Seeman Etal 1999 - The Form of Nicotine in Tobacco. Thermal Transfer of Nicotine and Nicotine Acid Salts To Nicotine in The Gas Phase

The Formof Nicotine in Tobacco.
Thermal Transfer of Nicotine and

Nicotine Acid Salts to Nicotine in the Gas Phase
Jeffrey I . Seeman,* Jay A Fourni er,* John B. Pai ne I I I ,* and Bruce E. Waymack
Phi l i p Morri s, P.O. Box 26583, Ri chmond, Vi rgi ni a 23261-6583
Thermal transfer to ni coti ne i n the gas phase from neat ni coti ne, from vari ous ni coti ne carboxyl i c
aci d sal ts, and from endogenous ni coti ne i n Burl ey, Bri ght, and Ori ental tobacco sampl es has been
exami ned by thermogravi metri c/di fferenti al thermal anal ysi s/mass spectroscopy and evol ved gas
anal ysi s. Under the condi ti ons used i n these studi es, the peak transfer temperatures of these
substances to ni coti ne i n the gas phase are ni coti ne and ni coti ne acetate, both ca. 110-125 C;
ni coti ne mal ates, ca. 110-210 C for ni coti ne to mal i c aci d rati os of 1:0.56 and 1:1 and ca. 160-210
C for a ni coti ne to mal i c aci d rati o of 1:2; (S)-ni coti ne bi s[(2R,3R)-hydrogen tartrate] di hydrate, ca.
195-210 C; and tobacco sampl es, a range of ca. 160-220 C. These resul ts suggest that ni coti ne
i s mostl y protonated i n tobacco l eaf. I n al l cases, the temperature of the transfer of ni coti ne to the
gas phase was found to be many hundreds of degrees bel ow the temperatures observed around the
coal of a burni ng ci garette (smol der, ca. 500-775 C; dynami c smoki ng, 600 to over 950 C). Wi thi n
the narrow zone of a puffi ng ci garette that encompasses an i ntermedi ate temperature range (125-
250 C), ki neti c data suggest that these temperatures are not suffi ci ent to vol ati l i ze si gni fi cant
amounts of nonprotonated ni coti ne, assumi ng any exi sts at al l , duri ng the short puff durati on (2 s).
I t i s concl uded that nonprotonated ni coti ne and protonated ni coti ne (sal ts of ni coti ne wi th natural
tobacco carboxyl i c aci ds) wi l l transfer ni coti ne to smoke wi th comparabl e yi el ds and effi ci enci es
duri ng the smoki ng process.
Keywords: Nicotine; nicotinecarboxylic acid salts; thermal transfer; gas phase; tobacco; thermo-
gravimetric/ differential thermal analysis; mass spectroscopy analysis; TGA/ DTA/ MS; evolved gas
analysis; EGA; bound nicotine
I NTRODUCTI ON
(S)-(-)-Ni coti ne (1), hereafter ni coti ne, i s the pri n-
ci pal al kal oi d i n tobacco
(Nicotiana tabacum), the Bri ght, Burl ey, and Ori ental
vari eti es of whi ch are the pri nci pal raw materi al s of the
tobacco i ndustry (Akehurst, 1981). Hypotheti cal l y, thi s
wel l -known and extremel y wel l studi ed (Seeman, 1987;
Seeman, 1984; Seeman, 1983) substance can exi st i n one
or more (Schmel tz and Hoffmann, 1977; Stedman, 1968)
of three forms i n ci garette bl end components: nonpro-
tonated ni coti ne (1), monoprotonated ni coti ne (2), and
di protonated ni coti ne (3) (Brunnemann and Hoffmann,
1974). (I n al l structures herei n, Z refers to a general
ani on, not necessari l y i denti cal to other Zs wi thi n the
scheme.)
The effi ci ency of transfer of ni coti ne from tobacco to
smoke has been the subject of consi derabl e di scussi on
and attenti on i n the past few years (Kessl er et al ., 1996;
Kessl er et al ., 1997; Freedman, 1995; U.S. Food and
Drug Admi ni strati on, 1996). I n thi s paper, we present
evi dence whi ch i ndi cates (1) that ni coti ne i s present
pri mari l y i n one or both protonated forms i n tobacco and
i s l i kel y to be di protonated when heated to temperatures
requi red to rel ease ni coti ne from tobacco, (2) that
nonprotonated ni coti ne (1) and the ni coti ne carboxyl i c
aci d sal ts such as those found i n tobacco (2 and 3)
transfer ni coti ne to the gas phase at temperatures bel ow
about 220 C, and (3) that ni coti ne sal ts i n tobacco and
nonprotonated ni coti ne, i f i t exi sts i n tobacco at al l , are
l i kel y to transfer ni coti ne to the gas phase duri ng the
smoki ng process wi th comparabl e yi el ds and effi ci enci es.
Evi dence wi l l al so be presented that i mpl i es a faci l e
proton-transfer between 1, 2, and 3 under thermal or
smoki ng condi ti ons.
MATERI ALS AND METHODS
Thermogravimetric/Differential Thermal Analysis/
Mass Spectrometry (TG/DTA/MS). A VG I nstruments
quadrupol e mass spectrometer (EGA300SL) was i nterfaced to
a Sei ko si mul taneous TG/DTA uni t (TG/DTA 300) vi a a fl exi bl e
fused si l i ca-l i ned stai nl ess steel capi l l ary (0.3 mm i .d. 6 ft
Presented, i n part, at the Soci ety for Research on Ni coti ne

and Tobacco, March 1996, at the Tobacco Chemi sts Research
Conference, September 1997, and at the Ameri can Chemi cal
Soci ety Nati onal Meeti ng, AGFD-035, August 23, 1998.
5133 J. Agric. Food Chem. 1999, 47, 51335145
10.1021/jf990409b CCC: $18.00 1999 American Chemical Society
Published on Web 11/06/1999
l ong). No modi fi cati on to the Sei ko bal ance was necessary,
because coupl i ng was made usi ng a Tefl on bal l joi nt di rectl y
attached to the end of a quartz furnace tube. An open sampl e
pan confi gurati on wi th hori zontal purge gas fl ow across the
sampl e faci l i tated sampl e/purge gas i nteracti on and rapi d
escape of gaseous reacti on decomposi ti on products. One end
of the capi l l ary was posi ti oned i n the furnace tube downstream
of the sampl e pan, and the other end of the capi l l ary was
connected to the mass spectrometer through a mol ecul ar l eak
(si l i con carbi de fri t) backed by a rotary pump.
Thi s system provi des mi ni mal transi t ti me of evol ved gas
from the TG/DTA to the mass spectrometer. To prevent
condensati on, the transfer l i ne was heated to about 170 C by
appl yi ng an ac vol tage across the l ength of the stai nl ess steel
capi l l ary sheath. Sampl es, approxi matel y 3-10 mg for ni coti ne
and the ni coti ne aci d sal ts and 20 mg for tobacco sampl es, were
heated i n pl ati num pans at rates of 5 C mi n
-1
under about a
100 mL mi n
-1
fl ow of ei ther hel i um or a mi xture of 21%oxygen
i n hel i um (hereafter someti mes referred to as 21% oxygen),
i n case oxi dati ve l oss of ni coti ne was to be si gni fi cant. MS data
were col l ected usi ng a mul ti pl e i on moni tori ng (MI M) mode
i n whi ch speci fi c i ons were moni tored as di scussed bel ow
(secti on 3b). Peak ni coti ne appearance temperatures were
determi ned by recordi ng the maxi ma of the MS i on fragment
of mass-to-charge rati o (m/z) 84, the most i ntense peak of the
ni coti ne mass spectrum. I n some cases, parti cul arl y when
i nterference at m/z 84 mi ght be anti ci pated, the second most
abundant ni coti ne mass spectral fragmentati on peak, at m/z
133, was al so fol l owed. I n the fi gures herei n, onl y sel ected i on
fragments are shown. MS and TG/DTA data were converted
to ASCI I fi l es, and data reducti on/overl ap was performed i n
Mi crosoft EXCEL.
Ki neti c data were obtai ned usi ng the Sei ko TG/DTA uni t.
Ni coti ne and (S)-ni coti ne bi s[(2R,3R)-hydrogen tartrate] di -
hydrate were each subjected to TGA scans at heati ng rates of
5, 10, 15, and 20 C mi n
-1
under fl owi ng compressed ai r at
rates of 100 and 500 mL mi n
-1
. The TG curves were normal -
i zed to a gi ven sampl e wei ght pri or to cal cul ati ng acti vati on
energi es and degradati on/vol ati l i zati on ti mes (l i feti mes) by use
of a ki neti cs package, provi ded by Sei ko, whi ch uti l i zes the
noni sothermal method of Ozawa (Ozawa, 1965).
Evolved Gas Analysis/Mass Spectrometry (EGA/MS).
EGA/MS experi ments were conducted by heati ng sampl es at
20 C mi n
-1
under fl owi ng He (200 mL mi n
-1
). Sampl es were
contai ned i n ei ther a quartz boat (i f sol i d) or on quartz wool
(i f l i qui d) i nsi de an 8 mm i .d. quartz tube whi ch was heated
by a gol d refl ectance tube furnace. For tobacco sampl es, a
starti ng mass of about 500 mg was used. For the ni coti ne
carboxyl i c aci d sal ts, a starti ng mass of about 25 mg was used.
A porti on of the exi ti ng gases was di rected i nto a Bal zer
QMG511 mass spectrometer uti l i zi ng the Bal zer capi l l ary i nl et
system. The mass spectrometer was programmed to scan over
a mass range of 0-255 amu wi th an operati ng i oni zati on
energy of 18 eV. Data, at 2 C or 4 C i nterval s, were col l ected,
stored, compi l ed, and pl otted by a PDP-1103 computer system.
Agai n, ni coti ne evol uti on was fol l owed by moni tori ng the i on
fragment at m/z 84.
Preparation and Characterization of Compounds.
Warning: Ni coti ne i s severel y toxi c i n the quanti ti es de-
scri bed bel ow. Due care must be exerci sed whi l e handl i ng pure
ni coti ne and ni coti ne sal ts.
(S)-NicotineBis[(2R,3R)-hydrogen tartrate] Dihydrate(2c-
3c). (Someti mes 2c-3c i s referred to hereafter as ni coti ne
bi tartrate or the bi tartrate sal t or ni coti ne bi s-bi tartrate.)
