each carbon atom

o
o E.g. Halogens + Alkenes, Hydrogen Halides + Alkenes
 Occur readily under mild conditions
o Occurs through Heterolytic fission


 Bromine molecule polarised by ethene


 Br2 splits heterolytically and the Br+ ion attacks ethene as the
electrophile


 Br- ion attacks the unstable carbo-cation intermediary to form 1,2,
dibromoethane


 o Unsymmetrical addition
 E.g. Propene + Hydrogen Bromide


 Both intermediaries are possible, but one is more stable than the
other
 a) is only stabilised by one positive inductive effect, as it is a primary
carbo-cation
 b) is stabilised by two positive inductive effects, as it is a secondary
primary carbo-cation
 Thus, b) is preferentially formed


 Markovnikov’s rule: A hydrogen will attach to the carbon with the
greater number of hydrogens already attached to it
 Electrophilic substation reactions  Benzene
o Benzene does not behave like alkenes, despite its low saturation
o Prefers substitution over addition
o Electron ring highly stable
o Substitution reactions replace a Hydrogen atom with an electrophile

o
o High activation energy as this disrupts the symmetry of the pi bond ring

o
 Nitration of Benzene
o Replacement of H with NO2
o NO2+ formed by combining concentrated nitric and sulfuric acid
o Sulfuric acid protonates the nitric acid, nitric acid loses a water molecule and
forms NO2+

o
 Reduction of carbonyl compounds
o The reactions of
 Primary alcohol  aldehyde  Carboxylic acid
 Secondary Alcohol  ketone
o Can be reversed using a reducing agent
 Sodium Borohydride, NaBH4, in aqueous or alcoholic solution
 Lithium Aluminium Hydride, LiAlH4, anhydrous, such as dry ether with
aqueous acid
o Both reagents produce the Hydride ion H- which acts as a nucleophile on the
electron deficient carbonyl carbon

o
o NB: +H just means reduction, just as +O means oxidation. Here, it is the
addition of H-
 Reduction of nitrobenzene
o Nitrobenzene, C6H5NO2, can be converted to Phenylamine, C6H5NH2 in a 2-
stage reduction process
o Nitrobenzene is heated in reflux with Tin (Sn) and conc. HCl as catalysts


o The Phenylammonium ions react with NaOH to remove the H+ and form
Phenylamine


 Pathways of conversion of organic compounds

o
 Retro-Synthesis
o E.J. Corey, Chem nobel prize 1990
o The target molecule can be synthesised with its precursors
o It is strategically broken down into its precursors
o
Analytics

Understandings:

● The degree of unsaturation or index of hydrogen deficiency (IHD) can be used to

determine from a molecular formula the number of rings or multiple bonds in a molecule.

● Mass spectrometry (MS), proton nuclear magnetic resonance spectroscopy (1H NMR),
and infrared spectroscopy (IR) are techniques that can be used to help identify and to
determine the structure of compounds.

Applications and skills:

● Determination of the IHD from a molecular formula.

● Deduction of information about the structural features of a compound from percentage

composition data, MS, 1H NMR, or IR.

● The electromagnetic spectrum (EMS) is given in the data booklet in section 3. The regions
employed for each technique should be understood.

● The operating principles are not required for any of these methods.

● The data booklet contains characteristic ranges for IR absorptions (section 26), 1H NMR
data (section 27), specific MS fragments (section 28), and the formula to determine IHD. For
1H NMR, only the ability to deduce the number of different hydrogen (proton) environments
and the relative numbers of hydrogen atoms in each environment is required. Integration
traces should be covered but splitting patterns are not required.

 Spectroscopy:
 o Separation/detection/recording of energy changes.
o UV/Visible Spectroscopy
o Infrared Spectroscopy
o Nuclear Magnetic Resonance (NMR) Spectroscopy
 Spectrometry:
o Treatment of spectra.
o Mass Spectrometry
 Chromatography:
o Separation of a mixture.
o Gas chromatography
 Mass Spectrometry:
o During the ionisation process of mass spectrometry, the parent molecule
may split apart.
 Parent Atom/Molecule:
o An atom or molecule which only loses one/two electron(s) during the
ionisation phase, remaining otherwise unchanged. It appears at the very
most right peak in a mass spectrum.
o The fragmentation pattern is used to characterise the compound. The peak
furthest towards the right indicates the molar mass of the parent molecule.

o
o Therefore, 46 is the atomic mass of the parent molecule.
o The loss of one atomic mass unit (45), suggests the loss of a hydrogen atom.
o The loss of 15 atomic mass units (31), suggests a loss of a methane group.
o The loss of 17 atomic mass units (29), suggests a loss of a hydroxyl group.
o Thus, one can determine the structure of the molecule from the
fragmentation pattern found by a mass spectrometer.
 Nuclear Magnetic Resonance Spectroscopy

o
o Where the absorption occurs is called the ‘chemical shift’
o The position of that absorption tells us about the type of nuclei that give rise
to that absorption, within a specific chemical environment.


o This specific chemical environment is highly dependent on electron density.

Thus Methoxy Methane is different to ethane , despite having equal
numbers of hydrogens, the absorption is influenced by the presence of the
oxygen. Absorption is also influenced by multiple bonds.
o The absorption peak is integrated and the integration trace is a horizontal
line on the spectrum which rises a certain distance over each peak.
o Proton NMR is the spectrum produced by different types of hydrogen nuclei
(protons).
o A ‘type’ of hydrogen nuclei is determined by relative proximity to other
atoms. A hydrogen on a methyl group , is a different ‘type’ of hydrogen to a
hydrogen on a .
 o The position of the signal on the NMR spectrum (given by the chemical shift )
tells us about the type of hydrogen. (See Page 25 of IB Chemistry Data
Booklet)

o The area under each peak is directly related the number of identical protons
responsible for that signal.
o Tetramethylsilane is used as a standard.
 Identification Process:
o Using the integration trace, determine the ratio of peaks to one another.
o Multiply the ratio so that the sum is equal to the number of hydrogen. (If
molecular formula is given)
o Using the peaks location along the horizontal axis and Page 25 of the IB
Chemistry Data Booklet, determine what types of hydrogen exist.
o Calculate IHD.
o Note possible families of organic compounds.
o If the molecular formula given use the information gathered in the former
steps to identify the molecular structure.
o If the molecular formula is not given data from Mass Spectrometry or
Infrared Spectroscopy may be required
Medicinal Chemistry
Pharmaceutical products and drug action, D.1
o The human body’s defences
 The functioning of the body is a combination of thousands of chemical
reactions, known as metabolism
 This system is prone to breakdown
 Injury
 Genetic abnormalities
 Environmental abnormalities
 All accumulated with age
 Affected by microorganisms
 Called “invaders”
 Body’s “lines of defence” activate as the infection, or “invaders”
penetrate deeper
 Often manifest as symptoms
 E.g. fever
 Medicines work best by supplementing the body’s natural defence
systems
o Medicine and drugs: some terminology
 Medicine and drug have different meanings, and they are defined as;
 Drug
 A chemical that changes how the body works. This can be
beneficial or harmful
 Often associated with illegal narcotics, but has a broader
meaning
 Medicine
 A substance that improves health. It contains beneficial drugs
which can either be natural or synthetic, or a combination of
both.
 Synthetic medicines contain other non-active ingredients that
assist in the delivery or preservation of the drug
 The beneficial effect is called its therapeutic effect
NOS
 The placebo effect
o The power of suggestion
o Patients believe that they have been given a beneficial drug and thus gain
a therapeutic effect
o No rigorous explanation, no empiricism
o Generally accepted that about 1/3 of a control group taking a placebo
show some improvements
 Used as a constant in double-blind tests
o There needs to be a mechanism to establish a link between a placebo and
its therapeutic effect
 This requires experimental data that is quantitative and repeatable
 However, studies are very subjective and difficult to interpret
 Many other factors could account for the therapeutic effects, such
as spontaneous improvement, fluctuation of symptoms, answers of
politeness, and patient misjudgement
o No definite scientific explanation using the scientific method, and is thus
controversial

o Drugs can be administered in different ways

 This is affected by;
 Chemical nature of the drug, condition of patient, and the
most effective way of getting the drug to the target organ
 Some chemicals are broken down by metabolic processes, and
thus require more direct administration
 E.g. proteins such as insulin must be administered by blood
o Bioavailability of drugs: The amount that reaches the target
 Not all of the administered drug reaches the target
 The drug may be broken down in metabolic processes, or lost in the
absorption to the blood (incomplete absorption)
 The fraction that reaches the blood supply is the bioavailability
 By this definition, intravenous injections are 100% bioavailability
 Important when calculating dosage


