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Ind. Eng. Chem. Res. 2007, 46, 2220-2223
Simplified Estimation of the Octanol-Air Partition Coefficient Kia Sepassi* and Samuel H. Yalkowsky College of Pharmacy, The UniVersity of Arizona, Tucson, Arizona 85721
The octanol-air partition coefficient is commonly used to understand the extent of chemical partitioning between the atmosphere and organic matter in the environment. In this study, octanol-air partition coefficients were estimated by generating an expression from combining empirical equations for the molar octanol solubility and saturated vapor pressures of organic compounds. The resultant equation simply estimates octanol-air partition coefficients from boiling points, entropies of boiling, and heat capacity changes on boiling. Introduction
Koa )
Inhalation is the most important route of unintentional entry of chemicals into the human body.1 According to the United States Environmental Protection Agency (www.epa.gov), hazardous air pollutants may cause cancer or other serious health effects, as well as adverse environmental and ecological effects. The octanol-air partition coefficient is useful in establishing health guidelines for volatile organic compounds.2 Knowledge of this descriptor is important in determining the absorption and bioaccumulation of environmentally relevant compounds, and thus, its simple estimation is desirable. QSPR schemes for the estimation of this property have been developed but are limited to specific chemical classes.3-9 The methods of Abraham10 and Meylan & Howard11 are notable exceptions to the QSPR approaches. The aim of this manuscript is to generate an equation for the estimation of the octanol-air partition coefficient. This will be accomplished by combining empirical relationships for the molar octanol solubility and saturated vapor pressures of organic compounds. Background
(I)
where Coct and Cair are the molar concentrations of the solute in octanol and air, respectively. At saturation, the ratio of the concentrations of a solute in octanol and air can be approximated by the ratio of its molar solubility in octanol (Soct) to its saturated vapor pressure (VP). The latter is given in atmospheres divided by RT, where R is the ideal gas constant in L‚atm/mol‚K and T is the experimental temperature in units of kelvin. Thus, the unitless octanol-air partition coefficient can be estimated from the molar octanol solubility and saturated vapor pressure by * To whom correspondence should be addressed. Mailing address: College of Pharmacy, The University of Arizona,1703 East Mabel Street, Tucson, AZ 85721. E-mail:
[email protected]. Phone: 520-626-4309. Fax: 520-626-2466.
(II)
Equation II illustrates that the octanol-air partition coefficient is simply estimated from the molar octanol solubility and saturated vapor pressure. Octanol Solubility. Recently, Sepassi and Yalkowsky12 developed an empirical equation for the estimation of the molar octanol solubility of organic compounds. For organic liquids, they demonstrated that complete miscibility with octanol occurred for solvents having solubility parameters ranging from 15 to 28 (J/cm3)0.5. For these liquids, the molar octanol solubility (Soct) can be estimated by
log Soct ) 0.5
(III)
Since the molarity of neat octanol is 6.33 mol/L, 0.5 corresponds to a molar solubility of 3.17 mol/L for liquid solutes with solubility parameters in the above range. The molar octanol solubility of crystalline solutes was shown to be the product of the solubility it would have if it were a liquid and its ideal crystalline solubility. This was shown by Sepassi and Yalkowsky12 to be
The octanol-air partition coefficient is commonly used to describe the partitioning of a solute between the atmosphere and the organic matter in the environment. This relationship is given by
Coct Koa ) Cair
Soct VP/RT
log Soct ) 0.5 -
∆Sm(Tm - T) 2.3RT
(IV)
where ∆Sm is the entropy of melting and Tm is the melting point. Note, if the solute is a liquid at room temperature and has a solubility parameter in the above range, this equation is simplified to eq III. Vapor Pressure. The saturated vapor pressure of an organic compound can be estimated by the Clausius-Clapeyron equation and its melting point, boiling point, and transition properties. If the heat capacity change on melting is assumed negligible, the integrated form of the Clausius-Clapeyron equation is given by
log VP ) -
∆Sm(Tm - T) ∆Sb(Tb - T) ∆Cpb + 2.3RT 2.3RT 2.3R Tb Tb - T - ln (atm) (V) T T
[
]
where the saturated vapor pressure in atmosphere units is estimated from the melting point (Tm), boiling point (Tb),
10.1021/ie061156w CCC: $37.00 © 2007 American Chemical Society Published on Web 02/24/2007
Ind. Eng. Chem. Res., Vol. 46, No. 7, 2007 2221
reference temperature (T), entropy of melting (∆Sm), entropy of boiling (∆Sb), and heat capacity change on boiling (∆Cpb). Methods Octanol-Air Partition Coefficient. Equation II allows for the estimation of the octanol-air partition coefficient from the molar octanol solubility and saturated vapor pressure of a compound. Under room temperature conditions (R ) 0.0820578 L‚atm/mol‚K, T ) 298 K), eq II is simplified to
Koa )
24.47Soct VP
(VI)
Taking the logarithm of this equation and substituting in eqs IV and V leads to
log Koa ) 1.89 + ∆Sb(Tb - T) ∆Cpb Tb - T Tb (VII) - ln 2.3RT 2.3R T T
[
]
Figure 1. Log of the experimental and predicted octanol-air partition coefficients.
