Asprin: Development and Mechanism of Action

The pain reliving power of salicylic acid has been known for hundreds of years. Hippocrates recommended willow bark to relieve the pain of childbirth. (1) The active ingredient was later isolated by Leroux. Sodium salicylate was used as a treatment for rheumatiod arthritis in the late 1800s, but chronic patients suffered from severe stomach irritation. The father of a Baeyer chemist asked his son to search for a less irritating drug than sodium salicylate. Many derivatives were made, and the acetylated version found to be the best. Before the end of the century Baeyer had acetylsalicylic acid, or asprin, on the market.
The mechanism of action for asprin was determined much later. Asprin inhibits prostaglandin biosynthesis. Prostaglandins are released when cells are damaged and result in inflammation and fever. Asprin inhibits palatlet cyclooxygenase for the life of the platelet. Asprin acetylates a serine hydroxyl group in the active site of cyclooxygenase buy what can be thought of as a transesterification reaction. (2)
(1) Gross, M. and Greenberg, L. A. "The Salicylates: A Critical Bibliographical Review." Hillman: New Haven, CT.
(2) Van der Ouderaa, F. J., Buytenhek, M., Nugteren, D. H., and Van Dorp, D. A. 1980, Eur. J. Biochem. 109, 1.

Book Review Review

I was somewhat interested in reading a review of Mary Roach's new book-I read Stiff and was grossed-out and intrigued. Honestly, I couldn't get past the illustration. Has no one at the New York Times taken a course in organic chemistry? Really?
This illustration is wrong in so many ways.

You know you are on the path to fluency with organic chemistry when you quickly take inventory of all the valence mistakes, you are already there if that is all you notice.

The shifting carbonyl stretching frequency

Which of the following structures would you expect to have the strongest (higest wavenumber) streching frequency for the carbonyl stretch?
The key to this type of problem is realizing that there are two contributing forms to any carbonyl compound resonance hybrind. The one shown above, but also the polar charged form below.
You would expect that any group which could cause elctron donation to the carbonyl carbon would favor the polar form (right) and decrease the strecthing frequency. Similarly, any group that causes electron withdraw would enhance the double bond character (left) which increases the stretching frequency.
In this example you are looking at the effects through the conjugation of a phenyl ring. The stongest electron withdrawing group listed above is the nitro group, followed by chlorine, and the methyl group is slightly donating.
You also need to draw the resonance structures. Illustrating the withdraw of the nitro group on both the para and meta substituted phenol rings brings up a good point. You need to be able to draw a resonance strucure where the positive charge build up is next to the carbonyl. Think about what this would look like if you had the dipolar carbonyl-two adjacent positive charges = not a heavily contributing structure, therefore the double bond character is favored by this charge build up. The para substitution allows this but the meta does not (below). The correct answer for the problem above, methyl 4-nitrobenzoate, has a carbonyl strecthing frequency of 1700 cm-1.