o Administration of the drug
 The low bioavailability of an orally taken drug is known as the first
pass effect, meaning that as little as 20-40% of an orally taken drug
may reach the bloodstream
 Due to the digestive enzymes after swallowing, and the metabolic
processes that chemically alter the drug for processing
 Other methods avoid this effect by more direct administration
 Thus, an orally taken drug is required to be about 4 times as
concentrated as an intravenous drug.
 E.g. Morphine has only 30% bioavailability when taken orally,
so it is placed in an intravenous drip
o Solubility of drug
 Water solubility is necessary for circulation of the aqueous solution in
blood
 Lipid solubility assists in the passage of drugs through membranes in
absorption
 E.g. Codeine is more lipid soluble than morphine as it is a less polar
molecule and has a bioavailability of about 90%.
o Functional groups in the drug
 These can influence bioavailability, especially acid/base groups
  The pKa and the pKb values determine charges carried on the
molecules of the drug (now ions) at different pH’s
 This directly affects reactivity and solubility in different parts of the
body
o Psychological effects of drugs
 Complex
 Metabolism will cause more than one effect to occur
 Called side effects
 Different individuals respond differently to different drugs
 Healthcare providers keep several key factors in mind when deciding
drugs and their dosage
o Side effects
 The total effects of a drug can be separated into two categories
 Therapeutic effect, intended physiological effect
 Side effects, unintended physiological effects
 Side effects are broadly defined as unintended effects, and vary
largely between drugs and their functional groups
 Some are beneficial
 E.g. aspirin for pain relief, but also is good for preventing heart
disease
 Some are benign
 Headaches, nausea
 Some are detrimental
 Damage to organs
 These impacts must be evaluated before administration
 Patients must be aware of potential side effects as well, and their own
condition must be monitored
 Patients’ lifestyles must be adjusted to fit
 E.g. no driving, no using heavy machinery
 Bad case was the Thalidomide drug – birth defects
o Tolerance and addiction
 When a person is given many doses of a drug, they can develop a
tolerance
 This means a reduced response to the same dose of the drug
 Thus, higher doses are administered, and toxic side effects are more
probable
 The mechanism to why this develops is now well known
 Could be that the body metabolises drug more efficiently
 Could be that the receptors become less effective
 Some symptoms decrease while others maintain
 Dependence and addiction is different
 Occurs when patient requires drug to feel normal, and feels
withdrawal symptoms
 Symptoms can be mild, such as headaches from caffeine withdrawal,
to serious if the drug is toxic or shows tolerance, such as alcohol,
opiates, or barbiturate
o Dosage
 The dosage regime refers to the amount of the drug taken at one
time, and the frequency of administration
 Must take bioavailability, side effects and tolerance and addiction into
account
 Determining the right dosage is difficult due to variables
 Sex
 Age
 Weight
 Environment
 Diet
 Other drugs
 Ideal dosage is constant in blood concentration, but is impossible
without an intravenous drip
 All other methods lead to fluctuations in concentration between
doses
 The important thing is that the concentration maintains within a
range known as the therapeutic window


 The range of the therapeutic window varies between drugs greatly
 When window is small, the dosage must be closely monitored
so that toxic side effects are avoided
 The therapeutic window can be quantified as the Therapeutic index
 Defined as the ratio of the dose that produces toxicity to the
dose that produces a clinically effective response in a
population
 Relevant terms
 The minimum effective dose, ED50, is the dose that produces
the therapeutic effect in 50% of the population.
 The lethal dose, LD50, is the dose that is lethal to 50% of the
population. This is used in animal trials.
 The toxic dose, TD50, is the dose that is toxic to 50% of the
population. This is used in human studies.
 In animal studies, lethal doses are determined, but in human studies,
toxic doses are used.
 Therefore, the therapeutic index is determined differently for animals
and humans


 
 A higher value for the therapeutic index shows a wide margin
between doses that are toxic and doses that are therapeutic
 A low value means that the two doses are close, and any mistake
could lead to an adverse side effect


 A) is penicillin, b) warfarin
o Drug action and interaction with receptors
 Drug activity depends on the ability to bind with certain receptors
 Receptors are usually proteins, such as enzymes, chemical structures
on cell membranes, and DNA
 This binding inhibits normal biological activity, and interrupts the
development of disease
 Requires a chemical fit between receptor and drug
 The better the fit, the better the activity of the drug
 Binding of drug involves non-covalent bonding;
 Ionic bonds
 Hydrogen bonds
 Van der Waals forces
 Hydrophobic interactions
 Drug-receptor interactions made important contributions to advances
in approaches to drug design


o Development of new drugs
 Long and costly
 More investment into first-world health issues, such as diabetes,
cancer, heart disease, depression, ulcers
 Less investment into malaria, HIV AIDS, etc.
 Large demand for seasonal vaccines for flu viruses etc.
 Stringent laws on which drugs are allowed into the market
 Many candidate molecules fail to meet criteria
 10-12 years for a drug to go from development to market on
average
 Knowledge of drug-receptor processes has changed the drug
development process,
 Now, a molecular target is set and a drug is engineered to
interact with it
 This is known as rational drug design
 Better than trial and error with natural remedies


 Once the target molecule is identified, a lead compound is found
 The lead (Leed) compound shows desired pharmaceutical
activity that will suit its purpose, and is a good start for the
drug design and development process
 Often derived from plants
o E.g. Anti-cancer agent from Yew trees to develop Taxol
o E.g. Digitalis from foxglove for heart medications
o E.g. Microorganisms, E. Coli for insulin
 The effectiveness of the lead compound is optimised by further
synthesizing and testing chemically related compounds called
analogues
 A process called combinatorial chemistry enables production and
testing of many compounds and potential medicines in a very short
time
 Following this, tests are done on animals, under strict legislative
control
 For ethical and economic reasons, animal and human testing is
kept to a minimum
 Determining the safety and effectiveness of the drug gives an early
insight into the therapeutic index at an early stage
 From this, the therapeutic index for humans is and the dosage for
human trials is determined
Aspirins and penicillin, D.2
o Introduction to pain
 Pain is a sensation in the body
 When cell is damaged, releases prostaglandins
 Pain receptors are stimulated and send a signal to the brain
 Prostaglandins stimulate an inflammatory response and dilate blood
vessels near the site of injury
 This can cause swelling and increase pain
 Also affect temperature regulation, which may result in increased
temperature (fever)
o Painkillers (analgesics)
 Painkillers must intercept or block this pathway somewhere between
the source of the pain and the receptors in the brain
 So mild analgesics, such as salicylic acid, its derivatives and
paracetamol block the transmission of pain from source to brain
 This prevents stimulation of nerve endings at site of pain and inhibits
the release of prostaglandins
 This give relief to inflammation, fever and pain
 As these mild analgesics do not interfere with brain functioning, they
are not known as narcotics
 Prevents stimulation of pain transmission, and inhibits release of
prostaglandins
 Important definition
 Because these analgesics do not interfere with the functioning
of the brain, they are also known as non-narcotics
 NOS
o Development of aspirin
o 400BCE, chewing willow bark
o Early 1800s, demonstrated that an active ingredient in the bark is Salicilin,
which is converted to salicylic acid in the body
o 1890, Bayer company in Germany made an ester derivative of salicylic acid,
which was more palatable and less irritable to the body, while still being
effective
 Named aspirin, in recognition of the plant spirea which produces a
similar compound
 Widely used in the treatment of headaches, toothaches and sore
throat
 Also effective in reducing fever (antipyretic) andinflammation, it is
used to provide relief from rheumatic pain and arthritis
o Formation of aspirin
 Reactants are;
 Salicylic acid, ethanoic anhydride
 Products are
 Aspirin and ethanoic acid
 Reactants are warmed gently with conc. Sulphuric acid or phosphoric
acid as a catalyst. Aspirin is then isolated and purified
  Isolation
 Product is cooled to cause crystal formation and then suction
filtered and washed with cold water
 Aspirin, having a low solubility in water at low temperatures,
removes highly soluble acids while not leading to the loss of
the aspirin product
 Purification
 Recrystallisation
 Dissolve impure crystals in a minimum volume of hot ethanol,
which is a better solvent for impurities than for the aspirin
product
 A saturated solution of aspirin is formed
 As this solution is cooled slowly, the solubility of the aspirin
decreases, and it crystallises out of solution first
 It can be separated by filtration (decanting??) as the impurities
and unreactive salicylic acid remains in the solution
 Use IR Spectroscopy to tell the difference between ethanoic acid and
aspirin
 No OH group in aspirin
 Ester group present in aspirin
o Effects of aspirin
 Benefits
 Acts as an anticoagulant
o Useful in treatment of patients at risk from heart
attacks and strokes
 Regular intake of a low dose of aspirin may reduce risk of
colon cancer (more research needed)
 Negative effects
 Irritation and even ulceration of stomach and duodenum,
possibly leading to bleeding
 A large number of people, especially those prone to asthma
are also allergic to aspirin, so must be used with caution
 Synergistic effect of aspirin with ethanol
 Ethanol produces a synergic effect with a number of drugs
including aspirin, this means that the effect of the drug is
enhanced in the presence of alcohol which can be dangerous
 E.g. Aspirin + ethanol can increase risk of stomach bleeding
o Improving bioavailability of aspirin
 The problem
 Many medicines are either non-polar or relatively non-polar
molecules
 The drug needs to be taken to the target area by the blood
(aqueous solution)
 Their non-polarity or low polarity will cause slow uptake and
low bioavailability
 The solution
 Chemical modification to the aqueous solubility of aspirin
  The polarity of the molecule must be increased without
affecting its pharmaceutical activity, due to its greater
bioavailability and therefore its effectiveness
 In the case of molecules with with either acidic (carboxylic
acid) or basic (amine) groups, the polarity can be increased by
converting them into ionic salts/compounds such as chlorides
by adding either an alkali or an acid.
 These ionic salts dissolve in water due to the ion-dipole
interactions with water molecules that cause the ionic
structure to break up and the ions to disperse around the
water, increasing bioavailability
o Add NaOH
 Aspirin’s low solubility in water
 Can be made an ionic substance with the addiction of Sodium
Hydroxide due to it’s acid group
 Forms sodium 2-ethanoyloxybenzenecarboxylate
 C6H4(OCOCH3)COOH + NaOH → C6H4(OCOCH3)COO- Na++ H2O
 The structure of aspirin in the data booklet is the structure of the
insoluble aspirin, however this can still act as an analgesic
 The conjugate base now reacts with the acid in the stomach to form
the acidic aspirin molecule


