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Prediction of the aqueous solubility: Comparison of the general solubility equation and the method using an amended solvation energy relationship
Prediction of the Aqueous Solubility: Comparison of the General Solubility Equation and the Method Using an Amended Solvation Energy Relationship GANG YANG, YINGQING RAN, SAMUEL H. YALKOWSKY Department of Pharmaceutical Sciences, College of Pharmacy, The University of Arizona, 1703 E. Mabel Street, Tucson, Arizona 85721 Received 15 June 2001; revised 15 August 2001; accepted 23 August 2001
ABSTRACT: An Amended Solvation Energy Relationship (ASER) was recently reported to successfully predict the aqueous solubilities of a set of 664 organic compounds. The average absolute error and root mean square error are 0.43 and 0.62 log units, respectively. When the General Solubility Equation (GSE) is applied to the same set of compounds, it gives an average absolute error of 0.45 log units and a root mean square error of 0.62 log units. These results are similar to those of the ASER method. The advantages and disadvantages of each method are discussed. It is shown that when the two methods agree with each other, they also agree with the experimentally determined values. ß 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:517±533, 2002
Keywords:
aqueous solubility; estimation; Kow; melting point
INTRODUCTION Aqueous solubility is a crucial physical property in pharmaceutical and environmental research. Several methods for the prediction of the aqueous solubility have been published in recent years.1±13 The General Solubility Equation (GSE), as initially proposed by Yalkowsky and Valvani in 1980,2 and recently revised by Jain and Yalkowsky,13 has been used widely. The GSE relates the molar aqueous solubility (Sw) to the Celsius melting point (mp) and the octanol±water partition coef®cient (Kow) by the following simple equation: log Sw 0:5
0:01 mp
25
log Kow
1
The GSE has been shown to produce reasonable predictions for a wide variety of compounds.
An Amended Solvation Energy Relationship (ASER) was recently proposed to predict the aqueous solubility of organic compounds.14 The method starts with an equation that relates a solvation property (SP) to a sum of the following speci®c interaction terms: the excess molar refraction (R2), a combined dipolarity/polarizability H descriptor P (pH2 ), the overall solute hydrogen bond acidity ( Pa2 ), the overall solute hydrogen bond basicity ( bH 2 ), and the McGowan's characteristic molecular volume (Vx). In view of the in¯uence of intermolecular interactions on melting points and P P solubilities, a product term `` aH bH 2 2 '' was incorporated to partly account for the absence of a solid correction term, leading to the ASER as follows: X log Sw c rR2 sH aH 2 a 2 X X X H b bH k a bH 2 2 vVx 2 2
Correspondence to: Gang Yang (Telephone: 520-626-4308; Fax: 520-626-4063; E-mail: [email protected]) Journal of Pharmaceutical Sciences, Vol. 91, 517±533 (2002) ß 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association
where each term is determined by a separate formula and/or a set of group contribution values. Multiple linear regression analysis was used to
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YANG, RAN, AND YALKOWSKY
construct the prediction equation. This method was applied to a diverse set of 664 organic liquids and solids with satisfactory results. In this study, the GSE is applied to the same set of compounds and the prediction results are compared.
METHODS The melting point data for the 664 compounds were obtained from the AQUASOL dATAbASE, Merck Index, and several Internet databases. The octanol±water partition coef®cients were calculated with CLOGP1 software (Version 4.0, BioByte Corp., Claremont, CA). Experimental octanol±water partition coef®cients are listed if available. The experimental aqueous solubilities and the ASER predicted solubilities are those reported by Abraham and Le.14 The aqueous solubilities were also calculated using the GSE of Jain and Yalkowsky.13 For each calculation, the average absolute error (AAE) is determined as X . 3 AAE jlog Scalc log Sobs j n and the root mean square error (RMSE) as hX i1=2 RMSE log Scalc log Sobs 2 =n
4
where log Scalc and log Sobs are the logarithms of the predicted and experimental aqueous solubility, respectively, and n is the number of compounds.
RESULTS Octanol±Water Partition Coef®cient Experimental partition coef®cients were found for 530 of the 664 compounds. As shown in Figure 1, the calculated partition coef®cients using CLOGP1 are in very good agreement with the available measured values (MLOGP), with an AAE of only 0.121 log units. CLOGP1 version 4.0 seems to give more accurate estimations of octanol±water partition coef®cients than the previous version. Partition coef®cients calculated with CLOGP1 are used in the solubility calculations because they are easily determined and are available for compounds with no available experimental values. The CLOGP and the available MLOGP values for Abraham's data set are listed in the second and third column of the Appendix. JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 91, NO. 2, FEBRUARY 2002
Figure 1. Measured log P (MlogP) versus ClogP (n 530).
Melting Point Melting points (mps) were found for 662 of the 664 compounds. The other two compounds (hydrocortisone 21-acetate and morphine) decompose on melting and thus may not have true mps. (Note that the use of a decomposition temperature in the GSE gives a maximum solubility estimation. The predicted solubility would be lower if the true mp were higher than the decomposition temperature.) If polymorphs or hydrates of the compound exist, the mp of the most stable form in equilibrium with the solution should be used. The mps used in the GSE are listed in the fourth column of the Appendix. Note that an mp of 258C is used for all liquids so that the crystal term vanishes. Solubility The solubility values used by Abraham for the 664 compounds studied are listed in the 5th column of the Appendix. All of these values were con®rmed to be in agreement with the values in the AQUASOL dATAbASE. The solubilities predicted by Abraham's ASER and by the GSE are listed in columns 6 and 7 of the Appendix, respectively. They are also plotted against the experimental solubility values in Figure 2. The AAE for the 662 compounds is 0.446 log units and the RMSE is 0.622 log units using the GSE method; these values are consistent with the results of previous studies.13,15,16 As shown in Table 1, the results are
COMPARISON OF ASER AND THE GSE
519
similar when the two compounds that decompose before melting are included.
DISCUSSION In spite of the fact that the GSE uses only two input variables and does not use any training set or ®tted parameters, it gives quite reasonable predictions. The ASER method produces only marginally better predictions (Table 1). However, the ASER method uses seven coef®cients, six variables derived from a very large number of structural descriptor values, and multiple linear regression analysis. As can be seen in Table 1, both methods give better prediction for the 408 liquids than for the 256 solids. The AAE of the GSE prediction is 0.358 for liquids and 0.588 for solids. The ASER method gives an AAE of 0.338 for liquids and 0.575 for solids. The success of the GSE for liquid nonelectrolytes is based on the relationship between the octanol±water partition coef®cient and the water solubility originally proposed by Hansch et al.1 and validated by Yalkowsky and Valvani.2 When applied to solid compounds, the GSE assumes that the entropy of melting of organic nonelectrolytes obeys Walden's rule (i.e., DSm 56.6 J K 1 mol 1) and that the solid± liquid heat capacity difference is negligible (i.e., DCpm 0). (Note: CLOGP1 alone gives better prediction for liquids than solids.) the ASER P In P method, the product term `` aH bH 2 2 ''deals with hydrogen-bond interactions between acid and basic sites in the solid or liquid. The addition H of a term ``pH 2 p2 '' to deal with dipole±dipole interactions did not improve the prediction. The ASER method predicts aqueous solubilities from compound structures without the need of experimental mp values. However, it is limited by the availability of descriptors for the contribution of speci®c groups present in a compound to the six
Figure 2. Experimental log Sw versus predicted log Sw using (a) the ASER method and (b) the GSE method (n 664).
