Seeman Etal - Using Basic Principles to Understand Complex Science_ Nicotine Smoke Chemistry and...

Research: Science and Education

www.JCE.DivCHED.org Vol. 82 No. 10 October 2005 Journal of Chemical Education 1577

Tobacco and tobacco smoke chemistry (1) are importanttopics because of their health implications (24), and thusthese subjects can form the basis of instructive learning. Stu-dents are capable of understanding that science is complex.Real-world applications will require identification and con-sideration of many types of data, frequently stemming fromdiverse scientific disciplines (5). Student interest and learn-ing are improved when subjects of topical interest are includedin the curriculum.

Students are typically overwhelmed in their early chemis-try courses. They are thrust immediately into a swirling sea ofnew languages2: new elements, bonds, compounds, physicalproperties, names, reactions, and mechanisms. Memorizationoften becomes a survival tool. The teaching of basic principlesis one technique that can provide a solid foundation to stu-dents. However, the outcome in a scientific experiment maybe determined by a number of simultaneously operating phe-nomena acting in different directions such that even a qualita-tive prediction of the final result may not be possible.3 Thus,the use of a few basic principles to explain complex science canlead to incorrect or misleading conclusions. It is necessary thatall relevant fundamental principles be identified, recorded,evaluated, and, as appropriate, used. In addition, one must iden-tify and evaluate the underlying assumptions attendant witheach of the selected basic principles.

The effect of ammonia on the volatility of nicotine, 1,

N

N

CH3

H

1

from tobacco or tobacco smoke is an example of a complex,real-world system that is too complicated to be adequately

predicted by one or two basic principles. Rather, to under-stand the mechanisms of smoke formation (Figure 1), de-tailed experimental data and thoughtful analyses are required.There has been a tendency to assume that tobacco and to-bacco smoke are sufficiently similar to aqueous systems, suchthat the use of pH and pKa values will provide meaningfulpredictions (68). Aqueous ammonia and other compoundsthat can form ammonia during the smoking process areknown to be added to cigarette blend (9). The effect of am-monia on the transfer of nicotine from a puffing cigarette tosmoke has been predicted (6, 10, 11) based on the applica-tion of two basic principles: (i) the HendersonHasselbalchequation4 that allows the quantification of the relative con-centrations of bases (and acids) in a dilute aqueous solution;and (ii) the fact that salts are not volatile. Thus, it has beenproposed, based on first principles alone without supportingexperimental data, that ammonia in tobacco influencesnicotines thermal and smoke chemistry by modifying theposition of the 1 2 equilibrium distribution in tobaccoin favor of 1 (Figure 1) (6, 10, 12).

Of the three forms of nicotine 13, only nonprotonatednicotine 1 can volatilize. It is a reasonable hypothesis that in-creased concentrations of ammonia in the tobacco would alterthe position of the nicotine equilibrium shown in Figure 1 tofavor nonprotonated nicotine (1), thereby enhancing the trans-fer of nicotine from tobacco to smoke. This and closely relatedhypotheses were reported as scientific conclusions, thoughwithout supporting experimental data, in a recent article inthis Journal (6, 10), elsewhere in the chemical literature (7,13, 14), in the legal (15) and regulatory (12, 16, 17) litera-ture, on a university Web site (18), and on a science museumWeb site (19). Lastly, the thermal and smoke chemistry ofthe cocaine system has been provided as an analogy to sub-stantiate the resultant conclusions (6, 7, 10, 11, 14).

Using Basic Principles To Understand Complex Science:Nicotine Smoke Chemistry and Literature AnalogiesJeffrey I. Seeman1

SaddlePoint Frontiers, Richmond, VA 23236; [email protected]

Figure 1. Illustration of the interaction of ammonia, nicotine, and organic acids in the tobacco matrix and the volatilization of the non-charged species owing to the puffing cigarette.

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N

CH3HH

RCO RCO2

N

N

CH3H

2

23

heat

N

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CH3

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1 1

N

N

CH3

heat

in the tobacco matrix in the smoke

NH4 RCO2 NH3NH3 RCO H+ ++ 2 RCO H2

H H H

heat

heatRCO2


1578 Journal of Chemical Education Vol. 82 No. 10 October 2005 www.JCE.DivCHED.org

In this article, the experimental data for the position ofthe 1 2 3 equilibrium distribution in an aqueous so-lution are reviewed. We conclude that the position of thisequilibrium in water is insufficient (i) to predict the tobaccoand smoke experimental results; and (ii) to generalize to thethermal chemistry of other alkaloids. Application of severaladditional basic principles brings a more understandable andenriching learning experience to the student.

