Department of Chemistry course timetable

DRUG DISCOVERY (DD) (I)

(DD3) Targeted Anti-Cancer Therapeutics (2L)

The targeted delivery of effector molecules into diseased tissues has emerged as a promising strategy for the treatment of cancer and other serious conditions. Linking a therapeutic effector (e.g. cytotoxics, proinflammatory cytokines or radionuclides) to a ligand specific to a marker of disease results in preferential accumulation of the effector molecule at the target tissue. This offers the double benefit of increased effective concentrations at the intended site of action and low concentrations in healthy tissues, thus reducing side effects. In the course of these two lectures we will discuss strategies for the discovery of selective ligands against markers of disease, conjugation chemistry in the context of drug-delivery strategies, and examples of recently approved FDA drug conjugates for the treatment of cancer.

DRUG DISCOVERY (DD) (I)

(DD3) Targeted Anti-Cancer Therapeutics (2L)

The targeted delivery of effector molecules into diseased tissues has emerged as a promising strategy for the treatment of cancer and other serious conditions. Linking a therapeutic effector (e.g. cytotoxics, proinflammatory cytokines or radionuclides) to a ligand specific to a marker of disease results in preferential accumulation of the effector molecule at the target tissue. This offers the double benefit of increased effective concentrations at the intended site of action and low concentrations in healthy tissues, thus reducing side effects. In the course of these two lectures we will discuss strategies for the discovery of selective ligands against markers of disease, conjugation chemistry in the context of drug-delivery strategies, and examples of recently approved FDA drug conjugates for the treatment of cancer.

CHARACTERISATION TECHNIQUES (CT)

(CT6) Understanding NMR Spectroscopy (11L)

By now you will be familiar with the use of NMR as a qualitative tool for structure determination, but little has been said so far about what NMR spectroscopy actually is and how it works. One of the beauties of NMR is that you can use it every day to help in identifying chemical structures without ever having to worry about what is actually going on in the experiment. However, there comes a time when either our curiosity, or our need to understand more deeply what we are doing, brings us to the point where we really want to know what NMR is. This is where this course fits in.

The course starts out by considering the basic NMR experiment which, it turns out, is performed in rather a different way to virtually all other kinds of spectroscopy. Rather than looking for the absorption of radiation by the spins, we excite the spins with a short burst of radiation and then detect the ringing signal which is induced. The Fourier transform of this ringing signal is the familiar spectrum. In order to understand this most basic experiment we will have to develop the vector model, which is a precise semi-classical way of understanding the behaviour of the spins. Once we have the vector model we can begin to explore other experiments which involving pulses, including the famous spin echo experiment, which is the basis for many further developments.

Useful though the vector model is, it is not able to describe the behaviour of coupled spins, and in particular the important phenomena of coherence transfer and multiple quantum coherence. To deal with these effects we need the quantum mechanical approach offered by the product operator method. We will not concern ourselves too much with where this theory comes from, but will find that it can be used in a simple and intuitive way to explain all of the important phenomena in modern NMR. In particular, we will be able to understand how two-dimensional experiments, with such delightful names as COSY, DQF-COSY and HMQC work. It is these experiment which have so revolutionized the application of NMR over the past twenty years.

Time permitting, we will also look at relaxation in NMR spectroscopy. In contrast to most other kinds of spectroscopy, the excited states generated in pulsed NMR are very long-lived, and this means that it is relatively easy to study the way in which these states return to equilibrium – which is what relaxation is. The rate of relaxation gives important insight into molecular motion, and relaxation is also responsible for the nuclear Overhauser effect (NOE) which is an exceptionally important tool in structure determination by NMR.

Recommended books:

James Keeler Understanding NMR Spectroscopy , Wiley 2005 (The course will largely be based on this text) Hore, P. J., Nuclear Magnetic Resonance , OUP 1995.

CHARACTERISATION TECHNIQUES (CT)

(CT6) Understanding NMR Spectroscopy (11L)

By now you will be familiar with the use of NMR as a qualitative tool for structure determination, but little has been said so far about what NMR spectroscopy actually is and how it works. One of the beauties of NMR is that you can use it every day to help in identifying chemical structures without ever having to worry about what is actually going on in the experiment. However, there comes a time when either our curiosity, or our need to understand more deeply what we are doing, brings us to the point where we really want to know what NMR is. This is where this course fits in.