A sol uti on of commerci al l y avai l abl e (S)-(-)-ni coti ne (1) (114.98
g, 0.7087 mol ) i n 95% ethanol (490 mL) was sti rred magneti -
cal l y at room temperature and treated wi th a boi l i ng-hot
nearl y saturated sol uti on of (2R,3R)-(+)-tartari c aci d (213 g,
1.42 mol ) i n water (115 mL), added over about a mi nute as
rapi dl y as exothermi ci ty woul d permi t. The aci d sol uti on was
ri nsed i n wi th ethanol (10 mL, 95%). The mi xture was seeded;
then i t was eventual l y sti rred manual l y to promote crystal -
l i zati on of the product i n an easi l y fi l tered form. The mi xture
was chi l l ed i n an i ce bath to compl ete the crystal l i zati on; then
the sol i ds were fi l tered off (gl ass Buchner funnel ) and ri nsed
wi th i ce-col d 95% ethanol , unti l the ri nsi ngs came through
col orl ess, and no more col or was present i n the fi l tercake.
I mpuri ty mi nor al kal oi ds remai n i n sol uti on and were removed
by the fi l trati on process: the dark col or of unpuri fi ed ni coti ne
served as an i nternal i ndi cator for compl eti on of the washi ng
process. The sol i ds were dri ed i n ai r to yi el d 325 g of 2c-3c
(92%), mp: 89.5-92.5 C (dec). Li t. mp: 88-89 C (Pi ctet and
Rotschy, 1904).
13
C NMR (5% w/w i n D2O, i nternal standard
sodi um 3-tri methyl si l yl propi onate, TSP) 179.46*, 149.46,
148.41, 145.32, 133.92, 129.61, 75.84*, 72.17, 59.26, 41.36,
33.24, 24.45 (asteri sk (*) i ndi cates tartrate carbons). Thi s
crystal l i ne ni coti ne bi s-bi tartrate contai ns both monoproto-
nated (2c) and di protonated (3c) ni coti ne i n the crystal uni t
cel l and i s thus referred to as 2c-3c i n thi s report.
Thi s materi al was used as descri bed bel ow to prepare pure
ni coti ne. Sampl es of 2c-3c have remai ned stabl e i n our
l aboratory for more than a decade; the sal t i s, therefore, an
effecti ve means of stori ng ni coti ne. A sampl e (10.31 g) was
di ssol ved i n water (16.6 mL, pl us 3.4 mL for ri nsi ngs) and
gravi ty fi l tered through fl uted Whatman No. 1 paper. The
aqueous sol uti on was pl aced i n a Petri di sh i n a desi ccator,
accompani ed by two Petri di shes contai ni ng ethanol (125 mL
total , 95%). Over a peri od of weeks, coarse crystal s formed.
These were harvested as needed and dri ed on fi l ter paper. The
recrystal l i zed materi al was used for the TG/DTA/MS studi es
and for an X-ray structural determi nati on.
Purified (S)-(-)-Nicotine (1). Ni coti ne bi s-bi tartrate di hy-
drate (2c-3c) (115.04 g, 0.2308 mol ) and sodi um hydroxi de
pel l ets (40.13 g, ca. 1 mol ) were treated wi th water (100 mL).
Oi l y aqueous ni coti ne separated from the hot mi xture. Hexane
(100 mL) was added, and the mi xture was chi l l ed on i ce. The
mi xture was swi rl ed peri odi cal l y, unti l the three l i qui d phases
had become two. The pal e organi c phase was i sol ated, decanted
from any traces of aqueous phase, and then concentrated on
a rotary evaporator. A second hexane extract (100 mL) was
treated l i kewi se. The combi ned product was di sti l l ed [Kugel -
rohr, bp: 101-142 C (oven)/0.9 Torr]. Yi el d: 36.05 g (96%).
Opti cal rotati on: [R]
589
20
-170.61 (l i t.: -169.4) (Tate and
Warren, 1937); [R]
578
20
-179.53, [R]
546
20
-205.51 (l i t.: -204.2)
(Tate and Warren, 1937) (neat, 10.000 cm cel l ).
13
C NMR (H2O,
external TMS, TSP i nternal standard) 148.24, 147.74,
137.33, 136.53, 124.33, 68.18, 56.15, 38.88, 33.09, 21.64; TSP
at -2.86.
13
C NMR (neat l i qui d): 152.53, 151.56, 141.82,
137.26, 126.21, 71.51, 59.65, 43.04, 38.55, 25.57. (S)-(-)-
Ni coti ne prepared i n thi s manner was found to be free of
detectabl e mi nor al kal oi ds, as evi denced by GC/MS anal ysi s
as wel l as by
13
C NMR. The col orl ess product was stored under
ni trogen, protected from l i ght.
Association of (S)-(-)-Nicotinewith AceticAcid (2a). (S)-(-)-
Ni coti ne (0.815 g, 0.0050 mol ) and gl aci al aceti c aci d (0.905 g,
0.0151 mol ) were wei ghed together and swi rl ed unti l homo-
geneous. The mol ar rati o of aceti c aci d to ni coti ne was 3.00.
The resul tant oi l y 2a was used di rectl y i n the TG/DTA/MS
experi ments. For l i terature characteri zati ons, see Perfetti
(Perfetti , 1983) and Dezel i c and Ni col i n (Dezel i c and Ni col i n,
1967).
NicotineSalts with (S)-(-)-Malic Acid. (a) 1:0.56 Nicotine/
malicacid salt, as prepared bytitration of nicotinewith malic
acid toa pH of 5.60(2b). (S)-(-)-Ni coti ne (3.255 g, 0.0201 mol )
was di ssol ved i n water (10.00 g) i n a 100 mL graduated
cyl i nder, fi tted wi th a magneti c sti rri ng bar. A pH el ectrode
was i nserted, readi ng 9.68 i ni ti al l y. A sol uti on of (S)-(-)-mal i c
aci d (9.65 g) i n water to gi ve a total of 20.80 g of sol uti on was
added dropwi se to the sti rred ni coti ne sol uti on unti l the pH
permanentl y fel l to 5.60. A total of 3.28 g of mal i c aci d sol uti on
was requi red (0.0113 mol ). The mol ar rati o of ni coti ne to mal i c
aci d i n the resul ti ng sol uti on was 1.77. The resul ti ng sol uti on
was al l owed to evaporate i n ai r to afford a yel l owi sh syrup.
Thi s noncrystal l i ne 1:0.56 ni coti ne:mal i c aci d sal t may be
heterogeneous at room temperature, but because an aqueous
sol uti on of thi s mal ate has a pH of 5.6, i t i s referred to as 2b
herei n.
(b) 1:1.0Nicotine:malicacid salt (2b-3b). (S)-(-)-Mal i c aci d
(2.83 g, 0.0211 mol ) was di ssol ved i n 100% ethanol (5 mL)
5134 J. Agric. Food Chem., Vol. 47, No. 12, 1999 Seeman et al.
(boi l i ng water bath). (S)-(-)-Ni coti ne (3.255 g, 0.0201 mol ,
puri fi ed as above) was added to the sol uti on, fol l owed by ethyl
acetate (ca. 5.5 mL), added unti l opal escence nearl y persi sted.
The sol uti on was seeded (the seeds havi ng been obtai ned by
sl ow evaporati on of a 1:1 stoi chi ometri c sol uti on of ni coti ne
and mal i c aci d i n water) and al l owed to crystal l i ze. The sol i ds
were fi l tered off and ri nsed wi th ethyl acetate/100% ethanol
(1:1, v/v, 2 20 mL) and then ethyl acetate (2 10 mL). The
sol i ds were dri ed under sucti on. Yi el d: 5.07 g (85%). Mp
112.5-121.4 C (dec). Anal . Cal cd for C14H20N2O5: C, 56.75;
H, 6.80; N, 9.45. Found: C, 56.01, 56.08; H, 6.92, 6.96; N, 9.25,
9.03.
13
C NMR (D2O, TSP i nternal standard): 182.35, 179.68,
152.38, 151.15, 141.48, 132.29, 128.29, 72.58, 71.76, 59.01,
43.34, 41.11, 33.07, 24.41.
13
C NMR (sol i d state): 180.21,
175.33, 152.16*, 135.20, 131.14, 123.96, 69.92*, 55.43, 41.19*,
33.28, 22.63 (11 peaks for 14 carbons: based on peak shape
and chemi cal l ogi c, the peaks i ndi cated wi th an asteri sk are
bel i eved to be doubl y degenerate). The NMR chemi cal shi fts
of the crystal l i ne sol i d are consi stent wi th monoprotonati on
of ni coti ne wi thi n the crystal uni t cel l ; however, the mel t of
thi s sal t i s bel i eved to contai n both mono- and di protonated
ni coti ne, and i t i s therefore referred to as 2b-3b.
1:2.0 Nicotine:malic acid salt (3b). Ni coti ne and (S)-(-)-
mal i c aci d do not appear to form a homogeneous 1:2 sal t. A
sol uti on of ni coti ne (3.26 g, 0.02 mol ) and (S)-(-)-mal i c aci d
(5.40 g, 0.04 mol ) i n water and ethanol was permi tted to
evaporate at room temperature. The resi due formed a suspen-
si on of sol i ds i n syrup when seeded wi th the 1:1 mal ate sal t.
Because of the mol ar excess of mal i c aci d i n thi s sal t and i n
the absence of any data to the contrary, i t i s assi gned to be
pri mari l y the di protonated ni coti ne sal t 3b, when i n sol uti on
or i n a homogeneous mel t. A representati ve sampl e of thi s
mi xture was exami ned by TG/DTA/MS.
RESULTS AND DI SCUSSI ON
1. Goals of This Study. Scheme 1 depi cts the fate
of the ni coti ne mol ecul e, as the NH protons are formal l y
successi vel y l ost from the di protonated sal t 3 due to
di ssoci ati on of the sal t or decomposi ti on of the counte-
ri ons. Thi s scheme summari zes the two major questi ons
addressed herei n. (1) What are the forms of ni coti ne
present i n tobacco (1, and/or 2, and/or 3)? (2) I f more
than one form of ni coti ne i s present i n tobacco, do they
thermal l y transfer to ni coti ne i n the gas phase wi th
comparabl e yi el d and effi ci ency?
As wi l l be seen bel ow, the answers to these two
questi ons can be obtai ned usi ng much of the same
experi mental data.