Thermal Transfer of Alkaloids to SmokeNicotine and a number of related pyridine alkaloids are

natural tobacco constituents (20) and are transferred to smokeduring the heatingpuffing smoking process (1). Cocaine, 4,

NH3C

OO

CH3

O

O4

also a plant alkaloid, can be smoked in one form or an-other (21). Since the chemical structures of nicotine and co-caine are extremely different, the chemical and physicalproperties of their nonprotonated and protonated forms aredifferent as well. Moreover, volatility and thermal stabilityare separate properties and both must be considered whentrying to understand thermal chemistry. To expect these prop-erties to be the same for nicotine and cocaine just becauseboth are plant alkaloids is overextending some basic principlesof chemistry. These issues will now be discussed, beginningwith the relevant nicotine and tobacco chemistry.

The pH of aqueous extracts of ground Bright, Burley,and Oriental tobaccos is generally acidic, with pH 56 (9,22).5 Because tobacco in a cigarette is not a dilute aqueous

solution, the HendersonHasselbalch equation cannot beused to quantify the relative concentrations of nicotine (1)and its protonated forms 2 and 3 in tobacco. Nevertheless,because aqueous extracts of tobacco are acidic, it is likely thatnicotine in tobacco exists as nicotinium salts of the tobaccoorganic acids, for example, acetic, formic, and malic acids(Figure 1) (23).

During the puffing of a burning cigarette, a complextemperature gradient occurs with temperatures reaching over900 C in the coal (24, 25). Well before those extreme tem-peratures are reached in the tobacco matrix, the volatiles andsemi-volatiles such as water and nicotine have evaporated andtransferred to the smoke. Gases such as ammonia6 evaporatefirst, followed by water (about 90100 C) (26), and then,at somewhat higher temperatures (about 120200 C), bynicotine and other semi-volatiles (27). Salts such as thenicotinium carboxylic acids salts 2 and 3 are of much lowervolatility than nonprotonated nicotine (1) and the carboxy-lic acids themselves for a number of reasons: first, the saltsare of much higher molecular weight; second, and of greaterconsequence, the salts are ionic and as such, they can form amultitude of complexes or aggregates, incorporating otherpolar molecules as well as water and other compounds thatcan stabilize charge (28). At the stage that nonprotonatednicotine is volatilizing, the tobacco matrix is essentially de-hydrated. Hence, the effective acidity of the dehydrated, al-ready reacting tobacco matrix is unknown but is likely to beeffectively more acidic than predicted by the pH of the aque-ous extract of tobacco (27).

As shown in Figure 2, nicotine carboxylic acids salts canform nonprotonated nicotine in essentially three ways:

1. Simple acidbase dissociation at the higher temperatures canoccur. This is the most likely mechanism for nicotiniumsalts of weak monocarboxylic acids such as acetic acid.

Figure 2. Three thermally induced reaction pathways leading to the volatilization of nicotine: (A) acidbase dissociation; (B) decomposi-tion of the acid moiety; and (C) disproportionation. The counterion in reaction C can become a decomposition product of the originalcarboxylic acid; in any event, the counterion must be a carboxylic acid strong enough to resist reacting via reaction (A).

1

5 6 1

A

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+

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OH N

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+

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2

H H

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heat

heat

heat

CH3CO2H

2

2

N

N

CH3H

H HO2CCH2CH(OH)CO2

2N

N

CH3H

H HO2CCH2CH(OH)CO2

HO2CCH2CH(OH)CO22



Thermogravimetricmass spectroscopic (TGAMS) analy-ses are useful techniques to explore pyrolysis chemistry (27,29). In this technique, a sample is heated from (typically)room temperature to some chosen high temperature at aspecific heating rate, and the sample weight loss is moni-tored as a function of time and temperature. The evolvingsubstances are subjected to MS analyses, to establish theiridentities. TGAMS analysis of nicotine acetate (2) revealsformation and volatilization of nicotine at about 120 C,not much higher than observed for nonprotonated nico-tine (1) itself (about 100 C) (27).

2. The organic acids themselves can decompose. For example,TGAMS of nicotine malates (2 and 3) reveals the forma-tion of maleic anhydride (5) and acrylic acid (6) as severalof the decomposition products at ca. 170 C.