The course starts out by considering the basic NMR experiment which, it turns out, is performed in rather a different way to virtually all other kinds of spectroscopy. Rather than looking for the absorption of radiation by the spins, we excite the spins with a short burst of radiation and then detect the ringing signal which is induced. The Fourier transform of this ringing signal is the familiar spectrum. In order to understand this most basic experiment we will have to develop the vector model, which is a precise semi-classical way of understanding the behaviour of the spins. Once we have the vector model we can begin to explore other experiments which involving pulses, including the famous spin echo experiment, which is the basis for many further developments.

Useful though the vector model is, it is not able to describe the behaviour of coupled spins, and in particular the important phenomena of coherence transfer and multiple quantum coherence. To deal with these effects we need the quantum mechanical approach offered by the product operator method. We will not concern ourselves too much with where this theory comes from, but will find that it can be used in a simple and intuitive way to explain all of the important phenomena in modern NMR. In particular, we will be able to understand how two-dimensional experiments, with such delightful names as COSY, DQF-COSY and HMQC work. It is these experiment which have so revolutionized the application of NMR over the past twenty years.

Time permitting, we will also look at relaxation in NMR spectroscopy. In contrast to most other kinds of spectroscopy, the excited states generated in pulsed NMR are very long-lived, and this means that it is relatively easy to study the way in which these states return to equilibrium – which is what relaxation is. The rate of relaxation gives important insight into molecular motion, and relaxation is also responsible for the nuclear Overhauser effect (NOE) which is an exceptionally important tool in structure determination by NMR.

Recommended books:

James Keeler Understanding NMR Spectroscopy , Wiley 2005 (The course will largely be based on this text) Hore, P. J., Nuclear Magnetic Resonance , OUP 1995.

DRUG DISCOVERY (DD) (I)

(DD4) Fragment-based Drug Discovery (2L)

Fragment-based approaches to finding novel small molecules that bind to proteins are now firmly established in drug discovery and chemical biology. Initially developed primarily in a few centres in the biotech and pharma industry, this methodology has now been adopted widely in both the pharmaceutical industry and academia. After the initial success with kinase targets, the versatility of this approach has now expanded to a broad range of different protein classes such as metalloproteins and protein-protein interactions. In the course of these two lectures we will explore the different strategies for finding a fragment hit and the subsequent elaboration strategies used in order to increase potency to develop a lead compound.

CHARACTERISATION TECHNIQUES (CT)

(CT6) Understanding NMR Spectroscopy (11L)

By now you will be familiar with the use of NMR as a qualitative tool for structure determination, but little has been said so far about what NMR spectroscopy actually is and how it works. One of the beauties of NMR is that you can use it every day to help in identifying chemical structures without ever having to worry about what is actually going on in the experiment. However, there comes a time when either our curiosity, or our need to understand more deeply what we are doing, brings us to the point where we really want to know what NMR is. This is where this course fits in.

The course starts out by considering the basic NMR experiment which, it turns out, is performed in rather a different way to virtually all other kinds of spectroscopy. Rather than looking for the absorption of radiation by the spins, we excite the spins with a short burst of radiation and then detect the ringing signal which is induced. The Fourier transform of this ringing signal is the familiar spectrum. In order to understand this most basic experiment we will have to develop the vector model, which is a precise semi-classical way of understanding the behaviour of the spins. Once we have the vector model we can begin to explore other experiments which involving pulses, including the famous spin echo experiment, which is the basis for many further developments.

Useful though the vector model is, it is not able to describe the behaviour of coupled spins, and in particular the important phenomena of coherence transfer and multiple quantum coherence. To deal with these effects we need the quantum mechanical approach offered by the product operator method. We will not concern ourselves too much with where this theory comes from, but will find that it can be used in a simple and intuitive way to explain all of the important phenomena in modern NMR. In particular, we will be able to understand how two-dimensional experiments, with such delightful names as COSY, DQF-COSY and HMQC work. It is these experiment which have so revolutionized the application of NMR over the past twenty years.

Time permitting, we will also look at relaxation in NMR spectroscopy. In contrast to most other kinds of spectroscopy, the excited states generated in pulsed NMR are very long-lived, and this means that it is relatively easy to study the way in which these states return to equilibrium – which is what relaxation is. The rate of relaxation gives important insight into molecular motion, and relaxation is also responsible for the nuclear Overhauser effect (NOE) which is an exceptionally important tool in structure determination by NMR.

Recommended books:

James Keeler Understanding NMR Spectroscopy , Wiley 2005 (The course will largely be based on this text) Hore, P. J., Nuclear Magnetic Resonance , OUP 1995.

