So as a biochemistry major, I’m (as I’m sure all of us are) a sucker for finding cool ways to apply advanced chemistry concepts to biological molecules. Right now in Orgo II we’re studying aromaticity, and one of the first concepts we learned the other day was Huckel’s Rule. This rule states that if a cyclic, planar, fully conjugated molecule has 4n+2 pi electrons (where n can be any integer including zero), it is considered aromatic. The other part of this rule is that if a cyclic, planar, fully conjugated molecule has 4n pi electrons, it is considered anti-aromatic. Furthermore, an important concept to remember when dealing with aromaticity is that an aromatic compound is most stable when it is in its aromatic form, or in other words, is extremely unreactive if its aromaticity is being compromised. Anyway, in our pset due this morning we had a problem that asked for us to (1) determine whether the imidazole ring in the histidine side chain was aromatic and (2) to explain how this information could help us determine which of the two nitrogens in the ring gets protenated. If we look at the deprotenated imidazole ring on histidine (below), we can see that there are 6 pi electrons available in the ring. These 6 electrons come from the two double bonds and the lone pair of electrons belonging to the NH. We can therefore say that the ring is aromatic, since 4n+2=6, where n=1. When determining which of the two nitrogens will accept a proton, we have to now consider which nitrogen could compromise the aromaticity of the ring. The lone pairs on the NH belong to the 6 pi electrons that make the ring aromatic so if a proton were to be accepted by this nitrogen these electrons would be removed and the ring would be left with 4 pi electrons and since 4n=4, when n=1, the ring would become antiaromatic. A reaction that removes a ring’s aromaticity is extremely unfavorable. However, the other nitrogen’s lone pairs do not belong to the pi electrons in the ring and can therefore be used to accept a proton, hence why we see that that nitrogen gets protenated (below). Pretty cool!
Wow Carley. Not only did I love he fact that you gave us such a good example of how one can successfully transfer “learning” from one course to another, but also so clearly walked us through your thought process in reaching your conclusion. I had never thought of (or encountered) this explanation for which proton gets deprotonated or protonated. I learned a lot, thanks.