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Chemistry
of Drugs
ffirs.indd 1 6/11/2014 11:36:38 AM

ffirs.indd 2 6/11/2014 11:36:38 AM
Chemistry
of Drugs
David Barlow
Reader, Pharmacy Department,
King’s College London, UK
David Mountford
Lecturer, Pharmacy Department,
King’s College London, UK
Pharmaceutical Press
London • Chicago
ffirs.indd 3 6/11/2014 11:36:39 AM

Published by the Pharmaceutical Press
1 Lambeth High Street, London SE1 7JN, UK
© Pharmaceutical Press 2014
is a trade mark of Pharmaceutical Press
Pharmaceutical Press is the publishing division of the Royal Pharmaceutical Society

of Great Britain
First published 2014
Typeset by Laserwords Private Limited, Chennai, India

Printed in Great Britain by TJ International, Padstow, Cornwall
ISBN 978 0 85711 083 1
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system,
or transmitted in any form or by any means, without the prior written permission of the
copyright holder.
The publisher makes no representation, express or implied, with regard to the accuracy of the
information contained in this book and cannot accept any legal responsibility or liability for any
errors or omissions that may be made.
The right of David Barlow and David Mountford to be identified as the authors of this work
has been asserted by them in accordance with the Copyright, Designs and Patents Act, 1988.
A catalogue record for this book is available from the British Library.
ffirs.indd 4 6/11/2014 11:36:39 AM

Contents
Introduction to the FASTtrack series viii Amphoteric compounds 33

Prefaceix Simple buffer solutions 33
About the authors x Universal buffer solutions 34
Self-assessment34
1. Chemical structure and bonding�� 1
Cations and anions 2 4. Stereochemistry �� 37
Electron orbitals 2 Stereochemistry and its importance
in pharmaceutical science 37
Electronic configuration 2
Stereoisomers38
Molecular orbitals 3
Fischer’s convention of
Promotion5
stereochemical nomenclature 40
Hybridisation6
Conformational isomers 43
Bonding9
Stereoisomers of cyclic molecules 44
Valence shell electron pair
Geometric isomers 46
repulsion (VSEPR) 10
Topological isomers 47
Nucleophiles and electrophiles 10
Self-assessment48
Drawing chemical structures 11
Resonance/mesomerism12 5. Chemical reaction mechanisms�� 51
Drawing resonance hybrids 12 Nucleophiles and electrophiles 51
Self-assessment14 Reaction mechanisms 52
Curly arrows in reaction mechanisms 52
2. Intermolecular interactions �� 17
Radicals in reaction mechanisms 53
Importance of intermolecular
interactions in pharmacy 18 Fish hooks in reaction mechanisms 54
Coulombic/electrostatic interactions 19 Chemical reactivity 54
van der Waals interactions 20 Self-assessment55
Hydrogen bond interactions 22
6. Chemistry of electrophiles and
Molecular affinity and the free energy
of interaction 23 nucleophiles�� 59
Self-assessment23 Addition and substitution reactions 59
Electrophilic addition 59
3. Acids and bases �� 27 Nucleophilic substitution 69
Definitions of acids and bases 27 Elimination reactions 76
Acid and base strength 27 Competition between substitution
Quantifying the strengths of acids and elimination 83
and bases: pKa and pKb values 28 Self-assessment83
Importance of acids and bases
in pharmacy 29 7. Chemistry of aromatic compounds�� 87
Common acidic and basic Benzene87
functional groups 30 Naming of benzene derivatives 88
pH and pKa32 Reactivity88
ftoc.indd 5 6/5/2014 4:33:38 PM

vi Contents
Electrophilic substitution 90 Reasons for the prevalence of hetero

Electrophilic substitution versus aromatic groups in pharmaceuticals 144
electrophilic addition 91 Self-assessment145
Examples of electrophilic substitution 91
10. Amino acids, peptides and proteins �� 151
Monosubstituted benzene derivatives 95
Amino acids 151
Halogen substituents 97
Peptides152
Disubstituted benzene derivatives 97
Proteins154
Self-assessment99
Protein denaturation 161
8. Chemistry of carbonyl compounds �� 103 Protein assays 162
Reactivity of the carbonyl group 103 Fibrous proteins 162
Nucleophilic addition 103 Integral membrane proteins 162
Changes in hybridisation during Self-assessment163
nucleophilic addition 105
Stereochemistry in nucleophilic addition 106 11. Carbohydrates and nucleic acids �� 167
Examples of nucleophilic addition 106 Carbohydrates167
Addition of amines – imine and Nucleic acids 173
enamine formation 111 Self-assessment177
Reductive amination 112
12. Lipids and steroids �� 179
Addition–elimination112
Lipids179
Changes in hybridisation during
addition–elimination114 Simple lipids 180
Examples of addition–elimination 115 Membrane lipids 182
α-Hydrogen reactivity 120 Lipid aggregates 184
Examples of α-hydrogen reactions 122 Steroids184
Conjugate addition (Michael addition) 129 Classes of steroid 186
Examples of conjugate addition 130 Cortisol189
Reaction with amines and thiols 130 Bile acids 190
Self-assessment131 Cardiac glycosides 190
Self-assessment191
9. Chemistry of aromatic heterocyclic
compounds�� 135 13. Chemical stability of drugs�� 193
Aromaticity in heterocyclic compounds 135 Types of drug stability 193
Naming of heteroaromatic compounds 136 Functional group reactivity 194
The basicity of nitrogen heterocyclic Strategies to improve shelf-life stability 196
compounds137 Stability after administration 196
Reactivity of heteroaromatic Amide and ester hydrolysis 196
compounds138 Hydrolysis of enantiomers 197
Electrophilic substitution in pyridine 140 Strategies to improve drug stability
Electrophilic substitution with an after administration 198
activating group 141 Self-assessment200
Electrophilic substitution in pyrrole 142
Electrophilic substitution in indole 142 14. Drug metabolism�� 203
Substituted heteroaromatic Phases of metabolism 203
derivatives143 Site of metabolism 206
Nucleophilic substitution 143 Factors affecting drug metabolism 207
Examples of heteroaromatic drugs 144 Self-assessment209
ftoc.indd 6 6/5/2014 4:33:38 PM

Contents vii
15. Molecular spectroscopy and Gravimetric analysis 227

pharmaceutical analysis �� 211 Self-assessment227
Electromagnetic spectrum 211 16. Drug licensing and pharmacopoeia�� 231
Electromagnetic wave 213 Drug licensing 231
UV/visible spectroscopy 213 Marketing authorisations 232
Infrared spectroscopy 217 British Pharmacopoeia 232
Nuclear magnetic resonance Drug monographs 233
spectroscopy219
Identification tests 233
Mass spectrometry 222
Limit tests 233
Chromatography223
Using a drug monograph 234
Thin-layer chromatography (TLC) 223
Health care standards 239
High-performance liquid
Self-assessment240
chromatography 225
Gas chromatography 226 Answers to self-assessment 241
Volumetric (titrimetric) analysis 226 Index247
ftoc.indd 7 6/5/2014 4:33:38 PM

Introduction to the
FASTtrack series
FASTtrack is a series of revision guides created for undergraduate pharmacy students.

The books are intended to be used in conjunction with textbooks and reference
books as an aid to revision to help guide students through their exams. They provide
essential information required in each particular subject area. The books will also
be useful for pre-registration trainees preparing for the General Pharmaceutical
Council’s (GPhC) registration examination, and to practising pharmacists as a quick
reference text.
The content of each title focuses on what pharmacy students really need to know in
order to pass exams. Features include*:
■■ concise bulleted information
■■ key points
■■ tips for the student
■■ MCQs and worked examples
■■ case studies
■■ simple diagrams.
The titles in the FASTtrack series reflect the full spectrum of modules for the
undergraduate pharmacy degree.
Titles include:
Applied Pharmaceutical Practice
Complementary and Alternative Medicine
Law and Ethics in Pharmacy Practice
Managing Symptoms in the Pharmacy
Pharmaceutical Compounding and Dispensing
Pharmaceutics: Dosage form and design
Pharmaceutics: Drug delivery and targeting
Pharmacology
Physical Pharmacy (based on Florence and Attwood’s Physicochemical Principles
of Pharmacy)
Therapeutics
Additional questions are available at www.ontrackpharmacy.com by selecting the

FASTtrack option.
If you have any feedback regarding this series, please contact us at

feedback@fasttrackpharmacy.com.
*Note: not all features are in every title in the series.
viii
fbetw.indd 8 6/6/2014 4:40:16 PM

Preface
This text will undoubtedly be useful for stabilising the rogue leg of that annoyingly
wobbly 1960s coffee table in the “lounge” of your shared student house. It could
also be profitably employed to wedge the toilet door shut now that the locking bolt
has fallen off, or even find use as an aid to sleep when you find yourself suffering
insomnia. Its more prosaic use, however, but yet the use for which it was lovingly
crafted by its authors, is as a revision aid for Pharmacy students who are preparing
for examinations involving organic chemistry, elementary medicinal chemistry, and
biochemistry.
The book should be seen neither as a substitute for lecture notes, nor as a cheap
alternative to the more comprehensive textbooks. Rather, it should be viewed as a
valuable adjunct to your own lecture notes, and as a resource for you to gauge your
progress in learning as you swot up on the chemistry of drugs.
A detailed knowledge and understanding of the chemistry of drugs is
fundamental to the discipline of Pharmacy. Such knowledge and understanding
allows the practising Pharmacist to appreciate the methods by which drugs are
synthesised, the ways in which they are analysed and tested prior to licensing and
marketing, and the ways in which they are quality assured in manufacture. It is the
chemistry of the molecules that is responsible for their pharmacological activity; it is
their chemistry that determines the ways in which they are formulated as medicines;
and it is their chemistry that determines their stability on the shelf in the home, and
their stability and fate within the human body.
When you do delve inside this book, you might first like to revise one of the
topics (using your own notes) and then test yourself on that topic by attempting the
self-assessment multiple choice questions given at the end of the relevant chapter.
That way, you’ll get some idea as to the quality of your notes and/or revision of that
topic. You can then read and digest the material presented in that chapter, hopefully
improving your knowledge and understanding of the subject as you do so.
David Barlow
David Mountford
March 2014
ix
flast.indd 9 6/11/2014 11:16:10 AM