Table 1 Statistical Analysis of Predicted Log Sw Values Compared With Experimental Log Sw Values Parameter AAE RMSE
Method
All n 664
All 2a n 662
Liquids n 408
Solids n 256
ASER GSE AVG ASER GSE AVG
0.430 0.447 0.377 0.615 0.623 0.534
0.431 0.446 0.376 0.615 0.622 0.533
0.338 0.358 0.309 0.490 0.505 0.453
0.575 0.588 0.486 0.774 0.775 0.642
a
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parameters used. For example, dicarboxylic acids are not included in the ASER study because descriptors for these compounds have not yet been ®nalized. The applicability of the GSE depends on the availability of mp and octanol±water partition coef®cient data. As shown in previous studies, octanol±water partition coef®cients can be reliably predicted using CLOGP1 or other software.13,15,16 On the other hand, mp data are not always available, and a reliable general method of predicting mp from compound structures is not available currently. Most attempts to predict mp are either unsatisfactory or applicable to only a very small group of compounds.17±21 However, if mps can be predicted with a 308C error, it would correspond to only a twofold error in solubility. Fortunately, mps are available for most characterized compounds that do not decompose before melting. It is interesting to note that the average (AVG) of the predicted log Sw values using the two independent methods gives a better prediction than either method used alone. The results in Table 1 indicate that AAE and RMSE are
generally reduced when the average values are used. Furthermore, the two predictions differ by a factor of < 2 (0.30 log units) from each other for about half of the compounds. For > 60% of these 331 compounds, the average of the two calculations is within a factor of 2 of the observed value.
CONCLUSIONS Both the ASER and the GSE methods give satisfactory prediction for the compound set. The ASER is based on multiple linear regression analysis of a large training set that may or may not contain the required structural fragments, whereas the GSE is simpler and more userfriendly. However, the latter requires knowledge of either an experimentally determined or an estimated mp of the solute. This study provides support for the reliability of the GSE in estimating the aqueous solubilities of organic compounds. The GSE method can be used alone or in combination with the ASER calculation to provide con®rmatory results.
APPENDIX Compound Methane Ethane Propane Butane 2-Methylpropane Pentane 2-Methylbutane Hexane 2-Methylpentane 3-Methylpentane 2,2-Dimethylbutane 2,3-Dimethylbutane Heptane 2,2-Dimethylpentane 2,3-Dimethylpentane 2,4-Dimethylpentane 3,3-Dimethylpentane 2,2,3-Trimethylbutane Octane 2-Methylheptane 3-Methylheptane 4-Methyloctane 2,2,4-Trimethylpentane 2,3,4-Trimethylpentane Nonane
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
1.10 1.75 2.28 2.81 2.68 3.34 3.21 3.87 3.74 3.74 3.61 3.61 4.40 4.14 4.14 4.14 4.14 4.01 4.93 4.80 4.80 5.32 4.54 4.54 5.65
1.09 1.81 2.36 2.89 2.76 3.39
25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25
0.90 1.36 1.94 2.57 2.55 3.18 3.18 3.84 3.74 3.68 3.55 3.65 4.53 4.36 4.28 4.26 4.23 4.36 5.24 5.08 5.16 6.05 4.74 4.80 5.88
0.48 1.04 1.60 2.16 2.16 2.72 2.72 3.29 3.29 3.29 3.29 3.29 3.85 3.85 3.85 3.85 3.85 3.85 4.41 4.41 4.41 4.41 4.41 4.41 4.97
0.60 1.25 1.78 2.31 2.18 2.84 2.71 3.37 3.24 3.24 3.11 3.11 3.90 3.64 3.64 3.64 3.64 3.51 4.43 4.30 4.30 4.82 4.04 4.04 5.15
3.90 3.82 3.42 4.66
5.18 4.69 5.45
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APPENDIX (Continued) Compound 2,2,5-Trimethylhexane Decane Undecane Dodecane Tetradecane Hexadecane Cyclopentane Methylcyclopentane Propylcyclopentane Pentylcyclopentane Cyclohexane Methylcyclohexane cis-1,2-Dimethylcyclohexane trans-1,4-Dimethylcyclohexane Ethylcyclohexane Cycloheptane Cyclooctane Decalin Ethylene Propylene 1-Butene 2-Methylpropene 1-Pentene cis-2-Pentene trans-2-Pentene 2-Methyl-1-butene 3-Methyl-1-butene 2-Methyl-2-butene 1-Hexene 2-Methyl-1-pentene 1-Heptene trans-2-Heptene 1-Octene 1-Nonene 1-Decene 1,3-Butadiene 2-Methyl-1,3-butadiene 2,3-Dimethyl-1,3-butadiene 1,4-Pentadiene 1,5-Hexadiene Cyclopentene Cyclohexene 1-Methylcyclohexene Cycloheptene 1,4-Cyclohexadiene Ethyne Propyne 1-Butyne 1-Pentyne 1-Hexyne 3-Hexyne 1-Heptyne 1-Octyne 1-Nonyne
