Article pubs.acs.org/JPCB
Dissociation Constants of Parabens and Limiting Conductances of Their Ions in Water Ana Kroflič,† Alexander Apelblat,*,‡ and Marija Bešter-Rogač*,† †
Faculty of Chemistry and Chemical Technology, University of Ljubljana, SI-1000 Ljubljana, Slovenia Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer Sheva, 84105, Israel
‡
ABSTRACT: Precise measurements of electrical conductivities of methylparaben, ethylparaben, propylparaben, and butylparaben sodium salts in dilute aqueous solutions were performed from 278.15 to 313.15 K in 5 K intervals. Experimental conductivity data were analyzed applying the Quint−Viallard conductivity equations by taking into account the salt hydrolysis in aqueous solutions. These evaluations yield the limiting conductances of paraben anions and the dissociation constants of the investigated parabens in water. From temperature dependence of dissociation constants, the thermodynamic functions associated with the dissociation process were estimated. It was discovered that the contributions of enthalpy and entropy to the Gibbs free energy are quite similar. The Walden products of paraben anions in water are independent of temperature, indicating that the hydrodynamic radii are not significantly affected by temperature.
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ature and pH effect) were mainly reported.16−18 The basecatalyzed hydrolysis of methylparaben has also been proposed as a reference and test reaction for isothermal flow microcalorimeters used for determination of kinetic and thermodynamic parameters.21 Considering the importance of the interaction of parabens with micelles, a number of studies have been devoted to partitioning of parabens between water and micellar pseudophases and to the effect of micelles on the value of paraben dissociation constants.15,20 In this work, the precise values of electrical conductivities in dilute aqueous solutions of paraben sodium salts (RPBONa), namely methylparaben (MeBPONa), ethylparaben (EtPBONa), propylparaben (PrPBONa), and butylparaben (BuPBONa), in the 278.15−313.15 K temperature range are reported. A search in the literature failed to reveal any measurements of this kind so far. Applying the molecular model of hydrolysis of salt of weak organic base in water, it was possible to determine limiting conductances of paraben ions, λ0(RPBO¯,T), dissociation constants of parabens, K(T), and thermodynamic functions associated with the dissociation process from the experimental conductivities.
INTRODUCTION Alkyl esters of 4-hydroxybenzoic acid (called parabens and denoted here as RPBOH) are widely used in food, cosmetic, and pharmaceutical industry due to their antimicrobial activity, low toxicity, and low cost. They often serve as food additives and preservatives in cosmetics and are common constituents of shampoos, moisturizers, deodorants, antiperspirants, shaving gels, lubricants, and toothpastes. Their bactericidal and fungicidal properties are also utilized in topical and parenteral pharmaceuticals. Parabens have been the subject of numerous studies that have established not only their broad spectrum of action against microorganisms1,2 but also their efficiency, stability, and their lack of side effects.3,4 Despite these studies, a