About the authors
David Barlow is a reader in computational & molecular biophysics and head of the
pharmaceutical chemistry teaching section in the Pharmacy Department at King’s
College London. He is a biochemistry graduate with an MSc in bio-molecular
structural organisation and a PhD in crystallography.
His research over recent years has been primarily concerned with structural
and computational studies of drugs and drug delivery systems. These studies have
included: informatics and virtual screening of phytochemical libraries; development
of expert systems approaches for drug discovery and modelling of drug delivery;
development of novel software for modelling membrane structure; detailed
characterisation of the molecular architectures and membrane interactions of drug
and gene delivery vehicles; and the development and exploitation of heterologous
expression systems for production of integral membrane proteins and novel peptides
for use in pharmaceutical formulation.
David Mountford is a lecturer in medicinal chemistry at King’s College London,

having previously worked in the pharmaceutical industry as a senior medicinal
chemist working on a range of indications with an unmet medical need.
His current research is focused on the development of new methods for the
preparation of classes of compounds that are either poorly described or not described
at all in the literature. A second strand of research lies in the application of drug
discovery methods to biological targets: both those that are well described and
potentially new drug targets arising from original research being carried out at King’s
College London. In addition to using well established methods, he is working on the
development and evolution of existing drug discovery methods and their application
to those targets traditionally considered to be less druggable or undruggable.
flast.indd 10 6/11/2014 11:16:11 AM

chapter 1
Chemical structure and
bonding
Overview
After learning the material presented in this chapter you should:
■■ understand how an atom is structured, in terms of both the nucleus and the
electronic orbitals
■■ understand the assignment of an electronic configuration to atoms and ions
■■ be able to discuss how atomic orbitals combine to form molecular orbitals
■■ appreciate how sp3, sp2 and sp hybrid orbitals are formed
■■ be able to discuss how hybridised atoms form single, double and triple bonds
■■ understand the factors that determine molecular shape and bond angles, and
appreciate why some molecules deviate from theory
■■ review the drawing of resonance hybrids using the curly arrow notation.
■■ An atom is composed of a nucleus and a surrounding cloud of electrons.

■■ The nucleus contains both protons and neutrons and has an overall positive
charge.
■■ Fundamental properties
Particle Proton Neutron Electron
Charge +1 0 −1
Mass (amu) 1.00728 1.00866 0.00054
■■ The atomic number of an element is given by the number of protons in the

nucleus or the number of electrons in the unionised element.
■■ The mass number of an element is given by the sum of the protons and neutrons
(Figure 1.1).
■■ Atoms which contain the same number of protons in the nucleus but a different
number of neutrons are termed isotopes. Isotopes have different physical and
chemical properties.
Mass number (number of protons + neutrons) Figure 1.1

The chemical symbol.
12
6
C
Element name
Atomic number (number of protons)
c01.indd 1 6/11/2014 11:28:02 AM

2 Chemistry of Drugs
Cations and anions

■■ An atom can be ionised by either adding or removing an
electron. The addition of an electron results in the formation
of a negatively charged species, an anion. The removal of an
electron results in the formation of a positively charged species,
a cation.
Electron orbitals
■■ The electrons of an atom occupy discrete atomic orbitals. These
orbitals describe the probability of locating an electron in the
region outside the nucleus.
■■ In the same way that light demonstrates both wave and particle-
like behaviour, electrons also demonstrate this duality, and
hence an electron can be described by its mathematical wave
function.
■■ Individual atomic orbitals can accommodate a maximum of two
electrons. These must be of opposite spin and are termed spin-
paired.
■■ Atomic orbitals can be described as s, p or d orbitals (Figure 1.2).
■■ The three p orbitals are degenerate; they are each of the same
energy.
■■ The five d orbitals are degenerate; they are each of the same
energy.
Figure 1.2 z
Shapes of s, p and d y
atomic orbitals.
s orbital
x
s
z z z
y y y
p orbitals
x x x
px py pz
z z z z z
y y y y y
d orbitals
x x x x x
dx2–y2 dxz dz2 dyz dxy
Electronic configuration
■■ Atomic orbitals (Figure 1.3) are filled to give the lowest-energy
electronic configuration for an atom, the ground state.
c01.indd 2 6/9/2014 5:11:28 PM

Chemical structure and bonding 3
3d
KeyPoints
■■ Rules for filling atomic orbitals
4s
E 1. Aufbau principle: Electrons
N 3p are added to the lowest-
E
3s energy atomic orbital first.
R 2. Pauli exclusion principle:
G 2p
Y Each atomic orbital can
2s accommodate two electrons
with opposite spin.
3. Hund’s rule: Half-fill orbitals
1s of equivalent energy before
spin pairing.
Figure 1.3 Energy level diagram.
■■ The ground state electronic configuration of oxygen can be found

by accommodating eight electrons (Figure 1.4).
E E E
N 3s N 3s N 3s
E E E
R 2p R 2p R 2p
G 2s G 2s G 2s
Y Y Y
1s 1s 1s
CORRECT INCORRECT INCORRECT
Figure 1.4 Correct and incorrect filling of atomic orbitals for oxygen.
■■ When a shell of electrons becomes full it is

termed core. Core electrons typically do not
participate in chemical reactions.
KeyPoints
■■ Electrons in incomplete shells are termed ■■ Radicals are species with
valence. Valence electrons are available unpaired electrons.
■■ This is not the same as ions,
to participate in chemical reactions and
which have an overall charge.
bonding.
Molecular orbitals
■■ In the same way that electrons in an atom occupy atomic
orbitals, the electrons in a molecule occupy molecular orbitals.
■■ Molecular orbitals are formed from the linear combination of
the individual atomic orbital wave functions. This combination
can either be as the sum of the two wave functions or as the
difference of the two wave functions. That is,
Ψ = caψa + cbψb
Ψ* = caψa − cbψb
c01.indd 3 6/9/2014 5:11:28 PM

Tips where caψa and cbψb describe the

individual atomic orbitals, Ψ describes
■■ The bonding molecular orbital is the bonding molecular orbital and Ψ* the
lower in energy than the initial
antibonding molecular orbital.
atomic orbitals.
■■ The antibonding molecular ■■ The linear combination of two atomic
orbitals are higher in energy orbitals will result in the formation of two
than the initial atomic orbitals. molecular orbitals, one of which will be
bonding, the other antibonding (Figure 1.5).
Figure 1.5 Ψ∗ (antibonding)

Forming molecular orbitals from
individual atomic orbitals.
ψa ψb
Ψ (bonding)
■■ If the two atoms are identical, each will contribute equally to the
molecular orbitals. The bonding molecular orbital will be lower
in energy than the starting atomic orbitals by the same amount
as the antibonding molecular orbital is higher in energy than the
starting atomic orbitals.
■■ Each molecular orbital can accommodate a maximum of two
electrons, each with opposite spin.
■■ Molecular orbitals are filled with electrons in the same way as
atomic orbitals, starting at the lowest energy available molecular
orbital and spin pairing before filling the next highest molecular
orbital.
■■ In a hydrogen molecule (H2) each hydrogen atom is contributing
a single 1s electron; these are spin paired in the lowest energy
Tips molecular orbital, the sigma (σ)-bonding orbital.

The σ*-antibonding orbital remains empty
If you bring the two hydrogen 1s (Figure 1.6).
orbitals together so that they
overlap you can imagine a region of
increased electron density between
H H
the two atoms. This is like adding
the two hydrogen wave functions σ∗
together to create the bonding
molecular orbital. If you now H• 1s 1s • H
consider the region of overlap and
subtract one of the overlaps from
the other you would end up with
σ
nothing – a region without electron
density between the two atoms. H−H
This is what the antibonding
molecular orbital looks like.
Figure 1.6 Molecular orbitals for molecular hydrogen.
c01.indd 4 6/9/2014 5:11:29 PM

Figure 1.7
Molecular orbitals from
p orbitals.
π∗
2p 2p
■■ In the same way that s orbitals combine to give σ and σ* molecular

orbitals, p orbitals combine to give pi (π) and π* molecular orbitals
(Figure 1.7).
■■ Although s orbitals and p orbitals describe individual
atomic orbitals, they are not suitable for describing molecular
orbitals.
Promotion
■■ Promotion allows an element to increase the
number of bonds it can make through the KeyPoints
movement of a paired non-core electron to ■■ All group 2, 3 and 4 elements
an empty orbital. promote an electron in this
■■ In the case of carbon, paired 2s electrons way to increase their bonding
would only allow the formation of two capability.
covalent bonds. Promotion of one of these ■■ Phosphorus and sulfur are able
electrons to the empty 2p orbital allows to promote into nearby vacant
d orbitals to form five and six
all four electrons to participate in bonding
bonds respectively.
(Figure 1.8).
Electron
promotion
2p 2p
2s 2s
Two-bond mode Four-bond mode
Figure 1.8 Electron promotion in carbon.
c01.indd 5 6/9/2014 5:11:29 PM