 C6H4(OCOCH3) COO-+ H+ → C6H4(OCOCH3)COOH
o Penicillin
 Antibacterials are substances that kill or inhibit the reproduction of
bacteria that cause infectious disease
 E.g. Penicillin
 Group of compounds that are produced by fungi and inhibit the
growth of bacteria, and are thus called antibiotics
 Work via the beta lactam ring
 The structure can be seen as a dipeptide formed from two
amino acids, cysteine and valine
 Molecule contains a nucleus of a five-membered ring
containing a sulphur atom known as Thiazolidine, attached to
a four-membered ring, contain a cyclic amide group, known as
beta lactam.
 

The penicillin molecule works through the highly strained beta lactam
ring
 The beta-lactam is a four-membered square ring structure
which contains an amide group (-CONH-) and consists of one
nitrogen atom and three carbon atoms (and two hydrogen
atoms).
 As a result of the sp3 hybridisation of two of the three carbon
atoms and the single nitrogen atom and the sp2 hybridisation
of the third carbon atom, the preferred bond angles are
109°,107° and 120°.
 The ring is under high ring strain, and is favourable for it to break at
the amide group and bond covalently with the enzyme
transpeptidase as the bond angles are only 90
 This enzyme is now “trapped” and cannot be used to form more of
the cell wall structure in the cell, and so inhibits the production of the
cell wall
 The bacteria keeps expanding however, and so becomes vulnerable as
the cytoplasm and the organelles are now exposed outside the cell
 The bacteria keeps absorbing water and eventually explodes
o Weaknesses to penicillin-G
 Broken down by stomach acid before going into blood
 Different forms have been synthesized through adding side functional
groups and side chains to enable it to retain its activity even when
ingested
o Misuses of Penicillin-G
 Patient compliance
 Patients sometimes do not complete their full course of
medication
 This prolongs the disease as not all the bacteria are killed
 Prolonging the bacteria causes more chance of mutations and
thus resistance to bacteria
 As the bacteria lasts longer, it is able to be spread by the
patient
 Overuse of penicillin
 Often overprescribed
 First priority is to let immune system combat bacteria
 Overprescription weakens immune system
 Increased bacterial resistance to penicillin, passed onto later
generations of bacteria
  Can wipe out useful bacteria in the alimentary canal and thus
the destroyed bacteria can be replaced by harmful bacteria
 More patients are experiencing allergic reactions to penicillins
as more is being used and less effects are being experienced
 Use of penicillins in animal feedstock to promote growth
 Prevents bacterial infections but also used to prevent diseases
that affect growth
 Penicillins are thus passed onto the environment and move
into food chain
 Environmental bacteria that come into contact with penicillin
may cause mutations and thus a resistance to penicillin
o Modifications against bacterial resistance
 Additions or modifications of the side chains of Penicillin-G are used
to fight against bacterial resistance to penicillin
 E.g. ampicillin


 Modifications are necessary due to bacterial resistance

 Some bacteria mutate to produce a substance called beta-lactamase
or penicillinase
 This opens the four-membered ring and renders the penicillin useless
 Responses to this include;
 Synthesis of different forms of penicillin which are able to
withstand the effects of penicillinase,
o E.g. Methicillin, now replaced by oxacillin due to
methicillin resistant bacteria being widespread
 Both penicillin derivatives still have the beta-lactam ring but
have additional side-functional groups or side chains that
prevent the binding of the penicillinase enzyme, and so
protect the ring
 The control and protection of antibiotics to be prescription-
only drugs, so that their effects aren’t rendered ineffective by
inherited resistance. Furthermore, doctors are advised to not
overprescribe antibiotics
Opiates, D.3
o Analgesic properties of opiate
 Analgesics
 Drugs acting to relieve pain
 Opiates (opioids)
 Strong analgesics (don’t kill pain at the source)
 Opioid receptors
 Affect behaviour in brain
 Called narcotics
 Strong analgesic must enter the brain
 Blood-brain barrier
o Structure and synthesis of opioids
 Codeine
 Sometimes used in preparation with a non-narcotic drug in
second stage
 More mild than other analgesics
 Also slows down digestive processes
 Morphine
 Most well known
 Used in the reduction of pain
 Weakness of morphine is that it leads to a dependence
 Act in a way that the body relies on it, such as release of
endorphins, and as the body counteracts this influx of
hormone the lows feel lower
 Diamorphine
 Highest potential of causing addiction
 Produces euphoric effects
 Only legal in a few countries for extreme relief of pain
o Codeine
 Methylation of morphine
 Makes it less polar and makes it more effective
 The blood-brain barrier is consisted of lipids, and so the less polar a
molecule is the easier it is to pass through this
o Diamorphine
 Esterification of morphine
 Reduces polarity significantly
 This makes it more effective as now more can cross the blood-brain
barrier to have effects on the brain
 Reagent: Ethanoic acid and morphine  Diamorphine and water
o Effectiveness
 As a result of these structures and solubilities, the three drugs differ
in effectivity as;
 Codeine  morphine  diamorphine (increasing
effectiveness, narcotics and brain effects)
  NOS
o Morphine was isolated in 1803
o American civil war in 1860
o Addiction for many soldiers and users of diamorphine, harmful side effects
were not discovered until later

o Pain management
 WHO have created a three-step analgesic ladder to be a simple
guideline to encourage better global standards of pain management
 1: use mild analgesics
 2: Add a weak opioid such as codeine or tramadol
 3: In severe intractable pain, use strong opioids such as morphine,
methadone or possibly diamorphine
o Side effects of strong analgesics
 Constipation – therefore can be used to relieve diarrhoea
 Suppression of the cough reflex
 Constriction of pupil
 Feeling of well-being and contentment
 Lessening of fear and tension
 If drug is taken by intravenous injection
 HIV and hepatitis
o Narcotic effects and addiction
 Word “Narcotic” derived from the Greek word for numbness or
stupor
 Depress brain function, induce sleep and are potentially addictive
 Diamorphine is the most addictive, causes heroin addiction
 Short term
 Contentment
 Dulling of pain
 Reduction of fear and tension
 Long term
 Dependence, and withdrawal symptoms such as sweating and
anxiety
 Increased tolerance to drugs, therefore higher doses are
required and gets close to the TD50 and LD50
 The monetary requirement for supply is largely too much for
the consumer so may lead to life of crime
 Drug is taken by injection so blood infections such as HIV and
hepatitis are picked up via the hypodermic needle
 Helping heroin addicts break their dependence is very difficult
 Sometimes an alternate analgesic, such as methadone, is
administered. It is taken orally and has a longer lasting effect
 This can reduce craving and reduce symptoms of withdrawal
 Use is ethically controversial in many countries
 However has been shown to significantly reduce dependence and
reduce number of deaths caused by addictions
pH regulation of the stomach, D.4
 o How the stomach works
 Stomach digests food
 Enzymes facilitate the digestion of food
 Enzymes are acidic
 HCl is produced to kill bacteria as well as to create the right pH level
 Parietal cells line the stomach walls and produce HCl
o Harm of excess acidity in stomach
 Excess acid can be caused by over consumption of alcohol or caffeine
 Can also be caused through smoking or stress
 The condition produces gastric juice
 Commons symptoms or condition include acid indigestion, heartburn,
ulceration
 Scientific term is dyspepsia
 NOS
o Discovery of Helicobacter Pylori
o Bacteria
o Discovered in 1980
o A cause of stomach ulcers as it burrows into the stomach lining
o Led to the use of antibiotics alongside drugs that prevent acid
o How the body regulates acid secretion
 H2 receptor antagonists control the secretion of acid
 These bind to the receptors which bind to the histamine
which prevent the activation of acid production
 Activation through distension of stomach
 Hormones activate H2 receptors
 Histamine is one of these hormones
o Proton pump inhibitors
 Proton pumps are located within the parietal cells
 H+ ions are moved into the lumen of the stomach
 K+ ions moved into the parietal cell
 H+ ions moved against the equilibrium
 Requires ATP (Adenosine triphosphate)
 Proton pump inhibitors (Nexium)
 Used instead of a H2 receptor antagonist
 They block where the H+ ions are released and the K+ ions are
absorbed
 Stop the parietal cell from producing the H+ ions directly


