Exercise 12 Return to Index

Introduction

In 1928 Scottish bacteriologist Alexander Fleming noticed that a mould (Penicilluim notatum) that had grown accidentally on a staphylococcus culture plate was surrounded by a staph-free zone. Reasoning that the mould must have been producing something that prevented the staph bacteria from growing, Fleming isolated a compound from the mould and showed that it inhibited the growth of staph bacteria. He called this compound penicillin. Fleming's discovery signaled the birth of the use of antibiotics in medicine, and in 1945 he received the Nobel Prize in Physiology or Medicine in recognition of his work. The window at left contains a Jmol model of benzyl penicillin , also known as penicillin G.

In Exercise 7 we explored several features of the VMK related to stereochemistry, most notably the Atom:invert and the Compare:compare functions. This exercise introduces the Atom:drag function, which serves as a complement to the Atom:invert utility for situations where the latter function does not work, namely where chiral centers are part of a cyclic structure.

Instructions

1. From the Molecular Editor select Start with:PubChem, enter penicillin G in the text box, and click OK.

2. Load the Image control panel and click the NIH 2D Capture link.

Note that the stereochemistry is labeled at each of the three chiral centers of this compound. Note, too, that right clicking on the image allows you to save it as a gif image.

3. Return to the Edit control panel and type iupac into the Feedback Area & Script Command Field: and click Run Script.

The important part of the name that is returned is the numbering of the chiral atoms in this compound; 2S, 5R, 6R.

4. Load the Draw control panel.

5. Using the model that's in the Jmol window for reference, draw the structure of penicillin. Do not use any sterochemical bonds.

With 3 chiral centers, there are 2³ = 8 stereoisomers possible for penicillin G, so the chances are good that the structure you drew is one of the other 7 stereoisomers of the natural antibiotic.

6. Use the Load 3D: tool with one of the three options to load a 3D model of your drawing into the Jmol window.

7. Use the NIH 2D Capture from the Image control panel to check the stereochemistry of the new model.

8. From the Edit control panel select Append:PubChem and enter penicillin G again.

9. Click Compare:compare and note the stereochemistry at atoms 2, 5, and 6.

If you drew your structure correctly in step 5, the models will either be identical, diastereomers, or enantiomers. The directions that follow assume the two models were not identical.

10. Use the Model:delete command to delete the model you appended in step 8, i.e. penicillin G.

11. Use the Model:move command to center your model. Enlarge it with your mouse or with the Utility:size option.

12. With the Atom:invert command selected, click on an H atom attached to one of the chiral atoms that has the opposite stereochemistry from that in penicillin G. Drag that H atom in a direction approximately 180 degrees to the H-C bond axis. Do not release the mouse until the H-C bond is 4-5 times longer than a regular H-C bond.

13. Select either Jmol or NIH from the Opt: tool.

14. Repeat steps 2 and 9.

If your model at this point is a diastereomer of penicillin G, repeating steps 12-14 will allow you to match the stereochemistry at all three chiral centers.