Hybridisation
■■ The individual atomic orbitals on an atom must be combined in
a process termed hybridisation so that the resulting molecular
orbitals are of the correct geometry and type for bonding to
occur.
sp3 hybridisation
■■ In sp3 hybridisation the 2s and all three 2p orbitals are combined

to create four sp3 hybrid orbitals.
■■ Each hybrid orbital has a 1/4 contribution from each of the four
■■ The four sp3 hybrid orbitals are of an equivalent energy, which is
lower than the starting 2p orbitals but higher than the starting 2s
orbital.
■■ During hybridisation orbitals are not created or destroyed. The
four atomic orbitals mix to give four hybrid orbitals.
■■ Electrons in hybrid orbitals experience electron–electron
repulsion in the same way as electrons in atomic orbitals. Each
sp3 hybrid orbital will be occupied singly before spin pairing if
necessary (Figure 1.9).
■■ The four sp3 hybrid orbitals adopt a tetrahedral geometry to
minimise electron–electron repulsion between the hybrid
orbitals (Figure 1.10). Each hybrid orbital experiences identical
interactions with the other three hybrid orbitals. The four
hybrid orbitals must therefore be of equivalent energy: they
are degenerate.
Figure 1.9
sp3 hybridisation. 2p
Hybridisation
sp3 hybrid orbitals
2s
Figure 1.10
Geometry of sp3 hybrid orbitals.
109°
sp3 hybrid orbital

C
tetrahedral geometry
c01.indd 6 6/9/2014 5:11:29 PM

sp2 hybridisation
■■ In sp2 hybridisation the 2s and two of the 2p orbitals are

combined to create three sp2 hybrid orbitals. The remaining 2p
orbital remains unchanged by the hybridisation process.
■■ Each hybrid orbital has a 1/3 contribution from each of the three
■■ The three sp2 hybrid orbitals are of an equivalent energy, which
is lower than the starting 2p orbitals but higher than the starting
2s orbital.
■■ During hybridisation orbitals are not created or destroyed: the
three atomic orbitals mix to give three hybrid orbitals.
■■ Electrons in hybrid orbitals experience electron–electron
sp2 hybrid orbital will be occupied singly before spin pairing if
■■ The three sp2 hybrid orbitals adopt a trigonal planar geometry
to minimise electron–electron repulsion between the hybrid
orbitals (Figure 1.12). Each hybrid orbital experiences identical
interactions with the other two hybrid orbitals. The three
hybrid orbitals must therefore be of equivalent energy: they are
degenerate.
■■ The unhybridised 2p orbital will be perpendicular to the plane
of the sp2 hybrid orbitals as the hybrid orbitals will only have
contributions from the p orbitals along two of the coordinate
axes, px and py in Figure 1.12. The remaining pz orbital is
unchanged.
Unmixed 2p orbital Figure 1.11

sp2 hybridisation.
2p 2p
Hybridisation
sp2 hybrid orbitals
2s
z Figure 1.12
Geometry of sp2 hybrid orbitals.
sp2 hybrid orbital
C
120°
Unmixed 2p
orbital trigonal planar
geometry
c01.indd 7 6/9/2014 5:11:30 PM

sp hybridisation
■■ In sp hybridisation the 2s and one of the 2p orbitals are

combined to create two sp hybrid orbitals. The two remaining 2p
orbitals remain unchanged by the hybridisation process.
■■ Each hybrid orbital has a 1/2 contribution from each of the two
■■ The two sp hybrid orbitals are of an equivalent energy, which is
lower than the starting 2p orbital but higher than the starting 2s
orbital.
■■ During hybridisation orbitals are not created or destroyed. The
two atomic orbitals mix to give two hybrid orbitals.
■■ Electrons in hybrid orbitals will experience electron–electron
sp hybrid orbital will be occupied singly before spin pairing if
■■ The two sp hybrid orbitals adopt a linear geometry to minimise
electron-electron repulsion between the hybrid orbitals
(Figure 1.14). Each hybrid orbital experiences an identical
interaction with the other hybrid orbital. The two hybrid
orbitals must therefore be of equivalent energy: they are
degenerate.
■■ The two unhybridised 2p orbitals will be perpendicular to the sp
hybrid orbitals as the hybrid orbitals will only have contributions
from the p orbital along one of the coordinate axes, px in
Figure 1.14. The remaining py and pz orbitals are unchanged.
Figure 1.13 Unmixed 2p orbital

sp hybridisation.
2p 2p
Hybridisation
sp hybrid orbitals
2s
Figure 1.14 Unmixed 2p

Geometry of sp hybrid orbitals. orbital
y
180°
C x
sp hybrid orbital
Linear geometry
c01.indd 8 6/9/2014 5:11:30 PM

Comparison of hybridisation modes
Figure 1.15
2p 2p sp2 hybridisation of oxygen.
Hybridisation
sp2 hybrid orbitals
2s KeyPoint
■■ Hybridisation occurs for all
■■ Hybridisation involves the mixing of s and p
elements other than hydrogen.
orbitals to create new orbitals which possess In each case the mixing of
both s and p character. individual atomic orbitals is the
■■ The number of p orbitals mixed with the s same; the only difference is
orbital will affect the shape and character the number of electrons to be
of the hybrid orbital. The more p orbital distributed into the hybridised
contribution, the greater p character the new orbitals (Figure 1.15).
hybrid orbital will have (Figure 1.16).
■■ sp3 hybrid orbitals have greatest p character, whereas sp hybrid
orbitals have greatest s character.
Figure 1.16
Comparison of hybridised
orbital shape.
sp3 sp2 sp
Tip
Bonding The two atoms in a double or triple
bond must have the same
■■ σ bonds form from the overlap of two sp3 hybridisation – sp2 for a double
hybridised orbitals, two sp2 hybridised bond and sp for a triple bond.
orbitals or two sp hybridised orbitals which
each contain a single electron (Figure 1.17). Hydrogen atoms are
free to form σ bonds with sp3, sp2 and sp hybridised orbitals.
Figure 1.17
H Combining hybridised orbitals to
H form molecules.
H
H C C
H H
c01.indd 9 6/9/2014 5:11:30 PM

Figure 1.18
π bonding in formaldehyde.
H
C O
■■ π bonds form from the overlap of two adjacent p orbitals which

each contain a single electron (Figure 1.18).
Valence shell electron pair repulsion (VSEPR)

■■ When considering bond angles, the repulsion between different
types of electron pairs must be considered.
■■ Lone pair–lone pair repulsion is greater than lone pair–bonding
pair repulsion, which in turn is greater than bonding pair–
bonding pair repulsion (Figure 1.19).
■■ In addition to accounting for bond angles in molecules such
as ethane, VSEPR accounts for the distortions away from the
anticipated hybridisation bond angles, for example the 104.5°
bond angle observed in water.
Figure 1.19
Effect of lone pair–lone pair
repulsion in water. Greatest repulsion
Bonding pairs of
electrons pushed
closer together
O
Tip H
There is nothing magical about
electronegativity. As you go across
the periodic table the number of Least repulsion H
protons in the nucleus increases
but the corresponding electrons
are added to the same orbitals.
The result is that the electrons are
increasingly tightly held as you Nucleophiles and electrophiles
move from left to right. The
‘effective nuclear charge’ is ■■ Molecules that are electron-rich with either
increasing. As you go down a a free pair of electrons or a π bond that
period of the periodic table you they can donate are termed nucleophilic
have additional shells of electrons
(nucleus loving). Since nucleophiles
shielding the nucleus; this reduces
the effective nuclear charge. donate a pair of electrons they are also
Lewis bases.
c01.indd 10 6/9/2014 5:11:31 PM

■■ Molecules that are electron-deficient and are able to accept a pair

of electrons from a nucleophile are termed electrophilic (electron
loving). Since electrophiles accept a pair of electrons they are
also Lewis acids.
Drawing chemical structures

■■ Chemical structures can be represented graphically in a wide
range of ways (Figure 1.20).
■■ A simple molecular formula provides information on the atoms
present in a molecule but there is no information concerning
connectivity or structure.
■■ Structural and skeletal formulae both provide additional
information concerning the arrangement of atoms within a
molecule and their connectivity. Whereas the structural formula
displays all atoms present, the skeletal formula focuses on the
carbon framework and omits hydrogen atoms attached to carbon,
though those attached to other atoms are still included.
■■ For reaction mechanisms we will adopt the skeletal formula
approach.
■■ Molecular models are useful when considering chemical
reactivity and how molecules might interact with each other or
with a protein.
Water Ammonia Ethanol Acetone
Molecular H2O NH3 C2H6O C3H6O

formula
H H H O H
Structural
H O H H N H H C C O H H C C C H
formula
H H H H H
H O
Skeletal O
formula H H N OH
H H
Molecular
model
(ball-and-stick
type)
Molecular
model
(space-filling
type)
Figure 1.20 Different ways of representing a molecule.
c01.indd 11 6/9/2014 5:11:31 PM

Tips Resonance/mesomerism
■■ Not all resonance hybrids The electrons in a π bond are less tightly
■■
contribute equally.
bound to the individual atoms of the bond
■■ Major contributors will have a
than the electrons of a σ bond.
full valence shell, will have a
minimum of charges present ■■ A conjugated system is a series of overlapping
and, where charges exist, p orbitals which allows for the delocalisation
negative charges will be located of π electron density across the whole system.
on the most electronegative ■■ In a conjugated system an excess or deficiency
atoms and positive charges on in electron density associated with one atom
the most electropositive atoms.
can be propagated along the system through
the delocalisation of the π bonds.
■■ This delocalisation of π electron density can be represented
pictorially as a series of resonance hybrids or canonical structures.
The conjugated system does not exist as a single, individual
structure; rather it is a sum of the contributing resonance hybrids.
Drawing resonance hybrids

■■ Curly or curved arrows ( ) are used to represent the
movement of a pair of electrons and to convert between
individual resonance hybrids.
■■ Curly arrows always begin at an electron-rich source and point
towards an electron-deficient site (Figure 1.21).
Figure 1.21 ■ Arrows pointing between atoms indicate that a