o Antacids
  Anti-acids
 They are weak bases which neutralise stomach acids
 Strong bases cause harm to the stomach
 Antacids often come in the forms of
 Metal oxides
 Hydroxides
o 2HCl + Mg(OH)2  MgCl2 + 2H2O
o Mg(OH)2 is a laxative so it is removed through excretion
o Magnesium hydroxide is more soluble than aluminium
hydroxide
 Carbonates
o Sodium Carbonate and Hydrochloric acid
o Na2CO3 + 2HCl  2NaCl + CO2 + H2O
o Produces gas
 Hydrogen carbonates
 Fast and slow acting antacids
 Antifoaming agents
 Prevents the foamy acid from rising up to your oesophagus
 Alginates
 Stops the acid from flaring up and burning the top of your
oesophagus
 Neutralising layer (physical barrier)
o pH and buffering
 biological systems are very sensitive to pH change
 Therefore, complex buffering systems occur to prevent major
fluctuations in pH of the stomach
 Buffers resist the change of pH with the addition of small amounts of
acid or base
 pH depends on the interactions between its components


 Assumptions




Antiviral medications, D.5
o Viruses: Nature’s most successful parasites


Different shapes and sizes but are all very small
Range of 20-300nm, and are all sub-microscopic
 Means that they cannot be studied with a light microscope,
and an electron microscope must be used
 So simple that it is debated whether they should be classified as living
 Only two main components
 Protein
 Nucleic acid (DNA or RNA)
 No cellular structure
 No cell wall
 No cytoplasm
 Do not feed/excrete/grow
 Use cell material of the invaded cell to reproduce themselves
 Incapable of reproducing outside host cells
 Thus, are highly different from bacteria
 Take over the functioning of the host cell and use it for their own
reproduction
 Host cell’s components are used for assembly of viral particles,
and when the cell eventually dies the viruses are released into
the organism
 Viruses are usually specific for their host cell type, and different
strains exist that infect plants, animals and bacteria
o The war against viruses
 The body naturally responds by producing antibodies to fight viral
infections
 This is the immune response
 Leads to protection, or immunity from the same type of virus
 However, the virus can stay dormant in cells rather than being
eradicated, and can cause flare-ups of the same infection after it has
passed
 Herpes and cold sores
 Chicken pox and later shingles
 Many devastating diseases such as measles, meningitis, polio, AIDS,
Ebola and avian flu are caused by viruses
 Cause millions of deaths per year
 Treating viral infections is difficult as the viruses are in cells and so are
hard to target
 Antibiotics do not help as there is not specific structure in viruses that
can be targeted, like how penicillin targets the cell wall of bacteria
 Another problem is that they multiply very fast, as one host cell can
produce hundreds, if not thousands of the virus
 Therefore, the organism is entirely infected by the time
symptoms appear
 Viruses also mutate rapidly so their genetic material varies slightly,
and their response and susceptibility to drugs changes
 Successful treatments include vaccines, which are considered
preventative, or prophylactic treatments
 Work by stimulating the body to produce antibodies
specifically for that type of virus
 Eradicated smallpox and reduced measles, polio and cholera
 Mutations can reduce the effectiveness of vaccines
 E.g. Flu vaccines are only useful for known strains, as the
antibodies produced by the body only target the ones
specified by the vaccine
 Thus are changed every year for the virus
 Another strategy is to use medication known as antivirals
 Interfere with the viral life cycle and restrict reproduction of
viruses
 Some affect cells’ DNA so that viruses cannot use them to
reproduce
 Others block enzyme activity within the host cell
 Alter virus’s binding site on cell wall
 Prevents virus from entering/leaving cell
 Amantadine
 Good antiviral and prophylactic treatment
 Cage-like structure that prevents the entry of a virus into a cell
 Therefore best when used as a prophylactic which is difficult
 NOS
o Smallpox eradication
 Edward Jenner
 1749-1823
 Pioneered work that led to global eradication of smallpox
 However, his method would not be considered ethical today
 Observed that when people were contracted with cowpox (a mild
version of smallpox) they did not contract smallpox itself
 Tested on an 8-year old boy
 Injected with cowpox from a pustule
 Once cowpox developed, was treated until healthy then
given smallpox from a pustule
 Did not develop smallpox
 He was told he needed more proof
 Tested on more children, including his own baby son
 Work was slow to be accepted as the idea of infecting oneself
voluntarily was repulsive contextually
 Work spoke for itself and vaccines became widespread
 Jenner used careful observation and designed his scientific process
in a way that would find a way to benefit others
o Flu viruses, a case study into antivirals
 Influenza, AKA Flu, is a common virus that we can expect to
experience in our lives
 Symptoms
 Chills
 Headaches
 Sore throats
 Weakness
 Pneumonia
 Particularly serious in infants and elderly
 Also those with compromised immune systems (HIV/AIDS)
 Around half a million people die each year from the flu
 Fears of a global outbreak, called a pandemic
 Caused by two types of viruses, called influenza A and B
 Genetic material is RNA
 Two types of protein on their surface, which play a key role in their
life cycle
 Hemagglutinin (H)
o Glycoprotein that allows the virus to “dock” with host
cell before entering
 Neuraminidase (N)
o Enzyme that catalyses a cleavage reaction which allows
new viral particles to escape host cell and spread to
new cells
 o Enzyme works by snipping off a sugar molecule, called
sialic acid from the glycoproteins on the surface of the
cell membrane
 These two proteins come in different forms or subunits which
determine the naming of the virus type, e.g. H1N1, H1N3,
H5N1, which refers to the different types of molecules that are
present
o E.g. H1N1 pandemic in 2009, caused an estimated
250,000 deaths in Africa and SE Asia


 If the action of either of these proteins were interrupted, it would
drastically change their life cycle
 Neuraminidase (N) seems to be an easier protein to target for
vaccines, so that is what is focused
 Neuraminidase binds to sialic acid, which is the substrate, at a
specific region known as the active site
 This binding gives the catalytic action
o Provides pathway of lower activation energy
 Chemicals that interfere with this are called inhibitors and
usually have a specific “fit” with the enzyme
 Neuraminidase’s structure was discovered n 1993 with x-ray
crystallography
 A method of figuring out a crystal’s structure as crystalline
atoms cause a beam of x-rays diffract in different directions
 Enabled researchers to design a molecule that could bind at the active
site and so block the binding of substrate and thus act as an inhibitor
 The first neuraminidase inhibiters were designed in Australia
 Zanamivir (Relenza) – approved for use in 2000
 Oseltamivir (Tamiflu) – closely followed Relenza
 Both have a structure similar to sialic acid
 Both able to bind at the active site in neuraminidase
 This class of drug is active against both influenza A and B viruses
 Reduce symptoms and reduce time of recovery but must be taken 48
hours after symptoms appear
 