DRUG DISCOVERY (DD) (I)

(DD4) Fragment-based Drug Discovery (2L)

Fragment-based approaches to finding novel small molecules that bind to proteins are now firmly established in drug discovery and chemical biology. Initially developed primarily in a few centres in the biotech and pharma industry, this methodology has now been adopted widely in both the pharmaceutical industry and academia. After the initial success with kinase targets, the versatility of this approach has now expanded to a broad range of different protein classes such as metalloproteins and protein-protein interactions. In the course of these two lectures we will explore the different strategies for finding a fragment hit and the subsequent elaboration strategies used in order to increase potency to develop a lead compound.

DRUG DISCOVERY (DD) (I)

(DD5) Computational Approaches to Chemical Biology and Medicinal Chemistry (1L + 2W)

In this lecture and practical, Dr Bender will show how chemical and biological data can be used on the one hand to understand the bioactivity of drugs in living systems, and on the other hand how computers can be used to design novel bioactive compounds. This will cover both examples from the current research in his group, together with academia and pharmaceutical industry, as well as more fundamental aspects from the cheminformatics area which will be used in a computational drug discovery practical afterwards.

CHARACTERISATION TECHNIQUES (CT)

(CT6) Understanding NMR Spectroscopy (11L)

By now you will be familiar with the use of NMR as a qualitative tool for structure determination, but little has been said so far about what NMR spectroscopy actually is and how it works. One of the beauties of NMR is that you can use it every day to help in identifying chemical structures without ever having to worry about what is actually going on in the experiment. However, there comes a time when either our curiosity, or our need to understand more deeply what we are doing, brings us to the point where we really want to know what NMR is. This is where this course fits in.

The course starts out by considering the basic NMR experiment which, it turns out, is performed in rather a different way to virtually all other kinds of spectroscopy. Rather than looking for the absorption of radiation by the spins, we excite the spins with a short burst of radiation and then detect the ringing signal which is induced. The Fourier transform of this ringing signal is the familiar spectrum. In order to understand this most basic experiment we will have to develop the vector model, which is a precise semi-classical way of understanding the behaviour of the spins. Once we have the vector model we can begin to explore other experiments which involving pulses, including the famous spin echo experiment, which is the basis for many further developments.

Useful though the vector model is, it is not able to describe the behaviour of coupled spins, and in particular the important phenomena of coherence transfer and multiple quantum coherence. To deal with these effects we need the quantum mechanical approach offered by the product operator method. We will not concern ourselves too much with where this theory comes from, but will find that it can be used in a simple and intuitive way to explain all of the important phenomena in modern NMR. In particular, we will be able to understand how two-dimensional experiments, with such delightful names as COSY, DQF-COSY and HMQC work. It is these experiment which have so revolutionized the application of NMR over the past twenty years.

Time permitting, we will also look at relaxation in NMR spectroscopy. In contrast to most other kinds of spectroscopy, the excited states generated in pulsed NMR are very long-lived, and this means that it is relatively easy to study the way in which these states return to equilibrium – which is what relaxation is. The rate of relaxation gives important insight into molecular motion, and relaxation is also responsible for the nuclear Overhauser effect (NOE) which is an exceptionally important tool in structure determination by NMR.

Recommended books:

James Keeler Understanding NMR Spectroscopy , Wiley 2005 (The course will largely be based on this text) Hore, P. J., Nuclear Magnetic Resonance , OUP 1995.

DRUG DISCOVERY (DD) (I)

(DD5) Computational Approaches to Chemical Biology and Medicinal Chemistry (1L + 2W)

In this lecture and practical, Dr Bender will show how chemical and biological data can be used on the one hand to understand the bioactivity of drugs in living systems, and on the other hand how computers can be used to design novel bioactive compounds. This will cover both examples from the current research in his group, together with academia and pharmaceutical industry, as well as more fundamental aspects from the cheminformatics area which will be used in a computational drug discovery practical afterwards.

CHARACTERISATION TECHNIQUES (CT)

(CT6) Understanding NMR Spectroscopy (11L)

By now you will be familiar with the use of NMR as a qualitative tool for structure determination, but little has been said so far about what NMR spectroscopy actually is and how it works. One of the beauties of NMR is that you can use it every day to help in identifying chemical structures without ever having to worry about what is actually going on in the experiment. However, there comes a time when either our curiosity, or our need to understand more deeply what we are doing, brings us to the point where we really want to know what NMR is. This is where this course fits in.

The course starts out by considering the basic NMR experiment which, it turns out, is performed in rather a different way to virtually all other kinds of spectroscopy. Rather than looking for the absorption of radiation by the spins, we excite the spins with a short burst of radiation and then detect the ringing signal which is induced. The Fourier transform of this ringing signal is the familiar spectrum. In order to understand this most basic experiment we will have to develop the vector model, which is a precise semi-classical way of understanding the behaviour of the spins. Once we have the vector model we can begin to explore other experiments which involving pulses, including the famous spin echo experiment, which is the basis for many further developments.