X Y bond is formed between those two atoms.
Rules for drawing curly arrows.
■ Arrows pointing directly at atoms indicate that
X Y the electrons are located on that atom as an
unshared pair.
■ In the case of resonance one arrow will typically

X Y Z result in the movement of a second pair of
electrons as electron density is delocalised
across the system.
■■ Resonance hybrids are separated by a double-headed arrow; this

is distinct from the usual reaction arrows that denote irreversible
or reversible processes (Figure 1.22).
■■ In resonance, electrons always move away from a negative
charge to create a new double bond (Figure 1.23). Since carbon
can only form four bonds, the pre-existing double bond must
break and the electrons localise on the carbon at the other end.
In this way the negative charge has moved along the molecule.
Figure 1.22 A B Irreversible reaction

Different types of arrows.
A B Reversible reaction
A B Resonance
c01.indd 12 6/9/2014 5:11:32 PM

Figure 1.23
O O
Anions in resonance.
■■ If there is a positive charge present, the

Tips
electron pair will move towards this charge ■■ When moving a negative charge
to convert between resonance
through the breaking of one double bond and
structures two curly arrows are
the creation of a new double bond. In this required.
way it appears as though the positive charge ■■ When moving a positive charge
is moving along the molecule, though in to convert between resonance
reality it is electrons moving in the opposite structures only one curly arrow
direction (Figure 1.24). is required.
Figure 1.24
Cations in resonance.
■■ Although a conjugated system has the electron pairs delocalised

over the entire system, when using the curly arrow notation to
convert between resonance hybrids it is necessary to consider
the system as a series of localised π bonds.
■■ You should always draw benzene and its derivatives as localised
π bonds (Figure 1.25). The importance of this will be seen later
when considering the reactivity and chemistry of benzene and
its derivatives.
■■ Benzene derivatives experience resonance due to the overlapping
of adjacent p orbitals.
■■ This resonance can either push electron density into the ring or
withdraw electron density from the ring (Figures 1.26 and 1.27).
Figure 1.25
The drawing of benzene.
O O O O O
Figure 1.26
Resonance in the phenoxide
anion.
Figure 1.27
CH2 CH2 CH2 CH2 CH2
Resonance in the benzyl cation.
c01.indd 13 6/9/2014 5:11:32 PM

Self-assessment
1. Which of the following rules are not required when considering the filling of
atomic orbitals?
a. Aufbau principle
b. valence shell electron pair repulsion
c. Pauli exclusion principle
d. Hund’s rule
2. The following ground state electronic configuration describes which element?
1s2 2s2 2p5

a. nitrogen
b. oxygen
c. fluorine
d. chlorine
3. Which of the following ground state electronic configurations correctly describes

the sodium ion Na+?
a. 1s2 2s2 2p6
b. 1s2 2s2 2p6 3s1
c. 1s2 2s2 2p5 3s1
d. 1s2 2s2 2p5 3s2
4. The bent geometry of a water molecule is due to which of the following

factors?
a. The oxygen atom is sp hybridised.
b. Water molecules are able to hydrogen bond to each other.
c. The hydrogen atoms are only weakly bound to the central oxygen atom.
d. Non-bonded pairs of electrons on the oxygen atom are repulsed.
5. During hybridisation, the sp2 mode requires the mixing of which orbitals?
a. one s orbital and three p orbitals
b. one s orbital and two p orbitals
c. one s orbital and one p orbitals
d. only the three p orbitals
6. Which of the bonds labelled in the following molecule is shortest?
a b c
a. bond a
b. bond b
c. bond c
d. they are all carbon–carbon bonds and are therefore the same length
c01.indd 14 6/9/2014 5:11:32 PM

7. What is the hybridisation of the atom labelled in the following molecule?
N
C
a. sp3 hybridised
b. sp2 hybridised
c. sp hybridised
d. both sp2 hybridised and sp3 hybridised
8. Which of the following molecules can undergo resonance?

a.
b. NH2
c.
NH2
d. OH
9. Which of the following phenolate canonical structures is the lowest in energy?

a. O
b. O
c. O
d. O
c01.indd 15 6/9/2014 5:11:33 PM

10. Which of the following functional groups will donate electron density to an
adjacent double bond by resonance?
a. an ester
b. a nitro group
c. an amino group
d. a nitrile group
c01.indd 16 6/9/2014 5:11:33 PM

chapter 2
Intermolecular interactions
Overview
■■ know the different types of intermolecular forces involved in drug–water, drug–
membrane and drug–receptor interactions
■■ appreciate the relative strengths of the different intermolecular interactions
■■ understand the hydrophobic effect and its significance as regards drug–receptor

interactions, protein folding and surfactant micelle formation
■■ be able to use empirical formulae to calculate the potential energies of van der
Waals and electrostatic interactions.
■■ Intermolecular interactions describe the non-covalent interactions that exist

between molecules.
■■ The forces involved in intermolecular interactions are much weaker than those
involved in the ionic bonds in substances like sodium chloride, and they are
weaker than the forces involved in the sigma bonds (σ bonds) and pi bonds (π
bonds) which link together atoms in covalent compounds.
■■ The different types of intermolecular interactions include: dipole–dipole and van
der Waals interactions, Coulombic (or electrostatic) interactions and hydrogen
bonds.
■■ Each of these various interactions contributes to the enthalpy of an intermolecular
system.
■■ The enthalpy of a system is a measure of the total energy in that system, and
is measured using the SI unit of joules. The total enthalpy of a system cannot
be measured directly, and so when describing the process of two molecules
interacting with one another, it is usual to refer only to the change in enthalpy
(∆H) that results as a consequence of the interaction between the molecules.
If ∆H is negative, the interaction between the molecules leads to a release of
heat and the process is said to be exothermic. If ∆H is positive, the interaction
between the molecules requires input of energy, and the process is said to be
endothermic.
■■ The relative strengths of the different intermolecular forces are given in Table 2.1.
■■ There is invariably also an entropic contribution to the stability of intermolecular
interactions, which arises because of a change in the degree of disorder in the
system before and after the intermolecular interactions are established. When
two molecules are bound together via non-covalent interactions, their freedom of
17
c02.indd 17 5/31/2014 8:28:07 AM

Table 2.1 Strengths of intermolecular and intramolecular forces

Interaction/force Example Potential energy (kJ.mol-1)
Covalent bond C–C single bond 391
Ionic bond NaCl lattice energy -787
Coulombic/electrostatic Drug NH3+ and protein 87
interaction COO− at 4 Å separation in receptor-
binding site
Hydrogen bond C=O….H–N hydrogen bond with O...N 30
~3 Å
Dipole–dipole interaction H2O ... H2O ~2
van der Waals interaction Two CH3 groups in contact with one <1
(London dispersion force) another
movement and their freedom to change conformation become

more restricted, and such changes work to reduce the entropy of
the system.
■■ The hydrophobic effect describes an entropic contribution to the
stability of an intermolecular interaction that arises because of
changes in the behaviour of the solvent (water) in the system.
This effect is significant for protein folding, and in the formation
of surfactant micelles in water.
■■ In protein folding, the removal of the
non-polar amino acid residues to the
KeyPoints interior of the protein molecule – away
■■ Intermolecular interactions are from contact with the surrounding water
non-covalent interactions. molecules – results in water molecules
■■ The forces involved in being liberated to the bulk (to behave as
intermolecular interactions are liquid water), and this leads to a significant
weaker than those involved in
increase in the water entropy.
ionic or covalent bonds.
■■ In surfactant micelle formation, it is the
■■ Intermolecular interactions
include van der Waals (dipole– removal of the non-polar hydrocarbon
dipole and dipole–induced chain(s) of the surfactant molecules to the
dipole) interactions, hydrogen micelle interior – away from contact with
bonds and electrostatic water – that leads to water molecules being
interactions. liberated to the bulk, and thence to an
increase in solvent entropy.
Importance of intermolecular interactions

in pharmacy
It is the nature and the extent of the intermolecular interactions
that exist between a drug and its target receptor that determine the
efficacy of the drug.
It is the relative strengths of the intermolecular interactions
that exist between a drug and its surrounding solvent, and between
c02.indd 18 5/31/2014 8:28:07 AM

Intermolecular interactions 19
a drug and the lipid molecules that make up a cell membrane,

that determine how readily the drug passes into and across the
membrane and how readily, therefore, it is absorbed into cells.
It is by exploiting the intermolecular interactions between drugs
and surfactant molecules that the various colloidal drug delivery
vehicles like micelles and microemulsions are produced.
Coulombic/electrostatic interactions
Drug molecules that carry positive- or negative-charged groups
will tend to interact more favourably with water, by virtue of the
electrostatic/Coulombic forces between their charged groups and the
water dipoles (Figure 2.1).
When drugs with positive- and/or negative-charged groups bind
in the binding site at their target receptor, the complex formed will
be stabilised significantly by any ionic interactions between the
charged groups on the drug and oppositely charged groups located
in complementary positions within the binding site.
The favourable interactions formed between charged drug
molecules and their surrounding solvent mean that charged drug
molecules do not readily cross cell membranes – there is an energy
penalty associated with the stripping of the hydration shell from the
charged groups (otherwise referred to as desolvation of the charged
groups).
The strength of an electrostatic interaction can be quantified
by the associated potential energy of the interaction (UC), which is
computed according to the empirical formula:
q1 ¥ q2
U c = 332 ¥
ε ¥ r12
where q1 and q2 are the charges on the two charged groups involved
in the interaction (measured in electron charges), r12 is their distance
δ+ H H Figure 2.1
O Water dipole and ion–dipole
H
H electrostatic interactions.
O Na+ (A) Water dipole (µ = 1.85
O
H Debye) – arising because
δ– H H of the uneven sharing
O O of electrons between
1.8 D H CI–
H H its oxygen and hydrogen
H
O atoms.
H
H H O (B) Ion–dipole electrostatic
interactions between
B
δ+ the formally charged Na+
and Cl- ions and their
A surrounding water dipoles.
c02.indd 19 5/31/2014 8:28:08 AM

