Environ. Sci. Technol. 2008, 42, 456–458
The pKa Values of PFOA and Other Highly Fluorinated Carboxylic Acids KAI-UWE GOSS* UFZ Helmholtz Centre for Environmental Research, Permoserstr. 15, 04318 Leipzig, Germany
Received August 31, 2007. Revised manuscript received October 23, 2007. Accepted October 29, 2007.
The dissociated and nondissociated species of any organic acid differ largely in their physicochemical behavior. The ratio of both species in aqueous systems is determined by the respective pKa value. For perfluorooctanoic acid recent fatemodeling studies have applied a pKa value of 2.8. This value likely is too high by 3 log units. Here, the correct value is estimated to be close to -0.5 based on analogy considerations and molecular modeling. Calculated pKa values for other highly fluorinated carboxylic acids are also presented.
Introduction Perfluorinated carboxylic acids are highly persistent and have been detected in environmental samples around the globe. It has long been known that the partition behavior of ionizable organic compounds such as perfluorinated carboxylic acids strongly depends on their degree of dissociation (1). The neutral form of perfluorooctanoic acid (PFOA) has an estimated log Kair/water of around -2.4 and a log Kow of 4.3 (2) suggesting that both sorption in soils and sediments, as well as volatilization and transport in air, are important processes for its environmental fate. In contrast, the anionic perfluorooctanoate (PFO) is not expected to partition into the gas phase at all, and sorption by most soils and sediments, which usually carry a net negative charge, is expected to be much smaller than for the neutral species (3). PFOA is expected to have a rather small pKa value such that more than 99% of the compound will occur in its anionic form under most environmental conditions. The latter has led to the conclusion that the environmental partitioning of PFOA will be dominated by the anionic form (4); however, this is not necessarily correct. If 1% of the PFOA molecules in water occur in their neutral form (i.e., if pH ) pKa + 2) then the logarithm of the effective air/water distribution ratio for this compound would still be log Dair/water ) -4.4 (Dair/water ) Kaw Racid where Racid is the fraction of the acid in its neutral form, Racid ) 1/1 +10pH-pKa, see ref 1). This implies a partitioning from water into the gas phase that is still likely to matter for the transport behavior of a compound (5) despite the fact that the anionic form–which does not partition into the gas phase at all– dominates the speciation with 99%. The following concrete example illustrates this: in a rain cloud with 0.1 mL water per 100 L of air and a pH value of 5, PFOA would stay mostly in the air (96%) if we assume a pKa value of 2.8, whereas it would reside almost completely in the water (99%) if we assume a pKa value of -0.5 (both calculations are based on a log Kair/water of -2.4). Hence, we may expect that partitioning from water to the air might still be relevant if PFOA had a pKa value of 2.8 as assumed in the literature while this * Corresponding author phone: ++ 41 341 235 1411; fax: ++ 41 341 235 2625; e-mail:
[email protected]. 456
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partition process would hardly matter if the pKa value was -0.5 as suggested here. In the human stomach with a pH of around 2 this difference in pKa values is also likely to be relevant. Hence, it is obvious that an estimation of the environmental fate of PFOA and other perfluorinated carboxylic acids requires accurate knowledge of their speciation so that correct distribution ratios between air and water and other compartments can be calculated. To this end we need to know the pKa values of the compounds of interest as well as the pH of all relevant environmental compartments. The latter is complicated by the fact that currently used global fate models do not include such information. As for appropriate pKa values, past modeling of PFOA partitioning has been done using a pKa value of 2.8 (4, 6) which upon review of the original literature, was actually measured in a 50/50 v/v ethanol/water solution (7). The experimental determination of the pKa values of perfluorinated compounds actually poses an immense problem because of the extremely low water solubility of the neutral form of these compounds. Hence, a classical titration experiment does not seem feasible. In the past, various researchers have overcome similar problems by measuring titration curves in alcohol/water mixtures of various composition and extrapolating the results to pure water (e.g., refs 8, 9). The pKa values that are determined in alcohol-water systems increase with