A facile synthesis and application of protoporphyrin derivatives on reducing the tobacco specific N-nitroamines levels of smoke

Article abstract of DOI:10.1142/S1088424613500089

Two protoporphyrin derivatives were prepared by a facile method using inexpensive hemin as starting material. They were added to cigarette filters to reduce the carcinogenic tobacco specific N-nitroamines (TSNAs), especially toward NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) and NNN (N-nitrosonornicotine) for environment protection and public health. The reduction level of TSNAs was reached to 37.6% from MSS, with greater reductions when more porphyrin was included in the filter. The decrease level for NNK by protoporphyrin derivatives is more effective than NNN. The interaction between protoporphyrin derivatives and TSNAs (NNK and NNN) were investigated by fluorescence spectra and UV-visible titration. The correlation coefficients were 0.978～0.997 and the binding constants was the scope from 1.26 × 10³ to 4.04 × 10⁴. The interaction mechanisms between protoporphyrin derivatives and, NNK and NNN are possibly the co-interaction of hydrogen bond binding and strong π-π stacking.

Full text of DOI:10.1142/S1088424613500089

Journal of Porphyrins and Phthalocyanines
J. Porphyrins Phthalocyanines 2013; 17: 309–316
DOI: 10.1142/S1088424613500089
Published at http://www.worldscinet.com/jpp/
A facile synthesis and application of protoporphyrin
derivatives on reducing the tobacco specific
N-nitroamines levels of smoke
FeiY.Taoa,b, Chang G. Wangb, KuoY. Mab, Dong L. Lib, Lan L.Tanb, Ji Zhanga,
Ya Daib* and Xiao Q.Yua*
a Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan
University, Chengdu 610064, China
b Harmful Components and Tar Reduction in Cigarette, Sichuan Key Laboratory Technical Research Center, Chuanyu
Branch of China Tobacco Corporation, Chengdu 610066, China
Received 16 November 2012
Accepted 20 January 2013
ABSTRACT: Two protoporphyrin derivatives were prepared by a facile method using inexpensive hemin
as starting material. They were added to cigarette filters to reduce the carcinogenic tobacco specific
N-nitroamines (TSNAs), especially toward NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone)
and NNN (N-nitrosonornicotine) for environment protection and public health. The reduction level of
TSNAs was reached to 37.6% from MSS, with greater reductions when more porphyrin was included
in the filter. The decrease level for NNK by protoporphyrin derivatives is more effective than NNN.
The interaction between protoporphyrin derivatives and TSNAs (NNK and NNN) were investigated by
fluorescence spectra and UV-visible titration. The correlation coefficients were 0.978~0.997 and the
binding constants was the scope from 1.26 × 103 to 4.04 × 104. The interaction mechanisms between
protoporphyrin derivatives and, NNK and NNN are possibly the co-interaction of hydrogen bond binding
and strong p–p stacking.
KEYWORDS: protoporphyrin derivatives, hemin, tobacco-specific N-nitrosamines, binding constant,
cigarette smoke.
smoke is a complex mixture of more than 4700 chemicals
INTRODUCTION
and contains hundreds of toxicants.
There are more than 1.2 billion smokers worldwide and
Most of the nitroamines are characterized with functio-
more than 4 million of them die annually from smoking-
nal group of N–NO, and tobacco-specific nitrosamines
related disease [1]. Multiple epidemiological studies have
(TSNAs) are the carcinogenic agents identified in tobacco
shown that cigarette smoke is related to the development
of cardiovascular disease, stroke, lung carcinoma, chronic
bronchitis, chronic obstructive pulmonary disease, and
and tobacco smoke [6, 7]. N-nitrosoanabasine (NAB),
N-nitrosoanatabine (NAT), 4-(methylnitrosamino)-1-(3-
pyridyl)-1-butanone (NNK), and N-nitrosonornicotine
emphysema [2]. Cigarette smoking is causally related
(NNN) are the main components of TSNAs (Fig. 1). They
to the cancers of the lung, oral cavity, larynx, pharynx,
are formed during the curing, processing, fermentation,
nasal cavity, esophagus, liver, pancreas, kidney, urinary
and combustion of tobacco [8–10].