of separation (in Å), and epsilon (ε) is the bulk dielectric constant of
their surrounding/intervening medium. The dielectric constant for
water (at 298 K) is ~80, and the dielectric constant for the interior
(so-called hydrophobic core) of a globular protein is ~4.
The dielectric constant for a given medium, ε, is the ratio of the
permittivity in that medium relative to that in a vacuum; it thus has
no units.
van der Waals interactions

van der Waals forces are the weakest of the intermolecular forces.
They include the forces that arise through dipole–dipole, dipole–
induced dipole and transient dipole–induced dipole interactions.
In molecules where there are covalent bonds joining atoms that
have a (marked) difference in electronegativity, the atoms involved
will not share the bond electrons equally, with the result that the
bond is polarised. Each of the joined atoms in this case carries a
partial charge – one of the atoms carries a partial positive charge and
the other a partial negative charge. Molecules of this type are said to
have a permanent dipole (Figure 2.1).
Molecules with permanent dipoles interact
Tip with one another, and also with molecules that
Water has an anomalously high carry full electrical charges (i.e. molecular ions),
melting point and boiling point via electrostatic forces.
because of its large dipole moment The resultant of all dipoles within a molecule
(1.85 Debye), and because of its is quantified by its dipole moment m (which is
extensive network of hydrogen measured in Debye). Dimethyl sulfoxide (DMSO),
bonds involving the oxygen lone pyridine and indole have dipole moments of
pair electrons and the protons on
3.96 D, 2.03 D and 2.11 D, respectively.
neighbouring water molecules.
In drug molecules, there are permanent
dipoles associated with any carbon–oxygen,
carbon–halogen and carbon–nitrogen bonds,
and the common functionalities involved include hydroxyl groups
and amine groups.
A force of attraction also arises when a molecule with a
permanent dipole approaches close to a molecule that lacks a
permanent dipole, but which, because of the approaching dipolar
molecule, develops an induced dipole.
Two molecules, both of which lack permanent dipoles, can also
experience a force of attraction, due to transient dipole–induced
dipole interactions. All molecules (even those lacking permanent
dipoles) will have a transient dipole, because the electrons in the
molecule are constantly moving and so, at any given instant, will be
unevenly distributed across covalent bonds. This uneven electron
distribution in one molecule leads to the momentary generation of
c02.indd 20 5/31/2014 8:28:08 AM

Figure 2.2
Molecule 1 Molecule 2 Transient dipole–induced
dipole interactions.
Molecule 1 Molecule 2
δ–
δ+
Molecule 1 Molecule 2
δ– δ–
δ+ δ+
a polarisation within a nearby molecule, and the result is a system

with interacting dipoles (Figure 2.2).
van der Waals attraction is at a maximum when the interacting
molecules are in intimate contact, with the contacting atoms
separated by a distance which corresponds to the sum of their van
der Waals radii (Figure 2.3).
Molecules 1 and 2 have no net dipole (Figure 2.2, top). At a
given instant, molecule 1 develops a transient dipole and approaches
molecule 2 (Figure 2.2, centre); as it does so, its transient dipole causes
an induced dipole to be set up within molecule 2 (Figure 2.2, bottom).
Molecules whose atoms are forced to approach one another
closer than the sum of their van der Waals radii will experience a
5 Figure 2.3
V/ε Lennard-Jones potential.
4
–1
0 1 rm 2 r/σ
c02.indd 21 5/31/2014 8:28:08 AM

repulsive force, which increases very sharply the closer the atoms
are forced together (Figure 2.3).
The strength of a van der Waals interaction can be quantified by
the associated potential energy of the interaction (UVDW), which is
computed according to the empirical (Lennard-Jones) potential:
12
 σ 
6
 σ 
UVDW = 4ε ¥   −  
 r12   r12  

where σ is the distance at which the interaction energy is zero (in Å),
ε measures the maximum strength of interaction for the interacting
atoms (in J.mol−1) and r12 is their distance of
KeyPoint separation (in Å).
The Lennard-Jones interaction potential
■■ van der Waals interactions are
maximised when molecules are energy (V) is a function of the distance of atomic
in intimate contact with one separation, r (the former normalised with respect
another (that is, when they to ε and the latter with respect to σ). rm is the
have atoms separated by a distance at which the potential energy is a
distance equal to the sum of minimum, and σ is the interatomic separation
their van der Waals radii. when the energy of interaction is zero (Figure 2.3).
Hydrogen bond interactions

Hydrogen bonds are attractive interactions formed between hydrogen
bond donor and hydrogen bond acceptor groups.
Hydrogen bond donor groups are chemical groups that have
a hydrogen atom bonded to an electronegative atom (in drug
molecules, generally, O and N atoms). Hydrogen bond donor groups
commonly found in drug molecules include hydroxyl (OH) groups,
amides (CONH) and primary and secondary amine (RNH2 and R2NH)
groups.
Hydrogen bond acceptor groups are chemical groups that have
an atom with one or more lone pairs of electrons. Hydrogen bond
acceptor groups commonly found in drug molecules include fluoro-
and chloro- groups, carbonyl (C=O) groups, amides (CONH), and
primary, secondary and tertiary amine (NH2, R2NH and R3N) groups.
The hydrogen atom involved in a
hydrogen bond is effectively ‘shared’ between
KeyPoint the two heteroatoms involved in the acceptor

and donor groups.
■■ Hydrogen bonds involve the The force of (electrostatic) attraction
sharing of a proton between associated with the hydrogen bond is
two electronegative atoms
sufficiently strong that the acceptor and donor
(typically, O or N).
heteroatoms approach closer than the sum of
c02.indd 22 5/31/2014 8:28:08 AM

their van der Waals radii. The hydrogen bond

formed between the peptide CO and NH groups
Tip
within the alpha helix of a folded protein, for The oral availability of the majority
of drug molecules falls within the
example, typically has the O and N atoms at
criteria of Lipinski’s rule of five:
around 2.8 Å separation, whereas the sum of molecules that are orally active
the van der Waals radii for the O and N atoms is will generally have a molecular
1.52 + 1.55 = 3.07 Å. mass < 500, a log(octanol–water
partition coefficient) no greater
Molecular affinity and the free than 5, contain no more than five
hydrogen bond donor groups and
energy of interaction have no more than 10 hydrogen
bond acceptor groups.
Interactions between molecules can involve any
or all of the various different intermolecular
forces outlined above.
The change in Gibbs free energy that is associated with an
interaction between two molecules (∆G, J.mol−1) is (1) a function
of the change in enthalpy in the system (∆H, J.mol−1), which arises
because of changes in the molecules’ bonding arrangements (e.g. the
formation of hydrogen bonds between the interacting molecules) and
(2) because of changes in the system entropy (∆S), which stem from
changes in the molecules’ orientational and conformational freedom.
The equation that relates ∆G, ∆H and ∆S is simply:
∆G = ∆H − T¥ ∆S
where T is the temperature (in Kelvin).

The change in Gibbs free energy associated with any
intermolecular interaction provides a measure of the affinity between
the two molecules. The lower (the more negative) the associated ∆G,
the greater the affinity of the interacting molecules for one another.
Self-assessment
1. The strength of interatomic interactions follows the order:
a. ionic > dipole–dipole > van der Waals
b. hydrogen bond > van der Waals > dipole–dipole
c. covalent bond > van der Waals > hydrogen bond
d. van der Waals > hydrogen bond > dipole–dipole
2. If there is a net gain in entropy associated with an intermolecular interaction,

and if the associated enthalpy gain is twice the gain in entropy, the change in
Gibbs free energy for the interaction will be:
a. ∆G = 3∆S
b. ∆G = ∆S
c. ∆G = (2 - T) ∆S
d. ∆G = (T - 2) ∆S
c02.indd 23 5/31/2014 8:28:08 AM

3. How many hydrogen bond donor groups are found in the analgesic drug
paracetamol (below, right)?
a. 1
b. 2 HN OH
c. 3 O
d. 4 CH 3
4. The general anaesthetic, halothane (below right) will not be attracted to other
molecules of halothane as a result of:
a. hydrogen bond interactions Br Cl
b. ionic interactions
F 3C H
c. van der Waals forces
d. dipole–dipole interactions
5. Given a near-perfect complementarity between aspirin (below) and the binding

site on its target enzyme, cyclooxygenase, which of the following interactions
will contribute most to the stability of the system when the drug inserts in the
enzyme-binding site?
COOH
O CH3
a. van der Waals interactions involving the drug’s methyl group

b. the hydrogen bond formed by the drug’s carbonyl group
c. the ionic interaction(s) involving the drug’s ionised carboxyl group
d. dipole–dipole interactions involving the drug’s ester group
6. The antibiotic amikacin (below) is predicted to have low oral bioavailability

and this can be explained by the fact that:
NH2
HO OH
O
H
HO HN NH2
O
H2N O O
OH OH OH
O
H 2N
OH
OH
a. it has too many rings

b. it has a molecular mass < 500
c. it has no charged groups
d. it has too many hydrogen bond acceptor groups
c02.indd 24 5/31/2014 8:28:09 AM