CLOGP 5.06 5.98 6.51 7.04 8.10 9.16 2.79 3.31 4.37 5.43 3.35 3.87 4.39 4.39 4.40 3.91 4.47 4.79 1.27 1.80 2.33 2.20 2.86 2.86 2.86 2.73 2.73 2.73 3.38 3.25 3.91 3.91 4.44 4.97 5.50 1.90 2.30 2.70 2.37 2.90 2.31 2.87 3.39 3.43 2.39 0.39 0.92 1.45 1.98 2.51 2.51 3.04 3.57 4.10
MLOGP 5.01 6.50 6.10 8.00 3.00 3.37 3.44 3.61
4.00 4.45 1.13 1.77 2.40 2.34 2.80
2.67 3.39 3.99 4.57 5.15 1.99 2.47 2.87 2.86 2.30 0.37 0.94 1.46 1.98 2.73 3.32 3.92 4.51
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25
5.05 6.98 7.59 7.67 7.96 8.40 2.64 3.30 4.74 6.08 3.10 3.85 4.30 4.47 4.25 3.51 4.15 5.19 0.40 1.08 1.94 2.33 2.68 2.54 2.54 2.73 2.73 2.56 3.23 3.03 3.73 3.82 4.44 5.05 5.51 1.87 2.03 2.40 2.09 2.68 2.10 2.59 3.27 3.18 2.06 0.29 0.41 1.24 1.64 2.36 1.99 3.01 3.66 4.24
4.97 5.53 6.09 6.66 7.78 8.90 2.48 3.00 4.12 5.24 3.08 3.61 4.18 4.10 4.16 3.69 4.31 4.98 0.60 1.17 1.73 1.73 2.29 2.34 2.32 2.31 2.26 2.35 2.83 2.85 3.41 3.44 3.97 4.53 5.10 1.54 2.09 2.53 1.99 2.56 1.87 2.50 3.07 3.07 2.02 0.13 0.45 1.16 1.66 2.25 2.30 2.91 3.46 4.02
4.56 5.48 6.01 6.54 7.60 8.66 2.29 2.81 3.87 4.93 2.85 3.37 3.89 3.89 3.90 3.41 3.97 4.29 0.77 1.30 1.83 1.70 2.36 2.36 2.36 2.23 2.23 2.23 2.88 2.75 3.41 3.41 3.94 4.47 5.00 1.40 1.80 2.20 1.87 2.40 1.81 2.37 2.89 2.93 1.89 0.11 0.42 0.95 1.48 2.01 2.01 2.54 3.07 3.60
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APPENDIX (Continued) Compound Dichloromethane Trichloromethane Tetrachloromethane Chloroethane 1,1-Dichloroethane 1,2-Dichloroethane 1,1,1-Trichloroethane 1,1,2-Trichloroethane 1,1,2,2-Tetrachloroethane 1,1,1,2-Tetrachloroethane Pentachloroethane Hexachloroethane 1-Chloropropane 2-Chloropropane 1,2-Dichloropropane 1,3-Dichloropropane 1-Chlorobutane 1-Chloro-2-methylpropane 2-Chlorobutane 1-Chloropentane 2-Chloro-2-methylbutane 1-Chlorohexane 1-Chloroheptane Chloroethylene 1,1-Dichloroethylene cis-1,2-Dichloroethylene Trichloroethylene Tetrachloroethylene Hexachloro-1,3-butadiene Bromomethane Dibromomethane Tribromomethane Tetrabromomethane Bromoethane 1,2-dibromoethane 1-Bromopropane 2-Bromopropane 1-Bromobutane 1-Bromo-2-methylpropane 1-Bromopentane 1-Bromohexane 1-Bromoheptane 1-Bromooctane Iodomethane Diiodomethane Iodoethane 1-Iodopropane 2-Iodopropane 1-Iodobutane 1-Iodoheptane Bromochloromethane Bromodichloromethane Chlorodibromethane 1-Chloro-2-bromoethane
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
1.25 1.95 2.88 1.47 1.78 1.46 2.48 2.05 2.64 3.03 3.63 4.61 1.99 1.99 1.99 1.71 2.52 2.39 2.52 3.05 2.92 3.58 4.11 1.52 2.37 1.77 2.63 3.48 4.90 1.08 1.53 2.37 3.43 1.60 1.74 2.13 2.13 2.66 2.53 3.19 3.72 4.25 4.78 1.47 2.31 2.00 2.52 2.52 3.05 4.64 1.39 2.09 2.23 1.60
1.25 1.97 2.83 1.43 1.79 1.47 2.49 2.07 2.62 2.62 3.22 4.14 2.04 1.90 1.99 2.00 2.64
25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 90 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25
0.63 1.17 2.31 1.06 1.29 1.06 2.00 1.48 1.74 2.18 2.60 3.67 1.47 1.41 1.60 1.62 2.03 2.00 1.96 2.73 2.51 3.12 4.00 1.75 1.64 1.30 1.96 2.54 4.92 0.79 1.17 1.91 3.14 1.09 1.68 1.73 1.59 2.37 2.43 3.08 3.81 4.43 5.06 1.00 2.34 1.60 2.29 2.09 2.96 4.81 0.89 1.54 1.90 1.32
0.99 1.59 2.60 1.02 1.35 1.29 2.18 1.70 2.21 2.52 3.03 4.23 1.57 1.49 1.81 1.84 2.12 2.05 2.06 2.69 2.85 3.24 3.80 1.11 1.73 1.38 2.28 3.12 5.12 0.82 1.56 2.47 3.74 1.29 1.72 1.85 1.77 2.40 2.40 2.96 3.52 4.07 4.63 1.30 2.42 1.77 2.32 2.26 2.88 4.54 1.32 1.84 2.12 1.69
0.75 1.45 2.38 0.97 1.28 0.96 1.98 1.55 2.14 2.53 3.13 4.11 1.49 1.49 1.49 1.21 2.02 1.89 2.02 2.55 2.42 3.08 3.61 1.02 1.87 1.27 2.13 2.98 4.40 0.58 1.03 1.87 3.58 1.10 1.24 1.63 1.63 2.16 2.03 2.69 3.22 3.75 4.28 0.97 1.81 1.50 2.02 2.02 2.55 4.14 0.89 1.59 1.73 1.10
2.33 3.11 2.52 3.66 4.15 2.13 1.86 2.61 3.40 4.78 1.19 1.88 2.67 3.42 1.61 1.96 2.10 2.14 2.75 3.37 3.80 4.36 4.89 1.51 2.30 2.00 2.54 2.89 3.08 4.70 1.41 2.10 2.24