bladder, cervix, and myeloid leukemia [3–5]. Cigarette
TSNAs play an important role as causative agents
in cancer of the esophagus, pancreas, and oral cavity
associated with smoking. Among the TSNAs, NNK
and NNN are the most carcinogenic ones in laboratory
animal [11, 12]. NNK induces lung tumors in rodents
*Correspondence to: Xiao Q. Yu, email: xqyu@scu.edu.cn, tel:
+86 028-85415886, fax: +86 028-85415886 and Ya Dai, email:
dycy@263.net, tel: +86 028-86005609, fax: +86 028-86005607
Copyright © 2013 World Scientific Publishing Company

310
F.Y. TAO ET AL.
O
porphyrin [26]. Owing to their unique structures,
porphyrins have a wide range of applications in
bionics, materials chemistry, pharmaceutical chemistry,
electrochemistry, optical physics and chemistry, as well
as analytical chemistry [27–31]. In our previous study
[32], tetraphenylporphyrin compounds were applied
in tobacco industry to effectively decrease the harmful
components such as TSNAs and B[a]P in MSS. Its low
yields for the large scale preparation limited its further
application. This encourages us to further investigate
alternative porphyrin compounds for the application to
reduce the harmful components in cigarette smoke.
In this study, the protoporphyrin derivatives were
prepared using inexpensive hemin as starting materials
by a facile synthesis, and the derivatives were added to
cigarette filters to investigate the variation of the NNK
and NNN level in the main stream smoke (MSS). The
hemin had been applied widely in pharmaceutical
industry, food industry with aboundant source and low
cost. The interactions of protoporphyrin derivatives with
NNK and NNN were investigated using fluorescence
spectra and UV-vis titration. A possible mechanism
for the reduction of TSNAs level by protoporphyrin
derivatives is discussed.
O
N
N
N
N
O
N
N
NNK
NNN
N
N
N
N
O
O
N
N
NAT
Fig. 1. Chemical Structure of typical TSNAs
NAB
independent of the route of administration [13]. NNN
induces tumors of the esophagus and nasal cavity in rats,
the lung in mice, the respiratory tract in hamsters, and
the nasal cavity in mink [13, 14]. A mixture of NNK
and NNN produced oral cavity tumors in rats [15].
According to the International Agency for Research on
Cancer, NNK and NNN are carcinogenic to humans [16].
Consequently, in order to protect environment and public
health, it is necessary to reduce the level of nitrosamines
in environmental tobacco smoke and decrease the
content of TSNAs, specially, reducing the level of NNK
and NNN.
EXPERIMENTAL
General
NMR spectra were measured on a Bruker AMX-
400. The H NMR (400 MHz) chemical shifts were
Theremovaloftobacco-specificnitrosamines(TSNAs)
from cigarette smoke has attracted growing interest over
the past years in tobacco chemistry [17–21]. Different
methods were adopted to reduce TSNAs. Different
additives were put into cigarette filter to reduce the
nitrosamine level of the smoke, which is applied widely
in cigarette industry. Previous studies have indicated the
removal of carcinogenic TSNAs from cigarettes smoke
by adding zeolite-like calcosilicate [22, 23]. Although
zeolite-like calcosilicate effectively reduced TSNAs level
in mainstream smoke (MSS), it affected the inhaled taste
feeling and it is also expensive for large scale application.
Some g-AlOOH superstructures were prepared and
added to the filter and/or cut fillers. The decrease in the
amounts of four TSNAs in cigarette smoke by adding
three-quarter-sphere-like g-AlOOH superstructures into
cut tobacco was very effective, but its harsh conditions
(high temperature and high pressure) for preparation
limited its further application in large scale [24].
Hemoglobin and some porphyrins have been shown
to be promising cigarette filter additives to remove the
hazardous components, such as carcinogenic N-nitroso
compounds [25]. The compounds containing porphyrin
structures play important roles in photosynthesis, gas
transport (hemoglobin, myoglobin), vitamin structure
(cobalamin), and the metabolism of living organisms.