increasing alcohol volume fraction. For existing compound data one finds that a pKa value measured in a 50/50 alcohol/water mixture is typically about one log unit higher than what is measured in water (8, 9). Hence, existing literature data do already suggest that the true pKa of PFOA should be smaller than 2.8. However, any type of titration experiment may also be subject to the following artifact that leads to an overestimation of the pKa value. Organic compounds with a long perfluorinated tail do possess distinct surface active properties. Sorption to interfaces such as the water surface or the walls of a glass vessel may occur to an extent that is unknown for “ordinary” molecules (10). If the aqueous concentration of the nonionic species of the compound is significantly reduced, e.g., by sorption to the walls, in an titration experiment then the titration curve that measures the concentration of the ionic species as a function of pH will be shifted significantly toward higher pH values without affecting its shape as can be shown by the following calculations. The fraction of total compound that is present as the ionic species, RPFO, if no sorption takes place is given by the following expression: RPFO ) 1 -
1 1 + 10pH-pKa
(1)
For the case that the neutral species sorbs with a partition constant, Ksorbens/water, to an available sorbens with the amount, Msorbents, in a water volume, Vwater, an expression for RPFOis derived as follows: RPFO ≡
cPFO in waterVwater cPFOAsorbedMsorbens + cPFO in waterVwater + cPFOA in waterVwater (2)
Dividing by cPFO in water Vwater yields RPFO ) 1+
1 cPFOAsorbed Msorbens cPFO in water Vwater
10.1021/es702192c CCC: $40.75
+
cPFOA in water
(3)
cPFO in water
2008 American Chemical Society
Published on Web 12/12/2007
TABLE 1. pKa values of Propionic Acid and Butyric Acid and Their Analogues with the Final CH3-Unit exchanged by a CF3-Group (17) compound
pKa
CH3CH2COOH CH3CH2CH2COOH
4.9 4.8
pKa CF3CH2COOH CF3CH2CH2COOH
3.0 4.2
TABLE 2. Comparison between Experimental (17) and Calculated pKa Values of Carboxylic Acids with Various Degrees of Fluorination
FIGURE 1. Titration curve for a hypothetical acid with pKa ) 0 for the case that (a) no sorption occurs and (b) the nonionic species sorbs to a sorbens such that only one out of 1000 molecules of the nonionic species resides in the aqueous phase while the rest is sorbed (i.e., Ksorbens/water × Msorbens/Vwater ) 1000), whereas the ionic species does not sorb significantly. The figure shows theoretical calculations. With the Hendersson-Hasselbalch equation, cPFO cPFOA in water 10pH-pKa this can be rewritten as
in water
1
RPFO ) 1+
cPFOAsorbed cPFOA in water
Msorbens 1 + pH-pKa 10pH-pKa Vwater 10
)
(4)
Eventually, when we substitute cPFOA sorbed/cPFOA in water by the sorption constant of the neutral species, Ksorbens/water, we get: RPFO )
1 Msorbens 1 1 + Ksorbens⁄water +1 Vwater 10pH-pKa
(
)
compound
experimental pKa
SPARC pKa
COSMOtherm pKa
CF3COOH CHF2COOH CH2FCOOH CF3CH2COOH CF3CH2CH2COOH
-0.3 1.2 2.7 3.0 4.2
1.35 1.99 3.26 3.15 4.22
0.9 2.0 2.9 3.3 3.8
adjustment is based on a calibration with existing experimental data. Another software suitable for the prediction of pKa is the commercial quantum-chemical model COSMORS (14, 15). In this case the free-energy difference between the neutral and the ionized form of a molecule is calculated and related to the pKa values of the compounds based on a calibrated equation. Whereas the COSMO-RS approach has not been validated as comprehensively as the SPARC software there, it is, in general, expected to predict pKa values with a standard deviation of 0.5 (14). Note, however, that the COSMO-RS method was only developed and validated for the pH scale from 0 to 14 (16).
(5)
Figure 1 provides an example for both titration curves, with (eq 5) and without sorption (eq1). One can see that pKa values higher than the true value would be derived from a titration curve if such a sorption process went unnoticed and a correction for it was not made. It is quite conceivable that such sorption artifacts occur not only in pure water but also in alcohol/water mixtures. Typically, sorption from an alcohol/water mixture would be expected to be reduced compared to sorption from the pure aqueous phase but it may still be substantial. And in fact, there are even cases reported where the addition of a cosolvent did not decrease sorption of an organic acid from the aqueous phase (11). The focus of this work is specific to a reassessment and revised estimate of the pKa for PFOA for which the correct pKa value will be argued to be more likely close to -0.5. Calculated pKa values for other fluorinated carboxylic acids will also be presented.
