MCTP Maryland Collaborative for Teacher Preparation Drugs and Molecular Symmetry Thomas C. O'Haver Department of Chemistry and Biochemistry University of Maryland College Park, MD 20742 (301) 4051831 to2@umail.umd.edu Project supported by NSF Cooperative Agreement No. DUE 9255745 Copyright 1994, Maryland Collaborative for Teacher Preparation -------------------------------------------------------------------- Chemistry 121/122 Name__________________________________ Fall, 1994 Partner ______________________________ Drugs and Molecular Symmetry 1. Chains and rings. We have seen and constructed models of many organic molecules that have chains of carbon atoms. It is also common for atoms to form closed rings. Most drugs, for example, contain rings or 5 or 6 atoms. Using your molecular model kit, construct a hydrocarbon with the formula C6H12, consisting of a ring of six CH2 groups. This is called cyclohexane. Then construct another hydrocarbon with the formula C6H6, consisting of a ring of six CH groups with alternating single and double bonds between the carbons. This is called benzene, and it is by far the most common ring structure, found over and over again in many different naturally occurring organic compounds. a. What geometrical arrangement is characteristic of the atoms in the benzene molecule but not those of the cyclohexane molecule? b. What is the smallest ring of CH2 units you have make without straining the bonds? 2. Making aspirin. a. Construct models of acetic acid (the acid in vinegar) and salicylic acid (derived from the active ingredient in the ancient folk remedy willow bark tea), according to the structures on page 304 (Figure 11.2)*. With the help of your partner, act out a little animation in which these two molecules come together, breaking and forming bonds in such a way that aspirin and water are formed. b. Although this reaction is shown in the book* as proceeding from left to right only, it often turns out that chemical reactions are at least partly reversible, like the reaction of H+ and OH- to form water. That is, in this case, it might be possible for aspirin to react with water to produce acetic acid and salicylic acid. Of course, aspirin that you buy in the store is dry, meaning that the water produced in its synthesis has been removed. But it is possible that in storage, some water in the air (humidity) might leak in and cause the breakdown of aspirin into acetic acid and salicylic acid. How could you tell if that occurs? Perhaps by smell. If acetic acid is produced in sufficient quantity, you should be able to smell it - it smells like vinegar. Sniff the bottle of commercial aspirin making the rounds in the classroom and see if you can find any personal evidence that aspirin is reacting with water. 3. Form and function. Construct models of morphine and demerol (page 308 *). Your model kits is not big enough to make both, so work with a neighboring group. Compare the overall shapes of these two molecules. a. For what purpose is demerol used? (Check the Physician's Desk Reference) b. Construct a small but chemically reasonable modification of either the morphine molecule or the demerol molecule that would make it a different molecule (with a different formula), but would not modify the "active area" that is common to both morphine and demerol. Would you expect that this molecule might have some pain-killing properties? Why? c. The model you just constructed might be called a "designer drug". Supposed that no one ever made that particular modification before. Would it be a controlled substance, legally? That is, would there be laws proscribing its possession and use? If it were found to be possible to make and it turned out to be addictive, should it be a controlled substance? What legal problem does this possibility present to drug enforcement agencies? 4. Left- and right-handed molecules. a. Construct a model like the one on page 309* that has a single carbon atom in the center and four different atoms or groups attached to it. Construct its mirror image also. Are the two mirror pairs really identical or are they distinct? Hint: try to superimpose them by laying them side by side. b. Place the model against a piece of paper so that three of the atoms touch the paper. Mark the positions of each touching atom, as shown on page 310* (figure 11.11). Then try to match the same three positions with the other mirror image. Do both fit or only one? c. Construct a model that has a carbon atom in the center but only three different atoms attached to it, that is, that has two of one kind of atom instead of four different atoms. Make its mirror image also. Are the two mirror pairs really identical or are they distinct? d. Try part b with this model. Do both fit or only one? e. What would you predict for carbons that have fewer than three different attached atoms? Would this give distinct left and right handed forms or not? On the basis of these observations, formulate a rule for predicting when a carbon atom will give distinct left and right handed forms? f. In general, very simple molecules such as water and methane (CH4) are symmetrical and do not have distinct left and right handed forms. What is the simplest molecular model you can construct, using only C, H, and O, that does have distinct left and right handed forms, that is, is not superimposable with its mirror image? g. Some bottles containing small samples of a liquid are being passed through the class. These are samples of the left- and right-handed forms of "carvone", a fragrant molecule that, because it is an asymmetrical molecule, is not superimposable with its mirror image. Smell them carefully. Can you notice any difference between the smell of these two forms? (Hint: one is associated with a popular type of chewing gum and the other is associated with rye bread). What does this experience suggest about the molecular symmetry of the smell receptors in our noses? 5. Polarized light. a. Describe the optical behavior of the "polarizing" filters that you took home last class. b. Is the light from the overhead fluorescent lights polarized? Describe what you did to determine whether the light is polarized. What did you observe? c. Two small battery-operated laser pointers are circulating around the classroom. Is the laser light polarized? Describe what you did to determine whether the light is polarized. What did you observe? Warning: do not direct the laser beam into your eye. 6. Molecular symmetry and polarized light. If a polarized light source passed through a polarizing filter whose direction of polarization is perpendicular (90!) to the direction of polarization of the light source, no light can get through. But if some transparent substance that can rotate the plane of polarized light is placed between the polarized light source and the filter, then some light will be transmitted (unless the rotation just happens to be 180!). Such material are called optically active. The rotation can be either to the left or to the right. a. Use a laser and a polarizing filter to test the ability of: sugar syrup, water, ethanol, isopropanol (rubbing alcohol), and glycerin to rotate polarized light. b. Find the structures of those substances in the book* and determine which ones are superimposible with their mirror images. Glycerin, also known as glycerol, is on page 337*. For sugar, you can use glucose (page 335*) as a model. c. Build a molecular model for glucose as shown on page 335* and a mirror image of this model. Are they superimposable? d. Would you expect the degree of rotation of to be related to the path length of light through the medium? Why or why not? How could you test this experimentally? e. Using a laser and a polarizing filter, or two polarizing filters, measure the rotation of sugar syrup per centimeter, that is, how many degrees would a 1.0 centimeter path length rotate the polarized light? f. What is the thalidomide drug tragedy and what does it have to do with molecular symmetry? Name another drug mentioned in the textbook* that has drastically different properties in its left and right hand forms. -------------------------------------------------------------------- Bibliography * American Chemical Society, "Chemistry in Context: Applying Chemistry to Society", Wm. C. Brown Publishers, 1994.