7. A cationic drug molecule is unlikely to bind and become buried within a

protein-binding site if the binding site features a prominent:
a. phosphate group
b. primary amine group
c. sulfonate group
d. carboxylate group
8, Molecules whose constituent atoms exhibit little variation in electronegativity:

a. will have high dipole moments
b. will not experience a significant force of mutual attraction as a result of van der
Waals interactions
c. are unlikely to contain hydrogen bond donor groups
d. will interact with one another primarily through ionic interactions
9. Drug molecules based on open chain structures, when compared against those
that have the same pattern of functional groups but are based around aromatic
and fused ring systems:
a. will tend to have a greater affinity for their target receptor because their
conformational entropy will increase as a result of complex formation
b. will tend to have lower affinity for their target receptor because their
conformational entropy will decrease as a result of complex formation
c. will tend to have greater affinity for their target receptor because their
conformational entropy will decrease as a result of complex formation
d. will tend to have lower affinity for their target receptor because their
conformational entropy will increase as a result of complex formation
10. If two drugs, A and B, bind in an enzyme’s active site and drug A occupies all of
the available space while drug B occupies only some of the space:
a. drug A is likely to have a greater affinity for the enzyme compared with drug B
because of increased van der Waals interactions
b. drug B is likely to have a greater affinity for the enzyme compared with drug A
because of increased van der Waals interactions
c. drug A is likely to have a greater affinity for the enzyme compared with drug B
because of the reduction in solvent entropy caused through water elimination
from the active site
d. drug B is likely to have a greater affinity for the enzyme compared with drug A
because of the reduction in solvent entropy caused through water elimination
from the active site
c02.indd 25 5/31/2014 8:28:09 AM

c02.indd 26 5/31/2014 8:28:09 AM
chapter 3
Acids and bases
Overview
■■ be able to identify acidic and basic functional groups in drug molecules
■■ be able to assess the strength of an acid or base
■■ know the pKa values of common acidic and basic groups
■■ understand why knowledge of acids and bases is important in pharmacy
■■ be able to use the pKa values of acidic and basic groups to determine the ionisation
state of a drug molecule at a specific pH
Definitions of acids and bases

The Brønsted–Lowry definition of an acid is a species able to donate a proton (H+),
and the corresponding definition for a base is a species able to accept a proton.
The (negatively charged/anionic) species that remains after an acid has lost a
proton is known as the conjugate base, and the (positively charged/cationic) species
created when a base accepts a proton is the conjugate acid.
The reaction between an acid and base can thus be written as the word equation:
acid + base conjugate acid + conjugate base
and if we consider the reaction between an acid HA and a base B we have the
equation:
HA + B A − + HB +
where A- is the conjugate base and HB+ is the conjugate acid.
Acid and base strength

The strength of an acid describes how readily it yields a proton when in solution. A
strong acid is one that is fully ionised (that is, fully dissociated) in (aqueous) solution.
Examples of strong inorganic acids include hydrochloric acid (HCl), sulfuric acid
(H2SO4) and nitric acid (HNO3). When hydrogen chloride (gas) is dissolved in water it
dissociates completely to produce proton and chloride ions:
HCl H + + Cl −
A weak acid is only partially dissociated in solution. Examples of weak

acids include carbonic acid (H2CO3) and ethanoic acid (also known as acetic acid,
CH3COOH). The solution of a weak acid contains both the free (unionised) acid
27
c03.indd 27 6/5/2014 4:40:23 PM

Tip and the conjugate base. In solution, therefore,

ethanoic acid exists in equilibrium with
The names of drug salts can often ethanoate (CH3COO-) ions:
be used to tell whether the parent
drug is acidic or basic. So, for CH3COOH CH3COO − + H +
example, we can deduce that the
opiate morphine must be basic In like manner, a strong base is a base
because its commonly used salts, that is fully ionised in aqueous solution and a
morphine hydrochloride and weak base is one that is only partially ionised
morphine sulfate, indicate that they in aqueous solution. Examples of strong
are produced by the addition of a bases include sodium hydroxide (NaOH) and
weak base (morphine) to a strong potassium hydroxide (KOH). In solution,
acid – for these two salts, either
sodium hydroxide is fully dissociated as sodium
hydrochloric acid or sulfuric acid.
Likewise, the name of the and hydroxide ions:
antibiotic salt, penicillin G sodium, NaOH → Na + + OH −
indicates that it is formed by the
addition of a weak acid (penicillin Examples of weak bases include ammonia
G, also known as the benzyl (NH3) and methylamine (CH3NH2). An aqueous
penicillin) to a strong base; the solution of ammonia (gas) contains an
strong base in this case is sodium
equilibrium mixture of the free base (ammonia)
hydroxide.
and the conjugate acid (an ammonium ion,
NH4+):
NH3 + H2 O NH 4 + + OH −
Quantifying the strengths of acids and bases: pKa

and pKb values
The strength of an acid in aqueous solution is quantified by its acid
dissocation constant, Ka. If we consider the equilibrium that exists
for an acid HA in solution:
HA A − + H +
KeyPoints Ka is obtained as:
 A −  ¥ H + 
■■ Strong acids are fully Ka =    
dissociated in aqueous [HA]
solution.
■■ Weak acids are only partially where […] indicate the molar concentrations of
dissociated in aqueous each of the species, HA, A- and H+.
solution. The stronger the acid, the more readily it
■■ Strong bases are fully ionised dissociates in solution (forming A- and H+ ions)
in aqueous solution. and so the higher its Ka value.
■■ Weak bases are only partially
The negative logarithm of Ka (-log10Ka) is the
ionised in aqueous solution.
■■ The strength of an acid or base pKa of the acid (pKa = log10 (1/Ka)). Strong acids
can be quantified by its pKa. have high Ka values and so have low pKa values.
Weak acids have low Ka values and so have high
pKa values.
c03.indd 28 6/5/2014 4:40:23 PM

Acids and bases 29
The strength of a base in solution can be quantified by its

association constant, Kb. If we consider the equilibrium that exists
for a base B in aqueous solution:
B + H2O OH − + HB +
Kb is obtained as:
OH −  ¥  HB + 
Kb = 
[B ]
where […] indicate the molar concentrations of
each of the species, B, OH- and HB+. Tip
The stronger the base, the more readily it is Solubility for acidic and basic
protonated in solution (forming HB+) and so the drugs will vary with the pH of their
higher its Kb value. solution. An acidic drug will be
The negative logarithm of Kb (-log10Kb) is most soluble under alkaline
the pKb of the base. Strong bases have high Kb conditions and will be least soluble
under acidic conditions. Basic
values and so have low pKb values. Weak bases
drugs will have highest solubility in
have low Kb values and so have high pKb
acidic conditions and least
values. solubility in alkaline conditions. An
The strength of a base can also be quantified amphoteric drug will have its
by means of the pKa of its conjugate acid. The lowest solubility at its isoelectric
pKa value for a base is related to its pKb value as: point.
pK b = pK w − pK a
where Kw is the ionic product for water:
K w = OH −  ¥ H + 
In aqueous solutions at 25ºC, Kw ~ 10-14 M, and so pKw ~ 14 and:

pK b = 14 − pK a
The percentage ionisation for an acidic drug

Tips
can be calculated as: ■■ Weakly acidic drugs are
essentially totally ionised at pH
100 values ≥ 2 units above their
Per cent ionisation =
1+ (antilog (pK a − pH)) pKa.. They are almost totally
unionised at pH values ≥ 2
and for a basic drug it is calculated as: units below their pKa and are
50% ionised at pH values equal
100 to their pKa.
Per cent ionisation =
1+ (antilog (pH − pK a )) ■■ Weakly basic drugs are
essentially totally ionised at
pH values ≥ 2 units below their
Importance of acids and bases in pKa.. They are essentially totally
unionised at pH values ≥ 2
pharmacy units above their pKa and are
50% ionised at pH values equal
The majority of drugs contain weakly acidic to their pKa.
or weakly basic functional groups. There are
c03.indd 29 6/5/2014 4:40:24 PM

many too that contain both types of group and such compounds are
described as amphoteric compounds.
The ionisation state of a drug that contains acidic and/or
basic functional groups will depend on the pH of the medium it is
dissolved in. This in turn will influence the drug’s solubility, the
way in which it is formulated as a medicine, its absorption and
distribution within the body and its pharmacological activity.
Many of the pharmaceutical excipients that are used in
formulating drugs as medicines also contain acidic and/or basic
functional groups.
Common acidic and basic functional groups

The chemical structures and pKa values for various acidic and basic
functional groups that are commonly found in drug substances
are shown in Table 3.1, together with examples of drugs in which
they are found. Table 3.2 provides a similar listing for some of the
commonly used pharmaceutical excipients that contain acidic and/
or basic functional groups.
Table 3.1 Acidic and basic functional groups commonly found in drug substances
Acidic groups
Carboxyl R-COOH Ibuprofen (analgesic)
(pKa 2–4)
COOH
Phenol Ar––OH Phenol (used in antiseptic mouth spray)
(pKa ~10)
OH
Sulfonamide R-SO2NH2 Diclofenamide (antiepileptic)
(pKa 8–10) H2NO2S SO2NH2
Cl Cl
Imide R-CO-NH-CO-R Phenytoin (antiepileptic)
(pKa 8–10) O
HN
NH
O
c03.indd 30 6/5/2014 4:40:25 PM

Acids and bases 31
Basic groups
Primary aliphatic R-NH2 Amfetamine (for treatment of attention deficit
amine hyperactivity disorder)
(pKa 9–10) NH2
CH3
Secondary aliphatic R-NH-R Isoprenaline (β2-agonist)

amine OH
H
(pKa 9–10) HO N
HO
Tertiary aliphatic R-N(R)2 Amitriptyline (antidepressant)

amine
(pKa 9–10)
Quaternary amine Bethanechol (for treating postsurgical urine

(pKa n/a; cationic +
retention)
R-N (R)3
species exists at all O
pHs)
H2N O N(CH3)3 Cl
Aromatic amine Ar––NH2 Benzocaine (local anaesthetic)

(pKa 2–4) O
H2N
Pyridine Pyridoxine (vitamin B6)

OH
(pKa ~5.5)
N
HO
OH
H3C N
Imidazole N Dacarbazine (anticancer agent)