2. pH of Tobacco and Implications for the
Degreeof Protonationof NicotineinTobacco. The
determi nati on of the form(s) (1 versus 2 versus 3) of
ni coti ne i n tobacco i s compl i cated as tobacco i s not a
homogeneous enti ty and any i sol ati on method woul d de
facto di srupt the endogenous state of the system (Tso,
1990). Tobacco cel l wal l s and structural components can
create mi croenvi ronments whi ch coul d, i n pri nci pl e,
i nhi bi t or prevent the i nteracti on among vari ous tobacco
consti tuents. Thus, the tobacco matri x i s such that al l
tobacco components may not necessari l y be i n equi l i b-
ri um wi th each other. However, extensi ve chemi cal
changes occur duri ng the curi ng of the tobacco (Tso,
1990; Peel e et al ., 1995; Wi erni k et al ., 1995). I n
addi ti on, chemi cal and physi cal changes occur to tobacco
duri ng the ci garette manufacturi ng process, whi ch
i ncl ude repeated heati ng, moi steni ng, dryi ng, and mi x-
i ng steps. Modi fi cati ons whi ch occur both duri ng the
curi ng of tobacco and duri ng the manufacture of ci ga-
rettes l i kel y i ncrease the mobi l i ty of ni coti ne and other
compounds wi thi n the tobacco matri x and may hel p to
establ i sh an equi l i bri um between the tobacco al kal oi ds
and the natural tobacco aci ds.
Can pH measurements of tobacco extracts be useful
model s or i ndi cators of the form of ni coti ne i n tobacco?
One means of approachi ng an understandi ng of the
rel ati ve concentrati ons of aci ds and bases i n tobacco and
an understandi ng of the extent of N-protonati on of
ni coti ne as contai ned i n tobacco i s to measure the pH
of aqueous extracts of tobacco. Whi l e the l i terature i s
repl ete wi th references to the pH of tobacco (Browne,
1990; Wi l l i amson and Chapl i n, 1981; Pankow et al .,
1997; Li ang and Pankow, 1996; Akehurst, 1981; Wynder
and Hoffmann, 1967), the concept of tobacco pH does
not have preci se meani ng. The pH of tobacco i s
typi cal l y determi ned by extracti ng a tobacco sampl e
wi th water, perhaps fi l teri ng the resul tant mi xture and
measuri ng the pH of the resul tant di l ute aqueous
sol uti on. Thus, pH of tobacco i s not an i ntri nsi c
property of matter but rather an arbi trary experi mental
construct that vari es wi th the experi mental condi ti ons
chosen.
Whi l e tobacco can have a hi gh equi l i bri um moi sture
content (10% or more) (Akehurst, 1981), tobacco i s, by
no means, a di l ute aqueous sol uti on. Any use of the pH
of tobacco must be done wi th the understandi ng that
i t i s onl y a rough approxi mati on of the hydrogen i on
acti vi ty wi thi n tobacco. An observed pH val ue of a
tobacco extract i s si gni fi cantl y i nfl uenced by a number
of factors, i ncl udi ng the vol ume of water empl oyed to
extract the quanti ty of tobacco taken as wel l as the
rel ati ve water extractabi l i ty and sol ubi l i ty of the vari ous
aci ds and bases i n the tobacco. Nonethel ess, the pH of
tobacco may be a useful , though certai nl y l i mi ted,
conceptual devi ce. I t i s cruci al that any use of the pH
of tobacco takes i nto consi derati on i ts mode of experi -
mental determi nati on and al l assumpti ons underl yi ng
both i ts experi mental determi nati on and any appl i ca-
ti on.
Tabl e 1 l i sts representati ve determi nati ons of the pH
of vari ous tobaccos (Browne, 1990; Akehurst, 1981).
Tabl e 2 summari zes the rel ati ve proporti ons of ni coti ne
(1) and i ts protonated forms (2, 3) i n di l ute aqueous
sol uti on at sel ected val ues of pH. Gi ven the observati on
that aqueous extracts of ci garette tobaccos are aci di c
(Tabl e 1) (Akehurst, 1981; Browne, 1990; Wynder and
Hoffmann, 1967), i t can be deduced rel i abl y that the
underl yi ng tobaccos are aci di c as wel l and that the
ni coti ne contai ned therei n wi l l at l east be formal l y
monoprotonated i f not di protonated.
One aspect of thi s work i s the eval uati on of the effect
of the degree of protonati on of ni coti ne (e.g., from
Scheme 1 Table 1. Representative Literature Values of the pH of
Tobacco
tobacco l eaf type pH
a,b
aromati c (Ori ental ) 4.9
fl ue cured (Bri ght) 5.5
Burl ey 5.8
a
The procedure to obtai n the pH of tobacco i s typi cal l y as
fol l ows: an aqueous extract of the tobacco i s obtai ned and fi l tered;
the pH of tobacco i s the pH of the resul tant aqueous sol uti on.
b
See: Wynder and Hoffmann, 1967; Akehurst, 1981; Browne,
1990.
Thermal Transfer of Nicotine to the Gas Phase J. Agric. Food Chem., Vol. 47, No. 12, 1999 5135
substrates 1-3or from the tobacco matri x) on the ease
of thermal transfer to ni coti ne i n the gas phase. The
pH of an aqueous tobacco extract does not i ncorporate
the changes to the tobacco caused by heat: evaporati on
of vol ati l e substances, i ncl udi ng water; i ncreased fl ui d-
i ty of materi al s wi thi n the tobacco; pyrol yti c changes.
A di scussi on of aci di ty functi ons (Ni gretto and Jozefow-
i cz, 1973; Cox and Yates, 1983; Rochester, 1970) and
the meani ng of aci di ty under nonaqueous condi ti ons i s
outsi de the scope of thi s study. Consequentl y, the
form(s) of ni coti ne just pri or to the transfer to the smoke
(or gas phase) i s as compl ex a questi on as the charac-
teri zati on of the heated materi al i tsel f.
Addi ti onal evi dence of ni coti nes protonated state i n
tobacco i s the observati on that ni coti ne nei ther sub-
stanti al l y evaporates nor si gni fi cantl y autoxi di zes whi l e
i n storage i n cured tobacco. By contrast, nonprotonated
ni coti ne exposed to ai r i s vul nerabl e to both evaporati on
and/or autoxi dati on.
3. TG/DTA/MS Analysis. (a) Choice of Substrates.
To expl ore Scheme 1 chemi stry, several sal ts or associ a-
ti ons of ni coti ne wi th carboxyl i c aci ds were prepared and
subjected to thermal anal ysi s i n tandem wi th mass-
spectral moni tori ng. I n thi s work, the pri mary tacti c was
to exami ne the thermal properti es of monoprotonated
and di protonated ni coti ne carboxyl i c aci d sal ts i n whi ch
the aci d was ei ther i denti cal to or el se very si mi l ar to
the carboxyl i c aci ds found i n tobacco. The sal ts sel ected
were desi gned to shed l i ght as to the temperature
ranges such sal ts rel ease ni coti ne (1) to the gas phase,
gi ven consi derati ons of vari abl e aci d strength, vol ati l i ty,
and stabi l i ty.
Whi l e the preparati on of vari ous ni coti ne aci d sal ts
has been known for many years, many of these are sal ts
of i norgani c aci ds (Johnstone and Pl i mmer, 1959; Sted-
man, 1968). Sal ts of ni coti ne wi th trul y strong i norgani c
aci ds (hydrochl ori c, ni tri c, sul furi c, phosphori c, and
deri vati zed phosphori c) are not found i n tobacco because
these aci ds are more than adequatel y neutral i zed i n
tobacco by an excess content of strong i norgani c bases.
The combi ned i on charge of potassi um, cal ci um, and
magnesi um i ons i n tobacco si gni fi cantl y exceeds the i on
charge of the combi ned strong i norgani c aci ds present
(Wynder and Hoffmann, 1967; Bokel man and Ryan,
1985). Consequentl y, the thermal chemi stry of sal ts
such as ni coti ni um sul fate, ni coti ni um chl ori de, or
ni coti ni um ni trate was not exami ned i n thi s study.
I n tobacco, the natural aci ds associ ated wi th ni coti ne
are of the carboxyl i c aci d type (Akehurst, 1981; Wynder
and Hoffmann, 1967). Ni coti ne sal ts of organi c aci ds are
frequentl y not crystal l i ne and can have a vari ety of
stoi chi ometri es (Perfetti , 1983). As a representati ve of
a vol ati l e, thermal l y stabl e, rel ati vel y weak organi c
carboxyl i c aci d, the ni coti ne sal t wi th aceti c aci d was
exami ned. The l i terature suggests that thi s sal t contai ns
ni coti ne and aceti c aci d i n a 1:3 mol ar rati o (Perfetti ,
1983). Mi xi ng ni coti ne and aceti c aci d i n thi s rati o
resul ts i n mi l d exothermi ci ty and the formati on of a
vi scous oi l . Aceti c aci d serves as the prototype for the
behavi or of the cl ass of al kanoi c aci ds hi gher than formi c
aci d such as those that occur i n tobacco and tobacco
smoke (Stedman, 1968).
By abundance and aci d strength, the pol ycarboxyl i c
aci ds such as mal i c and ci tri c aci ds are the domi nant
aci ds i n tobacco. Pol ycarboxyl i c aci ds as a cl ass are
general l y stronger than the monocarboxyl i c aci ds. I m-
portantl y, pol ycarboxyl i c aci ds have greatl y reduced
vol ati l i ty rel ati ve to monocarboxyl i c aci ds. Whereas
ni coti ne ci trates and mal ates are hi ghl y water sol ubl e,
ni coti ne sal ts of some of the other aci ds found i n tobacco
can have very l ow water sol ubi l i ty (Perfetti , 1983;
Crooks and Lynn, 1992).
(S)-Ni coti ne bi s[(2R,3R)-hydrogen tartrate] di hydrate
(2c-3c) was sel ected to provi de an exampl e of a bi s-
protonated ni coti ne cati on. Tartari c aci d was chosen as
an exampl e of a pol yfuncti onal carboxyl i c aci d because
thi s sal t wi th ni coti ne i s crystal l i ne and wel l character-
i zed. Note, however, that tartari c aci d i s not a si gni fi -
cant component of tobacco. Thus, i n addi ti on, three
di fferent sal ts wi th an i mportant tobacco component,
(S)-(-)-mal i c aci d, 2b, 2b-3b, and 3b, were prepared
for exami nati on. The mal ate sal ts had di fferent ni coti ne:
mal i c aci d rati os, i n an attempt to exami ne both
monoprotonated and di protonated substances. Onl y one
of these three mal ate sal ts was crystal l i ne, thi s havi ng
a 1:1 stoi chi ometry between ni coti ne and mal i c aci d.
(b) Observed Behavior of theSaltsand BurleyTobacco
under TG/ DTA/ MS Conditions. I n the TG/DTA experi -
ments, the wei ght l oss as wel l as the temperature
di fferenti al between the sampl e and a reference (al u-
mi na) are recorded as a functi on of temperature duri ng
the di ssoci ati on/vol ati l i zati on/decomposi ti on of the start-
i ng sampl e. I nterfaci ng the MS to the TG/DTA uni t
provi des a means of i denti fyi ng (qual i tati vel y) these gas-
phase di ssoci ati on/vol ati l i zati on/decomposi ti on products.