Examples include heme, which is the iron porphyrin in
hemoglobin, and chlorophyll, which is a magnesium
1
given in ppm relative to internals reference TMS.
ESI-MS and HR-MS spectral data were recorded on a
Finnigan LCQDECA and a Bruker Daltonics BioTOF mass
spectrometer, respectively. Fluorescence excitation and
emission spectra were obtained using Fluoro Max-4
Spectrofluorophotometer (HORIBA Jobin Yvon).
UV-vis absorption spectra were recorded on a Hitachi
PharmaSpec UV-1900 UV-visible spectrophotometer.
Unless otherwise noted, materials were obtained from
commercial suppliers and were used without further
purification.
Standardized NNK, NNN were obtained from Sigma-
Aldrich (St. Louis, MO). Hemin was extracted from
animal fresh blood in our laboratory [33]. All of the
solvents were dried according to the standard methods
prior to use. All of the solvents were either HPLC or
spectroscopic grade in the optical spectroscopic studies.
TLC analyses were performed on silica gel GF254.
Synthesis of protoporphyrin derivatives
Synthesis of CY-1. To the round-bottom flask hemin
(10.0 g, 15.34 mmol) and 100 mL of 33% HBr in HOAc
wasadded, andthemixturewasstirredatroomtemperature
for 48 h. The resulting bromo-substituted protoporphyrin
solution was used directly in the next step. To the above
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PROTOPORPHYRIN DERIVATIVES ON REDUCING THE TOBACCO SPECIFIC N-NITROAMINES LEVELS OF SMOKE
311
solution, methanol (500 mL) was added slowly and
the solution was refluxed for 8 h. Then the solvent was
removed in vacuo, and the residue was suspended in
water and the pH was adjusted to 8–9 with 2 M NaOH
aq. solution. The solid was collected by filtration to give
crude CY-1. The crude product was recrystalized from
the mixture solvent of ethyl acetate and petroleum ether
to afford CY-1[34] (7.6 g, 11.61 mmol) with 75.7% yield.
1H NMR (CDCl3): d, ppm -3.66 (s, 2H, pyrrole-H), 2.28 (d,
6H, J = 4.4 Hz, CHCH3), 3.31 (m, 4H, CH2COO), 3.64–
3.37 (m, 24H, OCH3, CH3), 4.43 (m, 4H, CH2CH2COO),
6.07 (m, 2H, CH3CH), 10.10, 10.14, 10.53, 10.57 (4s, 4H,
meso-H). ESI MS (positive ion mode) (rel. int.): m/z 655
([M + H]+, 100). HRMS (ESI): m/z 655.3469 ([M + H]+,
100); calcd. for C38H46N4O6 + H 655.3417 ([M + H]+,
100). UV-vis (CH2Cl2): lmax, nm (log e) 399 (5.27), 498
(4.15), 532 (3.95), 569 (3.77) and 621 (4.62). IR: n, cm-1
3313.0, 2971.0, 2925.0, 2860.4, 1741.7, 1455.6, 1362.5,
1168.1, 1112.5, 1085.1, 964.9, 826.1, 743.0 and 678.5.