  Sialic acid
 NOS
o In many countries it is not a legal obligation to publish all data about drugs
o Estimated that around half of all drug data has not been shared
o This lack of transparency is a concern to some doctors, patients and
scientists
 Led to pressure from some watchdog organisations and regulators
to release all their data
o AIDS: a viral pandemic
 AIDS (Acquired immune deficiency syndrome), caused by the HIV
(Human immunodeficiency virus) was first diagnosed in 1981
 Syndrome means something whose cause has not been
discovered yet
 Transferred through bodily fluids such as blood, semen and mucus
 AIDS is characterised by a failure of the immune system
 Causes the body to fall prey to opportunistic diseases such as
pneumonia and cancer
 Infection has spread at an alarming rate, and it is estimated that
around 33 million people are HIV Positive, with a likelihood of
developing AIDS
 Cases reported all around the worlds
 Largely in Sub-Saharan Africa
 HIV primarily infects the white blood cells of the body
 CD4+T-Cells
  Virus binds to a specific receptor protein on the cell membrane then
penetrates
 HIV is a retrovirus
 Means that genetic material is in the form of RNA not DNA
 RNA is released into the cell and the enzyme reverse transcriptase
controls the synthesis of viral DNA from this RNA
 The viral DNA integrates into the cell’s DNA and is replicated when
the cell divides
 Viral particles are produced in the cell and are released when the cell
dies


o The fight against HIV infection
 3 reasons why HIV is much harder to defeat than other viruses
 1: the virus targets and destroys helper T cells which are the
viruses which should be defending against the virus
 2: The virus tends to mutate very rapidly, even in a patient. It
is thought that the HIV virus in one patient mutates more than
the influenza virus worldwide in a year. This means that much
of the virus escapes the immune response by the body, so the
patient must make a new response to the virus
 3: Virus often lies dormant within host cells, so the immune
system has nothing to respond to
 However, much progress has been made in response to the HIV virus
 These drugs are called antiretroviral drugs, or ARV’s or ART’s
(antiretroviral treatment)
 Around 20 now commonly available
 Do not cure infection, but suppress the symptoms of the infection
 Therefore, with appropriate treatments, HIV can be considered a
chronic disease rather than a fatal disease
 Antiretroviral treatments with pregnant women can prevent the
transmission of the disease to the child
 o Antiretroviral drugs
 These drugs target different stages of the HIV life cycle
 Binding and fusion of the virus to the receptor on the CD4 cell
membrane
 Reverse transcription of viral RNA to DNA in the host cell
 Integration of viral DNA into the host chromosome
 Release of new viral particles by budding from the host cell
surface
 Of these, the inhibitors of the transcriptase are the most common
 Such as AZT, AKA Zidovudine
 First antiretroviral drug to be produced
 Best results come from a combination of antiretroviral drugs
 Combination treatments are usually two reverse transcriptase
inhibitors and a third treatment, all amalgamated into a pill
 Cost is around $12,000 per year per patient
 This area is developing rapidly as more drugs are being produced
 Medical personnel must know how to tailor prescriptions to certain
patients
 Some may benefit from some drugs and some may not
 Considerations must be made of;
 Side effects
 Potency
 Expense
 Convenience
 Prevention of transmission
 Generally, need to be sustained throughout life
 Intense research is ongoing
 Hopes of a vaccine are existent (to help control infection in HIV
positive patients)
 A preventative vaccine has not been produced to give immunity to
those who are not infected
 Due to the variable nature of the virus within the cells
 Immune responses are too slow in the case of HIV
 NOS
o Development of effective antivirals is an example of many interdisciplinary
endeavours
o Technology such as electron microscopes and x-ray crystallography have
provided insights into structures that could otherwise not have been
known
o Advances in molecular biology have provided insights into the role of viral
proteins and genetic material in the viral life cycle
o Has helped the development of new drugs against viruses
o At best, science is an interdisciplinary process in which discoveries from
multiple disciplines commune to achieve a common goal

Environmental chemistry, D.6
o Solvent waste
 Greatest source of wastage in pharmaceutical industry
 80% of the mass of wastage is due to solvents
 They are typically disposed of via incineration, which releases their
toxicity to the atmosphere
 Solvent suitability is determined by toxicity (carcinogenic), safety
(explosive, flammable), and environmental effects (contamination of
soil, groundwater, ozone depletion)
 Chlorinated, aromatic and ether molecules are usually unsuitable,
whilst water, alcohols and esters are often suitable
 Solvent recycling is a far more sustainable approach than incineration,
reusing the solvents in the synthesis process is a far better alternative
to incineration


o Ramifications of nuclear medicine
 Radioactive waste is disposed of depending on high-level or low-level
waste
 High level
o Emits strong ionising radiation, isotopes have long half-
lives
o Usually stored first in refined cooling ponds for 5-10
years, then transferred to dry storage in reinforced and
shielded structures deep underground.
 Can risk contamination of water supply
o Sources include waste from nuclear power plants
 Low level
o Emits weak ionising radiation, isotopes have short half-
lives
o Disposal includes interim storage in a sealed container,
then disposal into a waste dump by conventional
means
o Sources include clothing, shoes and paper towels or
other things contaminated with nuclear material
 Most nuclear waste is low-level and toxic as well as radioactive
 If it is not properly disposed, it can cause grave damage to
environmental organisms and humans
o Antibiotic waste
 The use of broad spectrum antibiotics has resulted in the evolution of
highly resistant and problematic “superbugs”. The overuse of
antibiotics has resulted in resistant bacteria developing
  This is caused by the overuse of antibiotics, which are used
therapeutically and prophylactically for animals
 There are also used as pesticides, sanitizers and as sterilizing agents in
biological research
 This is further propagated by improper drug disposal, which
contaminates surface, ground and drinking water supplies
 The animal consumption of antibiotics, causes water and soil pollution
as well as further human exposure to antibiotics
o Oseltamivir, precursor to Tamiflu
 Tamiflu is a highly effective antiviral drug, yet is extremely difficult to
obtain and current procedures have a very low yield
 Consequently, there is a proportionally considerable amount of
wastage in the formation of the key element of Tamiflu, which is
shikimic acid – previously harvested from the fruit Star anise, grown in
china and south vietnam
 Fermentation reaction of genetically engineered bacteria (low yields)
 Harvesting pine tree needles, and Indian sweetgum trees (low yields)
o Green chemistry – methodological improvements
 Viagra
 Reduction of solvent
 Avoidance of toxic reagents and use of natural reagents and
enzymes
 Produces just a quarter of the original amount of waste
 Ibuprofen
 Reduction of steps from 6 to 3, which improves atom economy
from 40% to 77%
 Lyrica
 Natural reagent with water as the solvent reduces 3 million
tonnes CO2 emission
Taxol: a chiral auxiliary case study, D.7
o Optical isomerism: Chiral drugs exist in two forms with different activities
 Chiral molecules have two mirror images
 Enantiomers
 Arise whenever a carbon is bonded to four different groups
 Usually the two enantiomers have identical chemical properties, but
may react differently in a chiral environment, such as with the
enzymes and receptors in the body


 This shows why in a chiral receptor environment, only one
enantiomer is chemically active
 Biological synthesis within cells (in vivo) only produces one
enantiomer, such as morphine from the opium seed
 When synthesised outside the body (in vitro) the mixture is a
racemate which is a mixture of the enantiomers
 Thus, the challenge of finding out whether physiological
effects of each isomer, and whether drugs can be marketed as
a mixture or as a single enantiomer
 E.g. the Thalidomide tragedy
 Only one isomer had desired effects (R) of sleep inducing
 The other isomer (S) caused foetal defects


 Drugs marketed as racemates include;
 Fluoxetine (Prozac)
 Ibuprofen
 Undergo enantiomer interconversion in vivo
 Nowadays is more common
 Around 50% of all marketed drugs are single enantiomers
 E.g. Taxol
o Taxol: A powerful anti-cancer drug
 
AKA Paclitaxel

In a group of related compounds knowns as taxoids

First identified in 1971 through a screening by the US national cancer
institute
 Potent effects on solid tumours
 Approved for use in 1992
 Used primarily in breast and ovarian cancers
 Anti-cancer properties derive from an ability to bind to a protein
called tubulin
 Tubulin is the main component of microtubules which form
structures called spindles during cell division
 Taxol prevents breakdown of these spindles and hinders cell division
 Prevents growth of tumour
 First isolated from pacific yew trees (Taxus sp.) in 1970s
 Large environmental impact as it is only 0.0004% efficient in
extraction
 This process takes the bark off trees, and kills the trees, which take
200 years to regrow
 Also part of a sensitive ecosystem, which is very
environmentally important
 This caused many groups to try and find alternative synthesis
pathways and analogues
o Asymmetric synthesis: the production of a single enantiomer of Taxol
 The major challenge is that Taxol has 11 chiral carbon centres
 This means it can exist in a large number of enantiomers, which may
either be beneficial or harmful to the body
 Only one enantiomer has the desired therapeutic effect
 Isolating this is possible, but is very wasteful
 Therefore, it is beneficial to have a reaction pathway to only produce
one enantiomer
 Asymmetric synthesis, enantioselective synthesis


 One strategy uses a chiral auxiliary
 This is a chiral molecule that binds to the non-chiral reactant,
and physically blocks one reaction site with steric hindrance,
ensuring the next reaction occurs from the other side
 This forces the reaction to occur with specified stereochemistry
 The auxiliary can be taken off and recycled after the reaction
 Taxol is such a complex molecule that it takes 30 steps to synthesize it
 Such a poor yield it is impractical
  A more efficient process is now to use the needles and leaves of yew
trees from Europe and the Himalayas
 This does not damage the trees as the removal of bark does, and is
more sustainable
 The compound is called 10-DAB
 This process is called semi-synthetic synthesis as it starts with a
precursor from nature
 This addresses some of the environmental concerns (associated with
harvesting tree bark which kills trees) but it creates new challenges
for the pharmaceutical industry
 Conversion of 10-DAB to Taxol requires 13 solvents and a range of
other organic products.
 Large number of reactants is associated with a low yield
 A promising development is that some fungi produce Taxol in
fermentation reactions
 Plant cell fermentation technology is being used to extract Taxol
directly from plant cell cultures and to purify it with chromatography
 This removes the harmful solvents from the process
 Enantiomers can be identified with a polarimeter
 Measures angle of rotation of polarised light with an analyser