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APPENDIX (Continued) Compound 1,1,2-Trichlorotri¯uoroethane 1,2-Dichlorotetra¯uoroethane Diethyl ether Dipropyl ether Diisopropyl ether Dibutyl ether Methyl propyl ether Methyl butyl ether Methyl tert-butyl ether Ethyl propyl ether Propyl isopropyl ether Ethyl vinyl ether Dimethoxymethane 1,1-Diethoxyethane 1,2-Diethoxyethane 1,2-Propylene oxide Tetrahydrofuran 2-Methyltetrahydrofuran Tetrahydropyran Propionaldehyde Butyraldehyde Valeraldehyde Caproaldehyde 2-Ethylbutanol 2-Ethylhexanol trans-Crotonaldehyde 2-Ethyl-2-hexanol 2-Butanone 2-Pentanone 3-Pentanone 3-Methyl-2-butanone 2-Hexanone 3-Hexanone 3-Methyl-2-pentanone 4-Methyl-2-pentanone 3,3-Dimethyl-2-butanone 2-Heptanone 4-Heptanone 2,4-Dimethyl-3-pentanone 2-Octanone 2-Nonanone 5-Nonanone 2-Decanone Cyclohexanone Carvone Camphor Menthone Methyl formate Ethyl formate Propyl formate Isopropyl formate Butyl acetate Isobutyl formate Isopentyl formate
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
3.29 2.85 0.87 1.93 1.49 2.91 0.87 1.40 1.05 1.40 1.71 1.01 0.43 0.93 0.93 0.25 0.53 1.04 0.95 0.30 0.83 1.36 1.89 1.75 2.81 0.52 2.59 0.32 0.85 0.85 0.85 1.38 1.38 1.38 1.25 1.25 1.91 1.91 1.91 2.44 2.97 2.97 3.49 0.86 2.01 2.18 2.83 0.26 0.26 0.79 0.57 1.77 1.19 1.72
3.16 2.82 0.89 2.03 1.52 3.22 1.21 1.66 0.94
25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 177 25 25 25 25 25 25 25 25
3.04 2.74 0.09 1.10 1.10 1.85 0.39 0.99 0.24 0.66 1.34 0.85 0.48 0.43 0.77 0.59 0.49 0.11 0.03 0.58 0.01 0.85 1.30 1.52 2.13 0.32 2.46 0.52 0.19 0.28 0.12 0.80 0.83 0.67 0.74 0.72 1.45 1.30 1.30 2.05 2.58 2.58 3.30 0.60 2.06 1.96 2.35 0.58 0.15 0.49 0.63 1.37 1.01 1.52
2.62 2.41 0.34 1.43 1.64 2.54 0.44 0.95 0.23 0.86 1.44 0.39 0.79 0.59 0.15 0.70 0.18 0.15 0.37 0.55 0.00 0.54 1.09 1.10 2.24 0.29 2.04 0.31 0.24 0.27 0.26 0.80 0.81 0.80 0.80 0.82 1.35 1.35 1.36 1.89 2.47 2.47 3.02 0.28 2.70 2.15 2.63 0.61 0.08 0.50 0.39 1.05 0.96 1.52
2.79 2.35 0.37 1.43 0.99 2.41 0.37 0.90 0.55 0.90 1.21 0.51 0.93 0.43 0.43 0.25 0.03 0.54 0.45 0.20 0.33 0.86 1.39 1.25 2.31 0.02 2.09 0.18 0.35 0.35 0.35 0.88 0.88 0.88 0.75 0.75 1.41 1.41 1.41 1.94 2.47 2.47 2.99 0.36 1.51 3.20 2.33 0.76 0.24 0.29 0.07 1.27 0.69 1.22
1.04 0.18 0.84 0.66 0.13 0.47 0.95 0.59 0.88 1.78
0.29 0.91 0.82 0.84 1.38 1.31 1.20 1.98 2.04 1.86 2.37 3.14 2.88 3.73 0.81 2.38 0.03 0.83 1.78
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APPENDIX (Continued) Compound Methyl acetate Ethyl acetate Propyl acetate Isopropyl acetate Isobutyl acetate Pentyl acetate Isopentyl acetate Methyl propionate Ethyl propionate Methyl butyrate Ethyl butyrate Propyl butyrate Methyl pentanoate Ethyl pentanoate Propyl propanoate Pentyl propanoate Methyl hexanoate Ethyl hexanoate Ethyl heptanoate Methyl octanoate Ethyl octanoate Methyl nonanoate Ethyl nonanoate Methyl decanoate Ethyl decanoate Methyl acrylate Glyceryl triacetate Malonic acid diethyl ester Acetonitrile Propionitrile Acrylonitrile Ethylamine Propylamine Butylamine Pentylamine Hexylamine Heptylamine Octylamine Diethylamine Dipropylamine Dibutylamine Trimethylamine Triethylamine Tripropylamine Nitromethane Nitroethane 1-Nitropropane 2-Nitropropane Chloropicrin Acetamide N,N-Dimethylacetamide Urea o-Ethyl carbamate Acetic acid
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
0.18 0.71 1.24 1.24 1.64 2.30 2.17 0.71 1.24 1.24 1.77 2.30 1.77 2.30 1.77 2.83 2.30 2.83 3.36 3.36 3.88 3.88 4.41 4.41 4.94 0.80 0.67 1.13 0.39 0.13 0.29 0.13 0.39 0.92 1.45 1.98 2.51 3.04 0.54 1.60 2.66 0.02 1.40 2.98 0.28 0.25 0.77 0.55 1.60 1.11 0.80 1.66 0.18 0.19
0.18 0.73 1.24 1.22 1.76 2.29 2.25 0.82 1.21 1.29 1.71 2.15 1.96
25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 81 25 132 25 25
0.46 0.04 0.72 0.55 1.21 1.89 1.92 0.14 0.66 0.82 1.28 1.92 1.36 1.75 1.34 2.25 1.87 2.35 2.74 3.17 3.39 3.38 3.80 4.69 4.10 0.22 0.60 0.82 0.26 0.28 0.15 2.06 1.52 0.96 0.27 0.25 0.90 1.46 1.03 0.46 1.44 1.32 0.14 2.28 0.26 0.22 0.80 0.62 2.00 1.58 1.11 0.96 0.85 2.00
0.36 0.18 0.74 0.64 1.20 1.84 1.76 0.22 0.75 0.76 1.30 1.86 1.32 1.84 1.30 2.42 1.85 2.39 2.94 2.96 3.50 3.52 4.06 4.07 4.61 0.25 0.73 0.53 0.80 0.42 0.35 1.20 0.65 0.09 0.46 1.01 1.57 2.12 0.43 0.67 1.77 0.86 0.32 1.85 0.63 0.15 0.49 0.40 2.07 1.86 1.34 2.32 0.79 1.18