Synthesis of CY-2. To the round-bottom flask CY-1
(4.0 g, 6.11 mmol) and 200 mL of 1 M NaOH methanol
solution was added, and the mixture was refluxed for
2 h. TLC monitored the disappearance of CY-1. Then
the solvent was removed in vacuo, and the residue was
dissolved in water then the pH was adjusted to 4–5
with AcOH to give CY-2 [35] (3.56 g, 5.68 mmol) with
93.0% yield. 1H NMR (DMSO-d6): d, ppm -3.97 (s, 2H,
pyrrole-H), 2.18 (d, 6H, J = 5.6 Hz,CHCH3), 3.07 (t, 4H,
J = 8.4 Hz, CH2COO), 3.60–3.69 (m, 18H, OCH3, CH3),
4.32 (t, 4H, J = 8.4 Hz, CH2CH2COO), 6.15 (q, 2H, J =
5.6 Hz, CH3CH), 10.19, 10.43, 10.51, 10.58 (4s, 4H,
meso-H). ESI MS (positive ion mode) (rel. int.): m/z 627
([M + H]+, 100). HRMS (ESI): m/z 627.3170 ([M + H]+,
100), calcd. for C36H42N4O6 + H 627.3104 ([M + H]+,
100). UV-vis (CH2Cl2): lmax, nm (log e) 397 (5.02), 498
(3.99), 532 (3.81), 568 (3.68) and 619(3.40). IR: n, cm-1
3424.3, 3304.1, 2989.5, 2906.4, 2869.3, 2804.8, 1704.5,
1556.2, 1399.6, 1260.9, 1177.8, 1103.6, 1066.5, 973.8,
826.1, 743.0 and 668.9.
3310.7, 2959.0, 2929.5, 2867.7, 1733.6, 1610.2, 1455.6,
1387.2, 1230.3, 1166.2, 1097.6, 967.6, 834.8 and 740.0.
Synthesis of CY-4. To the round-bottom flask CY-3
(4.0 g, 5.86 mmol) and 100 mL of 1 N NaOH methanol
solution was added, and the mixture solution was refluxed
for 4 h. TLC monitored the disappearance of CY-3.
Then the solvent was removed in vacuo and the residue
was dissolved in water then the pH was adjusted to
4–5 with AcOH to give CY-4 (3.10 g, 4.36 mmol) with
1
89.7% yield. H NMR (DMSO-d6): d, ppm -3.93 (s, 2H,
pyrrole-H), 0.78 (t, 6H, J = 7.2 Hz, OCH2CH2CH2CH3),
1.38–1.46 (m, 4H, OCH2CH2CH2CH3), 1.66–1.72 (m, 4H,
OCH2CH2CH2CH3), 2.16 (d, 6H, J = 6.4 Hz, CHCH3),
2.94 (t, 4H, J = 7.2 Hz, CH2COO), 3.66–3.75 (m, 16H,
CH3,OCH2-), 4.34 (t, 4H, J = 7.2 Hz, CH2CH2COO), 6.15
(q, 2H, J = 6.4 Hz,CH3CH), 10.22, 10.60, 10.65, 10.80 (4s,
4H, meso-H). ESI MS (positive ion mode) (rel. int.): m/z
711 ([M + H]+, 100). HRMS (ESI): m/z 711.4062 ([M +
H]+, 100); calcd. for C42H54N4O6 + H 711.4043 ([M + H]+,
100). UV-vis (CH2Cl2): lmax, nm (log e) 399 (5.12), 497
(4.13), 529 (3.99), 568 (3.95) and 618 (3.67). IR: n, cm-1
3442.8, 3304.1, 2952.4, 2915.3, 2869.3, 1713.4, 1445.6,
1371.4, 1223.8, 1159.2, 1094.0, 844.7, 733.4 and 687.4.
Addition and analysis of protoporphyrin derivatives
CY-2 and CY-4 to cigarettes filters
Cigarette filters consisting of acetate cellulose and cut
filters of brand A were obtained from Chengdu Cigarette
Factory (Chengdu, China). During machine molding of
the filters, protoporphyrin derivatives were added to the
filter through the carrier. Protoporphyrin derivatives-
modified filters were then attached to cigarettes. Modified
cigarettes were produced containing 0.0, 5.0, 15.0, 30.0,
and 45.0 μg of the protoporphyrin derivatives per filter.
Control cigarettes were prepared using unmodified
acetate cellulose filters of brand A. Cigarettes containing
protoporphyrins derivatives were used to investigate the
reduction of TSNAs (NNK and NNN ) in MSS (main
stream smoke).
