Dr. Glaser's "Chemistry is in the News"
To Accompany Bruice, Organic Chemistry, 3/e.
Chapter 11. Reactions at an sp³ Hybridized Carbon III: Substitution and Elimination Reactions of Compounds with Leaving Groups Other than Halogen. Organometallic Compounds.

Editorial Comments

Polycyclic aromatic hydrocarbons (PHAs) consist of fused aromatic rings. These compounds also are known under the name of polynuclear aromatic hydrocarbons (PNAs). Benzo[a]pyrene is one of the more famous compounds in this class and it consists of five aromatic rings. Use the ChemFinder and take a look at the structures of pyrene, benzo[a]pyrene and benzo[e]pyrene. View the structures of these PHAs in the visualization center accompanying Chapter 15.

The chemical transformation of PAHs into the reactive carcinogens involves enzymatic oxidation using Cytochrome P450. This oxidation is an epoxidation of one of the aromatic C=C bond. For example, the epoxidation of benzene results in benzene oxide. The structure of benzene oxide is shown in the visualization center accompanying Chapter 11.

Exposure to these polycyclic aromatic hydrocarbons has been linked to cancers of the bladder, esophagus, larynx, lung, mouth, skin and stomach in lab animals, in workers in some occupations - and in the people living on Cypress Lane in Daly City, California. The records show that the 150-unit subdivision was atop a contaminated fill that contained toxic scrapings from the next-door PG&E site.

Questions

Question 1: In vivo the conversion benzo[a]pyrene to 4,5-benzo[a]pyrene oxide and 7,8-benzo[a]pyrene oxide is accomplished by Cytochrome P450. What reagent would you use for the epoxidation of an aromatic compound in the laboratory?

Answer 1: See text.

Question 2: Can you draw the structures of benzo[a]pyrene and of the two main products of epoxidation, 4,5-benzo[a]pyrene oxide and 7,8-benzo[a]pyrene oxide.

Answer 2: See text, p. 445, or ChemFinder.

Question 3: Describe how 7,8-benzo[a]pyrene oxide is converted into the active "diol epoxide" carcinogen. Discuss the possible reaction of this "diol epoxide" with the amino group of 2'-deoxyguanosine.

Answer 3: Hydrolysis of 7,8-benzo[a]pyrene oxide followed by a second cytochrome P450 epoxidation of the non-aromatic double bond gives the "diol epoxide". The epoxide portion reacts with the amino group of the guanine.

Question 4: What trend has been observed between the number of rings and the reactivity of polynuclear aromatic hydrocarbons? How can this trend be explained?

Answer 4: These compounds become more reactive as the number of fused aromatic rings increases. The number of resonance forms, and hence the stability, per ring decreases.

Chemistry & Society.
Question 5: Greater care is being taken these days about contaminants and controls are tougher. Yet, the problem of cleaning up already existing sites is a gigantic one. At the very least, the responsible administrators should review the records so that hazardous areas can at least be abandoned without causing more damage that they already have. Don't you think so?