Materials and Methods The large public interest in the environmental fate of perfluorinated compounds and the various attempts to model their fate demonstrate an urgent need for preliminary pKa values that should be as accurate as possible. The work presented here tries to accomplish this goal by using analogy considerations and by applying two models for predicting pKa values, namely SPARC and COSMO-RS. According to a comprehensive validation, the software SPARC (http:// ibmlc2.chem.uga.edu/sparc/) is quite successful in predicting the pKa values of organic acids (12). In brief, the known pKa value for the reaction center of a molecule is adjusted for the influence exerted by the rest of the molecule (13). This
Results and Discussion What We Can Learn from the Analogy. The pKa values of acetic acid and trichloroacetic acid are 4.75 and 0.77, respectively. The significant shift comes from the electronwithdrawing properties of the chlorine atoms. The same effect occurs for fluorine substituents where the pKa drops to 2.7 for monofluoro acetic acid and to -0.3 for trifluoro acetic acid. Another important feature of fluorination has been pointed out by Henne and Fox (17): A decrease in the pKa is still observable even if the perfluorinated alkyl chain is separated from the carboxylic group by one or two CH2 units (Table 1). Hence, if we add a perfluorinated chain to trifluoroacetic acid to receive PFOA we should certainly expect to see the pKa drop even slightly below the value of -0.3 for trifluoroacetic acid. What We Can Learn from Model Predictions. To get an idea on how SPARC and COSMOtherm perform on fluorinated compounds, a comparison between available experimental values and corresponding predictions was made (Table 2). It appears that both, SPARC and COSMO-RS, overestimate the pKa values in cases where the carbon just next to the carboxylic group is completely fluorinated. In contrast, the effect of fluorination further away from the COOH group is covered quite well. For PFOA the calculated pKa values are -0.11 (SPARC) and 0.7 (COSMO-RS). Based on the validation in Table 2 and the other considerations above we might expect that these values are still somewhat too high so that an estimate of -0.5 still seems to be the most reasonable estimate that we can provide. The difference between a pKa value of -0.5 as suggested here and 2.8 as suggested in the literature is quite substantial (see examples in the introduction). Table 3 lists calculated pKa values for a number of other highly fluorinated carboxylic acids that might be of enviVOL. 42, NO. 2, 2008 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
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TABLE 3. pKa Values for Various Highly Fluorinated Carboxylic Acids of Environmental Concern Calculated with SPARC and COSMO-RS F(CF2)nCOOH, n ) 3–11 F(CF2)3COOH F(CF2)7COOH F(CF2)11COOH F(CF2)nCH2COOH, n ) 2–10 F(CF2)2CH2COOH F(CF2)6CH2COOH F(CF2)10CH2COOH F(CF2)nCF)CHCOOH, n ) 2–10 F(CF2)2CF)CHCOOH F(CF2)6CF)CHCOOH F(CF2)10CF)CHCOOH F(CF2)nCH2CH2COOH, n ) 2–10 F(CF2)2CH2CH2COOH F(CF2)6CH2CH2COOH F(CF2)10CH2CH2COOH F(CF2)nSO2N(H)CH2COOH, n ) 2–10 F(CF2)2SO2N(H)CH2COOH F(CF2)6SO2N(H)CH2COOH F(CF2)10SO2N(H)CH2COOH F(CF2)nSO2N(CH3)CH2COOH, n ) 2–10 F(CF2) 2SO2N(CH3)CH2COOH F(CF2)6SO2N(CH3)CH2COOH F(CF2)10SO2N(CH3)CH2COOH F(CF2)nSO2N(C2H5)CH2COOH, n ) 2–10 F(CF2) 2SO2N(C2H5)CH2COOH F(CF2)6SO2N(C2H5)CH2COOH F(CF2)10SO2N(C2H5)CH2COOH
SPARC
COSMO-RS
0.4 -0.1 -0.2
0.7 0.7 0.8
3.1 2.6 2.5
3.4 3.5 3.5
2.9 2.5 2.4
3.3 3.3 3.4
4.0 3.7 3.6
4.2 4.2 4.2
3.5 3.2 3.2
3.6 3.6 3.6
3.5 3.3 3.2
3.3 3.4 3.1
3.5 3.2 3.2
3.3 3.3 3.3
ronmental relevance. Both models predict a significant influence of the degree of fluorination of the first and–to a lesser extent–the second carbon atom next to the carboxylic group. This is in good agreement with the experimental findings by Henne and Fox (17) collected in Table 2. Furthermore, COSMO-RS predicts little influence of the length of the perfluorinated carbon tail beyond the 3 carbon atoms that are directly neighboring the COOH group. Instead, SPARC does predict a slight decrease of the pKa by 0.3–0.5 units when the fluorinated tail increases from 2 to 10 carbon atoms. In an earlier work we had not found any such influence of the length of the perfluorinated tail on the H-bond properties of the OH-group in telomer alcohols (10). Thus, COSMO-RS results appear more reasonable than the SPARC results in this respect. As discussed above, the calculated pKa values for the perfluorinated carboxylic acids, F(CF2)nCOOH, are probably too high especially for the COSMO-RS calculations (see validation in Table 2 and discussion above). For all other acids exhibiting no fluorination at the carbon atom next to the COOH-group one may expect the COSMO-RS values to be correct within 0.5 units. This is further corroborated by a good agreement with the SPARC-calculated values for the molecules with the shortest perfluorinated tails. In summary, one can conclude that accurate pKa values are certainly crucial for any assessment of the fate of
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perfluorinated acids in the environment. A difference as large as three units as it exists between the value for PFOA used in recent publications, and the one suggested here can have a substantial impact on the expected partition behavior of this compound. While the presented work could not provide exact experimental values for PFOA and other acids, it probably provides the most reasonable numbers that are available so far.
Acknowledgments I thank Mark Russell (DuPont) for providing the list of perfluorinated carboxylic acids that are of environmental relevance and one anonymous reviewer for helpful comments.
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ES702192C
