It is some 550 years since the eponymous Jean Nicot sent tobacco and seeds from Portugal to Paris, passing Nicotiana tabacum from the Americas to Northern Europe by way of the Iberian peninsula. Nicotine itself was subsequently extracted and synthesized, culminating in the identification of the spatial orientation of the natural (S) isomer in the late 1970s (Domino, 1999). Up to 10% of the nicotine in tobacco smoke is the (R) isomer, probably arising from racemization during combustion (Benowitz, 1986). Nicotine has gained particular prominence as the addictive constituent of most tobacco based products and, to a lesser extent, as an effective insecticide.
Nicotine, 3-(1-methyl-2-pyrrolidinyl) pyridine, has a molecular weight of 162.23 and is a volatile, colorless base (pKa=8.5) that turns brown and acquires the typical odor of tobacco on exposure to light. Roughly 69% of its pyrrolidine nitrogen is ionized (positively charged) at pH 7.4 and 37°C, whereas its pyridine nitrogen is un-ionized. This feature of nicotine renders its absorption and renal excretion highly pH dependent, because uncharged lipophilic bases pass easily over lipoprotein membranes and charged organic bases do not. For example, nicotine is primarily ionized at the pH (5.5) of smoke from the flue-cured tobaccos in most American cigarettes, and buccal absorption is minimal (Gorrod and Wahren, 1993). By contrast, smoke from air-cured tobaccos in pipes, cigars, and many European cigarettes is less acidic and is well absorbed through