3. Disproportionation reactions can form nonprotonated nico-tine. For example, the TGAMS of nicotine malates revealsa low-temperature (115 5 C) transfer of nicotine to thegas phase and higher temperature transfers (about 160 Cand about 200 C). The disproportionation reaction shownin Figure 2C is the likely mechanism for the lower tempera-ture transfer.

Do ammonia or ammonia-forming substances in the to-bacco blend of commercial cigarettes affect the transfer of nico-tine to the smoke, as proposed in the literature (6, 7, 10, 11)?The answer to this question has relied exclusively on the useof a reasonable application of two basic principles: thatnicotinium salts 2 and 3 are not volatile and that 2 and 3must first be converted to nonprotonated nicotine (1) in or-der for nicotine to be transferred to smoke by heat. However,these considerations require that the ammonia must be present

in the source matrix and that the alkaloid must have a suffi-ciently high vapor pressure to be volatilized prior to the de-composition of the alkaloid by heat. Indeed, the balancebetween vapor pressure and thermal stability leads to a cru-cial third basic principle: the yield of evaporative transfer of asubstance depends on the balance between two factors, namely,the substances vapor pressure and its thermal stability.

The thermal reactivity of protonated alkaloids and pos-sible transfer from biomaterials to smoke aerosols can be de-scribed by two possible scenarios (30).

Scenario 1: The protonated alkaloid is converted thermally toits nonprotonated form. The resultant nonprotonated amineis then thermally volatilized. Nicotine carboxylic acid salts asfound in tobacco are examples of systems in which volatiliza-tion of the nonprotonated alkaloid occurs at temperatures be-low those required for thermal decomposition (27, 30).

Scenario 2: Upon being heated, the protonated alkaloid de-composes prior to formation of its nonprotonated form andvolatilization. Cocaine hydrochloride is an example of this sce-nario (21, 30).

These two scenarios will be discussed in turn. When injectedinto a preheated chamber, nicotine decomposes above about300 C in air (31) and above 600 C in inert atmospheres(Figure 3) (3234).7 In tobacco, nicotine likely exists as itscarboxylic acid salts, protonated by natural tobacco acids suchas malic acid, acetic acid, and formic acid. These salts decom-pose well below 300 C . For example, TGAMS studies ofnicotinium acetate and nicotine malate show volatilization tonicotine at about 120 C and 110170 C , respectively (27,35). These and other nicotinium carboxylic acid salts transfernicotine to the gas phase in greater than 90% yields and with

Figure 3. Graphical representation of the approximate temperatures at which various processes occur in the nicotinenicotine carboxylicacid salt system. As found in thermal analysis studies (TGAMS) (30), nicotine evaporates at ca. 120 C. Nicotine carboxylic acid salts,as found in tobacco, are transformed into nonprotonated nicotine that evaporates. Depending on the carboxylic acid structure, this occursfrom about 120220 C. When injected into a preheated oven, nicotine will begin to decompose at about or slightly lower than 300 Cin air and about 600 C in inert atmospheres (27).7

conversion of nicotinecarboxylic acid salts 2

and 3 to nonprotonatednicotine 1 and

volatilization of nicotine 1

decompositionof nicotine in

air begins

evaporation ofnonprotonated

nicotine 1

0 100 200 300 400 500 600

decomposition ofnicotine in inert

atmospheres begins

heat

N

N

CH3

H

1 1

N

N

CH3

heat

N

N

CH3H

2

H Hheat

Temperature / C

N

N

CH3HH

RCO2

3

H RCO2 RCO2



Figure 4. Graphical representation of the temperatures at which various processes occur in the cocainecocaine hydrochloride system.When heated, at about 110 C, cocaine hydrochloride (7) decomposes to benzoic acid and other products without formation andvolatilization of nonprotonated cocaine. When subjected to temperatures from about 160575 C, nonprotonated cocaine (4) will bothevaporate and partially decompose, the partitioning favoring decomposition at higher temperatures (30, 3040).

cocaine hydrochloridedecomposes upon heating

otherunidentified

products

somedecomposition

products

CO2H

Cl

NH3C H

OO

CH3

O

O

NH3C

CO2H

OH

NH3C

OO

CH3

O

O

NH3C

volatilization

OO

CH3

O

O

7

4

heat

heat

0 100 200 300 400 500 600

Temperature / C

+ +

+

essentially complete retention of configuration (Figure 3) (30).Thus, it has been concluded that nonprotonated nicotine andprotonated nicotine transfer nicotine to the gas phase withessentially the same efficiency from tobacco, when thecounterions are the endogenous tobacco carboxylic acids ortheir thermal decomposition products (27).