where the unitless octanol-air partition coefficient is estimated from the boiling point, entropy of boiling, and heat capacity change on boiling. It should be noted that the terms relating to the solid in eqs IV and V are eliminated when they are combined. Entropy of Boiling. The entropy of boiling can be estimated by Trouton’s rule, which states that the entropy of boiling for non-hydrogen bonded organic compounds can be assumed a constant value of 88 J/mol‚K. Myrdal et al. proposed the following empirical equation for the more accurate estimation of the entropy of boiling
∆Sb ) 86 + 0.4τ + 1421HBN (J/mol‚K)
(VIII)
where τ is the molecular flexibility number and HBN is the hydrogen bond density number (HBN).13 The molecular flexibility number is given by
τ ) SP3 + 0.5SP2 + 0.5RING - 1
(IX)
where SP3, SP2, and RING denote the number of nonring, nonterminal sp3 and sp2 atoms and the number of independent fused ring systems in a molecule. The molecular hydrogen bond density number is determined from
HBN )
xOH + COOH + 0.33xNH2 MW
(X)
where OH, COOH, and NH2 denote the number of hydroxyl, carboxylic acid, and amine groups on a compound.13 MW is the molecular weight of the compound. Heat Capacity Change on Boiling. Experimental data for the heat capacity change on boiling are scarce due to the difficulty involved in obtaining gas phase heat capacities over large temperature ranges. Sepassi et al. generated the following empirical equation for the estimation of the heat capacity change on boiling at the boiling point using the molecular flexibility number14
∆Cpb ) -91 - 1.2τ (J/mol‚K)
Figure 2. Error distribution as a function of reported octanol-air partition coefficients.
gas-chromatographic methods.10,15-21 Multiple values were obtained for some compounds, and original references for the measurements are provided. The available boiling points of these compounds ranged from 305 to 809 K and were obtained from MPBPWIN version 1.41 provided by the United States Environmental Protection Agency.22 Since the current method relies on knowledge of the molecular structure and boiling point, compounds with unknown boiling points are not included in this table. Appendix II in the Supporting Information contains 52 octanol-air partition coefficients at 25 °C obtained from octanol solubility and vapor pressure ratios.10 These values are shown separately here since they may or may not be considered experimental. The boiling points of these compounds were also obtained from MPBPWIN version 1.41.22 Results and Discussion Octanol-Air Partition Coefficient. The final equation used for the estimation of the octanol-air partition coefficient is obtained by substituting eqs VIII and XI into eq VII, leading to
(XI)
It should be noted that this equation along with eq VIII were developed from independent data sets. Experimental Data Appendix I in the Supporting Information contains 207 octanol-air partition coefficients at 25 °C obtained using various
log Koa ) 1.89 +
(86 + 0.4τ + 1421HBN)(Tb - T) 2.3RT Tb (-91 - 1.2τ) Tb - T - ln (XII) 2.3R T T
[
]
This equation is only applicable to those organic compounds with solubility parameters in the range of complete miscibility
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Ind. Eng. Chem. Res., Vol. 46, No. 7, 2007
Table 1. Octanol-Air Partition Coefficients of Chlorobenzenes Reported at 25 °C name
log Koaa
log Koab
mean
log Koac
errord
CBZ 1,2-D2CBZ 1,3-D2CBZ 1,4-D2CBZ 1,2,3-T3CBZ 1,2,4-T3CBZ 1,3,5-T3CBZ 1,2,3,4-T4CBZ 1,2,3,5-T4CBZ 1,2,4,5-T4CBZ P5CBZ H6CBZ
4.99 4.89 4.92 5.65 5.54 5.38 6.25 6.09 6.10 6.75
4.48 4.27 4.32 5.32 5.10 4.89 5.83 5.78 5.80 6.50 7.55
4.74 4.58 4.62 5.49 5.32 5.14 6.04 5.94 5.95 6.63
3.74 4.71 4.56 4.56 5.51 5.41 5.29 6.28 6.11 6.07 6.79 7.88
0.03 0.02 0.06 -0.02 -0.09 -0.15 -0.24 -0.17 -0.12 -0.16
a
Reported values of Lei et al.23 b Reported values of Staikova et al.24 c Estimated from eq XII. d Difference between the mean value and those predicted by eq XII.