0.32 0.21 0.74 0.74 1.14 1.80 1.67 0.21 0.74 0.74 1.27 1.80 1.27 1.80 1.27 2.33 1.80 2.33 2.86 2.86 3.38 3.38 3.91 3.91 4.44 0.30 0.17 0.63 0.89 0.37 0.21 0.63 0.11 0.42 0.95 1.48 2.01 2.54 0.04 1.10 2.16 0.48 0.90 2.48 0.78 0.25 0.27 0.05 1.10 1.05 1.30 1.09 0.68 0.69
2.67 2.42
3.87 4.41 0.80 0.25 0.96 0.34 0.16 0.25 0.13 0.47 0.97 1.49 2.06 2.57 3.09 0.58 1.67 2.83 0.16 1.45 2.79 0.35 0.18 0.87 0.80 2.09 1.09 0.77 1.66 0.15 0.17
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APPENDIX (Continued) Compound Hexanoic acid Decanoic acid Methacrylic acid Chloroacetic acid Trichloroacetic acid Methanol Ethanol 1-Propanol 2-Propanol 1-Butanol 2-Methylpropan-1-ol Butan-2-ol 1-Pentanol 2-Pentanol 3-Pentanol 2-Methylbutanol 3-Methylbutan-1-ol 2-Methylbutan-2-ol 3-Methyl-2-butanol 2,2-Dimethylpropanol 1-Hexanol 2-Hexanol 3-Hexanol 2-Methylpentanol 3-Methyl-2-Pentanol 4-Methylpentanol 2-Methyl-2-pentanol 3-Methyl-2-pentanol 4-Methyl-2-pentanol 2-Methyl-3-pentanol 3-Methyl-3-pentanol 2-Ethyl-1-butanol 2,2-Dimethyl-1-butanol 3,3-Dimethyl-1-butanol 3,3-Dimethyl-2-butanol 1-Heptanol 2-Heptanol 3-Heptanol 4-Heptanol 2-Methyl-2-hexanol 3-Methyl-3-hexanol 3-Ethyl-3-pentanol 2,2-Dimethylpentanol 2,4-Dimethyl-2-pentanol 2,4-Dimethyl-3-pentanol 1-Octanol 2-Octanol 3-Octanol 2-Methyl-2-heptanol 3-Methyl-3-heptanol 2-Ethyl-1-hexanol 1-Nonanol 2-Nonanol 1-Decanol
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
1.92 4.04 0.66 0.08 1.68 0.76 0.24 0.29 0.07 0.82 0.69 0.60 1.35 1.13 1.13 1.22 1.22 1.00 1.00 1.09 1.88 1.66 1.66 1.75 1.53 1.75 1.53 1.53 1.53 1.53 1.53 1.75 1.62 1.62 1.40 2.41 2.19 2.19 2.19 2.06 2.06 2.06 2.15 1.93 1.93 2.94 2.72 2.72 2.59 2.59 2.81 3.47 3.25 4.00
1.92 4.09 0.93 0.22 1.33 0.77 0.31 0.25 0.05 0.88 0.76 0.61 1.56 1.19 1.21 1.29 1.16 0.89 1.28 1.31 2.03 1.76 1.65
25 31 25 61 57 25 25 25 25 25 25 25 25 25 25 25 25 25 25 53 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25
1.06 3.44 0.00 1.81 0.60 1.56 1.10 0.62 0.43 0.00 0.10 0.47 0.60 0.29 0.24 0.47 0.51 0.15 0.18 0.40 1.24 0.89 0.80 1.11 0.72 1.14 0.49 0.71 0.80 0.70 0.36 1.17 1.04 0.50 0.62 1.81 1.55 1.47 1.40 1.08 0.98 0.85 1.52 0.92 1.22 2.39 2.09 1.98 1.72 1.60 2.11 3.01 2.74 3.63
0.99 3.19 0.05 0.87 0.01 1.59 1.04 0.49 0.70 0.06 0.07 0.07 0.62 0.41 0.43 0.64 0.61 0.33 0.43 0.51 1.17 0.96 0.98 1.19 1.19 1.18 0.87 0.97 0.97 1.01 0.91 1.21 1.23 1.19 1.02 1.73 1.53 1.52 1.52 1.42 1.46 1.50 1.79 1.45 1.59 2.28 2.06 2.08 1.99 2.01 2.32 2.84 2.63 3.40
1.42 3.60 0.16 0.22 1.50 1.26 0.74 0.21 0.43 0.32 0.19 0.10 0.85 0.63 0.63 0.72 0.72 0.50 0.50 0.87 1.38 1.16 1.16 1.25 1.03 1.25 1.03 1.03 1.03 1.03 1.03 1.25 1.12 1.12 0.90 1.91 1.69 1.69 1.69 1.56 1.56 1.56 1.65 1.43 1.43 2.44 2.22 2.22 2.09 2.09 2.31 2.97 2.75 3.50
1.47 2.72 2.31 2.24 2.22
3.00 2.90
3.67 4.57
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APPENDIX (Continued) Compound 2-Undecanol 1-Dodecanol 1-Tetradecanol 1-Pentadecanol 1-Hexadecanol 1-Octadecanol Cyclohexanol Cycloheptanol Cyclooctanol 4-Pentene-1-ol 1-Hexene-3-ol 2-Butoxyethanol Ethanethiol Butanethiol Dimethyl sul®de Diethyl sul®de Di-n-propyl sul®de Diisopropl sul®de Dimethyl disul®de Diethyl disul®de Thiourea Triethyl phosphate Benzene Toluene Ethylbenzene o-Xylene m-Xylene p-Xylene Propylbenzene Isopropylbenzene 1,2,3-Trimethylbenzene 1,2,4-Trimethylbenzene 1,3,5-Trimethylbenzene 2-Ethyltoluene 4-Ethyltoluene Butyltoluene Isobutyltoluene tert-Butylbenzene 1,2-Diethylbenzene 1,4-Diethylbenzene 1,2,4,5-Tetramethylbenzene 2-Isopropyltoluene 4-Isopropyltoluene Pentylbenzene tert-Pentylbenzene Pentamethylbenzene Hexylbenzene Hexamethylbenzene Styrene Diphenylmethane Bibenzyl Biphenyl 4-Methylbiphenyl Naphthalene
CLOGP 4.31 5.06 6.11 6.64 7.17 7.70 1.27 1.83 2.38 0.87 1.38 0.84 1.17 2.23 0.84 1.90 2.96 2.52 1.74 2.80 1.02 0.28 2.14 2.64 3.17 3.09 3.14 3.14 3.70 3.57 3.54 3.59 3.64 3.62 3.67 4.68 4.55 3.97 4.15 4.20 4.04 4.02 4.07 4.76 4.50 4.49 5.29 4.99 2.87 4.21 4.59 4.03 4.53 3.32
MLOGP 5.13 6.36
1.23
0.83 2.28 1.05 1.95 2.84 1.77 1.02 0.80 2.13 2.73 3.15 3.12 3.20 3.15 3.72 3.66 3.59 3.63 3.58 3.53
4.11 3.72 4.00 4.10 4.90 4.56 5.52 4.61 2.95 4.14 4.79 4.01 4.63 3.30
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MP
log Sw Obsvd
log Sw ASER
log Sw GSE
