sample lecture

50 %
50 %
Information about sample lecture

Published on October 16, 2007

Author: Christian


Discovery and Development of Penicillin:  Discovery and Development of Penicillin The idea that moulds or fungi could be used to treat wounds extends back at least to Greek and Roman times and remained popular into the 20th century. In 1876, the physicist John Tyndall noted that Penicillium moulds killed some types of bacteria. In 1877, Pasteur noticed that some airborne organisms prevented the growth of anthrax bacteria, and realised that “these facts may, perhaps, justify the greatest hope from the therapeutic point of view”. Over the succeeding decades, several scientists observed the effect of Penicillium on bacteria, but none pursued this finding. The term “antibiosis” was coined by Jean-Paul Vuillemin in 1889 to describe the fight for survival between two living organisms. By 1928 there were several hundred scientific papers on this subject. Discovery of penicillin:  He named the substance that killed the bacteria ‘penicillin’, and he demonstrated that it was highly effective against a range of pathogenic bacteria. However, he found that penicillin was quite unstable, and that it seemed unlikely to be useful in vivo. He was unable to make further progress. Others attempted to develop his work but were thwarted by the difficulty of isolating penicillin and by its instability. Discovery of penicillin Alexander Fleming, a Scottish doctor working in St Mary’s Hospital in London had a long-standing interest in antibacterial substances and was acutely aware of the need to discover much more effective agents. As a result of a highly improbable series of events in July 1928, he noticed that a colony of the mould Penicillium notatum was causing staphylococcus cells to undergo lysis (bursting) (see the actual culture plate below). Unlike others who had made similar observations, Fleming realised the potential of this phenomenon. Development of penicillin:  Development of penicillin In 1938 and 1939, Professor Howard Florey, an Australian physiologist who was Head of the School Pathology in Oxford, and Dr Ernst Chain, a German chemist in the same School surveyed the literature on ‘antibiosis’ and decided to focus on Penicillium notatum in their efforts to find new antibacterial agents. As World War II began in Europe, Chain and Norman Heatley, an English biochemist, worked on the problems of (i) finding optimum conditions for the growth of the mould, and (ii) finding techniques for isolating the chemically sensitive active principle, penicillin. Despite the difficulties of working in wartime, they made great advances and by May 1940 they had enough crude penicillin to test it. On May 25/26th they injected virulent streptococci into eight mice. Four of the mice were treated with penicillin, they other four were the ‘control’ group. Within 12 hours the controls were all dead, the four who had been given penicillin survived. The Oxford group knew they were on the verge of a momentous development. That same morning, the evacuation of Dunkirk began; Great Britain’s future had never looked so bleak. First tests of penicillin:  First tests of penicillin Heroic efforts by the Oxford group produced enough penicillin to test on patients in early 1941. The first patient was terminally ill, but she did not suffer any adverse reaction – penicillin was not toxic. The second patient was dying of septicaemia, after a scratch on his face became infected. Sulfonamides did not help, but penicillin brought about a dramatic improvement. Unfortunately, the course of treatment did not completely eradicate the pathogens, and when he suffered a relapse there was no more penicillin available and the 43 year old patient died. The third patient was four-and-a-half-year-old Johnny Cox. Some measles spots on his left eyelid became infected and that led to formation of a blood clot in a vein behind his eye. When admitted to hospital the doctor predicted “that he would be in his grave in three days”. First tests of penicillin, contd.:  First tests of penicillin, contd. Johnny was put on an intravenous penicillin drip. He improved steadily and within a week he was talking and playing. A week later he suffered a major setback, and despite receiving more penicillin he died a few days later. However, an autopsy showed that the infection had nearly been cleared, and that Johnny had died as a result of a ruptured aneurysm in a weakened artery. The next two patients, a boy and a baby, were both cured. It was clear that penicillin was far more effective than any previous antibacterial drug – a revolution in human health was about to begin. Full scale development of penicillin was achieved in the USA and by the end of WWII, it had already saved many thousands of lives. Don’t forget::  Don’t forget: Howard Florey 1898-1968 Nobel Prize 1945 Ernst Chain 1906-1979 Nobel Prize 1945 Norman Heatley 1911-2004 2. Structure & Reactivity:  2. Structure & Reactivity What is the chemical structure of the drug that started the antibiotic era? The structure was unexpected and was finally determined by X-ray crystallography. The active compound obtained from Penicillium notatum was called penicillin G. The key feature of this structure is a b-lactam ring – an amide contained within a four-membered ring. Other features are: A fused five membered ring containing sulfur A carboxylic acid group attached to the five-membered ring An acylamino side chain attached to the b-lactam. Before we can understand how penicillin works, we need to take a closer look at the structures of organic compounds. 2.1 Shapes of molecules, VSEPR:  2.1 Shapes of molecules, VSEPR The first aspect that we need to consider is the shapes of molecules. The geometrical arrangement of bonds around the atoms determines the shape of molecules For the elements in the second row of the periodic table, e.g. carbon, nitrogen and oxygen, the bond angles are determined by one factor: repulsion between pairs of electrons. Valence Shell Electron Pair Repulsion (VSEPR) theory predicts that the pairs of valence shell electrons around an atom will be arranged as far apart as possible so as to minimise electronic repulsions between them. Bonding pairs and lone pairs will both cause repulsions, so the shape will depend on the total number of pairs of electrons. However, the two pairs of a double bond or the three pairs of a triple bond are all in the same region of space so they count as only one pair. VSEPR in action:  VSEPR in action VSEPR in action:  VSEPR in action Shapes of organic molecules: tetrahedral carbon:  Shapes of organic molecules: tetrahedral carbon When carbon has four single bonds, it has a tetrahedral shape – the four bonding pairs point to the corners of a tetrahedron, because that’s the furthest apart they can get. Ethane is a simple example. Each carbon atom is at the centre of a (virtual) tetrahedron, with the four atoms to which it is bonded occupying the corners of the tetrahedron, and all the bond angles are approximately 109°. Remember that ‘ordinary’ bonds ( ) are in the plane of the paper, wedged bonds ( ) are projecting out of the paper and dashed bonds ( ) are projecting behind the plane. Shapes of organic molecules: trigonal carbon:  Shapes of organic molecules: trigonal carbon When carbon atoms have one double bond (and 2 single bonds), they are trigonal, i.e. the carbon and the three atoms to which it is attached are all in the same plane, and the bond angles are approximately 120°. This is because two of the bonding pairs form one double bond and so are aligned with each other. Thus there are effectively three pairs of electron that get as far apart as possible. Ethene (ethylene), acetone (CH3COCH3) and benzene are examples: 2.2 Shapes of molecules: chiral centres and chirality:  A tetrahedral carbon that has four different groups attached to it, is termed a chiral centre. Penicillin G contains three chiral centres (in red below). There are two different ways of arranging four groups around a tetrahedral carbon. This gives rise to two different structures, that are stereoisomers, isomers that differ only in the arrangement of atoms in space The particular 3D orientation of atoms around a chiral centre is called its configuration. Most (but not all) molecules that contain chiral centres are chiral, i.e. they are not superimposable on their mirror images. Penicillin G is a chiral molecule. 2.2 Shapes of molecules: chiral centres and chirality Chirality, contd.:  Chirality, contd. There are two possible structures for chiral molecules, that differ only in the three-dimensional orientation of the atoms in space. The two possible mirror-image forms are called enantiomers. Many biomolecules, e.g. amino acids and sugars, are chiral. They, like penicillin G, occur in enantiomerically pure form in living organisms, i.e. only one enantiomer is formed in biosynthesis. Enantiomers often have different biological activity, e.g. often only one enantiomeric form of a chiral drug will have the desired therapeutic activity, because only that one will ‘fit’ the target biomolecule which is itself chiral. This is analogous to a hand fitting into a glove. Shape of Penicillin:  Shape of Penicillin For simplicity, let’s look at the shape of 6-aminopenicillanic acid, a derivative lacking the side chain. Note the tetrahedral and trigonal carbons, the pyramidal nitrogen and the angular sulfur. Note also the ‘butterfly’ shape of the fused ring system. Trigonal Tetrahedral Pyramidal Angular