Synthesis of CY-3 [36]. The preparation method of
CY-3 is the same with that of CY-1 except using n-butanol
as substrate, and the yield was 71.3%. 1H NMR (CDCl3):
d, ppm -3.70 (s, 2H, pyrrole-H), 0.71–0.75 (t, 6H, J= 7.2 Hz,
OCH2CH2CH2CH3),0.78–0.86(m,6H,OCH2CH2CH2CH3),
1.19 (q, 4H, J = 7.2 Hz, OCH2CH2CH2CH3), 1.42–1.50 (m,
8H, OCH2CH2CH2CH3), 1.73–1.77 (m, 4H, OCH2CH2-
CH2CH3), 2.25 (d, 6H, J = 6.8 Hz, CHCH3), 3.28 (q, 4H, J =
6.4 Hz, CH2COO), 3.64–3.75 (m, 16H, CH3, OCH2-), 4.08
(q, 4H, J = 6.4 Hz, OCH2CH2CH2CH3), 4.42 (t, 4H, J =
6.4 Hz, CH2CH2COO), 6.10 (q, 2H, J = 6.8 Hz, CH3CH),
10.09, 10.11, 10.61, 10.62 (4s, 4H, meso-H). ESI MS
(positive ion mode) (rel. int.): m/z 823 ([M + H]+, 100).
HRMS (ESI): m/z 823.5387 ([M + H]+, 100); calcd.
for C50H70N4O6 + H 823.5295 ([M + H]+, 100). UV-vis
(CH2Cl2): lmax, nm (log e) 400 (5.37), 499 (4.33), 533
(4.14), 568 (4.01) and 621(3.81). IR: n, cm-1 3435.2,
A
fully automatic smoking machine (RM200,
Borgwaldt Technik GmbH, Hamburg, Germany ) was
used to generate and trap MSS from the 20 cigarettes.
NNK and NNN were detected by gas chromatography-
thermal energy analysis spectrometry with an Agilent
6890 GC and a Thermo 610 TEA (Thermo Fisher
Scientific, Waltham, MA) [37]. Gas chromatography
mass spectrometry and gas chromatography thermal
energy analysis spectrometry results were used to
calculate the percentage reductions in TSNAs in the MSS
from protoporphyrin derivatives modified cigarettes in
comparison with the control cigarettes.
Mechanism studies
The interaction between protoporphyrin derivatives
andTSNAs(NNKandNNN)werestudiedbyfluorescence
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F.Y. TAO ET AL.
spectra using Fluoro Max-4 Spectrofluorophotometer
(HORIBA Jobin Yvon). A stock solution of the guest
NNK and NNN, and host protoporphyrin derivatives
CY-2 and CY-4 were prepared in dichloromethane. The
concentrations of NNK and NNN solutions were 1.45
mM and 3.61 mM, respectively. The concentrations
of protoporphyrin derivatives (CY-2 and CY-4) were
5.74 μM and 4.92 μM respectively. The fluorescence
intensity was measured by the addition of different
volumes TSNAs to 3 mL of host protoporphyrin
derivative solution. The fluorescence intensity for
different concentrations of TSNAs were plotted to obtain
the protoporphyrin derivatives fluorescence spectrum.
The fluorescence change of protoporphyrin derivatives
after the addition of TSNAs conforms to the Benesi-
hildebrend equation (Equation 1) [38].
derivatives (4 × 10-6 M) and the mixture was vortexed for
10 s, then the spectrum were recorded.
RESULTS AND DISCUSSION
Synthesis of protoporphyrins derivatives
In this study, protoporphyrin derivatives CY-2 and
CY-4 were prepared using cheap and abundant hemin
as starting material. The deferrous reaction of porphyrin
center and HBr addition on double bond were carried
out in a “one pot reaction” (Scheme 1). Especially, the
bromo-substituted compounds need not be purified and
can be directly used. In the following step using different
alcohols as reactant, the nucleophilic substitution of
Br group by alkyloxy group is associated with the
esterification of carboxylic acid. The titled compounds
could be easily obtained by simple saponification
by NaOH. Only easy operations such as extraction,
acidification, filteration and recrystallization were needed
to obtain the pure products. In the preparation of CY-2,
less amount of demonomethyl by-product was detected,
and it was easy to be removed by recrystallization.