25 25 40 46 56 61 25 25 25 25 25 25 25 25 25 25 25 25 25 25 176 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 80 25 25 25 25 50 25 164 25 26 52 70 45 80
2.94 4.80 5.84 6.35 7.00 8.40 0.44 0.88 1.29 0.15 0.59 0.42 0.60 2.18 0.45 1.34 2.58 2.24 1.44 2.42 0.32 0.43 1.64 2.21 2.77 2.80 2.82 2.77 3.37 3.27 3.20 3.31 3.40 3.21 3.11 4.06 4.12 3.66 3.28 3.75 4.59 3.76 3.77 4.64 4.15 4.00 5.21 5.23 2.82 4.08 4.62 4.35 4.62 3.60
3.75 4.50 5.61 6.17 6.73 7.84 0.64 1.22 1.83 0.28 0.88 0.24 0.80 1.91 0.57 1.54 2.65 2.45 1.51 2.58 1.14 0.23 1.96 2.51 3.05 3.02 3.01 3.00 3.61 3.57 3.48 3.47 3.47 3.52 3.50 4.16 4.17 4.07 4.10 4.08 4.06 4.04 4.01 4.71 4.71 4.60 5.28 4.92 2.96 4.35 4.91 4.26 4.83 3.60
3.81 4.56 5.76 6.35 6.98 7.56 0.77 1.33 1.88 0.37 0.88 0.34 0.67 1.73 0.34 1.40 2.46 2.02 1.24 2.30 0.01 0.22 1.64 2.14 2.67 2.59 2.64 2.64 3.20 3.07 3.04 3.09 3.14 3.12 3.17 4.18 4.05 3.47 3.65 3.70 4.09 3.52 3.57 4.26 4.00 4.24 4.79 5.88 2.37 3.72 4.36 3.98 4.23 3.37
COMPARISON OF ASER AND THE GSE
527
APPENDIX (Continued) Compound 1-Methylnaphthalene 2-Methylnaphthalene 1,3-Dimethylnaphthalene 1,4-Dimethylnaphthalene 1,5-Dimethylnaphthalene 2,3-Dimethylnaphthalene 2,6-Dimethylnaphthalene 1-Ethylnaphthalene 2-Ethylnaphthalene 1,2,3,4-Tetrahydronaphthalene Indan Acenaphthene Acenaphthylene Fluorene 1-Methyl¯uorene Anthracene 2-Methylanthracene 9-Methylanthracene 9,10-Dimethylanthracene Phenanthrene 1-Methylphenanthrene 2-Methylphenanthrene Fluoranthene Benzo[a]¯uorene Benzo[b]¯uorene Pyrene 7,12-Dimethylbenz[a]anthracene Naphthacene Chrysene 5-Methylchrysene 6-Methylchrysene 5,6-Dimethylchrysene Triphenylene Perylene Benzo[b]¯uoranthene Benzo[ j]¯uoranthene Benzo[k]¯uoranthene Cholanthrene 3-Methylcholanthrene Benzo[a]pyrene Benzo[e]pyrene Benzo[ghi]perylene Picene Fluorobenzene 1,3-Di¯uorobenzene 1,4-Di¯uorobenzene Benzyl tri¯uoride Chlorobenzene 1,2-Dichlorobenzene 1,3-Dichlorobenzene 1,4-Dichlorobenzene 1,2,3-Trichlorobenzene 1,2,4-Trichlorobenzene 1,3,5-Trichlorobenzene
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
3.81 3.81 4.31 4.31 4.31 4.26 4.31 4.34 4.34 3.71 3.15 3.77 3.62 4.07 4.57 4.49 4.99 4.99 5.49 4.49 4.99 4.99 4.95 5.25 5.25 4.95 6.66 5.66 5.66 6.16 6.16 6.61 5.66 6.12 6.12 6.12 6.12 6.12 6.62 6.12 6.12 6.58 6.84 2.28 2.43 2.43 3.03 2.86 3.45 3.57 3.57 4.04 4.16 4.28
3.87 3.86 4.42 4.37 4.38 4.40 4.31 4.39 4.38 3.49 3.18 3.92
25 35 25 25 82 103 109 25 25 25 25 95 90 116 87 216 205 79 183 100 123 57 110 187 212 150 122 357 255 117 160 128 199 278 167 165 216 173 179 179 178 278 366 25 25 25 25 25 25 25 54 25 25 63
3.70 3.77 4.29 4.14 4.68 4.72 4.89 4.17 4.29 4.37 3.04 4.63 3.96 5.00 5.22 6.35 6.96 5.89 6.57 5.26 5.85 5.84 6.00 6.68 8.04 6.18 7.02 8.60 8.06 6.59 6.57 7.01 6.73 8.80 8.23 8.00 8.49 7.85 7.92 8.70 7.80 9.02 7.87 1.80 2.00 1.97 2.51 2.38 3.05 3.04 3.27 4.00 3.59 4.48
4.16 4.12 4.77 4.79 4.79 4.79 4.72 4.78 4.73 3.83 3.31 4.37 4.11 4.61 5.17 5.36 5.83 5.87 6.35 5.12 5.71 5.71 5.98 6.79 6.77 6.12 8.13 7.07 6.93 7.49 7.49 8.06 6.67 7.40 7.38 7.52 7.60 7.45 8.04 7.83 7.92 8.51 8.80 2.02 2.15 1.98 2.50 2.75 3.42 3.52 3.48 4.17 4.16 4.22
3.31 3.41 3.81 3.81 4.38 4.54 4.65 3.84 3.84 3.21 2.65 3.97 3.77 4.48 4.69 5.90 6.29 5.03 6.57 4.74 5.47 4.81 5.30 6.37 6.62 5.70 7.13 8.48 7.46 6.58 7.01 7.14 6.90 8.15 7.04 7.02 7.53 7.10 7.66 7.16 7.15 8.61 9.75 1.78 1.93 1.93 2.53 2.36 2.95 3.07 3.36 3.54 3.66 4.16
4.18 4.97 4.45 5.07 5.69 4.47 5.08 4.86 5.16 5.68 5.77 4.88 5.80 5.90 5.81
5.49 5.82 6.11 6.42 6.13 6.44 6.63 7.11 2.27 3.01 2.89 3.43 3.53 3.44 4.14 4.05 4.19
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APPENDIX (Continued) Compound 1,2,3,4-Tetrachlorobenzene 1,2,3,5-Tetrachlorobenzene 1,2,4,5-Tetrachlorobenzene Pentachlorobenzene Hexachlorobenzene 2-Chlorotoluene 4-Chlorotoluene Benzyl chloride 1-Chloronaphthalene 2-Chloronaphthalene 2-Chlorobiphenyl 3-Chlorobiphenyl Bromobenzene 1,2-Dibromobenzene 1,3-Dibromobenzene 1,4-Dibromobenzene 1,3,5-Tribromobenzene 1,2,4,5-Tetrabromobenzene 2-Bromotoluene 4-Bromotoluene 1-Bromonaphthalene 2-Bromonaphthalene Iodobenzene 1-Iodonaphthalene o-Fluorobromobenzene m-Fluorobromobenzene o-Chlorobromobenzene m-Chlorobromobenzene p-Chlorobromobenzene o-Chloroiodobenzene m-Chloroiodobenzene p-Chloroiodobenzene p-Bromoiodobenzene Anisole 2-Chloroanisole 3-Chloroanisole 4-Chloroanisole Diphenyl ether Benzaldehyde p-Methoxybenzaldehyde Acetophenone Benzophenone Anthraquinone Methyl benzoate Ethyl benzoate Dimethyl phthalate Diethyl phthalate Di(2-ethylthexyl)phthalate Benzonitrile Phthalonitrile Aniline o-Toluidine m-Methylaniline p-Methylaniline
