1. Chemistry of Cigarette Smoke
Chem. Catalyst-Day 3
Define third-hand smoke.

2. Chemistry of Third-hand Smoke (THS)
Residual nicotine from tobacco smoke sorbed to the indoor surfaces constitute THS. It stays for weeks or months.
During that period, it can be exposed to pollutants:
such as ozone O3 that enter the building from outdoors or is generated by using air cleaners.
As well as Nitrous acid, HNO2. or HONO
'Certain compounds - such as ambient nitrous acid or nitrogen dioxide - are present in higher quantities indoors rather than outdoors,' explains Hugo Destaillats, who led the research at Lawrence Berkeley National Laboratory in California, US. This is because they are generated by combustion from indoor gas supplies, fireplaces or the use of electronic equipment. 

3. Oxidation of Sorbed Nicotine by Ozone
nicotinaldehyde
+ atmospheric O3 N O NH O
HCH O
cotinine
We turn now to a new area of research: What happens to the nicotine that accumulates indoors?. Now we are studying the reactivity of sorbed nicotine (on indoor surfaces) to ozone.
Nicotine not only sorbs very strongly and quickly to indoor surfaces, but also remains sorbed for a long time (weeks or months). During that period, it can be exposed to oxidants that enter the building from outdoors. Ozone is a common oxidant, and our studies show that nicotine sorbed to surfaces can react with ozone and generate the oxidation products that are shown in this slide, among others. Formaldehyde is a carcinogen. Our results suggest that combination of indoor surfaces loaded with nicotine from habitual smoking and high ozone levels can be an important source of these secondary pollutants. Besides infiltration of outdoor air, another source of indoor oxidants is the use of ozone generators as “air cleaners.”
formaldehyde
N-dimethylformamide
Generation of secondary pollutants,
Most are toxics and formaldehyde is a carcinogen.

4. The source of Nitrous Acid in Indoor Air
Nitrogen (N2) gas in the air reacts with oxygen (O2) when natural gas is burning. i.e. gas stove, heating system, car engine, etc.
The products are: nitrogen monoxide or nitrogen dioxide (NO, NO2)
N2 + O2  NO2
The nitrogen dioxide reacts with water vapor in the air and produces nitrous acid.
NO2 + H2O  HNO2 or
HONO

5. Experimental Schematics

6. ? NNA NNK + Nitrous acid (HONO) Nicotine
1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal
NNK
4-(methylnitrosamino)-1-(3-pyridinyl)-1-butanone

7. Reaction of THS with ambient HONO
Three main TSNAs are formed in the reaction of sorbed nicotine and gaseous HONO:
1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal) (NNA),
4-(methylnitrosamino)-1-(3-pyridinyl)-1-butanone (NNK),
N-nitroso nornicotine (NNN).
Destaillats and his team used cellulose as a model indoor material, and placed a block of it inside a truck belonging to a smoker for three days. They then analysed the block and compared the results with lab-based tests based on cellulose exposed to vaporised nicotine in a tubular-flow reactor. 'We found that ambient gases [in the truck] reacted with residual nicotine to generate tobacco-specific nitrosamines that are known to be carcinogenic.'
More health risks from smoking
Two of the compounds - N-nitroso nornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridil)-1-butanone (NNK) are also found in tobacco smoke, so have been well-studied in the past. But a third compound was identified that is not usually present in tobacco smoke: 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal), termed NNA. Since it is absent from smoke, NNA has not been investigated in detail, but the team is hopeful that toxicologists will now undertake studies. 

8. Formation of TSNAs from nitrosation of nicotine.
[HONO] = 65 ppb
Formation of TSNAs from nitrosation of nicotine. (A) Surface concentrations of NNA and NNK. In field experiments, sample Truck-A was obtained inside the cabin of a smoker’s truck by wiping the stainless-steel surface of the door of the glove compartment, on which 0.6 μg cm-2 of nicotine was present. Another sample (Truck-B) was collected on clean cellulose substrates that were attached to cabin surfaces for 3 days, over which 34 cigarettes were smoked. The cellulose surface sorbed nicotine passively (1.4 μg cm-2) and also served as reaction medium for the formation of TSNAs. In lab experiments, cellulose substrates were exposed to nicotine vapor (9.1 μg cm-2) and subsequently exposed to HONO (Nic). The same substrates were exposed to sidestream smoke in an environmental chamber, leading to loadings of 1.9 μg cm-2 nicotine, with negligible levels of NNA and NNK (Sorbed SHS). After a 3-hour exposure of this sample to HONO, formation of NNA and NNK on the surface was observed (THS). (B) Time course of nicotine loss and production of NNA and NNK. Cellulose substrates were impregnated with nicotine with an initial surface concentration [N]0 of 1.45 μg cm-2 and subsequently exposed to [HONO]0 = 95 ppbv in a tubular-flow reactor over different periods of time (relative humidity 45%). A biexponential model was fitted to the nicotine surface concentration profile to derive the contributions of desorption and chemical reaction processes. [TSNA] corresponds to the surface concentrations of NNA and NNK, and [N] represents the surface concentration of nicotine. Concentrations were determined by using the exposed geometric areas.
Sleiman M et al. PNAS 2010;107:
©2010 by National Academy of Sciences

9. Concentration vs. Time
time-concentration profiles for surface nicotine and TSNAs in laboratory experiments. Both NNA and NNK formed rapidly, reaching maximum concentrations within the first hour. The graph indicates very little decay of NNA and NNK.
Sleiman M et al. PNAS 2010;107:

10. Tobacco Specific Nitrosamines
TSNA*
Structure MW
(g mol-1)
Pvapor
(mmHg)
NNA
207.2
1.92 x 10-7
NNN
2.52 x 10-5
NNK
177.2
2.15 x 10-7
*Toronto Research Chemicals, Ontario, Canada

11. Analysis of cellulose loaded with SHS before and after reaction with HONO
Nicotine
Quinoline
NNA (after 3H)
NNK(after 3H)
Initial (t=0)
After 3h reaction (μg)
Nicotine (μg)
33.4
0.32
NNN
< LOD
NNA (ng)
0.1 28
NNK (ng)
<LOD
3.1 11