Add a comment

Related presentations

Related pages

Sample lectures - Courses - University of Westminster, London

Sample lectures; Sample lectures. Dominic Harris lecture. Lucy Bullivant lecture. Stelarc lecture. Andrew Holmes lecture. Tim Macfarlane lecture (part 1)
Read more

Home | Simple Lecture

Simple-lecture is an online tutorial and coaching platform for school students, both junior and senior. We provide lessons and courses aligned to various ...
Read more

Sample Lecture Evaluation Form | Evaluation Forms

SAMPLE EVAULATION FORM #3 . In order to continue to improve the quality of educational programming, the Department of [Company], would appreciate you ...
Read more

Sample Lectures - Villanova University

Villanova’s online certificate, undergraduate and graduate degree programs allow you to experience instructor-led streaming video lectures, and ...
Read more

Sample lectures | Saïd Business School

We offer a number of online lectures to give you a taste of the type of teaching you will receive on the Oxford Executive MBA. Kathy Harvey, Programme ...
Read more

Sample Lectures - YouTube

Sample Lectures which we did @ MKCL. Sorry for such a DELAY
Read more

Sample Lectures | Karlshochschule International University

Our "Sample lectures" offer you a direct insight into how we teach. On selected dates, you have the chance to attend real seminars, offering a unique ...
Read more

Sample Lectures, Osher Lifelong Learning Institute ...

See sample course lectures from the Osher Lifelong Learning Institute at UMass Boston to get a feel for the learning experience we offer for those 50+.
Read more

Some example lectures, Goldsmiths, University of London

Goldsmiths, University of London is in South East London. We offer undergraduate and postgraduate degrees as well as teacher training (PGCE), Study Abroad ...
Read more

Sample lectures - London School of English

Instructions; Visas and immigration; Find your Market Manager; Dates and Fees; Brochure request; Photographs; Videos. Client testimonials; Sample training ...
Read more