with octanol, i.e., 15-28 (J/cm3)0.5. Fortunately, this range includes the vast majority of environmentally relevant compounds. Figure 1 shows that eq XII estimates octanol-air partition coefficients at 25 °C over twelve orders of magnitude with reasonable accuracy for the data in Appendix I (×) and II (+). The average error and average absolute error are -0.10 and 0.32 log units for the data in Appendix I (n ) 207) and -0.08 and 0.36 log units for the data in Appendix II (n ) 52). Combining these two data sets (n ) 259) leads to an average error and average absolute error of -0.10 and 0.33 log units, respectively. The combined data set represents polycyclic aromatic hydrocarbons, linear alkanes, PCB’s, chlorobenzenes, dioxins, etc. Figure 2 depicts the error distribution in estimating octanolair partition coefficients as a function of the reported values. Note that, from the total number of reported octanol-air partition coefficients (n ) 259), only 7 are predicted above one log unit from the reported value. To illustrate the range of reported octanol-air partition coefficient values, experimental values for the chlorobenzenes obtained from various references are presented in Table 1. For the majority of the compounds listed in Table 1, the values estimated by eq XII are within the range of the experimental values. For example, the log octanol-air partition coefficient of 1,3-dichlorobenzene ranges from 4.27 to 4.89, corresponding to a 4-fold difference between the two values. The mean value for this compound is 4.58, and the value estimated from eq XII is 4.56. Conclusion A new nonregression based equation for the estimation of the octanol-air partition coefficient was developed and validated on a structurally diverse data set. This new equation provides reasonable estimates of the octanol-air partition coefficients from the boiling point, entropy of boiling, and heat capacity change on boiling. The transition properties, entropy of boiling, and heat capacity change on boiling were estimated from empirical equations. From the total number of 259 octanol-air partition coefficients, 97% are estimated to within one log unit from the reported value. Example Calculating the Octanol-Air Partition Coefficient of 2-Pentanone at 298 K Using Equation XII.
Calculated transition properties:
Tb ) 375.4 K, T ) 298 K, τ ) 1.5, MW ) 86.1 g/mol, and HBN ) 0. ∆Sb ) 86 + 0.4τ + 1421HBN ) 86 + 0.4(1.5) + 1421 (0) ) 86.6 J/mol‚K ∆Cpb ) -91 - 1.2τ ) -91 - 1.2(1.5) ) -92.8 J/mol‚K Substituting In eq XII:
log Koa ) 3.20 (estimated) log Koa ) 3.19 (experimental) Supporting Information Available: Appendix I containing octanol-air partition coefficients determined from gas-chromatographic methods and Appendix II containing octanol-air partition coefficients determined from octanol solubility and vapor pressure ratios. Included in both appendices are the chemical name, CAS number, molecular weight, boiling point, and reference for the reported value. The error and absolute errors in log units are also provided. This material is available free of charge via the Internet at http://pubs.acs.org. Literature Cited (1) Hau, K.; Connell, D.; Richardson, B. Mechanism of acute inhalation toxicity of alkanes and aliphatic alcohols. EnViron. Toxicol. Pharmacol. 1999, 6, 159. (2) Hau, K. M.; Connell, D. W.; Richardson, B. J. Use of Partition Models in Setting Health Guidelines for Volatile Organic Compounds. Reg. Toxicol. Pharmacol. 2000, 31, 22. (3) Chen, J. W.; Quan, X.; Zhao, Z.; Yang, F. L.; Schramm, K. W.; Kettrup, A. Quantitative Structure-Property Relationships for Octanol-Air Partition Coefficients of PCDD/Fs. Bull. EnViron. Contam. Toxicol. 