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
4.63 4.75 4.75 5.35 6.06 3.35 3.35 2.70 4.03 4.03 4.49 4.49 3.01 3.67 3.87 3.87 4.73 5.19 3.50 3.50 4.18 4.18 3.27 4.44 3.15 3.15 3.44 3.72 3.72 3.98 3.98 3.98 4.13 2.06 2.75 2.91 2.91 4.24 1.50 1.78 1.58 3.18 2.62 2.11 2.64 1.56 2.62 8.71 1.57 1.01 0.91 1.36 1.36 1.41
4.64 4.66 4.60 5.18 5.73 3.42 3.33
46 54 139 50 227 25 25 25 25 60 32 25 25 25 25 87 121 182 25 29 25 54 25 25 25 25 25 25 67 25 55 53 90 37 25 25 25 28 25 25 25 49 284 25 25 25 25 25 25 140 25 25 25 43
4.57 4.63 5.56 5.65 7.68 3.52 3.08 2.39 3.93 4.14 4.54 4.88 2.55 3.50 3.54 4.07 5.60 6.98 2.23 3.19 4.35 4.40 3.01 4.55 2.70 2.67 3.19 3.21 3.63 3.54 3.55 4.03 4.56 1.85 2.46 2.78 2.78 3.96 1.19 1.49 1.28 3.12 5.19 1.85 2.32 1.66 2.35 6.96 1.00 2.38 0.41 2.21 0.85 1.21
4.77 4.80 4.79 5.37 6.00 3.36 3.31 2.18 4.36 4.36 4.99 4.96 2.98 4.02 4.06 4.06 5.13 5.88 3.59 3.53 4.69 4.62 3.42 5.16 3.29 3.25 3.90 3.92 3.88 4.43 4.42 4.42 4.64 2.04 2.92 2.90 2.78 4.58 1.36 1.53 1.53 3.56 3.73 1.89 2.41 1.32 2.31 8.94 1.45 1.10 1.01 1.50 1.46 1.44
4.34 4.54 5.39 5.10 7.58 2.85 2.85 2.20 3.53 3.88 4.06 3.99 2.51 3.17 3.37 3.99 5.19 6.26 3.00 3.04 3.68 3.97 2.77 3.94 2.65 2.65 2.94 3.22 3.64 3.48 3.78 3.76 4.28 1.68 2.25 2.41 2.41 3.77 1.00 1.28 1.08 2.92 4.71 1.61 2.14 1.06 2.12 8.21 1.07 1.66 0.41 0.86 0.86 1.09
4.10 4.14 4.53 2.99 3.64 3.75 3.79 4.51 5.13
3.25
2.11 2.68 2.98 2.78 4.21 1.47 1.76 1.58 3.18 3.39 2.12 2.64 1.56 2.47 7.45 1.56 0.99 0.90 1.32 1.32 1.39
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APPENDIX (Continued) Compound o-Chloroaniline m-Chloroaniline p-Choroaniline o-Nitroaniline m-Nitroaniline p-Nitroaniline Ethyl-p-aminobenzoate Risocaine Butamben N-Methylaniline N-Ethylaniline N,N-Dimethylaniline N,N-Diethylaniline 1-Naphthylamine p, p-Biphenyldiamine Benzylamine Procaine Diphenylamine Azobenzene Nitrobenzene o-Nitrotoluene m-Nitrotoluene p-Nitrotoluene o-Chloronitrobenzene m-Chloronitrobenzene p-Chloronitrobenzene o-Nitroanisole p-Nitroanisole 1,2-Dinitrobenzene 1,3-Dinitrobenzene 1,4-Dinitrobenzene 2,4-Dinitrotoluene 2,6-Dinitrotoluene 2,4,6-Trinitrotoluene 1,3,5-Trinitrobenzene 1-Nitronaphthalene 2,3-Dichloronitrobenzene 3,4-Dichloronitrobenzene Benzamide Acetanilide p-Fluoroacetanilide p-Chloroacetanilide p-Bromoacetanilide 4-Nitroacetanilide Phenacetin Lidocain Benzoic acid o-Toluic acid m-Toluic acid p-Toluic acid o-Chlorobenzoic acid m-Chlorobenzoic acid p-Chlorobenzoic acid 2-Bromobenzoic acid
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
1.96 1.96 1.96 1.92 1.38 1.38 2.03 2.55 3.08 1.64 2.17 2.34 3.23 2.09 1.58 1.09 2.54 3.62 3.85 1.88 2.30 2.38 2.38 2.40 2.60 2.60 1.82 2.10 1.63 1.63 1.63 2.05 2.05 1.71 1.37 3.06 3.11 3.19 0.65 1.16 1.56 2.13 2.28 1.46 1.77 1.95 1.88 2.38 2.38 2.38 2.10 2.70 2.70 2.20
1.90 1.88 1.88 1.85 1.37 1.39 1.86 2.43 2.87 1.66 2.16 2.31 3.31 2.25 1.34 1.09 2.14 3.50 3.82 1.85 2.30 2.42 2.37 2.52 2.47 2.39 1.73 2.03 1.69 1.49 1.47 1.98 2.10 1.60 1.18 3.19 3.05 3.12 0.64 1.16 1.47 2.12 2.29 1.66 1.58 2.26 1.87 2.40 2.37 2.27 2.05 2.68 2.65 2.20
25 25 73 72 114 146 89 75 58 25 25 25 25 49 128 25 61 52 69 25 25 25 55 34 43 84 25 54 118 90 173 69 65 81 123 59 61 41 128 114 153 178 165 215 135 68 122 105 112 182 142 158 243 149
1.52 1.37 1.66 1.96 2.19 2.37 2.10 2.45 3.08 1.28 1.70 1.92 3.03 1.92 2.70 1.54 1.78 3.50 2.75 1.80 2.33 2.44 2.49 2.55 2.77 2.92 1.96 2.41 3.10 2.29 3.39 2.82 3.00 3.22 2.89 3.54 3.48 3.20 0.96 1.33 1.78 2.84 3.08 2.69 2.35 1.71 1.55 2.06 2.14 2.60 1.89 2.59 3.31 2.28
1.96 1.82 1.77 1.75 1.44 1.23 2.03 2.60 3.17 1.61 2.21 2.46 3.59 2.45 2.74 0.43 2.23 3.63 4.28 1.87 2.42 2.57 2.43 2.61 2.59 2.75 2.16 2.11 1.98 1.66 1.66 2.22 2.30 2.12 1.55 3.72 3.37 3.44 0.40 0.89 1.11 1.81 2.09 1.83 1.74 2.41 1.06 1.74 1.66 1.61 1.52 1.77 1.85 1.74