 NOS
o Advances in technology have allowed productions of chemicals previously
only obtainable from nature
o This allows more sustainable production of pharmaceuticals
o As the demand for chemotherapeutic products increases, the pressure on
the pharmaceutical industry increases to match this demand with supply
Nuclear Medicine, D.8
o Unstable atomic nuclei emit radiation
 Stability depends on nucleons (protons and neutrons)
 This varies in different isotopes of each element
 Stable nuclei have balanced forces and so are not radioactive
 Unstable nuclei have unbalanced forces and so are radioactive
 Unbalanced forces causes a release of energy and spontaneously
decay to form more stable nuclei
 Called Radioactivity
 Unstable nuclei are called radionuclei
o Radioactivity involves the emission of energy and particles from the nucleus
 The emissions are known as radiation
o Natural Radionuclides
 Occur in the environment in air, water and soil
 Include Uranium 235, Potassium 40 and Carbon 14
 All elements with an atomic number greater than 84 are generally
radioactive
 Means that they have no naturally occurring stable isotope
o Induced or artificial radionuclides
 Nuclei that are made unstable through procedures such as
 Bombardment reactions with neutrons or alpha particles (He
Nuclei)
 Many radionuclei used in nuclear medicines are produced in
this way
NOS:
 Discovery of radioactivity
o Came through intuition which caused probing into the cause
o Stumbled across the unexpected
o Henri Becquerel
 French physicist who studied phosphorescence in late 1800s
 Noticed that photographic plates became fogged when close to
uranium salts, even in the absence of sunlight
 Traced cause to radiation from Uranium
 Concluded that this caused gases to ionise
 Discovery of radioactivity in 1896 inspired the work for the Curies,
who discovered other sources of natural radioactivity and isolated
Polonium and radium.
 Nobel Prize in Physics in 1903 was awarded jointly to Becquerel and
the Curies

o Atomic nuclei
 Have a highly complex structure
 Discoveries in particle accelerator data
 Made up of nucleons, which are made up of quarks
 In sets of 3 (for nucleons)
 Have antiparticles
  Equivalent mass but opposite charge and particle number
(baryon number, lepton number, etc.)
 Particles and antiparticles eliminate each other and release energy
called gamma rays, in E=mc2

o
o When radionuclides decay, one or more of the following events occur in the
nucleus
 Ejection of a neutron
 Ejection of a proton
 Conversion of a neutron to proton with the ejection of an electron
(Beta minus decay)
 Conversion of a proton to a neutron with the ejection of a positron
(Beta plus decay)
 Release of energy in gamma rays
o This gives rise to different types of radiation, and results in a new nuclide
 May be radioactive and continue to decay, or may not
 Number of protons may change, so then a different element will form
 This is shown in nuclear equations


o Alpha radiation
 Ejection of particles from the nucleus
 The ejection particle is a He nucleus


 Causes the mass number of the radionuclide to decrease by 4 and the
atomic number to decrease by 2


o Beta radiation
 Beta minus: A neutron in the nucleus turns into a proton and emits an
electron and an anti-neutrino


 Beta plus: A proton becomes a neutron and emits a positron and a
neutrino
 
o Gamma Radiation
 Usually accompanies alpha and beta decay
 Nucleus emits a photon (particle with no mass) in the gamma ray
electromagnetic spectrum


 Wavelength = hc/E
 Nucleus does not change when photon is emitted, stays the same
element
 Nucleus changes from a high to low nuclear energy level
 Gamma rays were identified through the diffraction of gamma rays,
emitted from decaying nuclei, into crystals and measuring the
diffraction angle/patterns
 Electromagnetic waves have a wavelength of 0.0005 to 0.1nm, and
have frequencies above 1019 Hz
o Radioactive emissions have an ionising effect
 Known as ionising radiation because it can cause the removal of
electrons from an atom
 Forms highly unstable radicals, electrons in the outer shell are
removed
 Some radicals are highly reactive, and immediately react
 E.g. oxidation
 This is why radioactivity is dangerous for organic matter (us)
 Exposure to emissions causes ionisation of biological molecules in
cells
 Largely radicals such as Hydrogen radical and hydroxyl radical
 Large effect on DNA – double helix structure which can break down
when ionised
 Causes death or cell mutations (Cancer)
 Different types of radiation have a different ionisation density
 Refers to the average energy released along a unit length of
their track
 Alpha particles have a high ionisation density, due to their
large size and 2+ charge
 X rays and gamma rays have a low ionisation density
 This means that at the same dose they produce radicals more
sparsely within a cell
 Therefore, alpha particles are more destructive to biological
material
 Radiation’s ionising effect is also a useful tool in diagnosis and
treatment of many medical conditions and diseases
o Half-life of an isotope determines the rate of radioactive decay
 Is random and spontaneous
  Random meaning you cannot know which nucleus in a sample
will decay when there is a decay required
 Spontaneous means the decay happens unassisted, meaning
the rate of decay cannot be affected in any way
 Radiation is spontaneous and only depends on the nature of the
substance
 Not affected by temperature, pressure or the presence of other
substances
 Follows first-order reaction kinetics
 Rate =
 No need to explain the mathematics involved
 It can be expressed in the integrated form as;

 is the concentration of reactant at
 is the concentration of reactant at time
 Half-life is the time taken for the concentration of a reactant to
decrease to half of its original value
 So at this time,


 This shows that radioactive decay is constant
 Only depends on the rate constant of the reaction, usually known as
the decay constant
 Thus, the rate of radioactive decay DOES NOT depend on the starting
amount of radionuclide
 For any particular isotope, it will take the exact same amount of time
for it to be reduced to half its original value.
 100g to 50g is the same as 0.1g to 0.05g


 The value of the half-life of an isotope has an inverse relationship with
the rate of the radioactive decay
 Rate of radioactive emission is referred to as the isotope’s activity
 Is a measure of the number of nuclear disintegration per unit time
 SI unit is becquerel (Bq), = nuclei per second