Especi al l y i mportant are the maxi ma of the MS data
curves whi ch typi cal l y correspond to the wei ght l oss rate
maxi ma (di fferenti al thermogravi metry, DTG). Due to
chromatographi c effects of the si l i ca transfer l i ne and
resi dues i n the TG/DTA furnace tube, some peak-tai l i ng
i s observed i n the MS data curves. Tabl e 3 shows
sel ected masses wi th reported abundances (range of
1-999) for ni coti ne and possi bl e pyrol ysi s products of
the ni coti ne carboxyl i c aci d sal ts. The most abundant
mass-spectral i on fragment of ni coti ne appears at a
mass-to-charge rati o, m/z, of 84 (Duffi el d et al ., 1965;
Gl enn and Edwards, 1978). Myosmi ne i s a major
decomposi ti on product of ni coti ne at temperatures
greater than 300 C i n ai r (Kobashi et al ., 1963) and
above 600 C i n an i nert atmosphere (Woodward et al .,
1944; Jarboe and Rosene, 1961). I t shoul d be noted that
under the condi ti ons used, recordabl e l evel s of myo-
smi ne (4) were not observed (m/z 146).
Table 2. Relative Amounts of Nonprotonated and
Protonated Nicotine as a Function of pH in a Dilute
Aqueous Solution
a
pH
% nonprotonated
ni coti ne (1)
% monoprotonated
ni coti ne (2)
5.8 0 100
b
6.0 1 99
6.4 2 98
6.6 4 96
6.8 6 94
7.0 9 91
7.2 13 87
a
Based on pKas for ni coti ne of 8.0 and 3.1.
b
At pH 5.3, 0.6% of
the total ni coti ne al kal oi d i s i n the di protonated form 3; as pH
drops bel ow 5.3, the percentage of 3ri ses rapi dl y. At pH 3.1, 50%
of the al kal oi d i s 3 and 50% i s 2.
Si nce ani oni c decomposi ti on has a major beari ng on
the ni coti ne thermal evol uti on profi l e from ni coti ne
carboxyl i c aci d sal ts, the mass spectral moni tori ng was
adjusted to cater to the speci fi c decomposi ti on chemi stry
of the vari ous counteri ons. Thus, the system wi th aceti c
aci d moni tored the i on fragments at m/z 43 and 60,
pri nci pal i ons of aceti c aci ds mass spectrum. For
tartari c aci d, i on fragments speci fi c to acetal dehyde at
m/z 29 and 44 (al so the domi nant i on for carbon di oxi de)
were fol l owed, si nce tartari c aci d appears to decarboxy-
l ati vel y dehydrate to form formyl aceti c aci d, whi ch i s
further decarboxyl ated to gi ve acetal dehyde. Mal ate
systems fol l owed the i on fragments to be expected for
mal ei c anhydri de (m/z 54) and acryl i c aci d (m/z 72), both
anti ci pated decomposi ti on products of the mal ate ani on.
I n al l runs, i on fragments speci fi c to water at m/z 17
and carbon di oxi de at m/z 44 were al so moni tored.
I n the temperature range i n whi ch nonprotonated
ni coti ne evaporates, two general cl asses of compl ex
chemical reactions can be expected to occur with nicotine/
carboxyl i c aci d sal ts. The fi rst i nvol ves di ssoci ati on and/
or dehydrati on and decomposi ti on of the carboxyl i c
counteri on (Scheme 1). The second cl ass of chemi cal
reacti on i nvol ves proton transfer between the vari ous
ni coti ne speci es. I n the case of monoprotonated sal ts, a
di sproporti onati on reacti on can convert them to a
mi xture of the di protonated sal t and free ni coti ne (eq
1).
The di sproporti onati on equi l i bri um i s di spl aced by the
evaporati on of nonprotonated ni coti ne (1). To the extent
that the ni coti ne di cati on (3) i s not vol ati l e, the tem-
perature range of the ul ti mate rel ease of ni coti ne from
3i s di ctated by the stabi l i ty of the counteri on. Equati on
1 wi l l be equal l y val i d whether proton transfer occurs
di rectl y between the parti ci pants as shown or whether
such proton transfer occurs vi a other speci es contai ned
wi thi n the medi um or tobacco matri x. One of the
mechani sti c pathways embedded i n eq 1 i s the associ a-
ti on-di ssoci ati on reacti on between ni coti ne and aci d
exempl i fi ed i n Scheme 1. Di ssoci ati on becomes more
i mportant for sal ts or associ ati ons of ni coti ne wi th
weaker aci ds.
Fi gures 1A and 1B show overl ays of TG and MS
curves for ni coti ne (1) run under hel i um and 21%
oxygen, respecti vel y. TG/MS resul ts i ndi cate that under
the condi ti ons used, the peak transfer of ni coti ne to the
gas phase occurs between about 110 and 120 C, wel l
bel ow ni coti nes boi l i ng poi nt of 247 C.
The TG and MS curves for ni coti ne acetate (2a) run
under hel i um are shown i n Fi gure 2. I ni ti al wei ght l oss
appears to be due to the di ssoci ati on of the ami ne sal t
and subsequent vol ati l i zati on of aceti c aci d (m/z 43 and
60) at a peak temperature of about 80 C. A peak
temperature of about 115 C i s observed for the vol a-
ti l i zati on of ni coti ne; i nteresti ngl y, thi s temperature i s
essenti al l y that observed for the si mpl e evaporati on of
free ni coti ne (1) (Fi gure 1A). Therefore, the acetate sal t
of ni coti ne does not appear to be stabl e at temperatures
above ca. 90 C, even starti ng wi th as many as 3 mol
equi v of aceti c aci d rel ati ve to ni coti ne. Si mi l ar resul ts
were obtai ned for ni coti ne acetate (2a) run i n 21%
oxygen.
(S)-Ni coti ne bi s[(2R,3R)-hydrogen tartrate] di hydrate
(2c-3c) i s a crystal l i ne sal t, the X-ray structure of
whi ch i ndi cates that i n the sol i d state not al l of the
ni trogen atoms of ni coti ne are protonated, despi te the
stoi chi ometry. The uni t cel l was found to contai n four
ni coti ne mol ecul es, equi val ent i n pai rs, varyi ng i n
conformati on and degree of protonati on on ni trogen.
Two of the ni coti ne mol ecul es were monoprotonated (on
the pyrrol i di ne ri ng, e.g., 2c); the other two were
di protonated (3c). I n a mel t, nearl y al l of the ni coti ne
i s l i kel y to be di protonated 3c. Thus, the X-ray structure
has l i ttl e rel evance to the ensui ng pyrol ysi s chemi stry.
Fi gures 3A and 3B show TG and MS curves for thi s sal t
run under hel i um and 21% oxygen, respecti vel y. MS
resul ts i ndi cate that the i ni ti al wei ght l oss at about 80
C corresponds to i ni ti al dehydrati on (m/z 17, about 5%
of the total wei ght l oss) fol l owed by decomposi ti on/
di ssoci ati on of the ni coti ne bi tartrate sal t i nto water
(m/z 17), carbon di oxi de (m/z 44), acetal dehyde (m/z 29),
and ni coti ne (m/z 84). I mportantl y, ni coti ne evol uti on
peaks at about 200 C. Thermal l oss of water from the
hydrated sal ts (and from the tobacco matri x, see experi -
ments bel ow) occurs pri or to transfer of ni coti ne to the
gas phase. I t appears that greater than 95%of the total
materi al i s transferred to the gas/aerosol phase by ca.
Table 3. Mass Spectral Features of Nicotine and Possible Pyrolysis Products in the Thermal Treatment of 1, 2a, 2b,
2b-3b, 3b, 2c-3c, and Burley Tobacco
masses
a
17 26 29 43 44 45 54 60 72 76 84 133 146
compound abundances
ni coti ne 8 28 34 21 999 308
acetal dehyde 57 999 328 814 17
aceti c aci d 28 12 132 999 47 874 570
mal ei c aci d 810 180 60 100 780 300 999
mal ei c anhydri de 999 23 1 83 6 471
mal i c aci d 390 23 54 8 999 3
tartari c aci d 3 160 115 62 155 80 2 999
acryl i c aci d 543 99 118 125 350 17 26 759
carbon di oxi de 999 11
water 212
myosmi ne 858
a
From NI ST/EPA/MSDC Mass Spectral Database Versi on 2.0, November, 1988.
230 C, i .e., a carbonaceous resi due of l ess than 5% of
the ori gi nal wei ght remai ned to be decomposed at hi gher
temperatures i n oxygen.
Fi gure 4 shows the TG/DTA for (S)-ni coti ne bi s-
[(2R,3R)-hydrogen tartrate] di hydrate (2c-3c) run un-
der 21% oxygen. The overal l DTA curve for the decom-
posi ti on of the ni coti ne bi tartrate sal t i s general l y
endothermi c, due to the vol ati l i zati on of water and
ni coti ne; however, the di sconti nui ty i n the curve i s
i ndi cati ve of the exothermi c nature expected for the
tartrate moi ety decomposi ti on. The si mi l ar nature of the
data curves run i n hel i um and i n 21% oxygen are
suggesti ve of the thermal stabi l i ty of the ni coti ne
bi tartrate sal t wi th respect to oxi dati on.
Fi gures 5-7 show the TG and MS curves for the three
di fferent ni coti ne mal ate sal ts heated i n hel i um, these
havi ng mal i c aci d:ni coti ne mol ar rati os of 0.56, 1, and
2, respecti vel y. The decomposi ti on/di ssoci ati on of the
ni coti ne mal ate sal ts proceeds vi a a more el aborate
route than the ni coti ne acetate and bi tartrate sal ts.
Fi gure 5 shows the TG/MS curves for the 1:0.56 ni coti ne:
mal i c aci d sal t mi xture. The MS data i ndi cate that the
i ni ti al 40% wei ght l oss, i n the temperature range of
about 50-150 C, i s due to the evaporati on of water (m/z
17) fol l owed by the vol ati l i zati on of ni coti ne (m/z 84,
peaki ng at about 110 C). At temperatures i n excess of
150 C, the sal t begi ns to decompose/di ssoci ate i nto
water, carbon di oxi de, mal ei c anhydri de (m/z 54), acryl i c
aci d (m/z 72), and ni coti ne. Two addi ti onal peaks for
ni coti ne evol uti on are observed at about 165 and 200
C. The presence of mal ei c anhydri de and acryl i c aci d
were confi rmed by separate pyrol ysi s GC/MS work.
