1. medicines and drugs antibacterials

2. Diseases caused by bacteria  tuberculosis,  syphilis,  cholera,  salmonella,  bronchitis,  anthrax,  meningitis,  gonorrhea,  chlamydia.

3. antibacterials  Antibacterials are drugs that kill or inhibit the growth of bacteria that cause infectious diseases.  Peniciliins are antibacterials produced by microrganisms to be used against microrganism.

4. Historical development of penicillins  Alexander Fleming, Howard Florey and Ernst Chain shared the Nobel Prize (1945) for “the discovery of penicillin and its curative effect in various infectious diseases”.  Discovered by chance that penicillin inhibited growth or killed bacteria; Fleming had left a bacteria culture and later found a clear zone in the culture in which bacteria had been killed. That zone had been contaminated by a fungus called Penicillium notatum.

5. Historical development of penicillins Howard Florey and Ernst Chain  overcame the problems associated with isolating and concentrating penicillin as penicillin G  showed that penicillin is harmless and effective on mice  first to use penicillin on a human  grew penicillin in large amounts  grew strains of penicillin in corn-steep liquor

6. structure of penicillin – determined in 1950s C 16 H 18 O 4 N 2 S (M r = 334) functional groups:  4-membered ring with N (Beta-lactam ring)  phenyl/benzene ring  amide  carbonyl  carboxylic acid  tertiary amine  secondary amine  sulphur atom

7. penicillin action  A Beta-lactam ring is part of the core structure of penicillins and other beta-lactam antibiotics.  These Beta-lactam containing Penicillins work by deactivating the proteins (enzymes) that a bacteria needs to form a cell wall. This prevents the formation of cross-links within the cell wall.  As a result the bacterial cell absorbs too much water and bursts as the result of increased osmotic pressure.

9. beta-lactam ring in penicillin a four-membered square ring structure which contains an amide group (-CONH-) and consists of one nitrogen atom and three carbon atoms (and two hydrogen atoms).

10. beta-lactam ring  For each carbon and the nitrogen atom, identify the type of hybridization and preferred bond angles around each atom.  Referring to bond angles say why the ring is a strained structure

11. What causes the strain?  As a result of the sp 3 hybridization of two of the three carbon atoms and the single nitrogen atom and the sp 2 hybridization of the third carbon atom, the preferred bond angles are 109  and 120 .  However, the bond angles in the beta-lactam ring structure are only 90° this puts the beta-lactam ring structure under strain.

12. beta-lactam ring  Strains makes ring reactive.  Ring easily breaks open in the amide group, for instance, in the presence of an enzyme such as transpeptidase, to form covalent bonds with the transpeptidase.  This deactivates the transpeptidase that synthesizes the bacterial cell walls, thus inhibiting the growth of bacterial cell walls.  As a result water enters the bacteria cell causing it to burst due to increased osmotic pressure.

13. Cross-links (Conjunction)  When two bacterial cells are in close proximity, a bridge-like structure forms between them. This allows a copy of the plasmid as it is replicated, to be transferred to another cell.  Result: A bacterium that expresses the antimicrobial resistance encoded in the plasmid.

14. administering of antibacterials There are two types of antibacterials o broad-spectrum antibacterials are effective against a wide range of bacteria o narrow-spectrum only attack a limited range of bacteria

15. administering antibacterials With some diseases, e.g. tuberculosis (TB) it is important to administer a “cocktail” of different antibacterials because bacteria which cause TB are usually extremely resistant to penicillins so a mixture of different antibacterials is used.

16. Increased resistance to penicillin Bacteria have become resistant o resistant bacteria produce penicillinase, an enzyme, which breaks open the 4-memberd (Beta-lactam) ring in the penicillin molecule o resistant bacteria reproduce and pass on their resistance to succeeding generations

17. Bacteria resistance to penicillin The more bacteria are exposed to antibacterials, the more opportunities there are for the bacteria to mutate into bacteria that have genes to produce penicillinase.

19. Increased resistance because of misuse  Antibacterials are used in animal feedstock even when the animals do not have a disease. The antibacterials end up in the food chain  Over-prescription by doctors.  Patient compliance: Patients not completing a full course of penicillin or antibiotics

20. modifying side-chain of penicillin G Modern or semi-synthetic penicillins, such as ampicillin, are penicillin molecules in which the side-chain, an alkyl group, has been modified to alter its properties. In the case of ampicillin, the side chain now contains:  a benzene or C 6 H 5 ring, an amine (- NH 2 ) group and a hydrogen.

21. modifying the side-chain The different side-chain brings advantages: o Reduces the occurrence of penicillin resistant bacteria as the modified penicillins are able to withstand the action of an enzyme, penicillinase. o Resistance to breakdown by stomach acid (so can be taken orally); penicillin G had to be injected because it was broken down by stomach acid.