Molecule of the Day

Here is one with which many readers will be acquainted first hand: nicotine. Named after Jean Nicot, tobacco booster extraordinaire, nicotine is an alkaloid that occurs in the whole nightshade family, of which tobacco is a member. Typically people will give the structure on the left, below.

This is known as the “freebase.” This is a general term, but like the acronym HOMO, it tends to make nonchemists titter and chemists shrug. It refers to any alkaloid (protonatable nitrogen compounds - cocaine is one, which is why crack is the best-known freebase to the lay public) in its unprotonated form (hence “free base”). Under physiologic pH (in tobacco, or, say, your blood) it is protonated, and assumes the ionization state on the right, above.

As a general rule, charged compounds have a much harder time making it across membranes (say, your lungs, or just your blood vessels in your mouth, if you’re sucking on a bit of the old chaw). Tobacco manufacturers have taken to using a base to deprotonate some of the nicotine. This is where the “ammonia in cigarettes” story comes from. This makes it more bioavailable - the uncharged stuff gets a free pass across membranes.

Nicotine has been studied quite a bit. It binds to a class of receptors that bind acetylcholine natively:

In fact, the subclass of acetylcholine receptor upon which nicotine acts is termed the “nicotinic” class for just this reason. Despite the fact that it has a whole receptor class named after it, like much of the brain, Nicotine’s detailed pharmacology remains elusive. The vast majority of schizophrenics smoke - the causes and effects of this are still debated. It has been suggested, famously, that nicotine has an anti-Parkinson’s disease activity.

This is perhaps the only health perk of smoking, and less-harmful analogues are being researched for such things. Interestingly, for a long time, it was suggested that nicotine is benign, and it’s simply that “other stuff” in tobacco products that is so nasty. It turns out, however, that nicotine inhibits apoptosis, or programmed cell death, which is an important anticancer defense. Tobacco products also contain a nasty nicotine-derived nitrosamine (a famously carcinogenic functional group if there ever was one) called NNK. I believe this comes from the curing process; correct me if i’m wrong.

It is by the acetylcholinergic mechanism that nicotine can act as an insecticide (it is still used industrially, I believe; I at least know that certain sites advocating homemade bug treatments suggest you soak some cigar butts in water to make a homebrew bug killer). Many insecticides are actually closely related to neurotoxic compounds in humans (and exert their bug killing effect by neurotoxic means). Today’s compounds are pretty benign to mammals, but I know some can cause similar effects to nerve agents in humans in overdoses.

Night!