During the puffing of a cigarette, peak coal temperaturescan exceed 900 C though there is rapid decrease in tem-perature of the solid materials and gases surrounding themwith distance from the coal center (24). The nicotine in thetobacco never experiences these high temperatures in the puff-ing cigarette because it volatilizes well before 900 C (27, 30,36). The heat from combustion of the tobacco first transforms 2and 3 to nonprotonated nicotine (1) (Figure 3) that is then vola-tilized with additional heat (Figure 1). Ammonia is not neededand does not play any experimentally documented role in in-creasing the thermally-induced transfer of nicotine from tobaccoto smoke. Ammonium carboxylic salts can thermally convertto ammonia and the corresponding carboxylic acid, and am-monia, being a gas, can volatilize immediately. The nicoti-nium salts 2 and 3 can be converted to 1 as shown in Figure2 in the absence of ammonia. Immediately downstream (orbehind) the puffing coal is a region having low oxygen con-tent (37), thereby increasing the thermal stability of nicotinein the puffing cigarette owing to decreased oxidation andcombustion.

In contrast, cocaine hydrochloride (7) is thermally un-stable (Figure 4). Heating 7 results in degradation of the co-caine ring system without significant formation of cocaine,if any, in the resulting aerosol (21), forming instead benzoicacid and small ring heterocyclic compounds (38). Upon be-ing heated, nonprotonated cocaine (4) transfers in low-to-

moderate yields to the aerosol (39, 40). In order to transfercocaine to smoke from cocaine hydrochloride, the salt mustfirst be converted to its nonprotonated free base form 4 with,for example, sodium bicarbonate (21, 30, 40).

Comparison of Figures 3 and 4 demonstrates that thethermal chemistry of the nicotine system is quite differentfrom that of the cocaine system. As shown in Figure 3, thenicotine ring system is relatively stable at temperatures be-low about 300 C. Nonprotonated nicotine (1) can form fromeither mono- or diprotonated nicotine (2 and 3, respectively)readily at temperatures below 300 C and evaporate prior todecomposition of the nicotine ring system (Figure 2). In con-trast, the cocaine ring system is thermally unstable. Cocainehydrochloride, for example, thermally decomposes prior toits releasing nonprotonated cocaine to the vapor phase (Fig-ure 4).8

On the Use of Ammonia-Forming Compounds in theManufacture of Commercial Cigarettes

We now consider why some tobacco companies addammonia-forming compounds to some of their blend com-ponents. A blended commercial cigarette typically has a num-ber of components: Bright, Burley, and Oriental lamina(tobacco leaf ), expanded tobaccos (tobacco leaf processed todecrease its density, thereby decreasing the total quantity ofmainstream smoke produced), reconstituted tobaccos, andstem materials (1, 22, 41). Reconstituted tobaccos are sheetmaterials formed from tobacco dust and other reclaimed to-bacco materials formed during the manufacturing processes.The names and types of ingredients currently used in com-mercial cigarettes sold in the United States are described in



greater detail on cigarette manufacturers Web sites (4245).The only ammonia-forming compounds added to the blendsof Philip Morris USA commercial cigarettes are diammoniumphosphate, (NH4)2HPO4, and aqueous ammonia (42, 43),and these are added to some of the reconstituted tobacco ma-terials but not to the other blend components.

One type of reconstituted tobacco is a sheet material (castsheet process) formed from tobacco materials that have beenpulverized to a powder and, in a slurry, are bonded togetherwith an adhesive (22, 46). One type of adhesive used is to-bacco pectin.9 Pectins are used in the preparation of jelliesand other food products as gelling and adhesive agents. In-deed, pectins are the intercellular adhesive substances foundin the cell walls of all plant tissue. To make reconstituted to-bacco, tobacco pectin can first be extracted from the pulver-ized tobacco powders and then used to connect or cementthe individual tobacco particles together (47). Diammoniumphosphate is added to the tobacco slurry to release the cal-cium pectate crosslinkers, calcium phosphate precipitates, andaqueous ammonia is added to help solubilize the tobacco pec-tins (48). The resultant slurry is poured onto a heated mov-ing belt and, as the water is thermally driven off, the pectinsbind the tobacco particles together and a sheet is formed.Much of the ammonia and some of the nicotine is lost dur-ing the heating and sheet-making process. A second type ofreconstituted tobacco sheet is made using a paper produc-tion process (22). Sometimes, ammonia-forming compoundsare added to these reconstituted sheet materials as flavorants;ammonia is well known to react with sugars to form impor-tant nitrogenous flavors, for example, pyrazines, during cook-ing by the well-known Maillard or Browning Reaction (49).The reconstituted tobaccos are then shredded and blendedwith the other leaf tobaccos to produce the total tobaccoblend.

