Cation-pi interactions: Difference between revisions
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"... if nicotine activated ACh receptors found in muscle as potently as it does brain receptors, smoking would cause intolerable and perhaps fatal muscle contractions."<ref name="XD" /> | "... if nicotine activated ACh receptors found in muscle as potently as it does brain receptors, smoking would cause intolerable and perhaps fatal muscle contractions."<ref name="XD" /> | ||
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Like acetylcholine, nicotine has a cationic nitrogen when the pH is neutral | Like acetylcholine, nicotine has a cationic nitrogen when the pH is neutral or acidic. This occurs in nicotine's 5-membered methylpyrrolidine ring (see [http://en.wikipedia.org/wiki/Nicotine nicotine structure]), which has a pK<sub>a</sub> of 8.0<ref>In contrast, the 6-membered pyridine ring has a pK<sub>a</sub> of 3.1, so is uncharged at neutral pH. The uncharged or ''free base'' form of nicotine is more volatile than the charged form. Cigarette manufacturers have long added ammonia to tobacco to increase absorption of nicotine by smokers. See Summerfield, 1999 cited elsewhere for details.</ref><ref>Summerfield, J. H. An acid-base chemistry example: conversion of nicotine. J. Chem. Ed. 76:1397-8 (1999).</ref>. | ||
In 1998, Zhong ''et al.'' (with Dougherty)<ref name="zhong">PMID: 9770444</ref> provided evidence that the [http://en.wikipedia.org/wiki/Nicotinic_acetylcholine_receptor cation in acetylcholine] engages in a cation-pi interaction with Trp149 in the receptor, making an important contribution to the binding affinity. In 2002, Beene ''et al.'' (with Dougherty)<ref name="XD" /> provided evidence that no such cation-pi interaction is involved when nicotine binds to the muscle-type receptor, thus accounting in part for the lower affinity. | In 1998, Zhong ''et al.'' (with Dougherty)<ref name="zhong">PMID: 9770444</ref> provided evidence that the [http://en.wikipedia.org/wiki/Nicotinic_acetylcholine_receptor cation in acetylcholine] engages in a cation-pi interaction with Trp149 in the receptor, making an important contribution to the binding affinity. In 2002, Beene ''et al.'' (with Dougherty)<ref name="XD" /> provided evidence that no such cation-pi interaction is involved when nicotine binds to the muscle-type receptor, thus accounting in part for the lower affinity. | ||