controversy surrounding parabens has been mounting since late 1990s, when several studies suggested that parabens have an estrogenic activity.5−8 It has been even intensified in 2004 when Darbre et al. detected the traces of parabens in breast tumor tissue samples.9 Lately, it turned out that there is no proven link between parabens and breast cancer and that the estrogenic activity of parabens is immensely lower than that of estrogen.3,4,10−13 Due to the solubility limitations, parabens as water-soluble antiseptics are used in a form of sodium salts. They are relatively stable over a wide range of temperature and pH. Commercial parabens are synthetically produced, although some of them are also found in plants, for example, methylparaben in blueberries. Resistance of microorganisms to parabens14,15 and their degradation reactions16−18 as well as paraben behavior in micellar mixtures19,20 have been also investigated in the literature. From degradation reactions, the kinetic aspects of catalytic hydrolysis of parabens in alkaline solutions (temper© 2012 American Chemical Society
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EXPERIMENTAL SECTION Materials. Methyl-4-hydroxybenzoate sodium salt (methylparaben sodium salt, MePBONa, Fluka, Germany, PhEur, M = 174.13 g/mol), ethyl-4-hydroxybenzoate sodium salt (ethylparaben sodium salt, EtPBONa, Chemo GmbH, Germany, PhEur, M = 188.16 g/mol), propyl-4-hydroxybenzoate sodium Received: November 19, 2011 Revised: January 3, 2012 Published: January 5, 2012 1385
dx.doi.org/10.1021/jp211150p | J. Phys. Chem. B 2012, 116, 1385−1392
The Journal of Physical Chemistry B
Article
Table 1. Experimental Molar Conductances, Λexpt, of Paraben Sodium Salts in Aqueous Solution as a Function of Molality, m, and Temperature, Ta Λexpt 103m
a
278.15 K
283.15 K
0.2448 0.4766 0.7676 1.0543 1.4006 1.8129 2.2556 2.7064 3.1425 3.7060 4.3238 5.0049
50.15 48.42 47.41 46.85 46.39 45.94 45.68 45.44 45.28 45.10 44.93 44.75
58.77 56.61 55.34 54.60 53.90 53.42 53.07 52.76 52.55 52.31 52.09 51.83
0.2400 0.5027 0.8140 1.1239 1.4796 1.8543 2.2537 2.7139 3.3175 4.0577 4.9392
49.28 47.45 46.72 46.05 45.59 45.16 44.88 44.60 44.31 44.03 43.75
57.73 55.53 54.47 53.71 52.92 52.56 52.19 51.85 51.47 51.13 50.67
0.2699 0.5390 0.8451 1.1477 1.4899 1.8237 2.2219 2.6784 3.1925
48.76 46.88 45.95 45.41 44.96 44.61 44.28 44.00 43.76
57.11 54.82 53.64 52.93 52.30 51.89 51.49 51.15 50.83
0.2639 0.5302 0.8434 1.1704 1.5664 2.0087 2.4637 3.0336 3.6410 4.3703
48.71 46.73 45.77 45.10 44.57 43.88 43.57 43.31 43.03 42.67
57.04 54.70 53.47 52.64 51.62 51.09 50.76 50.38 50.10 49.60
288.15 K
293.15 K
298.15 K
Methylparaben Sodium Salt: b = 0.067 kg2·dm−3·mol−1 68.13 78.33 89.25 65.48 75.07 85.27 63.89 73.09 82.87 62.94 71.78 81.29 62.06 70.82 80.11 61.45 70.05 79.16 60.98 69.46 78.41 60.58 68.96 77.80 60.31 68.61 77.25 60.00 68.16 76.84 59.68 67.81 76.38 59.40 67.47 75.95 Ethylparaben Sodium Salt: b = 0.063 kg2·dm−3·mol−1 66.98 77.05 87.88 64.35 73.78 83.90 62.91 72.02 81.70 62.02 70.58 80.03 61.07 69.72 78.94 60.52 69.08 78.12 60.04 68.46 77.39 59.61 67.93 76.70 59.13 67.33 75.74 58.57 66.64 75.15 58.16 66.16 74.57 Propylparaben Sodium Salt: b = 0.060 kg2·dm−3·mol−1 66.22 76.13 86.76 63.41 72.73 82.65 61.92 70.88 80.42 61.04 69.72 79.00 60.26 68.81 77.90 59.74 68.18 77.11 59.24 67.55 76.36 58.81 67.03 75.69 58.44 66.52 74.88 Butylparaben Sodium Salt: b = 0.058 kg2·dm−3·mol−1 66.18 76.08 86.75 63.33 72.65 82.65 61.80 70.74 80.27 60.78 68.96 78.24 59.56 68.09 77.16 58.93 67.24 76.10 58.41 66.66 75.35 58.00 66.11 74.73 57.58 65.23 73.63 56.58 64.47 72.76