Conclusions

The chemical and physical properties of nicotine and itscarboxylic acid salts as found in tobacco provide an interest-ing example where application of one or two basic principlescan lead to conclusions inconsistent with the experimentaldata. The transfer of nicotine from tobacco to smoke cannotbe explained by the pH of an aqueous extract of the tobacco.Nicotine carboxylic acid salts are themselves not volatile. Thethermal conversion of nicotine salts to nonprotonated nico-tine and nicotines subsequent volatilization occurs at highefficiency via different pathways and at temperatures belowthat required for substantial thermal decomposition of thenicotine ring system. Hence, nicotine is transferred with es-sentially the same efficiency from tobacco to smoke regard-less of the form of the nicotine in the tobacco. In contrast,cocaine hydrochloride thermally decomposes prior to its con-version to free base cocaine and its volatilization.

Chemical subjects that are topical provide excellent op-portunities to increase the students interest in complex sci-entific subjects. Because of its health implications (2, 3) andrecent litigation and regulatory implications (11, 12, 16, 17),tobacco and tobacco smoke chemistry is an important topi-cal subject. The complexity of the science, as described in thisarticle, provides numerous topics having pedagogical and sub-stantive value. This article demonstrates that the vigilant search

for all the relevant concepts and experimental data is a criti-cal early step in any scientific investigation. Instructors mustintroduce the diversity of scientific disciplines generally nec-essary to interpret and comprehend our complex world (5).

Acknowledgments

This work was funded by Philip Morris USA Inc. Theauthor thanks John H. Summerfield for helpful and colle-gial discussions; Richard Carchman, Jay A Fournier, GerdKobal, and Edward B. Sanders for their intellectual contri-butions to this and related studies; and Charleen Callicutt,Charles Gaworski, John B. Paine, III, and Alan Goldsmithfor their technical contributions. The author especially thanksJ. Hodge Markgraf, three anonymous reviewers, and the Edi-tor for their very helpful and illuminating comments.

Notes

1. The author has published over 50 research papers, patents,and review articles on nicotine and tobacco alkaloid chemistry sincethe 1970s, mostly during his time as a research scientist with PhilipMorris. See, for example: Whidby, J. F.; Seeman, J. I. J. Org. Chem.1976, 41, 1585159; Seeman, J. I. Chem. Rev. 1983, 83, 83134;Seeman, J. I. Heterocycles 1984, 22, 165193; and Seeman, J. I.;Lipowicz, P. J.; Piad, J.-J.; Poget, L.; Sanders, E. B.; Snyder, J. P.;Trowbridge, C. G. Chem. Res. Toxicol. 2004, 17, 10201037.

2. The author thanks Dudley Herschbach, Harvard Univer-sity, for providing this metaphor to the author during a video in-terview at Harvard University, May 1999.

3. This logic is related to the Principle of Contradiction ofthe great 17th century German philosopher, mathematician, logi-cian, and universalist, Gottfried Wilhelm Leibniz. This principlestates that just because a scientific concept seems reasonable is notsufficient evidence that it is valid. For additional details, see: TheCambridge Companion to Leibniz; Jolley, N., Ed.; Cambridge Uni-versity Press: Cambridge, 1995.

4. The HendersonHasselbalch equation calculates the per-cent distribution of nonprotonated and protonated species in a di-lute aqueous solution. The input parameters are the pKa

s of thedissolved species and the pH of the aqueous solution. See: Voet,D.; Voet, J. G.; Pratt, C. W. Fundamentals of Biochemistry; JohnWiley: New York, 1999; p 34.

5. Because tobacco is not a dilute aqueous solution, the to-bacco pH is an indication of the relative molar quantities of wa-ter extractable acids and bases from tobacco. Tobacco pH cannotbe used quantitatively to calculate the percent distribution of vari-ous neutral and protonated (or deprotonated) bases (or acids) in asolid or heterogeneous environment.

6. Ammonia can form during the smoking process by pyroly-sis reactions from ammonium salts, amino acids, and proteins attemperatures greater than 150 C (29). Thus, the TGA of tobaccocan show the formation of ammonia at temperatures considerablyhigher than from the decomposition of simple ammoniumsalts (26).