In other words, the whole process was convenient and
efficient. It is promising for large scale application in the
future.
1
1
1
=
+
(1)
A - A0 K(Amax - A0 )[TSNAs] Amax - A0
in which A0 is the absorance of protophyrin derivatives,
A is the absorbance obtained with TSNAs, Amax is the
absorbance obtained with excess amount of TSNAs,
K is the association constant, and [TSNAs] is the
concentration of TSNAs added. The binding constant
K and the interaction between the protoporphyrin
derivatives and TSNAs are positively correlated. Larger
binding constants indicate stronger interaction between
the protoporphyrin derivatives and TSNAs.
Reduction of TSNAs in MSS by the addition
of protoporphyrin derivatives CY-2 and CY-4
NNK and NNN in MSS were greatly reduced by
adding CY-2 and CY-4 compounds to the cigarette
filters (Table 1). The addition of protoporphyrin
derivatives CY-2 and CY-4 reduced the levels of TSNAs
in MSS by up to 36.4% and 37.6%. Generally, more
The interaction between protoporphyrin derivatives
and, NNK and NNN was also investigated by UV-visible
spectrophotometer (Hitachi PharmaSpec UV-1900).
Various concentrations of NNK and NNN (2 × 10-3
M) were added to the solution of host protoporphyrin
HO
O
HO
O
Cl
Br
N
N
N
NH
33% HBr in HOAc
ROH
Fe
Reflux
HN
N
N
N
O
O
HO
HO
Br
Hemin
RO
O
HO
O
OR
OR
N
N
NH
N
NH
1N NaOH methanol solution
HN
HN
N
O
O
RO
HO
RO
RO
CY-1: R = Me
CY-3: R = n-Bu
CY-2: R = Me
CY-4: R = n-Bu
Scheme 1. Synthetic route for protoporphyrin derivatives CY-2 and CY-4
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PROTOPORPHYRIN DERIVATIVES ON REDUCING THE TOBACCO SPECIFIC N-NITROAMINES LEVELS OF SMOKE
313
Table 1. Percentage reduction (%) in the levels of NNK & NNN
in MSS (n = 5) after the addition of protoporphyrin derivatives
CY-2 & CY-4 to the cigarette filtera
fluorescence intensity of protoporphyrin derivatives CY-2
and CY-4 increased with the increase of the addition
amount of NNK and NNN. According to Equation 1, the
linear equation, coefficient, and slope (K) were obtained
from the 1/A–A0 and 1/[TSNAs] concentration curve
(Fig. 3). The plot of 1/(A–A0) against 1/[TSNAs] show
a linear relationship, indicating that protopotphyrin
derivatives associates with TSNAs in 1:1 stoichiometry.
The association constant K between protoporphyrin and
TSNAs is determined from the slope and intercept of
liner equation.
The binding constant (K) between CY-2 and, NNK and
NNN were 6.95 × 103 and 1.26 × 103 with the correlation
coefficient (r) of 0.997 and 0.982, respectively. The
binding constant (K) between CY-4 and, NNK and NNN
were 4.04 × 104 and 2.34 × 103 with the correlation
coefficient (r) of 0.988 and 0.978, respectively, (Fig. 3).
The binding constants indicate that the interaction
between the protoporphyrin derivatives CY-2 and CY-4
and, NNK and NNN was strong. Relatively larger
binding constants were observed between CY-2 and
CY-4, and NNK. Therefore, the interaction between the
protoporphyrin derivatives and NNK is stronger than
those involving NNN. These results were consistent with
the reduce level of TSNAs in MSS.
CY-2 (μg)
NNK
NNN
CY-4, μg NNK NNN
0
5
0
0
0
5
0
0
13.6
22.9
33.8
36.4
10.7
13.9
21.9
22.5
20.4
23.6
33.2
37.6
10.5
14.8
25.1
26.8
15
30
45
15
30
45
a The percentage reduction was calculated in comparision to the
level in control cigarettes with unmodified filters.
reduction of TSNA levels was achieved for cigarettes
containing more amounts of protoporphyrin derivatives
in the filter. With regard to both CY-2 and CY-4, the
reduction of NNK is more effective than the reduction
of NNN.