o Nuclear radiation in medical treatment
  Refers to the use of radiation in healthcare practice
 Diagnosis of disease
 This involves providing detailed information of an individual’s
internal organs, aka nuclear imaging
 Treatment of disease
 Particularly cancer, through destruction of targeted cells
 Known as radiotherapy
o Diagnostic techniques in nuclear medicine
 Involve attaching a radionuclide, known as a tracer, to a biologically
active molecule.
 This drug is called a radiopharmaceutical
 Taken orally or through injection
 The tracer can now be tracked inside the body, which emits gamma
radiation and is picked up by a gamma camera
 Nuclear imaging has an advantage of x-ray techniques as it can be
applied to soft tissue as well
 Also allows the functioning of organs inside the body to be
seen
 Radiopharmaceuticals are designed to target a certain part of the
body where the abnormality or disease is located
 E.g. Iodine for the thyroid gland, glucose for brain. Thus the
tracer is attached to these molecules
 This allows the medical practitioner to view organs from different
angles live, so abnormalities are easier to find
 Cold spots where the isotope is taken up sparsely
 Hot spots where the isotope is taken up in excess
 Can indicate malfunction in organ
 Easier to interpret if images are taken over time (long exposure)
 Tracers used must emit gamma rays with a high enough energy to
escape the body and must have a half-life long enough for the scan to
be complete before its decay. The most widely used one is;
 Technetium-99m,
 This is used in about 80% of all nuclear imaging as it has advantages
 Half-life of 6 hours, means the activity stays high for long
enough for metabolic processes to be examined by scanning,
but decays in time to minimise risk for patient
 Decay involved the release of gamma rays and low-energy
electrons (Gamma and beta minus decay). Radiation dose is
low as the electrons are low energy, and the gamma rays are
able to be detected by the camera without affecting the body
 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.
 Created in nuclear reactors, goes from molybdenum-99 to
technetium-99
o Positron emission tomography (Pet)
 Gives three-dimensional images of tracer concentration in the body.
  Radionuclide goes through beta-plus decay and emits a positron. This
accumulates in target tissue
 The positrons emitted immediately annihilate themselves with
electrons and release gamma radiation.
 These gamma rays are detected through a camera and their origin is
precisely determined.
 A common tracer here is Fluorine-18, which is bonded to glucose in
the radiopharmaceutical
 This is due to the uptake of glucose in cancer cells being different to
normal cells
 PET is now used with CT (computerised tomography), which uses X-
rays to obtain images. This combined technique gives better diagnosis
of a wide variety of diseases.
o Magnetic resonance imaging (MRI)
 Developed in 1977 to produce images of internal body organs
 Application of nuclear magnetic resonance spectroscopy
 Uses the fact that Hydrogen atoms have a magnetic moment due to
their odd number of protons and electrons
 When a powerful magnetic field is applied, radio waves are used to
generate an electronic signal that can be decoded by a computer to
produce 2D or 3D images
 Useful because Hydrogen atoms are present in water
 about 70% of body mass
 Does not use ionising radiation
 Used in cancer detection, diagnosis of soft tissue injuries and in
monitoring degenerative diseases
o Radionuclide therapy
 Cancer arises when cells lose their regulatory mechanisms for control
of growth and division. This abnormal growth is known as a tumour.
 Challenges include identifying and targeting the cancerous cells and
preventing division, whilst minimising damage to normal nearby cells
 The rapidly dividing nature makes cancer cells particularly sensitive to
damage by radiation.
 Due to the ionising effect, it primarily affects DNA that
controls cell division
 Radiation kills healthy cells too, and this is a major
consideration in the administration of radiotherapy.
 Radiotherapy treatments involve irradiating the affected area with
the aim of controlling or eliminating the cancer. Alongside surgery
and chemotherapy, it is a widely used cancer treatment
 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
 Yttrium-90 are also widely used in arthritis treatment
o External radiotherapy or teletherapy
 Here, the source of radiation is directed at the site of cancer in the
body from a radioactive source, usually cobalt-60
  Undergoes beta minus decay with gamma radiation
 Gamma radiation penetrates and damages cells, but mainly cancer
cells
 Recent developments in external radiotherapy procedures;
 Linear accelerator
o A particle accelerator that uses microwaves to
accelerate electrons, which are then aimed at a heavy
metal target to produce high-energy X-rays which are
directed at the tumour
 Gamma knife radiosurgery
o Tiny beams of gamma radiation are focused on a
tumour from approximately 200 cobalt-60 sources,
causing a strong dose to be delivered where the beams
converge
 Both techniques provide greater precision in the targeting of
the ionising radiation at the tumour with minimum damage to
the surrounding tissue
 Important for diseases such as brain cancer, where you do not
want collateral damage to brain tissue
o Internal Radionuclide therapy
 Radioactive material is taken into the body, either as an implant or as
a liquid.
 An implant is put near the site of the tumour and left for a
period of time
o Usually a radioactive metal in the form of a wire, seed
or a tube and is a gamma and/or beta emitter
o Sometime the patients are isolated due to the danger
to others
 Liquids are introduced either orally or by injections
o Phosphorous-32 for blood disorders
o Strontium-89 for secondary bone cancers, especially in
pain control
o Iodine-131 is used for thyroid cancer
 Targeted alpha therapy (Promising development, TAT)
 AKA Radioimmunotherapy
 Effective in the treatment of dispersed cancers
o This process is called metastasis
 Uses alpha-emitting radionuclides directed at the biological
target by attaching them to carriers such as antibodies.
o These then carry the radionuclide to the exact right
place
 Alpha radiation is effective here as;
o They have a very high ionising density and so a high
probability of killing cells at the target
o Alpha particle radiation is short range and so minimises
the irradiation of normal surrounding tissue
  Uses lead-212 to treat pancreatic, ovarian and melanoma
cancers



 Boron neutron capture therapy (BNTC), experimental development
 Experimental development of TAT
 Used primarily in the treatment of brain and neck tumours
 Effectively generates alpha particles at the target
 Patient is given a high dose of non-radioactive isotope boron-
10, which concentrates in malignant brain tumours
 This is followed by irradiation with neutrons for sufficient
energy to be absorbed by the boron – boron neutron capture
 Reaction is accompanied by the emission of high-energy alpha
particles, which kill the cancer cells

 Targeted nature of this treatments depends on the extent to
which the boron-10 is selectively absorbed by the tumour and
not taken up by healthy cells
 Other non-radioactive isotopes are being investigated for their
roles in tumours on other sites of the body


o Side effects of radiotherapy
 External therapy causes cancer more than internal
 Improvements have reduced the range and severity of side-effects of
many treatments
 Nonetheless, side effects do occur due to the nature of radiation
  The ionising effects of radiation cause changes in the DNA of healthy
and dangerous cells
 Particularly in those cells that divide rapidly, such as hair
follicle cells
 Common side-effects are;
 Fatigue
o Rest and regular hydration are important during
treatment
 Nausea
o More common when treatment is in digestive system
 Hair loss
o This occurs within the treatment area and is usually
temporary
 Sterility
o More likely if treatment is close to ovaries or testes
 Skin reaction
o Skin may become red, sore, or itchy in local area of
irradiation
NOS:
 Ionising effects of radiation
o Can both cause cancer and be used in its treatment
o This dichotomy presents a challenge, and its effects must be balanced
 This carries heavy responsibility
o Access to data can help quantify the risk (radiation levels, etc.)
o It is therefore important for medical personnel, industry and governments
to maintain in data banks and records of the relationship between
exposure and incidence of disease
Drug detection and analysis, D.9
o Drug isolation and purification
 It is common for drugs to be synthesized in mixtures including
solvents, reactants and catalysts
 Isolation into a pure form is often a lengthy synthesis process
 Techniques exploit different properties of the substances in the
mixture
 Difference in solubility
 Difference in volatility
o Organic structure and solubility
 Solubility depends on the substances ability to form stable bonds with
the solvent
 Organic molecules that are soluble in organic solvents such as hexane
or benzene are generally non-polar molecules that interact with
London dispersion forces
 The solutes here typically have a high hydrocarbon content
 Organic compounds that dissolve well in water typically have a higher
proportion of polar bonds that use dipole-dipole forces or hydrogen
bonding
 Include Hydroxyl (OH), Carboxyl (COOH), and Amino (NH2)
 Aldehydes, ketones, aminos and esters also add polarity to
molecule
 Solubility is an important factor in determining the drug’s ability to
reach the target in the body, as well as its bioavailability
 E.g. Aspirin is modified to increase aqueous solubility
 E.g. Fluoxetine, which is reacted with HCl to form a salt


 Produces antidepressant drug Prozac
 During isolation, solubility can be used to isolate different compounds
in the mixture
 Choosing a solvent that dissolves a particular component is called
extraction
 E.g. Caffeine is removed from coffee beans with liquid carbon
dioxide
 Solvent extraction exploits the fact that a solute may show the
greatest difference in solubility between two solvents that are
immiscible
 When given the chance to dissolve in both, the solvent
becomes unequally dissolved in both, resulting in a partition
  Solvent extraction can be illustrated as;


 This process is used for the extraction of penicillin

 Drug is extracted from aqueous solution using
trichloromethane as the solvent
o Organic structure and volatility
 Boiling point is determined by the strength of the intermolecular
forces
 These must be broken down for the substance to become a
gas
 Therefore, the stronger the intermolecular forces, the lower the
volatility and the higher the boiling point
 The factors that influence the strength of intermolecular forces are;
 Molecular size: volatility lowers as molecular size increases as
London dispersion forces increase
 Polarity: More polar functional groups cause lower volatility
due to their ability to form hydrogen bonds or dipole-dipole
interactions
 Functional groups that lower volatility


 Fractional distillation exploits differences in volatility

 Based on the same principles of evaporation and condensation as the
simple distillation process but achieves better separation through the
use of a fractionating column
 The process produces fractions
 Mixture of liquids that boil within a narrow temperature range
 Used for the isolation of drug products from liquid mixtures
 This process is used to separate chemical feed-stock, such as
phenols and toluene – used in the synthesis of many drugs
 The theory of fractional distillation is described with Raoults Law
 Mole fraction
o – Greek Letter “Chi”
o Refers to the fraction of the moles of the substance in
a mixture (Number of moles of the substance divided
by the number of moles in the mixture

o
 o Sum of the mole fractions of all the components is 1
o Mole fraction has no units
 Vapour pressure
o The pressure exerted by a vapour in equilibrium with
its liquid in a closed system at a specified temperature

o
o The further this equilibrium lies to the right, the higher
the vapour pressure
o More volatile substances have higher vapour pressure
at equilibrium
o In a solution of substances, A and B, the vapour above
the liquid will be a combination of A and B
o This depends on the relative volatilities of the two
substances
o Therefore, Ptotal = PA+PB
 Raoults Law
o States that the vapour pressure of a volatile substance
is the product of the vapour pressure of the pure
substance and its mole fraction in solution

o
o Therefore, the vapour pressure of a solution depends
on the individual vapour pressures of the components
and the proportion of liquids present
o Only applies to ideal solutions, where the two
substances are completely miscible
 Means that the two substances behave in the
same way mixed in solution as they would do
when they are pure
o Chemically alike compounds which have similar
intermolecular forces form ideal solutions