7. When injected into a chamber preheated 300 C in air,nicotine primarily forms myosmine (8) with about 40% unreactednicotine (50). When injected into a chamber preheated to 600 Cin helium, nicotine forms a variety of compounds, the major prod-ucts being 3-vinylpyridine and myosmine along with 34% unreactednicotine (32).



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High Magnetic Field Laboratory, Florida State University Re-search Foundation, Inc., Science, Tobacco & You. http://scienceu.fsu.edu/content/tobaccoyou/whatistobacco/additives.html(accessed Aug 2005).

19. Liberty (NJ) Science Center, The Science Behind Tobacco.http://www.lsc.org/tobacco/health/deliverySystems.html. http://www.lsc.org/tobacco/manufacturing/cigarettes.html (accessed Aug2005).

20. Schmeltz, I.; Hoffmann, D. Chem. Rev. 1977, 77, 295311.21. Hatsukami, D. K.; Fischman, M. W. J. Am. Med. Assoc. 1996,

276, 15801586.22. Browne, C. L. The Design of Cigarettes; Hoechst Celanese Cor-

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E. J. Agric. Food Chem. 1999, 47, 51335145.28. Perfetti, T. A. Beitr. Tabakforsch. Int. 1983, 12, 43-54.29. Sharma, R. K.; Chan, W. G.; Wang, J.; Waymack, B. E.;

Wooten, J. B.; Seeman, J. I.; Hajaligol, M. R. J. Anal. Appl.Pyrolysis 2004, 72, 153163.

30. Fournier, J. A.; Paine, J. B., III; Seeman, J. I.; Armstrong, D.W.; Chen, X. Heterocycles 2001, 55, 5974.

31. Kobashi, Y.; Sakaguchi, S. Sanken Ho 1960, 102, 1315.32. Jarboe, C. H.; Rosene, C. J. J. Chem. Soc. 1961, 24552458.33. Schmeltz, I.; Schlotzhauer, W. S.; Higman, E. B. Beitr.

Tabakforsch. 1972, 6, 134138.34. Woodward, C. F.; Eisner, A.; Haines, P. G. J. Am. Chem. Soc.

1944, 66, 914.35. Perfetti, T. A.; Norman, A. B.; Gordon, B. M.; Coleman, W.

M., III; Morgan, W. T.; Dull, G. M.; Miller, C. W. Beitr.Tabakforsch. Int. 2000, 19, 141158.

36. Seeman, J. I.; Fournier, J. A.; Paine, J. B., III. In 51st TobaccoChemists Research Conference: Winston-Salem, NC, 1997; Ab-stract 11.

37. Baker, R. R. Beitr. Tabakforsch. Int. 1981, 11, 116.38. Gotz, M.; Boldvai, J.; Posgay-Kovacs, E. Sci. Pharm. 1981,

49, 408419.39. Martin, B. R.; Lue, L. P.; Boni, J. P. J. Anal. Toxicol. 1989,

13, 158162.40. Nahahara, Y.; Ishigami, A. J. Anal. Toxicol. 1991, 15, 105

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43. Philip Morris Non-tobacco Ingredients. http://www.phi l ipmorri susa .com/product_fac t s / ingredient s /non_tobacco_ingredients.asp (accessed Jul 2005).

44. R. J. Reynolds Tobacco Ingredients. http://www.rjrt.com/TI/TIcig_ingred_summary.asp?cookiesTurnedOn=no (accessed Jul2005).

N

N

88. The analogies discussed in the literature (6, 7, 10, 11, 14)

and in this article involve the thermal and smoke chemistry of nico-tine carboxylic salts, as found in tobacco, and cocaine hydrochlo-ride, as obtained from the extraction of this natural product fromplant materials (see ref 21). Nicotine hydrochloride would not befound in tobacco but would be converted to a nicotine carboxylicacid salt and potassium or calcium chloride, given the presence ofcarboxylic acids in tobacco.

9. Pectins are polysaccharide substances found naturally aspartial methyl esters of poly-D-galacturonate sequences linked -(1 4) with (1 2)-L-rhamnose units irregularly interspersed. Itis the carboxylic acid group of galacturonic acid that participatesin the calcium crosslinking.

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50. Kobashi, Y.; Hoshaku, H.; Watanabe, M. Nippon Kagaku Zasshi(Chem. Soc. Jpn., Pure Chem. Sect. J.) 1963, 84, 7174.

Seeman Etal - Using Basic Principles to Understand Complex Science_ Nicotine Smoke Chemistry and...

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