The 1:1 ni coti ne:mal i c aci d crystal l i ne sal t (2b-3b)
heated under hel i um i s shown i n Fi gure 6. The i ni ti al
wei ght l oss at about 120 C i s attri buted to the vol ati l -
i zati on of ni coti ne (m/z 84). At temperatures i n excess
of 150 C, the data agai n i ndi cate the decomposi ti on/
di ssoci ati on of the sal t to water, carbon di oxi de, mal ei c
anhydri de (m/z 54), acryl i c aci d (m/z 72), and ni coti ne.
The two addi ti onal peaks for ni coti ne evol uti on at about
165 and 200 C observed duri ng the decomposi ti on/
di ssoci ati on of the 1:0.56 ni coti ne:mal i c aci d sal t mi xture
are agai n observed for the 1:1 crystal l i ne sal t.
The TG/MS data for the 1:2 ni coti ne:mal i c aci d sal t,
shown i n Fi gure 7, i s observed to be si mi l ar to those of
the 1:1 crystal l i ne ni coti ne mal ate sal t, wi th the excep-
ti on that the l ow-temperature (120 C) ni coti ne peak
i s now absent. The TG shows major wei ght l oss i n the
150-220 C temperature range due to the decomposi -
ti on/di ssoci ati on of the sal t. Onl y two ni coti ne (m/z 84)
evol uti on peaks are observed at about 165 and 205 C.
Carbonaceous resi dues wi th wei ghts of between 4%
and 9% of the ori gi nal wei ght were observed at tem-
peratures of 330 C for each of the ni coti ne mal ate sal ts.
These resi dues, pri mari l y pol ymeri zati on products of the
di carboxyl i c aci ds, combusted (m/z 44) i n oxygen at
temperatures around 500 C (data not shown).
The l ow-temperature (115 ( 5 C) transfer of ni coti ne
from both the 1:0.56 and 1:1 ni coti ne:mal i c aci d sal t
mi xtures i s essenti al l y the temperature range observed
for the vol ati l i zati on of nonprotonated ni coti ne i n hel i um
as wel l as i n 21% oxygen. The source of nonprotonated
ni coti ne from the ni coti ne mal ate sal ts i n thi s l ow-
temperature regi on may wel l be vol ati l i zati on ari si ng
from the di sproporti onati on of monoprotonated sal t (eq
1). Enough mal i c aci d was present to monoprotonate
ni coti ne but not enough to total l y di protonate i t. A
di sproporti onati on reacti on yi el ds, for two mol ecul es of
monoprotonated sal t, one mol ecul e each of the di proto-
nated sal t and free ni coti ne. A di sproporti onati on reac-
ti on al so expl ai ns the presence of a peak appearance
temperature of ni coti ne i n the 200 C regi on for the
1:0.56 sal t, a compound whi ch pri or to thermal treat-
ment i s l i kel y not to have any di protonated sal ts
present.
Fi gure 8 shows an overl ay of the ni coti ne (m/z 84)
evol uti on curves for the three ni coti ne mal ate sal ts. For
the sal ts whi ch contai n si gni fi cant concentrati ons of
monoprotonated sal t 2b, these data are consi stent wi th
the proposed di sproporti onati on of monoprotonated
ni coti ne (2) to di protonated ni coti ne (3) and nonproto-
nated ni coti ne (1) (whi ch vol ati l i zes i n the same l ow-
temperature regi on as that observed for nonprotonated
ni coti ne), fol l owed by further rel ease of ni coti ne vi a
decomposi ti on/di ssoci ati on of the resul tant di protonated
sal t(s). The two peaks, at about 165 and 200 C,
observed i n the ni coti ne evol uti on curves of Fi gures 5-8
can be attri buted to the decomposi ti on/di ssoci ati on of
Figure 1. (A) TG/MS of ni coti ne i n hel i um as a functi on of temperature. (B) TG/MS of ni coti ne i n 21% oxygen as a functi on of
temperature.
Figure 2. TG/MS of a ni coti ne acetate sal t i n hel i um as a
functi on of temperature.
di protonated ni coti ne mal ate resul ti ng i n the formati on
and further decomposi ti on of ni coti ne mal eate and/or
ni coti ne fumarate. I t i s of i nterest to note that the
ni coti ne mal ate sal t prepared wi th excess mal i c aci d (1:
2) does not show a ni coti ne peak i n the l ow-temperature
range of about 115 C, suggesti ng the ni coti ne i n thi s
sampl e i s total l y di protonated (consi stent wi th the TG/
MS data of the di protonated ni coti ne bi tartrate).
The di sproporti onati on reacti on of eq 1 ensures that
any vol ati l e carboxyl i c aci d too weak to di protonate
ni coti ne effecti vel y cannot prevent the vol ati l i ty of al l
of the ni coti ne at temperatures comparabl e to those
requi red to evaporate ni coti ne. Any di cati on that does
form as a resul t of di sproporti onati on may di ssoci ate
back to the monocati on, al l owi ng the ci rcl e l eadi ng to
compl ete di ssoci ati on to conti nue. Competi ng wi th any
di sproporti onati on of a monoprotonated ni coti ne sal t (2)
wi th a weak aci d i s the di rect di ssoci ati on reacti on i nto
free ni coti ne (1) and free carboxyl i c aci d HZ, portrayed
i n Scheme 1. Such di ssoci ati on can be dri ven to compl e-
ti on by removal of the aci d from the system by si mpl e
evaporati on shoul d the aci d be si gni fi cantl y more vol a-
ti l e than ni coti ne. Aceti c aci d was found to be such an
aci d, si gni fi cantl y precedi ng ni coti ne i nto the gas phase.
Figure 3. (A) TG/MS of ni coti ne bi tartrate i n hel i um as a functi on of temperature. (B) TG/MS of ni coti ne bi tartrate i n 21%
oxygen as a functi on of temperature.
Figure4. TG/DTA of ni coti ne bi tartrate i n 21% oxygen as a
Figure5. TG/MS of a ni coti ne mal ate sal t (1:0.56) i n hel i um
as a functi on of temperature.
Figure6. TG/MS of a ni coti ne mal ate sal t (1:1) i n hel i um as
a functi on of temperature.
Figure7. TG/MS of a ni coti ne mal ate sal t (1:2) i n hel i um as
a functi on of temperature.
Figure 8. Ni coti ne evol uti on, m/z 84, of the three ni coti ne
mal ate sal ts i n hel i um as a functi on of temperature.
On the basi s of the resul ts reported herei n, the
hi ghest temperature of free ni coti ne rel ease, whi ch wi l l
be from i ts di protonated form (3), wi l l depend on the
conjugate aci di c strength, the vol ati l i ty, and the thermal
stabi l i ty of the aci d counteri on. I f the i ntri nsi c temper-
ature of decomposi ti on of a gi ven organi c counteri on i s
bel ow the i ntri nsi c di ssoci ati on temperature of di pro-
tonated ni coti ne (3), i t wi l l be the counteri on decomposi -
ti on temperature that di ctates the vol ati l i zati on upper
temperature ranges of free ni coti ne. The amount of heat
needed to vol ati l i ze these pol ycarboxyl i c aci ds i ntact i s
greatl y i n excess of that needed to effect thei r decom-
posi ti on by dehydrati on and/or decarboxyl ati on and/or
cycl i c anhydri de formati on, whi ch l eads to the formati on
of weaker monocarboxyl i c aci ds (e.g., acryl i c aci d) or
nonaci ds (e.g., acetal dehyde and mal ei c anhydri de).
The peak appearance temperatures for ni coti ne from
1, 2a, 2b, 2b-3b, 3b, and 2c-3c determi ned i n thi s
study are summari zed i n Tabl e 4. These resul ts are
consi stent wi th reports by Lawson, Bul l i ngs, and Per-
fetti i n the patent l i terature (Lawson et al ., 1989a;
Lawson et al ., 1989b) whi ch report, wi thout ei ther
speci fi c data or experi mental detai l s, that organi c aci d
sal ts of ni coti ne decompose bel ow 200 C. Essenti al l y
three temperature ranges for the appearance of ni coti ne
were observed for the vari ous sal ts studi ed: 115 ( 5,
165 ( 5, and 200 ( 5 C. I t woul d have been attracti ve
to suppose that these three ranges corresponded to the
rel ease of ni coti ne from nonprotonated ni coti ne, mono-
protonated ni coti ne, and di protonated ni coti ne, respec-
ti vel y. However, more l i kel y, based on the observed
temperature profi l e of mass spectral i on evol uti on of the
substrates exami ned, i t i s that they encompass two true
ranges. The l ower range (115 ( 5 C) woul d correspond
to evaporati on/vol ati l i zati on of nonprotonated ni coti ne
(1) avai l abl e from the system ei ther by di ssoci ati on from
a weak aci d (as i s the case wi th aceti c aci d) or from
di sproporti onati on of the monocati on (2). The hi gher
range (160-210 C) woul d refl ect ni coti ne rel ease from
mostl y di cati oni c forms 3 as a resul t of vari abl e tem-
peratures of ani on decomposi ti on, whi ch i s dependent
on the thermal stabi l i ty of the counteri on or of counte-
ri ons deri ved from those ori gi nal l y present.
Fi gure 9 shows the TG/MS curves for Burl ey tobacco
l eaf run under hel i um. To obtai n a recordabl e MS
i ntensi ty for ni coti ne (m/z 84 and 133), a deeper TG
sampl e pan was fi l l ed wi th the Burl ey tobacco sampl e
and the vol tage to the secondary el ectron mul ti pl i er of
the MS was i ncreased. Thi s accounts for the observed
hi gher basel i ne and greater tai l i ng effects i n the MS
curves. The peak appearance temperature of ni coti ne
occurs between about 180 and 210 C. These tempera-
tures fal l wel l wi thi n the range observed for the ni coti ne
di carboxyl ate sal ts studi ed here. The l ack of a si gni fi -
cant ni coti ne appearance at ca. 115 C i ndi cates that
there i s no nonprotonated ni coti ne avai l abl e i n the
tobacco matri x at that temperature. Had there been
monoprotonated ni coti ne present at that stage and gi ven
that a di sproporti onati on reacti on (eq 1) woul d form
nonprotonated ni coti ne, peaks at ca. 115 C woul d have
been observed. We therefore i nfer that ni coti ne, at these
el evated temperatures i n the tobacco, i s di protonated.
A more detai l ed di scussi on of thi s poi nt i s presented i n
secti on 5.