2001, 66, 755. (4) Chen, J.; Xue, X.; Schramm, K.; Quan, X.; Yang, F.; Kettrup, A. Quantitative structure-property relationships for octanol-air partition coefficients of polychlorinated biphenyls. Chemosphere 2002, 48, 535. (5) Chen, J.; Harner, T.; Yang, P.; Quan, X.; Chen, S.; Shramm, K.; Kettrup, A. Quantitative predictive models for octanol-air partition coefficients of polybrominated diphenyl ethers at different temperatures. Chemosphere 2002, 51, 577. (6) Chen, J. W.; Harner, T.; Schramm, K. W.; Quan, X.; Xue, X. Y.; Wu, W. Z.; Kettrup, A. Quantitative relationships between molecular structures, environmental temperatures and octanol-air partition coefficients of PCDD/Fs. Sci. Total EnViron. 2002, 300, 155. (7) Chen, J.; Xue, X.; Schramm, K.; Quan, X.; Yang, F.; Kettrup, A. Quantitative structure-property relationships for octanol-air partition coefficients of polychlorinated naphthalenes, chlorobenzenes and p,p′-DDT. Comput. Biol. Chem. 2003, 27, 165. (8) Chen, J. W.; Harner, T.; Schramm, K. W.; Quan, X.; Xue, X. Y.; Kettrup, A. Quantitative relationships between molecular structures, environmental temperatures and octanol-air partition coefficients of polychlorinated biphenyls. Comput. Biol. Chem. 2003, 27, 405. (9) Puzyn, T.; Falandysz, J. Computational estimation of logarithm of n-octanol/air partition coefficient and subcooled vapor pressures of 75 chloronaphthalene congeners. Atmos. EnViron. 2005, 39, 1439. (10) Abraham, M. H.; Le, J.; Acree, W. E.; Carr, P. W.; Dallas, A. J. The solubility of gases and vapours in dry octan-1-ol at 298 K. Chemosphere 2001, 44, 855. (11) Meylan, W. M.; Howard, P. H. Estimating Octanol-Air Partition Coefficients with Octanol-Water Partition Coefficients and Henry’s Law Constants. Chemosphere 2005, 61, 640. (12) Sepassi, K.; Yalkowsky, S. H. Solubility Prediction in Octanol: A Technical Note. Pharm. Sci. Technol. 2006, 7, E1.
Ind. Eng. Chem. Res., Vol. 46, No. 7, 2007 2223 (13) Myrdal, P. B.; Krzyaniak, J. F.; Yalkowsky, S. H. Modified Trouton’s Rule for Predicting the Entropy of Boiling. Ind. Eng. Chem. Res. 1996, 35, 1788. (14) Sepassi, K.; Myrdal, P. B.; Yalkowsky, S. H. Estimating PureComponent Vapor Pressures of Complex Organic Molecules: Part II. Ind. Eng. Chem. Res. 2006, 45, 8744. (15) Hiatt, M. H. Analyses of fish tissue by vacuum distillation/gas chromatography/mass spectrometry. Anal. Chem. 1997, 69, 1127. (16) Hiatt, M. H. Bioconcentration factors for volatile organic compounds in vegetation. Anal. Chem. 1998, 70, 851. (17) Harner, T.; Bidleman, T. F. Measurement of Octanol-Air Partition Coefficients of Polycyclic Aromatic Hydrocarbons and Polychlorinated Naphthalenes. J. Chem. Eng. Data 1998, 43, 40. (18) Harner, T.; Green, N. J. L.; Jones, K. V. Measurements of OctanolAir Partition Coefficients for PCDD/Fs: A Tool in Assessing Air-Soil Equilibrium Status. EnViron. Sci. Technol. 2000, 34, 3109. (19) Shoeib, M.; Harner, T. Using Measured Octanol-air Partition Coefficients to Explain Environmental Partitioning of Organochlorine Pesticides. EnViron. Toxicol. Chem. 2002, 21, 984. (20) Wania, F.; Lei, Y. D.; Harner, T. Estimating Octanol-Air Partition Coefficients of Nonpolar Semivolatile Organic Comopunds from Gas Chromatographic Retention Times. Anal. Chem. 2002, 74, 3476.
(21) Odabasi, M.; Cetin, E.; Sofuoglu, A. Determination of octanol-air partition coefficients and supercooled liquid vapor pressures of PAHs as a function of temperature: Application to gas-particle partitioning in an urban atmosphere. Atmos. EnViron. 2006, 40, 6615. (22) MPBPWIN, v1.41; U.S. Environmental Protection Agency: Washington, D.C., 2000; www.epa.gov. (23) Lei, Y. D.; Wania, F.; Mathers, D.; Mabury, S. A. Determination of vapor pressures, octanol-air partition coefficients for polyfluorinated sulfonamide, sulfonamidoethanols, and telomere alcohols. J. Chem. Eng. Data 2004, 49, 1013. (24) Staikova, M.; Wania, F.; Donaldson, D. J. Molecular Polarizability as a single-parameter predictor of vapour pressures and octanol-air partitioning coefficients of non-polar compounds: a priori approach and results. Atmos. EnViron. 2004, 38, 213.
ReceiVed for reView September 1, 2006 ReVised manuscript receiVed January 11, 2007 Accepted January 26, 2007 IE061156W