O NH2
(pKa 6–7) N
H
N N
N N
NH
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Table 3.2 Acidic and basic pharmaceutical excipients
Stearic acid (CH2)16

H3C COOH
(tablet lubricant)
Aspartame
(sweetener)
O
OCH3
HOOC N
H
NH2 O
Sodium benzoate
COO Na
(preservative)
Citric acid
COOH
(soluble tablet disintegrant)
HOOC COOH
OH
Butylparaben O
(antimicrobial preservative) O
HO
Glycine
H2N CH COOH
(buffering agent and lyophilisation aid)
H
pH and pKa
The pH of a solution is the negative logarithm of its hydrogen
ion concentration, that is, pH = -log10[H+], or, alternatively,
pH = 1/log10[H+].
For an aqueous solution of a weak acid, HA, which has an acid
dissociation constant, Ka:
 A −  ¥ H + 
Ka =    
[HA]
The pH of the solution and the acid pKa are related by the
Henderson–Hasselbalch equation:
 A− 
pH = pK a + log  
[HA]
c03.indd 32 6/5/2014 4:40:27 PM

Acids and bases 33
where […] indicate the molar concentrations of each of the species,

HA and A-.
Amphoteric compounds
Substances that contain both acidic and basic functional groups are
known as amphoteric substances. An amphoteric molecule that has
both its acidic and basic groups ionised simultaneously is known as
zwitterionic.
Amphoteric compounds can potentially exist as cationic,
anionic, zwitterionic or neutral species in aqueous solution and their
precise ionisation state varies according to the pH of the solution
and the pKa values of their acidic and basic groups.
An amphoteric molecule that has one acidic group and one basic
group, with pKa values of pKa1 and pKa2, will exist as electrically
neutral species when the solution pH is midway between pKa1 and
pKa2, that is:
pK a1 + pK a2
pH =
2
Simple buffer solutions

A buffer solution is a solution that resists (major) changes in pH. An
acidic buffer is one that has a pH below 7. An alkaline buffer is one
that has a pH above 7.
Acidic buffers can be produced simply as a solution of a weak
acid and one of its salts. The composition of an acidic buffer and its
resulting pH are related according to the equation:
Ka =
[salt ] ¥ H + 
[acid ]
where […] indicate the molar concentrations of hydrogen ions, the
acid and its salt.
Alkaline buffers can be prepared simply by preparing a solution
containing a weak base and one of its salts. The composition of
an alkaline buffer and its resulting pH are related according to the
equation:
Ka =
[ base] ¥ H + 
[salt ]
where […] indicate the molar concentrations of hydrogen ions, the
acid and its salt.
Simple acidic and alkaline buffers are generally effective in
limiting changes in pH over a pH range within 1 log unit of the pKa
of the constituent acid or base. So, for example, an acidic buffer
c03.indd 33 6/5/2014 4:40:27 PM

based on benzoic acid, which has a pKa of 4.2, will only buffer
effectively over the pH range 4.2 ± 1.0, that is from pH 3.2 to pH 5.2.
Universal buffer solutions

A universal buffer solution is a buffer solution that buffers over a
wide pH range. Such buffers can be prepared using substances that
have two or more functional groups with pKa values separated by ≥2
pH units. Citric acid, for example, has three acidic groups, with pKa
values of 3.06, 4.78 and 5.40, and so it can buffer over the pH range
2.1–6.4.
Universal buffers that can buffer over even broader pH ranges
are prepared using mixtures of substances whose pKa values are
separated by ≥2 pH units. A mixture of citric acid, boric acid, diethyl
barbituric acid and potassium dihydrogen phosphate provides a
universal buffer with a working pH range of 2.4–12.
Self-assessment
1. In aqueous solution at pH 7, the molecules of the appetite suppressant
phentermine (shown below) will exist predominantly as:
a. cations
NH2
b. anions
c. neutral molecules
d. unionised species
2. In an aqueous solution pH 4.0, the concentration of hydrogen ions will be:

a. 104 mM
b. 10-4 M
c. 104 M
d. 10-4 mM
3. Aspirin (shown below) has a functional group with a pKa value of:
a. 0.5 COOH
b. 10.5 O
c. 7.5
O
d. 3.5
4. Ephedrine hydrochloride is used in the treatment of asthma. Ephedrine is:

a. a weak acid
b. a strong acid
c. a weak base
d. a strong base
c03.indd 34 6/5/2014 4:40:27 PM

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no related content on Scribd:
IX
ATHLETICS
CASES 3 AND 4
The strength, agility, and symmetry of the body were valued in the
highest degree by the Greeks, and with them physical training
occupied a much larger place than has been the case among other
peoples. Athletics were closely connected with religion, since
contests were held as a part of the funeral and memorial rites of
heroes, and likewise of the worship of the gods. They also had an
important practical end; Greek armies were always levies of citizens,
and since there was no considerable length of time during which the
Greek states were at peace before the period of Roman domination,
the safety of the state depended to a great extent upon the training
of its citizens. Gymnastic games and exercises were continued
throughout the greater part of a man’s life, contributing to good
health and physical development no less than to recreation.
This interest in athletics can be traced back to very early times in
the Boxer Vase from Crete dated in the sixteenth century B.C. (a
reproduction of this vase is in Case J in the First Room) and the
scenes of bull-leaping and the ivory leapers from Knossos
(reproductions on the south wall of the First Room and in Case H 2).
The Homeric poems contain many references to athletics, as the
funeral games of Patroklos in the Twenty-third Book of the Iliad, the
games among the Phaeacians in which Odysseus took part
(Odyssey VII), and Odysseus’ encounter with the beggar (Odyssey
XVIII, vv. 15ff.); but at this time sports were unorganized and no rules
had as yet been devised for them. The seventh century was
especially the period of organization during which the great festivals
became fixed in time and in the number and kind of contests, and by
570 B.C. the four great Panhellenic festivals—the Olympian, the
Pythian, the Isthmian, and the Nemean—were established.
FIG. 113. JUMPER WITH HALTERES

FIG. 114. DISKOS-THROWER
There are a large number of vases, especially those of the late

sixth and early fifth centuries, ornamented with scenes from the
wrestling-schools and gymnasia. The place is indicated by the
objects hung on the walls, such as jumping-weights, a diskos, or an
oil-flask and a strigil for removing sand and oil. The trainer is usually
present, represented as a mature man, wearing a himation and
carrying a forked rod. The flute-player in a long, spotted robe often
accompanies the exercises or plays for the jumper.
FIG. 115. ATHLETE THROWING A JAVELIN
FIG. 116. WRESTLERS

The principal athletic contests were foot-races of various
distances, including the torch-race, which corresponded to the
modern relay race, broad jumping, throwing the diskos and the
javelin, wrestling, and boxing. There were also the pentathlon (five
contests), which consisted of the jump, the foot-race, throwing the
diskos and the javelin, and wrestling; and the pankration, a
combination of wrestling and boxing.
FIG. 117. SCENE FROM THE PANKRATION
For jumping, weights called halteres were used; on the black-

figured lekythos on the middle shelf of Case 4 decorated with a
scene of athletes practising, two of the number hold halteres, the
drawing being sufficiently detailed to show the shape well. On the
psykter and a vase fragment on the same shelf are jumpers at the
take-off (fig. 113), and a boy preparing for a jump decorates the
interior of a kylix on the lower shelf in Case P in the Fifth Room.
A foot-race is represented on one of the Panathenaic amphorai in
the Third Room (Case N), and the cast of a bronze statuette in
Tübingen shows a contestant in the race for hoplites (heavy-armed
foot-soldiers), at the starting-line (top shelf of Case 3). The shield
which he carried on his left arm has been broken away.
Throwing the diskos was one of the oldest Greek sports. The
object was to throw it as far as possible, as in putting the shot. So
many representations of this sport have come down to us in statues,
vase paintings, coins, and gems, that it is possible to work out the
successive movements of the throw. The principle seems to have
been always the same, though individuals were allowed certain
differences in style. A bronze statuette in Case B in the Fourth Room
(fig. 114) shows one stance; the athlete is about to swing the diskos
down from the left to the right hand. The position preliminary to the
swing downwards to the side, the athlete now holding the diskos in
both hands, may be seen on the lekythos in Case 4; and one of the
figures on the psykter is in the same position. The well-known statue
by Myron, of which a cast stands in Gallery 22, shows the position
just preliminary to the throw, an instant before the diskos leaves the
hand.
FIG. 118. PANATHENAIC AMPHORA