4. EvolvedGasAnalysis. Transfer of ni coti ne to the
gas phase from vari ous tobacco types was eval uated
usi ng evol ved gas anal ysi s/mass spectrometry (EGA/
MS). The EGA/MS system had a much l arger sampl e
capaci ty compared to that of the TG/MS system, there-
fore, maki ng i t more sui tabl e for studyi ng tobacco
sampl es whi ch cannot be anal yzed conveni entl y usi ng
TG/MS techni ques. Fi gure 10 (curves a-d) depi ct the
transfer of ni coti ne to the gas phase from normal Burl ey
tobacco, a l ow-al kal oi d Burl ey, l ow-al kal oi d Burl ey wi th
added ni coti ne ci trate (1:2), and l ow-al kal oi d Burl ey
wi th added nonprotonated ni coti ne, respecti vel y. Nor-
mal Burl ey tobacco, when heated, resul ted i n a broad
tri pl et peak wi th maxi ma at about 180 and 210 C and
a shoul der at 240 C (Fi gure 10, curve a). A l ow-al kal oi d
Burl ey, when heated, shows (Fi gure 10, curve b) a weak
doubl et wi th maxi ma at about 190 and 220 C. Thi s
experi ment serves as a control for the two ni coti ne
addi ti on experi ments, shown i n Fi gure 10 (curves c and
d). When ni coti ne ci trate was added to the l ow-al kal oi d
Table 4. Peak Appearance Temperatures of Nicotine from1, 2a, 2b, 2b-3b, 3b, 2c-3c, and Burley Tobacco
substrate atmosphere
a
peak appearance
temp (C) of ni coti ne
b
fi gure
ni coti ne (1) hel i um 110 ( 5 1A
ni coti ne (1) 21% oxygen/He 115 ( 5 1B
ni coti ne acetate (2a) hel i um 115 ( 5 2
ni coti ne acetate (2a) 21% oxygen/He 120 ( 5
ni coti ne bi s[(2R,3R)-hydrogen tartrate] di hydrate (2c-3c) hel i um 200 ( 5 3A
ni coti ne bi s[(2R,3R)-hydrogen tartrate] di hydrate (2c-3c) 21% oxygen/He 200 ( 5 3B, 4
ni coti ne (S)-mal ate (2b) 1/0.56 ni coti ne/mal i c aci d hel i um 110 ( 5, 165 ( 5, 200 ( 5 5, 8
ni coti ne (S)-mal ate (2b) 1/0.56 ni coti ne/mal i c aci d 21% oxygen/He 120 ( 5, 165 ( 5, 190 ( 5
ni coti ne (S)-mal ate (2b-3b) 1/1.0 ni coti ne/mal i c aci d hel i um 120 ( 5, 165 ( 5, 200 ( 5 6, 8
ni coti ne (S)-mal ate (2b-3b) 1/1.0 ni coti ne/mal i c aci d 21% oxygen/He 120 ( 5, 170 ( 5, 200 ( 5
ni coti ne (S)-mal ate (3b) 1/2.0 ni coti ne/mal i c aci d hel i um 165 ( 5, 205 ( 5 7, 8
ni coti ne (S)-mal ate (3b) 1/2.0 ni coti ne/mal i c aci d 21% oxygen/He 170 ( 5, 205 ( 5
Burl ey tobacco
c
hel i um 195 ( 15 9
a
Fl ow 100 mL mi n
-1
.
b
Sampl es heated at 5 C mi n
-1
.
c
Large sampl e si ze used.
Figure 9. TG/MS of Burl ey tobacco l eaf i n hel i um as a
Burl ey sampl e and heated, a tri pl et (150, 180, and 215
C) was seen (Fi gure 10, curve c) si mi l ar to that
observed i n normal Burl ey (Fi gure 10, curve a), consi s-
tent wi th ni coti ne transfer temperatures observed for
protonated ni coti nes. When nonprotonated ni coti ne was
added to the l ow-al kal oi d Burl ey, a tri pl et was ob-
served (Fi gure 10, curve d) wi th maxi ma at about 145,
175, and 200 C. The weak shoul der observed at about
105 C i n Fi gure 10 (curve d) can be attri buted to the
presence of resi dual nonprotonated ni coti ne and/or the
di sproporti onati on of monoprotonated ni coti ne. These
resul ts suggest that suffi ci ent aci di ty i s present i n the
l ow-al kal oi d Burl ey to convert exogenous ni coti ne (1)
to i ts monoprotonated (2) and/or di protonated (3) form(s).
Si mi l ar studi es were performed wi th both Bri ght and
Ori ental tobaccos (the data are summari zed i n Tabl e
5).
The EGA data are consi stent wi th the TG/MS resul ts
whi ch show the peak ni coti ne evol uti on temperatures
from Burl ey tobacco l eaf i n the range of 180-210 C.
The EGA resul ts are al so consi stent wi th work reported
i n 1960 by Kobashi and co-workers (Kobashi et al ., 1960;
Kobashi and Sakaguchi , 1960) who found that addi ti on
of nonprotonated ni coti ne or, separatel y, ni coti ne tar-
trate to a l ow-al kal oi d fi l l er l ed to ci garette model s
whi ch had the same ni coti ne transfer effi ci ency to
mai nstream smoke. (Mai nstream smoke i s the smoke
whi ch travel s down the ci garette rod and through the
ci garette fi l ter.) Note that evi dence has been presented
(Jenki ns and Comes, 1976) that the transfer of ni coti ne
to mai nstream smoke i s the same from endogenous
ni coti ne and exogenousl y added ni coti ne.
5. Stability of Nicotine under Pyrolytic Condi-
tions. Transfer of Nicotine to the Gas Phase. I t i s
cruci al to demonstrate that ni coti ne i tsel f i s stabl e under
the thermal condi ti ons requi red to vol ati l i ze i t from
nonprotonated ni coti ne i tsel f or the thermal condi ti ons
requi red to form i t and vol ati l i ze i t from the vari ous
protonated ni coti nes 2and 3. Recentl y, i t was found that
heati ng sampl es of ni coti ne, (S)-ni coti ne bi s[(2R,3R)-
hydrogen tartrate] di hydrate, and the 1:0.56 and 1:1
ni coti ne mal ates i ndi vi dual l y from ambi ent tempera-
ture, at approxi matel y 400 C mi n
-1
, under a 500 mL
mi n
-1
fl ow of ei ther ai r or argon l ed to 92-100%
transfer effi ci ency (or yi el d) (Fourni er et al ., 1998). A
number of studi es have shown that ni coti ne i n the
absence of oxygen wi l l not begi n to decompose thermal l y
unti l temperatures i n excess of 600 C are reached (von
Eul er, 1965; Bal asubrahmanyam and Qui n, 1962; Jar-
boe and Rosene, 1961). Ni coti ne i s stabl e i n ai r unti l
temperatures exceed 300-350 C wi th a 2-s contact ti me
on a gl ass wool surface (von Eul er, 1965; Kobashi et al .,
1963). As ni coti ne vol ati l i zes wel l bel ow i ts boi l i ng poi nt
of 247 C (see Tabl es 4 and 5), pyrol ysi s studi es at
hi gher temperatures must be performed by i njecti ng
ni coti ne i nto a preheated tube i n one of a number of
fashi ons (Bal asubrahmanyam and Qui n, 1962; Jarboe
and Rosene, 1961; Schmel tz et al ., 1979; von Eul er,
1965). Addi ti onal l y, i n the TG/MS studi es reported
herei n, no mass spectral fragmentati ons were observed
for the i ons whi ch are markers for myosmi ne (m/z 146)
(Duffi el d et al ., 1965), the major thermal decomposi ti on
product of ni coti ne (von Eul er, 1965; Bal asubrahman-
yam and Qui n, 1962; Jarboe and Rosene, 1961).
The term transfer of ni coti ne to the gas phase does
not mean that al l of the ni coti ne remai ns i n the gas
phase duri ng, or after, a pyrol ysi s experi ment (or i n the
burni ng/puffi ng of a ci garette). Rather, i t i s an esti mate
that the i ni ti al thermal process puts the ni coti ne i nto
the gas phase near the heat source (or the coal ).
Subsequentl y, the travel of smoke al ong the pyrol ysi s
tube and cool i ng (or down the ci garette rod) causes
condensati on (someti mes referred to as rai ni ng out or
preci pi tati on) of most of the ni coti ne out of the gas phase
and i nto an aerosol (Jenki ns and Comes, 1976; House-
man, 1973; Crooks and Lynn, 1992).
Because thermal l y i nduced water evol uti on occurs at
l ow temperatures, the water content of the tobacco drops
si gni fi cantl y and the effecti ve aci di ty of the resi dual
tobacco may i ncrease duri ng the heati ng process. As
di scussed i n secti ons 3 and 4, evol uti on peaks at ca. 110
C (for nonprotonated ni coti ne) are not seen i n the
thermal treatments of the tobacco sampl es except when
excess nonprotonated ni coti ne i s added to the tobacco
sampl e. We therefore concl ude that endogenous ni coti ne
i n tobacco i n the regi on about to rel ease ni coti ne due to
the approachi ng heat i s l i kel y to be substanti al l y
di protonated.
Under smoki ng condi ti ons, the heat of the approach-
i ng coal woul d be expected to expel much of the water
content of tobacco, before ni coti ne rel ease became
si gni fi cant. The resul ts above emphasi ze that ni coti ne
Figure10. Ni coti ne evol uti on, m/z 84, of normal Burl ey (a),
a l ow-al kal oi d Burl ey (b), l ow-al kal oi d Burl ey wi th added
ni coti ne ci trate (c), and l ow-al kal oi d Burl ey wi th added non-
protonated ni coti ne (d) i n hel i um as a functi on of temperature.
