water-soluble. Its flash point is 95 °C and its auto-ignition temperature is 244 °C. Nicotine is readily volatile (vapor pressure 5.5 Pa at 25 °C) On exposure to ultraviolet light or various oxidizing agents, nicotine is converted to nicotine oxide, nicotinic acid (niacin, vitamin B3), and methylamine. Nicotine is chiral and hence optically active, having two enantiomeric forms. The naturally occurring form of nicotine is levorotatory with a specific rotation of [α]D=–166.4° ((−)-nicotine). The dextrorotatory form, (+)-nicotine is physiologically less active than (−)-nicotine. (−)-nicotine is more toxic than (+)-nicotine. The salts of (−)-nicotine are usually dextrorotatory; this conversion between levorotatory and dextrorotatory upon protonation is common among alkaloids. The hydrochloride and sulfate salts become optically inactive if heated in a closed vessel above 180 °C. Anabasine is a structural isomer of nicotine, as both compounds have the molecular formula . Nicotine that is found in natural tobacco is primarily (99%) the S-enantiomer. Conversely, the most common chemistry synthetic methods for generating nicotine yields a product that is approximately equal proportions of the S- and R-enantiomers. This suggests that tobacco-derived and synthetic nicotine can be determined by measuring the ratio of the two different enantiomers, although means exist for adjusting the relative levels of the enantiomers or performing a synthesis that only leads to the S-enantiomer. There is limited data on the relative physiological effects of these two enantiomers, especially in people. However, the studies to date indicate that (S)-nicotine is more potent than (R)-nicotine and (S)-nicotine causes stronger sensations or irritation than (R)-nicotine. To date, studies are not adequate to determine the relative addictiveness of the two enantiomers in people. Pod mod electronic cigarettes use nicotine in the form of a protonated nicotine, rather than free-base nicotine found in earlier generations. Preparation The first laboratory preparation of nicotine (as its racemate) was described in 1904. The starting material was an N-substituted pyrrole derivative, which was heated to convert it by a [1,5] sigmatropic shift to the isomer with a carbon bond between the pyrrole and pyridine rings, followed by methylation and selective reduction of the pyrrole ring using tin and hydrochloric acid. Many other syntheses of nicotine, in both racemic and chiral forms have since been published. Biosynthesis The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that comprise nicotine. Metabolic studies show that the pyridine ring of nicotine is derived from niacin (nicotinic acid)