303.15 K
308.15 K
313.15 K
100.85 96.15 93.26 91.38 89.93 88.78 87.86 86.97 86.48 85.94 85.39 84.87
113.17 107.58 104.00 101.96 100.29 98.89 97.78 96.71 96.06 95.43 94.82 94.20
126.10 119.55 115.31 112.93 110.86 109.18 107.83 106.68 105.96 105.16 104.50 103.75
99.25 94.68 91.64 90.01 88.72 87.67 86.79 85.74 84.90 84.13 83.42
111.62 106.14 102.52 100.55 98.98 97.56 96.70 95.52 94.50 93.61 92.69
124.66 118.25 113.83 111.56 109.67 108.03 106.61 105.63 104.38 103.33 102.34
98.19 93.23 90.44 88.86 87.51 86.54 85.66 84.88 83.89
110.32 104.45 101.11 99.22 97.67 96.49 95.42 94.30 93.44
123.17 116.15 112.10 109.94 108.17 106.75 105.29 104.16 103.44
97.80 93.13 89.60 88.05 86.76 85.47 84.48 83.10 82.48 81.60
109.87 104.12 100.21 98.34 96.72 95.35 94.18 92.56 91.77 90.85
122.65 115.79 111.47 109.25 107.27 105.73 103.40 102.64 101.63 100.62
Units; m, mol·kg−1; Λ, S·cm2·mol−1.
titration and taken into account in calculating the concentrations. Stock solutions were prepared by mass from pure compounds and demineralized distilled water. Demineralized water was distilled two times in a quartz bidestillation apparatus (Destamat Bi 18E, Heraeus). The final product with specific conductivity T|ΔS°| ≈ ΔH°, ∂ΔG°/∂T > 0, ∂ΔH°/∂T < 0, and ∂ΔS°/∂T < 0). Similar behavior is observed for many substituted phenols.36,37
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Figure 3. Values of ln[λ0(RPBO−)d2/3] as a function of 1/T: (■) methylparaben sodium salt; (●) ethylparaben sodium salt; (▲) propylparaben sodium salt; (▼) butylparaben sodium salt.
CONCLUSIONS Systematic determination of conductivity data for four paraben sodium salts was performed in dilute aqueous solutions from 278.15 to 313.15 K. The limiting conductances of paraben anions were evaluated by considering the hydrolysis effect after salts are dissolved in water. It was observed that the Walden products of paraben anions are almost independent of temperature. The conductivity measurements also permitted to determine the dissociation constants of parabens in water and the thermodynamic functions associated with the dissociation process.
The corresponding partial molar enthalpies associated with the ion movement are ΔHλ(MePBO¯) = 17.7 kJ·mol−1, ΔHλ(EtPBO¯) = 18.3 kJ·mol−1, ΔHλ(PrPBO¯) = 18.3 kJ·mol−1, and ΔHλ(BuPBO¯) = 18.6 kJ·mol−1, determined from eq 16. The Walden products in the investigated temperature range are practically temperature independent, η(T)λ0(MePBO¯,T) = 0.243 ± 0.003 S·cm2·equiv−1·Pa·s, η(T)λ0(EtPBO¯, T) = 0.232 ± 0.005 S·cm2·equiv−1·Pa·s, η(T)λ0(PrPBO¯,T) = 0.220 ± 0.005 1391
dx.doi.org/10.1021/jp211150p | J. Phys. Chem. B 2012, 116, 1385−1392
The Journal of Physical Chemistry B