Table 5. Peak Appearance Temperatures of Nicotine
fromVarious Tobacco Samples, As Determined by
Evolved Gas Analysis (EGA)
source of ni coti ne
peak appearance
temp (C) of ni coti ne
a,b
fi gure
Burl ey Tobacco Sampl es
Burl ey 180(m), 210(s), 240(m) 10a
l ow-al kal oi d Burl ey 190(w), 220(w) 10b
l ow-al kal oi d Burl ey +
ni coti ne ci trate
150(m), 180(s), 215(m) 10c
l ow-al kal oi d Burl ey +
nonprotonated ni coti ne
105(w), 145(m), 175(s), 200(s) 10d
Bri ght Tobacco Sampl es
Bri ght 160(s), 180(s), 210(m), 240 (m)
l ow-al kal oi d Bri ght 180(w), 210(w)
l ow-al kal oi d Bri ght +
ni coti ne ci trate
160(m), 195(s), 235(m)
Ori ental Tobacco Sampl es
l ow-al kal oi d Ori ental 180(w), 220(w)
l ow-al kal oi d Ori ental +
ni coti ne ci trate
160(s), 185(s), 220(w)
a
Performed under an atmosphere of hel i um and at a thermal
temperature heati ng rate of 20 C mi n
-1
.
b
w ) peak of weak or
l ow i ntensi ty; m ) peak of medi um or moderate i ntensi ty; s )
peak of strong or hi gh i ntensi ty.
i n tobacco cl osel y resembl es the pol ycarboxyl ate sal ts
of ni coti ne i n the thermal requi rements for ni coti ne
rel ease to the gas phase and i s si gni fi cantl y di fferent
from the behavi or to be expected for monocarboxyl i c aci d
sal ts of ni coti ne, as exempl i fi ed by the aceti c aci d-
ni coti ne system. I t i s the stronger (and si gni fi cantl y
abundant) pol ycarboxyl i c aci ds (Wynder and Hoffmann,
1967) whose ani ons wi l l resi st protonati on more than
those of the weaker monocarboxyl i c aci ds. Thi s work has
demonstrated that weak l ow mol ecul ar wei ght al i phati c
aci ds (such as aceti c aci d) precede ni coti ne i nto the gas
phase.
I mportantly, whatever carboxylic acids that are formed
duri ng the smoki ng process from aci di c precursors are
l i kel y to be weaker than thei r precursors. To the extent
that aci ds condense i n the cool er regi ons of the ci garette,
new ni coti ne carboxyl i c aci d sal ts may be formed. The
re-evaporati on of ni coti ne from such sal ts wi l l l i kel y be
more faci l e than for the ori gi nal rel ease process, as our
resul ts wi th ni coti ne acetate vs the ni coti ne pol ycar-
boxyl ates have demonstrated above.
The appearance temperatures of ni coti ne (Tabl es 4
and 5) are si gni fi cantl y l ower than the temperatures
observed near the coal of a puffi ng ci garette, ca. 600-
950 C (Baker, 1975, 1981, 1987; Kobashi et al ., 1960;
McRae et al ., 1987). These factors (i .e., the stabi l i ty of
the ni coti ne ri ng system and the hi gh temperature
ranges of a burni ng ci garette) combi ned wi th the mass
of the tobacco al l ow the di ssoci ati on and/or decomposi -
ti on and/or di sproporti onati on of ni coti ne carboxyl i c aci d
vol ati l i zati on to ni coti ne i n the gas state. I n concl usi on,
the TG/DTA/MS resul ts, combi ned wi th the thermal
stabi l i ty of the ni coti ne ri ng structure i n both i ts
nonprotonated and carboxyl i c aci d sal t forms, cl earl y
i ndi cate that ni coti ne carboxyl i c aci d sal ts wi l l transfer
ni coti ne to the gas phase i n thermol ysi s experi ments
and i n the smoki ng process wi th effi ci ency comparabl e
to that from nonprotonated ni coti ne i tsel f.
6. Transfer of Nicotine to the Gas Phase from
the Lower Temperature Regions of a Puffing
Cigarette. A more subtl e questi on i s now addressed:
I s i t possi bl e that wi thi n porti ons of the puffi ng ci ga-
rette, i ntermedi ate temperatures wi l l be experi enced
(e.g., i n the range of ca. 125-250 C) such that an
enhanced amount of ni coti ne wi l l vol ati l i ze from non-
protonated ni coti ne (1) but not from monoprotonated (2)
and/or di protonated (3) ni coti ne(s)?
i. Transfer Kinetics. The ti me avai l abl e duri ng the
puffi ng of a ci garette compared wi th the rates of
vol ati l i zati on can be eval uated. The Federal Trade
Commi ssi on (FTC) method defi nes a standard model for
experi mental smoki ng compari sons as fol l ows: a 35 mL
puff taken over a 2-s i nterval , fol l owed by a 58 s stati c
burn (Federal Regi ster, 1967; Pi l l sbury et al ., 1969).
That i s, the ti me duri ng whi ch a puff i s taki ng pl ace
and mai nstream smoke i s bei ng generated i s model ed
as 2 s.
I t i s useful to determi ne the reacti on fracti on di s-
soci ati on/decomposi ti on/vol ati l i zati on ti mes for 1-3,
that i s, the ti me i t woul d take to convert and/or transfer
1-3 to ni coti ne i n the gas phase at vari ous tempera-
tures. To eval uate thi s, ni coti ne (1) and (S)-ni coti ne bi s-
[(2R,3R)-hydrogen tartrate] di hydrate (2c-3c) were
each subjected to TG scans at four heati ng rates (5, 10,
15, and 20 C mi n
-1
) under fl owi ng compressed ai r at
rates of 100 and 500 mL mi n
-1
. A ki neti c software
package (uti l i zi ng the Ozawa method) was used to
cal cul ate acti vati on energi es and degradati on/vol ati l i za-
ti on ti mes (l i feti mes). The data cal cul ated at the two
di fferent fl ow rates are presented i n Tabl es 6 and 7. For
appearance of ni coti ne, a val ue of ca. 55-60 kJ/mol was
determi ned, consi stent wi th the l i terature val ue for the
heat of vapori zati on for ni coti ne of 51.6 kJ/mol (CRC
Handbook of Chemi stry and Physi cs, 1973). The acti va-
ti on energy determi ned for the mel ti ng of the ni coti ne
bi tartrate (2c-3c) and subsequent decomposi ti on and
transfer of ni coti ne to the gas phase was about 115 kJ/
mol .
Degradati on/vol ati l i zati on ti mes for ni coti ne and ni co-
ti ne bi tartrate were cal cul ated for temperatures of 150,
200, 250, and 300 C at reacti on fracti ons of 10%, 20%,
and 50%. Si nce the wei ght l oss observed for ni coti ne i s
vi a evaporati on, rather than decomposi ti on fol l owed by
vol ati l i zati on, as observed for the bi tartrate sal t, i t
fol l ows (as observed i n Tabl es 6 and 7) that fl ow rate
shoul d have a greater i nfl uence on the degradati on/
vol ati l i zati on ti mes of free ni coti ne than that of the sal t.
The data i n Tabl es 6 and 7 can be used to extrapol ate
degradati on/vol ati l i zati on ti mes for ni coti ne and the
natural tobacco carboxyl i c aci d sal ts of ni coti ne i n a
ci garette duri ng puffi ng (1050 mL mi n
-1
at FTC condi -
ti ons of a 2 s 35 mL puff). I t shoul d be noted that the
di protonated bi tartrate sal t i s thermal l y more stabl e
than the protonated sal ts of the other carboxyl i c aci ds
i nvesti gated; therefore, i t woul d be expected that the
degradati on/vol ati l i zati on ti mes of other protonated
sal ts (e.g., mal ates, acetates, ci trates) woul d be l ess than
that of the bi tartrate sal t.
I n the temperature range of 250-300 C, the data i n
Tabl es 6 and 7 suggest that the transfer rates of ni coti ne
to the gas phase from nonprotonated ni coti ne and the
carboxyl i c aci d sal ts of ni coti ne are comparabl e. I t i s
onl y wi thi n the temperature range from about 125 to
Table 6. Calculated Reaction Fraction Decomposition
Time (s) and Energy of Activation (Ea) To Transfer
Nicotine to the Gas Phase fromNicotine (1) and
(S)-Nicotine Bis[(2R,3R)-hydrogen tartrate] Dihydrate
(2c-3c) under a Compressed Air Flow of 100 mL min
-1
% transfer to ni coti ne i n the gas phase
from ni coti ne (1) from ni coti ne bi tartrate (2c-3c)
10% 20% 50% 10% 20% 50%
temp
(C)
ti me (s) to reach speci fi ed percentage of ni coti ne
i n the gas phase
150 30 55 130 1200 1900 3300
200 5.8 11 24 43 61 104
250 1.6 2.8 6.4 3.0 3.8 6.4
300 0.5 0.9 2.1 0.3 0.4 0.6
E
a 55 kJ/mol 115 kJ/mol
Table 7. Calculated Reaction Fraction Decomposition
Time (s) and Energy of Activation (Ea) To Transfer
Nicotine to the Gas Phase fromNicotine (1) and
(S)-Nicotine Bis[(2R,3R)-hydrogen tartrate] Dihydrate
(2c-3c) under a Compressed Air Flow of 500 mL min
-1
% transfer to ni coti ne i n the gas phase
from ni coti ne (1) from ni coti ne bi tartrate (2c-3c)
10% 20% 50% 10% 20% 50%
temp
(C)
ti me (s) to reach speci fi ed percentage of ni coti ne
i n the gas phase
150 16 34 85 940 1600 2900
200 2.5 5.6 14 31 48 82
250 0.6 1.3 3.3 2.0 2.8 4.6
300 0.2 0.4 1.0 0.2 0.3 0.4
E
a 60 kJ/mol 116 kJ/mol
250 C that di fferences i n the transfer rate of ni coti ne
to smoke from protonated ni coti ne and nonprotonated
ni coti ne (i f any nonprotonated ni coti ne i s, i n fact,
present) coul d be expected. However, wi thi n the 125-
250 C regi on of a ci garette rod duri ng puffi ng, the rate
of vol ati l i zati on of nonprotonated ni coti ne i s expected
to be smal l . For exampl e, extrapol ati ng the data i n
Tabl es 6 and 7, one can esti mate that i n the 200 C
regi on of a puffi ng ci garette, i t woul d take about 4-5 s
to vol ati l i ze 20%of any nonprotonated ni coti ne present.
Therefore, duri ng the rel ati vel y short ti me of a puff,
si gni fi cantl y l ess than 20% of any nonprotonated ni co-
ti ne i n the 125-250 C regi on coul d vol ati l i ze. Moreover,
thi s parti cul ar temperature zone of the ci garette rod i s
not onl y narrow (Baker, 1975, 1981, 1987), but i s al so
i n moti on (Crooks and Lynn, 1992), as the coal regi on
chases i t down the rod i n response to puffi ng acti on. The
ci garettes dynami c burn further decreases the ti me any
parti cul ar zone of tobacco i s exposed to thi s parti cul ar
temperature range to si gni fi cantl y l ess ti me than the
durati on of a puff. The combi ned effect of (1) the smal l
vol ume of tobacco wi thi n the 125-250 C regi on of a
puffi ng ci garette, (2) the bri ef ti me a parti cul ar zone of
tobacco i s exposed to thi s temperature range, (3) the
rel ati vel y l ow temperature (and avai l abl e energy) of the
regi on, and (4) the smal l content of nonprotonated
ni coti ne mul ti pl i ed together i ndi cate a mi nute possi bi l -
i ty of si gni fi cant transfer of ni coti ne to smoke from thi s
temperature regi on. Furthermore, there i s l i kel y to be
net condensati on of ni coti ne wi thi n the l ower temper-
ature part of thi s regi on as the aerosol begi ns to form
(see bel ow).
ii. Condensation of SmokeNicotineontotheTobacco.