  Shows that the sum of the blue and green lines for any point
on the X axis is the red line (sum of the vapour pressures of
the individual substances is the total vapour pressure)
 To find which substance contributes the most to the vapour
pressure (in equal amounts) draw a vertical line from the x-
axis at 0.5 for each ratio
 In the graph, B has a higher proportion of its molecules in
vapour form
o Fractional distillation – Application of Raoult’s law
 When a solution boils, the more volatile components have a higher
proportion of the vapour produced
 This forms a solution with a higher proportion of the more volatile
substance
 This is repeated to separate all the components
 A solution boils when the vapour pressure reaches the external
pressure


o Drug detection
 There is abuse of drugs in the sporting industry (Russia, Tour de
France)
 Concerns over drink driving
 Therefore there are now guidelines in specific countries about drug
use
 Laws govern which substances are banned and which are legal
 Thus, governments have methods of checking the amounts of
substances in a person’s body at any one time (drug detection)
o Steroid detection
 Lipids with four fused rings
 Known as a steroidal backbone
 E.g. Cholesterol


 Can be found in hormones – especially sex hormones
 Male steroid hormones are collectively called androgens
 E.g. Testosterone
 These are called anabolic steroids as they promote tissue growth,
especially muscles
 Used as performance enhancing drugs as they improve strength and
endurance
 Many anabolic steroids are synthesized from testosterone
 E.g. nandrolone, stanozolol, furazabol
 The use of anabolic steroids is banned by most sporting organisations
for medical and ethical reasons
 Toxic to liver
 Increased risk of cancer and heart problems
 Disturb hormone balance in body
 Cause changes in secondary sexual characteristics such as
body hair growth and fertility
 Most sporting authorities detect for these banned substances by
taking a collection of body fluid samples to analyse for these
substances
 One of the most common methods for detecting drugs is gas
chromatography-mass spectroscopy (GCMS)
 Gas chromatography splits the substances into pure chemicals
 Mass spectroscopy identifies and quantifies the components
o Gas chromatography
 Useful technique for separating and identifying the components of a
mixture
 Basic principle is that substances have different affinities for different
phases, a stationary phase and a mobile phase
 Affinity: the tendency to which a substance mixes/combines
with another
 The components of the mixture are separated as the mobile phase
moves through the stationary phase
 These phases are;
 Stationary phase: microscopic layer of a non-volatile liquid,
usually a polymer, coated on the walls of an inert solid support
 Mobile phase: an inert carrier gas, such as helium
 The components of the mixture are separated by the different rates
at which they move through the two phases/the instrument
 These differ with the boiling points and the solubilities of
each substance
 These characteristics determine the interactions of the
molecules of each substance with the two phases
 The components partition themselves between the phases
 The lower the boiling point and solubility, the more the substance is
present in the gas, and the faster it moves
 The higher the boiling point and solubility, the more the substance is
present in the liquid, and the slower it moves


 Steps
 The mixture is heated to boiling point and injected into
instrument as a mixture with the inert carrier gas phase
 The gases move through the tubing columns and separate
depending on their boiling point and solubility
o NB: The temperature of the column is controlled and is
typically lower than the initial temperature so that the
components with higher boiling points may condense
and dissolve in the liquid phase on the surface of the
tubing
 Each component of the mixture is eluted (removed from the
tubing) at a certain interval of time, aka retention time
 Detector is used to record the passage of each compound, and
records it
  The area under the peak is the concentration of the substance
relative to a known standard
 The temperature of the column controls the retention times and
therefore the separation of the substances
 E.g.


 In GC-MS, some of the sample is put directly into a mass spectrometer
to avoid having to identify compounds from their retention times


o Mass spectrometry
 (Already gone through in Chapter 11)
 Vaporises sample, ionises it with bombardment of electrons to
produce positive ions, accelerated and deflected with magnetic field,
and separated and categorised based on their respective deflections
 Molecules often fragment into functional groups/structures that can
be identified with mass to charge ratios
 Molecules tend to break in predictable places (functional groups) so
their structure can be determined by the mass spectrometry result
 Computer databases have expected and possible results for
fragmentation patterns, so structures can quickly be identified
 (Section 28 of data booklet)


o Techniques used for the detection of ethanol
 Ethanol, C2H5OH, is the alcohol found in many liquor drinks
 The polar OH group allows it to form hydrogen bonds with water, and
so it is readily available in aqueous solution
 Therefore, can readily dissolve in bloodstream and pass to all parts of
the body
 This is why the effects of ethanol are noticeable shortly after
intake
 Acts as a depressant, which depresses the central nervous system
 Decreases its activity
 Leads to short term changes in behaviour and long-term
dependence
 A person whose judgement is impaired by ethanol/alcohol in their
system is said to be impaired which is potentially dangerous
 Therefore, countries have limits for Blood Alcohol
Concentration for activities such as driving
 Procedures tests bodily fluids for alcohol concentration in mass per
volume
 BAC = mass of ethanol per cm3/mL of blood
 Process uses the equilibrium of ethanol (aq) and ethanol (g) in lungs

 The equilibrium constant for this reaction is constant at a
certain temperature
 So, the measurement of alcohol concentration of the breath
can be used to measure the alcohol concentration in the blood
 Instruments that do this are called breathalysers
 Roadside breathalysers use redox to measure ethanol concentration
 Ethanol can be oxidised to ethanoic acid and ethanal with
Potassium dichromate (K2Cr2O7)
 In this reaction, Chromate (IV) is reduced to Chromate (III)
o Colour changes from orange to green


 This colour change can be measured using a photocell and so
determine the ethanol concentration
 This is often a preliminary test and is followed up by an
intoximeter if one fails the preliminary
 Intoximeter
  An instrument known as an alcosensor uses the
electrochemical reactions in a fuel cell to measure alcohol
concentration
 Two platinum electrodes with an acid bridge in between
 When the exhaled air with ethanol in it is passed over the
cells, any ethanol is oxidised at the anode to form ethanoic
acid
o
 The protons and electrons released from this reaction are
moved to the cathode where they reduce oxygen into water
o
 Thus the overall reaction is;
o
 The electric current produced by this reaction is then
measured to calculate blood alcohol concentration
 This method is portable and widely used
 NOS
o Advances in technology have led to improvements in drug detection in
bodily fluids and the environment
o Now this means that concentrations that were previously deemed too low
can now be measured
o This has made possible higher regulation of drug usage and prescription
 Sometimes led to changes in regulations and laws
o Authorities depend on the scientific data to pass judgement and uphold
these regulations and laws
o It is therefore imperative that the data collected is reliable and have clearly
stated uncertainties

o Organic structure analysis and identification

 A major part of the preparation of drugs in pharmaceuticals is the
characterisation of products
 Uses Mass spectroscopy, IR Spectroscopy, and Proton NMR
 Their usage in identifying drugs is the same as how these processes
identify organic compounds from reactions (Chapter 11)
 E.g. Aspirin and Salicylic acid
o Mass Spectroscopy
 Used to confirm the presence of a compound based on the peak of
the parent molecular ion
 The presence or absence of other peaks (representing ionised
sections of the molecule) help identify the compound and its
structure
 This can be used to determine impurities
 Done by the presence of their characteristic molecular ion
and/or fragment peaks
 E.g. Aspirin and Salicylic acid
 
 The presence of the parent molecular ions can be seen in the
mass spectroscopy spectra
 The parent peak in aspirin is small (not uncommon) as the
majority of the molecule is fragmented in the ionisation
process (Salicylic acid (top), Aspirin (bottom))


 Other peaks usually indicate other molecular fragments
o E.g. C7H5O2+ at 121 after the loss of OH
o IR Spectroscopy
 Functional groups show as characteristic absorption peaks in IR Spec.
 Groups are influenced by the surrounding chemical environment
(other electrons)
 This can act as a molecular fingerprint that can be compared to the IR
spectra of pure substances
o Proton NMR
 AKA HNMR,
 Very sensitive technique that enables chemists to check the identity
of the sample from;
 Chemical shifts
 Number of peaks
 Integrated area
 Splitting patterns
 Impurities will show as their own peaks/characteristics
 E.g. Aspirin




 The splitting of peaks occurs when there are other protons

(Hydrogens) bonded to carbons directly adjacent to the one in
question
 The number of peaks in the split is one more than the number
of adjacent protons
 E.g. Hydrogen number 3 and 4 have a triplet as the splitting
pattern, as they are in the aromatic ring and they have two
adjacent protons each.


 The integrated area ratio shows the ratio of the number of different
protons in each chemical environment
 The HNMR spectrum allows for differentiation between salicylic acid
and aspirin as salicylic acid does not have the singlet at 2.3 ppm
chemical shift as it does not have an ester group with a methyl group