The art of fighting in heavy armor, hoplomachy, was taught to
Greek boys by a special master as part of their athletic training. A
most interesting scene of this kind decorates the shoulder of a hydria
of the late sixth or early fifth century where two men armed with
helmet and shield are fencing with spears to the music of a flute-
player (Case Y in the Fourth Room). Plato alludes more than once to
the attention given to this branch of physical training in his day, and
the prestige enjoyed by teachers of the art.
FIG. 119. YOUTH BINDING ON A FILLET
Throwing the javelin also had a practical value as preparation for

warfare and was one of the commonest sports of the palaistra. In the
pentathlon it was thrown for distance only, but there were
competitions in throwing at a target at the Panathenaea and, no
doubt, on other occasions. A thong, fastened near the center of
gravity, and twisted around the hardwood shaft, acted like the rifling
of a gun in insuring greater accuracy. One of the figures on the
black-figured lekythos is preparing to throw a javelin, and the artist
has represented the thong in such a way that the method of using it
can easily be understood. The thrower holds the shaft in his hand
with the first and second fingers inserted into loops in the end of the
thong. As he throws, the thong unwinds, giving the missile a whirling
motion (fig. 115).
The use of the bow and the sling, as has been said in the section
on Armor, was also taught in the palaistra at Athens.
The pankration, a combination of wrestling and boxing, was one of
the most popular Greek sports. In it ground-wrestling and hitting
were allowed. Two scenes from the pankration are represented on a
skyphos in Case 4. On one side the winner has thrown his opponent
backward and is about to strike him, while the other holds up his
hand, probably as a signal of defeat (fig. 116). On the other side the
combatants have their hands covered with the thongs which served
as boxing-gloves. The man on the ground has thrown the other by a
neck-hold (see head-band, p. 89). There are two boxers in the group
of athletes on a krater on the top shelf of Case Q in the Fifth Room,
and a boxing scene is represented on one of the Panathenaic
amphorai.
The value of the prizes given for athletic skill varied greatly, from
the wreath of olive at Olympia and the parsley leaves of Nemea to
articles of considerable value and, in a few cases, even money. At
the Panathenaea the prizes were jars of oil in greater or less
numbers, and the painted vases known as Panathenaic amphorai.
Probably only one of these was given to a victor. They bear on one
side a picture of the contest in which the vase was won, and on the
other, the figure of Athena with an inscription, “From the games at
Athens” (fig. 118). When the prize took the form of a wreath, the
victor first bound a fillet or band of wool around his head and upon
this the official in charge of the games placed the wreath. The act of
tying the fillet was often represented by Greek sculptors; the most
famous example is, of course, the Polykleitan statue known as the
Diadoumenos, of which a cast stands in Gallery 22. The beautiful
bronze statuette in Case D in the Sixth Room has the same motive
(fig. 119), and on the psykter in Case 4 a boy who holds in his hands
the palms signifying victory is being crowned by an official.
X
RACES AND RIDING
CASE 5
In the Homeric period cavalry was not employed in battle, but

princes and nobles drove about the field in chariots from which they
descended to fight. The bodies of these chariots were just large
enough for the warrior and his driver to stand side by side, since
lightness and quickness of movement were essential. The chariot in
the Third Room (fig. 120) is of the type in use among the Etruscans;
the Greek type in the earliest pictures which we have is more open
and slightly different in shape. An excellent representation of the
Greek chariot may be seen on a large amphora on Pedestal R 3 in
the same room, and this drawing also shows the light harness in use
and the method of arranging it. War-chariots were used on occasion
for racing, as at the funeral games of Patroklos in the Twenty-third
Book of the Iliad; and at a later period, when nobles no longer rode
to battle and armies of citizens were the rule in Greece, the chariot
remained as a racing vehicle. The principal feature of the Olympic
games from the year 680 B.C. was the chariot race for four horses,
and a victory in this event brought much-coveted renown to the
owner of the horses and his city. The Greeks of Italy and Sicily were
devoted to this sport, their interest being reflected in their coin types,
of which the finest are the Syracusan (fig. 121). Some examples will
be found in the Ward Collection in the Gold Room.
FIG. 120. BRONZE CHARIOT
FIG. 121. RACING CARS ON SYRACUSAN COINS

FIG. 122. LAMP. SCENE FROM THE CIRCUS
A very beautiful bronze statue found at Delphi, no doubt a

dedication after a victory, represents a young charioteer in the long
white chiton which was his traditional dress (Cast No. 462 in Gallery
22), and a fragment of a relief from the Mausoleum (Cast No. 741 on
the east wall of Gallery 25) shows another with flying hair and
garment as he strains forward toward the goal. One of the
Panathenaic amphorai in the Third Room was a prize in a chariot
race at Athens, as we know from the drawing on one side (fig. 123).
Another event in the games at Athens was a race for two horses
harnessed to a little cart in which the driver sat, but this contest was
never so important as the race for four horses. At other games the
chariot was the vehicle used for two horses as well as for four. These
sports were naturally very costly, and under the Roman rule they
gradually died out in Greece as races in the circus in Rome and
other Italian cities took their place. Chariot races were the earliest of
the free shows at Rome and were always the most popular, the great
attraction of the circus being not the speed of the race, but its
danger. Some clay lamps from Cyprus are decorated with reliefs of
chariots and horses, showing how the passion for racing spread over
the Roman world (Case 5, fig. 122).
FIG. 123. PANATHENAIC AMPHORA
CHARIOT RACE
FIG. 124. BIT USED IN TRAINING

HORSES
FIG. 125. HORSE’S MUZZLE
Riding was the usual mode of travel in Greece, as it is still in many

parts of that mountainous country; and, while carts and carriages of
various kinds gradually came into service among the Romans, in
Italy, too, the horse was the commonest means of travel. But
although the Greeks and Romans were good horsemen, they were
probably not the equals of the best modern riders, owing to the fact
that they had no saddles and no stirrups. As a result of the absence
of stirrups, able-bodied persons mounted with the help of a spear or
staff, while old men were handed up by slaves. Women rode only
upon a pillion, and probably not very often in that way. The custom of
nailing metal shoes upon the hoofs of horses was not known, but
shoes made of metal, leather, or rushes were adjusted before
passing over a specially bad road, and could later be removed when
no longer needed. Two bits are shown on the bottom of Case 4. One
is quite simple, consisting of two bars joined by a double link, which
probably belongs to the sixth century, though no doubt this type was
in use for a long period (fig. 127); the other, probably of the fifth or
fourth century, is very severe. Xenophon in his treatise on
Horsemanship (X, 6) describes this variety and explains its use in
training horses (fig. 124). Branding was practised even for valuable
animals. On a small amphora in Case C in the Fifth Room decorated
with a picture of the Sun in his chariot, one of the horses is branded
with a sun surrounded by rays. It was customary to muzzle horses
when they were taken out for exercise or for some other purpose
without a bridle. Probably the muzzles were usually made of leather,
but bronze was employed on special occasions or by the wealthy.
Two bronze muzzles, one of a simple, the other of a more elaborate
form, are exhibited (Case 4, fig. 125).
FIG. 126. YOUNG HORSEMAN
FIG. 127. BRONZE BIT
Greek boys received lessons in riding in the course of their athletic

training, which was, of course, a preliminary military training as well.
In Attica a troop of ephebes, young men in military service, patrolled
the borders as a mounted guard. The decoration on a krater in Case
P in the Fifth Room and a relief in Case A in the Sixth Room
represent members of this troop in their short cloaks fastened on the
shoulder and their broad-brimmed hats. The fine relief, No. 13 in the
Sculpture Gallery, also represents an ephebe (fig. 126) or one of the
Diaskouri in this guise. Hunting deer and boars from horseback was
a favorite sport which required skill in the rider, and riding-races of
various types were a feature of the games. One of the Panathenaic
amphorai was a prize for a horse-race at Athens, as the decoration
shows.
The bronze statuette of a horse at the head of the main staircase
allows us to see the type of animal bred in Greece, and is at the
same time a work of the greatest spirit and delicacy.
XI
GLADIATORS
CASES 3 AND 5
Combats of gladiators formed part of the funeral rites of the

Etruscans, and in Campania they were offered as entertainment to
guests at feasts. The Romans adopted the custom from their
neighbors, the first public show of gladiators taking place in 264 B.C.
For six centuries they continued to be a favorite amusement in Italy
and the provinces, until Honorius made them illegal in 404 A.D. The
great popularity of the sport is proved by the frequency with which it
was represented on articles of common use, such as vases, dishes,
lamps, seal-rings, and in sculpture, mosaic, and painting for the
decoration of walls.
In early times the combatants were prisoners of war who fought
with their own arms and equipment for the entertainment of their
conquerors, and later, when men were recruited in other ways, the
arms of the early enemies of Rome were in a great measure retained
as belonging especially to this sport. Gladiators received a careful
training in schools kept for the purpose. They were divided into
several classes, according to their weapons and manner of fighting,
and were called by the name of the peoples whose arms they had
adopted. They usually fought in pairs, each from a different class,
though occasionally a number engaged in a mêlée. The most

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is a trade mark of Pharmaceutical Press

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Typeset by Laserwords Private Limited, Chennai, India

ISBN 978 0 85711 083 1

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Introduction to the FASTtrack series viii Amphoteric compounds  33

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Electrophilic substitution 90 Reasons for the prevalence of hetero­

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15. Molecular spectroscopy and Gravimetric analysis 227

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FASTtrack is a series of revision guides created for undergraduate pharmacy students.

Additional questions are available at www.ontrackpharmacy.com by selecting the

If you have any feedback regarding this series, please contact us at

*Note: not all features are in every title in the series.

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David Mountford is a lecturer in medicinal chemistry at King’s College London,

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■■ An atom is composed of a nucleus and a surrounding cloud of electrons.

■■ The atomic number of an element is given by the number of protons in the

Mass number (number of protons + neutrons) Figure 1.1

c01.indd 1 6/11/2014 11:28:02 AM

Cations and anions

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■■ The ground state electronic configuration of oxygen can be found

CORRECT INCORRECT INCORRECT

■■ When a shell of electrons becomes full it is

c01.indd 3 6/9/2014 5:11:28 PM

Tips where caψa and cbψb describe the

Figure 1.5 Ψ∗ (antibonding)

Tips molecular orbital, the sigma (σ)-bonding orbital.

c01.indd 4 6/9/2014 5:11:29 PM

■■ In the same way that s orbitals combine to give σ and σ* molecular

Two-bond mode Four-bond mode

Figure 1.8 Electron promotion in carbon.

c01.indd 5 6/9/2014 5:11:29 PM

■■ In sp3 hybridisation the 2s and all three 2p orbitals are combined

sp3 hybrid orbital

c01.indd 6 6/9/2014 5:11:29 PM

■■ In sp2 hybridisation the 2s and two of the 2p orbitals are

Unmixed 2p orbital Figure 1.11

sp2 hybrid orbital

c01.indd 7 6/9/2014 5:11:30 PM

Introduction to the FASTtrack series viii Amphoteric compounds 33

Electrophilic substitution 90 Reasons for the prevalence of hetero

15. Molecular spectroscopy and Gravimetric analysis 227