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(18) Blaug, S. M.; Grant, D. E. J. Soc. Cosmet. Chem. 1974, 25, 495− 506. (19) Loh, W.; Volpe, P. L. O. J. Colloid Interface Sci. 1992, 154, 369− 377. (20) Vlasenko, A. S.; Loginova, L. P.; Iwashchenko, E. L. J. Mol. Liq. 2009, 145, 182−187. (21) O’Neill, M. A. A.; Beezer, A. E.; Labetaulle, C.; Nicolaides, L.; Mitchell, J. C.; Orchard, J. A.; Conor, J. A.; Kemp, R. B.; Olomolaiye, D. Thermochim. Acta 2003, 399, 63−71. (22) Barthel, J.; Wachter, R.; Gores, H.-J. Temperature Dependence of Conductance of Electrolyte in Nonaqueous Solutions. In Modern Aspects of Electrochemistry; Conway, B. E., Bockris, J. O’M., Eds.; Plenum Press: New York, 1979. (23) Barthel, J.; Feuerlein, F.; Neueder, R.; Wachter, R. J. Solution Chem. 1980, 9, 209−219. (24) Bešter-Rogač, M.; Habe, D. Acta Chim. Slov. 2006, 53, 391−395. (25) Kratky, O.; Leopold, H.; Stabinger, H. N. Z. Angew. Phys. 1969, 27, 273−277. (26) Herington, E. F. G. Pure Appl. Chem. 1976, 48, 1−9. (27) Quint, J.; Viallard, A. J. Solution Chem. 1978, 7, 137−153. (28) Quint, J.; Viallard, A. J. Solution Chem. 1978, 7, 525−531. (29) Quint, J.; Viallard, A. J. Solution Chem. 1978, 7, 533−548. (30) Bešter-Rogač, M.; Bončina, M.; Apelblat, Y.; Apelblat, A. J. Phys. Chem. B 2007, 111, 11957−11967. (31) Kielland, J. J. Am. Chem. Soc. 1937, 59, 1675−1678. (32) Robinson, R. A.; Stokes, R. H. Electrolyte Solutions; Butterworths: London, 1959. (33) Light, T. S.; Licht, S.; Bevilacqua, A. C. Electrochem. Solid-State Lett. 2005, 8, E16−E19. (34) Apelblat, A. J. Mol. Liq. 2002, 95, 99−145. (35) Brummer, S. B.; Hills, G. J. Trans. Faraday Soc. 1961, 57, 1816− 1822. (36) Hepler, L. G.; O’Hara, W. F. J. Phys. Chem. 1961, 65, 811−814. (37) Rosés, M.; Rived, F.; Bosch, E. J. Chromatogr. A 2000, 867, 45− 56. (38) Bešter-Rogač, M. J. Chem. Eng. Data 2011, 56, 4965−4971.
At all the temperatures, the values obtained for the limiting conductivities of methylparaben anion (MePBO¯) are very close to the values reported for the anion of 4-hydroxybenzoic acid sodium salt (p-salicylate anion, Sal-p¯) recently, for example, λ0(MePBO¯,298.15 K) = 27.38 S·cm2·mol−1 (Table 2) and λ0(Sal-p¯,298.15 K) = 26.93 S·cm2·mol−1.38 The same goes for the values of the corresponding partial molar enthalpies associated with the ion movement (ΔHλ(MePBO¯) = 17.7 kJ·mol−1 and ΔHλ(Sal-p¯) = 17.5 kJ·mol−1). Thus, it can be assumed that the methyl group does not hinder ionic movement distinctly in this case. On the other hand, the mobility of the paraben anion is decreasing with the alkyl chain length (27.38, 26.21, 24.98, and 23.81 S·cm2·mol−1 for methyl-, ethyl-, propyl-, and butylparaben at 298.15 K, respectively) and the corresponding partial molar enthalpies are becoming slightly higher. Finally, it can be concluded that the main difference between parabens and their analogue sodium p-salicylate is the pronounced hydrolysis effect. Namely, whereas sodium psalicylate shows typical behavior of a strong 1:1 electrolyte in water, aqueous solutions of parabens have a very high pH values.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected] (A.A.);
[email protected] (M.B.-R.). Tel: +386 1 2419 410 (M.B.-R.). Fax: +386 1 2419 425 (M.B.-R.).
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ACKNOWLEDGMENTS The authors are indebted to Dr. Matjaž Bončina for many fruitful discussions and his careful reading of the manuscript. Financial support by the Slovenian Research Agency through Grant No. P1-0201 is gratefully acknowledged.
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