Interaction between protoporphyrin derivatives
and NNK and NNN
Fluorescence spectra (Fig. 2) of CY-2 and CY-4 were
obtained with various doses of NNK and NNN. The
Fig. 2. Changes in fluorescence emission spectra of the protoporphyrin derivatives CY-2 (upper) and CY-4 (lower) in dichloromethane
with various concentrations (mM) of NNK (left) & NNN (right)
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F.Y. TAO ET AL.
Fig. 3. B-H fluorescence plot of CY-2 (upper) and CY-4 (lower) with NNK (left) and NNN (right)
The UV-visible spectra (Fig. 4) of protoporphyrin
derivatives CY-2 and CY-4 with different concentrations
of NNK and NNN were obtained. The intensity of
the characteristic absorption peak of protoporphyrin
derivatives CY-2 and CY-4 at 399 nm enhanced along
with the increase of the TSNA concentrations, finally
reaching saturated status. The spectral intensities for
the different concentrations of TSNAs were plotted to
obtain the protoporphyrin derivatives UV-vis spectrum.
A slight red shift (about 2 nm) was observed in the UV-vis
spectra. UV-visible spectrum experiments suggest that
protoporphyrin derivatives CY-2 and CY-4 could interact
strongly with NNK and NNN.
sizes, properties, functional groups, and chirality.
Strong p–p interactions may occur between porphyrins
and aromatic molecules [39], and this property has
been applied on the liquid chromatography stationary
phase [40]. Meanwhile, the hydrogen bond interaction
between prophyrins and small guest molecules was
generally used to construct supermolecular compounds,
and it plays important role in molecular recognition
[41–42]. We speculate that protoporphyrin derivatives
CY-2 and CY-4 may interact with NNK and NNN by the
hydrogen binds between NO functional groups and OH.
The p–p interactions between the macrocyclic structure
of porphyrin and the aromatic framework of pyridine
maybe another driving force.
Mechanism of TSNAs reduction by protoporphyrin
derivatives
CONCLUSION
Porphyrin molecules with the macrocyclic
“tetrapyrrole” have rigid structures and large aromatic
framework, specific binding of OH, NH2 functionalities
or other tailed ligands according to the hard-soft
acid-base paradigm, and the precise control on the
topology and substitution of the receptor through well-
established synthetic methodologies that allow the
prophyrin macrocycle to be decorated on demand. Many
porphyrin compounds were designed to specifically
recognize particular molecules with certain molecular
Protoporphyrin derivatives are potent additives in
cigarettes to reduce TSNAs levels in MSS and the
environment. The addition of protoporphyrin to cigarette
filters is economical, environmental friendly, and feasible
for cigarette production. The results of this study could
facilitate the development of low-harm cigarettes and
reduce the levels ofTSNAs in the environment to decrease
indoor air pollution. However, the potential transfer of
porphyrins to cigarette smoke or their dissolution in the
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PROTOPORPHYRIN DERIVATIVES ON REDUCING THE TOBACCO SPECIFIC N-NITROAMINES LEVELS OF SMOKE
315
Fig. 4. Change in absorption spectra of CY-2 (upper) and CY-4 (lower) in DCM with various amount NNK (left) & NNN (right);
the concentration of CY-2 & CY-4 was 4 μM
mouth and the toxicological consequences need to be
further evaluated in future studies.
3. IARC monographs. Tobacco Smoke and Involuntary
Smoking (IARC Monographs on the Evaluation of
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Acknowledgements
This work was financially supported by Chuanyu
Branch of China Tobacco Corporation. We also thank the
Analytical & Testing Center of Sichuan University for
Sample Analysis.
Supporting information
<<Text to be completed by authors>> Supplementary
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www.worldscinet.com/jpp/jpp.shtml.
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