As ni coti ne travel s down the rod duri ng puffi ng, i t i s
known that some of i t condenses onto, or i s otherwi se
entrai ned by, the tobacco as the temperature of ci garette
smoke decreases (Jenki ns and Comes, 1976; Houseman,
1973; Crooks and Lynn, 1992). Anal ysi s of puff-by-puff
ni coti ne del i very al so confi rmed the condensati on phe-
nomena (Crooks and Lynn, 1992). Thus, there i s si g-
ni fi cant fl ux of ni coti ne onto the tobacco i n l ower
temperature regi ons of a ci garette duri ng a puff rather
than vol ati l i zati on of ni coti ne off of the tobacco, i .e., a
net deposi ti on of ni coti ne i n these l ower temperature
regi ons i s what occurs. Greater than 95%of the ni coti ne
i n mai nstream smoke at the exi t poi nt of a ci garette i s
i n the parti cul ate phase, as woul d be expected from the
l ow vapor pressure of ni coti ne at 30 C (Ogden et al .,
1993).
7. Formation of and Transfer of Nicotineto the
Gas Phase fromCovalently Bound Nicotine Pre-
cursors. The cl ai m has been made that protonated
ni coti ne i n tobacco i s bound and does not transfer to
the smoker duri ng the smoki ng process (Kessl er et al .,
1996, 1997; Kessl er, 1994). One mi ght ask to what
extent i s protonated ni coti ne bound or unabl e to be
vol ati l i zed thermal l y? The resul ts descri bed above pro-
vi de strong evi dence that protonated ni coti ne i s ful l y
capabl e upon mi l d (ca. 200 C) thermal treatment to
transfer ni coti ne to the gas phase.
Another way of exami ni ng thi s questi on woul d be to
ask, i f one wanted to construct a bound ni coti ne, what
mi ght i t be? One experi mental answer i s to exami ne the
smoke chemi stry of a ni coti ne deri vati ve such as 5and/
or 6, where R i s a coval entl y bound substi tuent other
than a proton (i n these cases, formi ng a N-C bond).
To eval uate smoke chemi stry, researchers from gov-
ernment, academi a, and i ndustry have used the stan-
dard FTC smoki ng paradi gm to quanti fy ni coti ne and
tar del i veri es. Under these condi ti ons, i t i s known that
the transfer effi ci ency of ni coti ne i n commerci al ci ga-
rettes i s between 1% and 10% (Hoffmann et al ., 1995).
Transfer effi ci ency means the amount of ni coti ne de-
l i vered to mai nstream smoke di vi ded by the amount of
al kal oi d present i n the tobacco i n the ci garette before
smoki ng. Transfer effi ci ency i s anal ogous to the yi el d
of a chemi cal reacti on.
An aqueous sol uti on of N- and N-(3-methyl -2-but-
enyl )ni coti ni um ci trate (7 and 8, eq 2) was added to a
l ow-al kal oi d Burl ey-Bri ght tobacco mi xture (1:1).
The resul tant tobacco was equi l i brated overni ght and
handmade i nto nonfi l tered ci garettes. These ci garettes
were found to yi el d an addi ti onal amount of ni coti ne to
the mai nstream smoke, equal to a 10% transfer ef-
fi ci ency, based on the amount of 7and 8that was added
to each ci garette fi l l er (Seeman, 1982). As the net
transfer effi ci ency to ni coti ne i n the mai nstream smoke
for 7and 8i s wi thi n the experi mental range of transfer
effi ci enci es for ni coti ne i tsel f (Perfetti et al ., 1998), 7
and 8cannot be consi dered bound, i f by bound one
i mpl i es an i nabi l i ty for ni coti ne to be transferred to the
smoke. Si mi l ar resul ts have been reported for the
transfer to ni coti ne i n smoke from the reacti on products
of ni coti ne wi th ethyl ene oxi de (9 and 10, eq 3) i n the
tobacco matri x (Obi et al ., 1968).
SUMMARY, CONCLUSI ONS, AND I MPLI CATI ONS OF
THI S WORK
The ni coti ne ri ng system i s thermal l y qui te stabl e.
Ni coti ne carboxyl i c aci d sal ts transfer ni coti ne to the
gas phase by three types of mechani sms: deprotonati on,
decomposi ti on of the carboxyl i c aci d ani on, and di spro-
porti onati on. Under the TG/DTA/MS condi ti ons used i n
these studi es, the peak transfer temperatures from
ni coti ne i tsel f and from the vari ous ni coti ne carboxyl i c
aci d sal ts to ni coti ne i n the gas phase are ni coti ne and
ni coti ne acetate, both ca. 110-125 C; ni coti ne mal ates,
ca. 110-210 C for ni coti ne to mal i c aci d rati os of 1:0.56
and 1:1 and ca. 160-210 C for a ni coti ne to mal i c aci d
rati o of 1:2; and (S)-ni coti ne bi s[(2R,3R)-hydrogen tar-
trate] di hydrate, ca. 195-210 C. Decomposi ti on prod-
ucts of ni coti ne were not observed, even i n 21%oxygen.
The TG/DTA/MS and EGA/MS experi ments show
peak ni coti ne evol uti on temperatures from tobacco
sampl es i n the range of ca. 160-220 C, the same range
as the ni coti ne pol ycarboxyl i c aci d sal ts. EGA/MS
resul ts al so show that addi ti on of modest amounts of
nonprotonated ni coti ne to l ow-al kal oi d tobaccos resul ts
i n ni coti ne evol uti on peaks si mi l ar to those observed for
normal tobaccos. Under smoki ng condi ti ons, ni coti ne
rel ease occurs after much of what water was ori gi nal l y
present has fi rst evaporated. Ni coti ne i n ci garette
tobacco i s present l argel y (>95%, perhaps even >99%)
i n a protonated state at room temperature. Thermal l y
i nduced water evol uti on occurs at temperatures l ower
than those requi red for ni coti ne rel ease, possi bl y i n-
creasi ng the effecti ve aci di ty of the medi um. At the
temperature range where thermal rel ease of ni coti ne
from tobacco occurs, evi dence reported herei n suggests
that ni coti ne i s di protonated.
Nonprotonated ni coti ne and ni coti ne carboxyl i c aci d
sal ts, such as those found i n tobacco, are l i kel y to
transfer ni coti ne to the gas phase duri ng the smoki ng
process wi th comparabl e yi el d and effi ci ency. Mi l d heat
(300-400 C) shoul d be suffi ci ent to transfer ni coti ne
to the gas phase. I t fol l ows that the aci di ty of the
tobacco, as exami ned herei n, i s of l i ttl e consequence for
del i very of ni coti ne i nto the gas and, subsequentl y,
aerosol (or parti cul ate) phase.
Gi ven that the pri nci pal temperature range of ni co-
ti ne evol uti on from both tobacco and the di protonated
ni coti ne pol ycarboxyl i c aci d sal ts i s essenti al l y the same,
i t i s l i kel y the tobacco pol ycarboxyl i c aci ds (e.g., mal i c
aci d and ci tri c aci d) determi ne the ni coti ne evaporati on
temperature ranges from the tobacco matri x (l ess than
about 220 C, consi derabl y l ess than temperatures
observed around the coal of a burni ng ci garette). The
pol ycarboxyl i c aci ds are thermal l y l abi l e and decarbox-
yl ati vel y dehydrate or el i mi nate to form l ess aci di c
products, e.g., monocarboxyl i c aci ds.
The ki neti c resul ts from the TGA study suggest that
gi ven the contact ti me avai l abl e under smoki ng condi -
ti ons, whatever nonprotonated ni coti ne that mi ght exi st
i n the tobacco woul d onl y be transferred to smoke i n
si gni fi cant amounts at temperatures i n excess of about
300 C. At these temperatures there i s l i ttl e di fference
i n the rates of vol ati l i zati on of ni coti ne from ni coti ne
carboxyl i c aci d sal ts and evaporati on of nonprotonated
ni coti ne. The zone of a puffi ng ci garette that encom-
passes the temperature range 125-250 C i s physi cal l y
very smal l , and the rate of transfer of ni coti ne to the
gas phase i s l ow; therefore, any nonprotonated ni coti ne
contai ned wi thi n the l ower temperature regi ons (shoul d
some exi st) woul d l i kel y have i nsuffi ci ent ti me to
vol ati l i ze. Vol ati l i zati on of ni coti ne from l ower temper-
ature regi ons wi l l be further mi ni mi zed because the
smoke passi ng through these regi ons i s al ready satu-
rated wi th ni coti ne ori gi nati ng from the hi gher temper-
ature regi ons nearer the coal . I ndeed, because of con-
densati on of ni coti ne from the hot smoke comi ng from
the hi gher temperature regi ons to the l ower tempera-
ture regi ons of the ci garette rod duri ng puffi ng, a net
fl ux of ni coti ne onto the tobacco i n the l ower tempera-
ture regi ons i s l i kel y, rather than the reverse.
Ni coti ne coval entl y bound as N- and N-al kyl ni co-
ti ni um quaternary sal ts were found from previ ous work
to transfer ni coti ne to the smoke from a puffi ng ci garette
i n yi el ds si mi l ar to that found for the transfer of
endogenous ni coti ne to ni coti ne i n smoke. Protonated
ni coti ne cannot be consi dered bound, i f by the term
bound i t i s meant a form of ni coti ne whi ch wi l l not
readi l y transfer ni coti ne to smoke.
ACKNOWLEDGMENT
We thank Ms. Susan Laffoon for techni cal assi stance,
Drs. Ri chard I zak, Robi n Ki nser, A. C. Li l l y, and Ken
Shafer for hel pful suggesti ons, and Dr. Cathy El l i s for
support. I n addi ti on, we al so thank one of the revi ewers
of the manuscri pt (Dr. Thomas Perfetti ) for numerous
val uabl e comments.
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Recei ved for revi ew Apri l 23, 1999. Revi sed manuscri pt
recei ved Jul y 27, 1999. Accepted September 2, 1999.
JF990409B

Seeman Etal 1999 - The Form of Nicotine in Tobacco. Thermal Transfer of Nicotine and Nicotine Acid Salts To Nicotine in The Gas Phase

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