Useful though the vector model is, it is not able to describe the behaviour of coupled spins, and in particular the important phenomena of coherence transfer and multiple quantum coherence. To deal with these effects we need the quantum mechanical approach offered by the product operator method. We will not concern ourselves too much with where this theory comes from, but will find that it can be used in a simple and intuitive way to explain all of the important phenomena in modern NMR. In particular, we will be able to understand how two-dimensional experiments, with such delightful names as COSY, DQF-COSY and HMQC work. It is these experiment which have so revolutionized the application of NMR over the past twenty years.

Time permitting, we will also look at relaxation in NMR spectroscopy. In contrast to most other kinds of spectroscopy, the excited states generated in pulsed NMR are very long-lived, and this means that it is relatively easy to study the way in which these states return to equilibrium – which is what relaxation is. The rate of relaxation gives important insight into molecular motion, and relaxation is also responsible for the nuclear Overhauser effect (NOE) which is an exceptionally important tool in structure determination by NMR.

Recommended books:

James Keeler Understanding NMR Spectroscopy , Wiley 2005 (The course will largely be based on this text) Hore, P. J., Nuclear Magnetic Resonance , OUP 1995.

DRUG DISCOVERY (DD) (I)

(DD6) Process Chemistry (2L)

In these two complementary lectures, between which lunch will be provided for all participants, industry experts on process chemistry from GSK and Syngenta will share their experiences and challenges gathered over many years of experience.

Lecture 1: A GSK Case Study (1L) Dr Richard Horan

As potential new drugs approach launch there is an ever-increasing application of the tools of process chemistry (statistical experimental design, reaction kinetics, in-situ reaction monitoring etc) in order to define a control strategy that provides a thoroughly understood, robust reaction sequence that can be used to manufacture the drug to acceptable quality on an ongoing basis. This control strategy also forms a key part of any regulatory submission required before the drug can be sold. This lecture will present a recent case study on the process development carried out on a real GSK drug molecule and demonstrate the tools and approaches employed as the control strategy evolved.

Recommended text: Lee, S. and Robinson, G. Process Development: Fine Chemicals from Grams to Kilograms (Oxford Chemistry Primers); OUP: Oxford, 1995.

Lecture 2: What Influences a Reaction? Dr George Hodges (Syngenta)

Scale up is made complex by the fact that some parameters change while others remain constant. Successful scale up therefore requires an understanding of the reaction “driving force” and how it changes as a function of scale. This talk will go through building up a fundamental understanding of a reaction from both a chemical and engineering point of view and show how this can not only help in scaling-up, but can also be used to influence lab scale reactions in ways usually ignored.

Recommended text: Atherton, J. and Carpenter, K., Process Development - Physicochemical Concepts (Oxford Chemistry Primers) ; OUP: Oxford, 2000.

CHARACTERISATION TECHNIQUES (CT)

(CT6) Understanding NMR Spectroscopy (11L)

By now you will be familiar with the use of NMR as a qualitative tool for structure determination, but little has been said so far about what NMR spectroscopy actually is and how it works. One of the beauties of NMR is that you can use it every day to help in identifying chemical structures without ever having to worry about what is actually going on in the experiment. However, there comes a time when either our curiosity, or our need to understand more deeply what we are doing, brings us to the point where we really want to know what NMR is. This is where this course fits in.

The course starts out by considering the basic NMR experiment which, it turns out, is performed in rather a different way to virtually all other kinds of spectroscopy. Rather than looking for the absorption of radiation by the spins, we excite the spins with a short burst of radiation and then detect the ringing signal which is induced. The Fourier transform of this ringing signal is the familiar spectrum. In order to understand this most basic experiment we will have to develop the vector model, which is a precise semi-classical way of understanding the behaviour of the spins. Once we have the vector model we can begin to explore other experiments which involving pulses, including the famous spin echo experiment, which is the basis for many further developments.

Useful though the vector model is, it is not able to describe the behaviour of coupled spins, and in particular the important phenomena of coherence transfer and multiple quantum coherence. To deal with these effects we need the quantum mechanical approach offered by the product operator method. We will not concern ourselves too much with where this theory comes from, but will find that it can be used in a simple and intuitive way to explain all of the important phenomena in modern NMR. In particular, we will be able to understand how two-dimensional experiments, with such delightful names as COSY, DQF-COSY and HMQC work. It is these experiment which have so revolutionized the application of NMR over the past twenty years.

Time permitting, we will also look at relaxation in NMR spectroscopy. In contrast to most other kinds of spectroscopy, the excited states generated in pulsed NMR are very long-lived, and this means that it is relatively easy to study the way in which these states return to equilibrium – which is what relaxation is. The rate of relaxation gives important insight into molecular motion, and relaxation is also responsible for the nuclear Overhauser effect (NOE) which is an exceptionally important tool in structure determination by NMR.

Recommended books:

James Keeler Understanding NMR Spectroscopy , Wiley 2005 (The course will largely be based on this text) Hore, P. J., Nuclear Magnetic Resonance , OUP 1995.

CHARACTERISATION TECHNIQUES (CT)

(CT6) Understanding NMR Spectroscopy (11L)

By now you will be familiar with the use of NMR as a qualitative tool for structure determination, but little has been said so far about what NMR spectroscopy actually is and how it works. One of the beauties of NMR is that you can use it every day to help in identifying chemical structures without ever having to worry about what is actually going on in the experiment. However, there comes a time when either our curiosity, or our need to understand more deeply what we are doing, brings us to the point where we really want to know what NMR is. This is where this course fits in.

The course starts out by considering the basic NMR experiment which, it turns out, is performed in rather a different way to virtually all other kinds of spectroscopy. Rather than looking for the absorption of radiation by the spins, we excite the spins with a short burst of radiation and then detect the ringing signal which is induced. The Fourier transform of this ringing signal is the familiar spectrum. In order to understand this most basic experiment we will have to develop the vector model, which is a precise semi-classical way of understanding the behaviour of the spins. Once we have the vector model we can begin to explore other experiments which involving pulses, including the famous spin echo experiment, which is the basis for many further developments.

Useful though the vector model is, it is not able to describe the behaviour of coupled spins, and in particular the important phenomena of coherence transfer and multiple quantum coherence. To deal with these effects we need the quantum mechanical approach offered by the product operator method. We will not concern ourselves too much with where this theory comes from, but will find that it can be used in a simple and intuitive way to explain all of the important phenomena in modern NMR. In particular, we will be able to understand how two-dimensional experiments, with such delightful names as COSY, DQF-COSY and HMQC work. It is these experiment which have so revolutionized the application of NMR over the past twenty years.

Time permitting, we will also look at relaxation in NMR spectroscopy. In contrast to most other kinds of spectroscopy, the excited states generated in pulsed NMR are very long-lived, and this means that it is relatively easy to study the way in which these states return to equilibrium – which is what relaxation is. The rate of relaxation gives important insight into molecular motion, and relaxation is also responsible for the nuclear Overhauser effect (NOE) which is an exceptionally important tool in structure determination by NMR.

Recommended books:

James Keeler Understanding NMR Spectroscopy , Wiley 2005 (The course will largely be based on this text) Hore, P. J., Nuclear Magnetic Resonance , OUP 1995.

SOUND BITES (SB)

(SB4) Exploring Energy Landscapes: from Molecules to Nanodevices (1L)

The potential energy landscape provides a conceptual and computational framework for investigating structure, dynamics and thermodynamics in atomic and molecular science. This talk will summarise new approaches for global optimisation, quantum dynamics, the thermodynamic properties of systems exhibiting broken ergodicity, and rare event dynamics. Applications will be presented that range from prediction and analysis of high-resolution spectra to coarse-grained models of mesoscopic structures.

Selected Publications: D.J. Wales, Curr. Op. Struct. Biol., 20, 3-10 (2010) ; D.J. Wales, J. Chem. Phys., 130, 204111 (2009); B. Strodel and D.J. Wales, Chem. Phys. Lett., 466, 105-115 (2008); D.J. Wales and T.V. Bogdan, J. Phys. Chem. B, 110, 20765-20776 (2006); D.J. Wales, Int. Rev. Phys. Chem., 25, 237-282 (2006); D.J. Wales, "Energy Landscapes", Cambridge University Press, Cambridge, 2003.

NOVEL MATERIALS AND MICRODROPLETS (MM)

(MM2) Conjugated polymers: Synthesis, Devices and Research Challenges (2L)

Course Presented by Cambridge Display Technology

The first of the lectures in this section will cover polymer organic light emitting diode materials and the new and exciting challenges these pose for synthetic organic chemists. The second will consider the route from organic materials synthesis to high performance solution processable electro-optical devices.

SOUND BITES (SB)

(SB3) Climate change (1L)

John Pyle will give an overview of the current understanding of climate change. While CO2 is the largest contributor to anthropogenic climate change, focus will be given to some of the chemically-active greenhouse gases, including ozone, methane and nitrous oxide, pointing out some of the interesting atmospheric chemistry research issues.