1.46 1.46 1.94 1.89 1.77 2.09 2.17 2.55 2.91 1.14 1.67 1.84 2.73 1.83 2.11 0.59 2.40 3.39 3.79 1.38 1.80 1.88 2.18 1.99 2.28 2.69 1.32 1.89 2.06 1.78 2.61 1.99 1.95 1.77 1.85 2.90 2.97 2.85 1.18 1.55 2.34 3.16 3.18 2.86 2.37 1.88 2.35 2.68 2.75 3.45 2.77 3.53 4.38 2.94
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APPENDIX (Continued) Compound 4-Bromobenzoic acid m-Nitrobenzoic acid p-Nitrobenzoic acid o-Aminobenzoic acid Aspirin Phenylacetic acid Ibuprofen Naproxen Phenol 2-Methylphenol 3-Methylphenol p-Cresol 2,4-Dimethylphenol 2,6-Dimethylphenol 3,4-Dimethylphenol 3,5-Dimethylphenol 2,4,6-Trimethylphenol p-tert-Butylphenol Thymol p-Phenylphenol 2-Chlorophenol 3-Chlorophenol 4-Chlorophenol 4-Bromophenol 2,3-Dichlorophenol 2,4-Dichlorophenol 2,6-Dichlorophenol 3,4-Dichlorophenol 3,5-Dichlorophenol 2,3,4-Trichlorophenol 2,3,5-Trichlorophenol 2,3,6-Trichlorophenol 2,4,5-Trichlorophenol 2,4,6-Trichlorophenol 2,3,4,5-Tetrachlorophenol 2,3,4,6-Tetrachlorophenol 2,3,5,6-Tetrachlorophenol Pentachlorophenol o-Methoxyphenol p-Hydroxybenzaldehyde o-Aminophenol p-Aminophenol o-Nitrophenol m-Nitrophenol p-Nitrophenol Salicyclic acid p-Hydroxybenzoic acid 1,2-Benzenediol 1,3-Benzenediol 1,4-Benzenediol Methylparaben Ethyl-p-hydroxybenzoate o-Hydroxybenzamide p-Hydroxyacetanilide
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
2.85 1.84 1.84 1.21 1.02 1.41 3.68 2.82 1.47 1.97 1.97 1.97 2.47 2.47 2.42 2.47 2.97 3.30 3.20 3.36 2.15 2.48 2.48 2.63 2.84 2.96 2.63 3.17 3.29 3.58 3.58 3.37 3.58 3.37 4.30 4.09 4.09 4.68 1.32 1.44 0.62 0.25 1.85 1.85 1.85 2.19 1.56 0.88 0.81 0.81 1.98 2.51 1.28 0.49
2.86 1.83 1.89 1.21 1.19 1.41 3.50 3.34 1.47 1.95 1.96 1.94 2.30 2.36 2.23 2.35
246 142 242 145 135 77 76 153 41 31 25 33 28 49 63 64 71 98 48 167 25 34 43 66 59 45 67 67 68 79 57 56 68 70 116 70 114 174 28 25 175 189 44 97 113 159 217 104 110 170 128 117 140 169
3.54 1.68 2.80 1.52 1.72 0.89 3.76 4.20 0.00 0.62 0.68 0.73 1.19 1.29 1.38 1.40 2.05 2.41 2.22 3.48 1.06 0.70 0.70 1.09 1.30 1.55 1.79 1.25 1.34 2.67 2.67 2.64 2.21 2.34 3.15 3.10 3.37 4.28 1.96 0.96 0.72 0.80 1.74 1.01 0.74 1.82 1.41 0.62 0.81 0.17 1.83 2.35 1.82 1.03
2.16 1.53 1.55 1.02 1.13 1.09 3.93 3.89 0.73 1.44 1.26 1.33 1.82 1.96 1.73 1.80 2.39 2.77 2.81 3.18 1.56 1.37 1.30 1.60 2.22 2.25 2.22 1.81 1.83 2.57 2.60 2.71 2.64 2.67 3.26 3.49 3.39 3.48 1.21 0.67 0.47 0.13 1.86 1.04 0.85 1.48 1.07 0.42 0.27 0.32 1.48 2.02 1.11 1.02
4.56 2.51 3.51 1.91 1.62 1.43 3.69 3.60 1.13 1.53 1.47 1.55 2.00 2.21 2.30 2.36 2.93 3.53 2.93 4.28 1.65 2.07 2.16 2.54 2.68 2.66 2.55 3.09 3.22 3.62 3.40 3.18 3.51 3.32 4.71 4.04 4.48 5.67 0.85 0.94 1.62 1.39 1.54 2.07 2.23 3.03 2.98 1.17 1.16 1.76 2.51 2.93 1.93 1.43
3.31 3.30 3.20 2.15 2.50 2.39 2.59 2.84 3.06 2.75 3.33 3.52 3.77 3.72 3.69 4.21 4.12 3.88 5.12 1.32 1.35 0.62 0.04 1.79 2.00 1.91 2.26 1.58 0.88 0.80 0.59 1.96 2.47 1.28 0.51
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COMPARISON OF ASER AND THE GSE
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APPENDIX (Continued) Compound 1-Naphthol 2-Naphthol Phenylmethanol 1-Phenylethanol 2-Phenoxyethanol Ephedrine Thiophenol Phenylthiourea p-Toluenesulfonamide Furane Furfural Dibenzofurane Pyridine 2,3-Dimethylpyridine 2,4-Dimethylpyridine 2,6-Dimethylpyridine 3,4-Dimethylpyridine 3,5-Dimethylpyridine 2-Ethyl pyridine 4-Ethyl pyridine Cocaine Atropine Quinoline Isoquinoline Carbazole Antipyrene Morpholine Theophylline Caffeine Morphine Codeine Thiophene Imipramine Progesterone Testosterone Deoxycorticosterone Hydroxyprogesterone-17a Corticosterone Cortisone Hydrocortisone 17a-Methyltestosterone Prednisolone Hydrocortisone 21-acetate Estrone Estradiol Dexamethasone 5,5-Dimethylbarbituric acid 5-Methyl-5-ethylbarbituric acid Barbital 5-Ethyl-5-isopropylbarbituric acid Butabarbital Pentobarbital 5-Ethyl-5-(3-methylbutyl)barbital 5,5-Diisopropylbarbital
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
2.65 2.65 1.10 1.41 1.19 0.89 2.53 0.75 0.80 1.32 0.67 4.09 0.64 1.59 1.64 1.64 1.59 1.64 1.67 1.67 2.57 1.32 2.03 1.82 3.52 0.20 0.41 0.06 0.06 0.59 0.98 1.79 5.04 3.77 3.22 3.25 3.15 2.32 1.30 1.70 3.74 1.38 2.23 3.38 3.78 1.75 0.40 0.13 0.66 1.05 1.58 2.11 2.11 1.45
2.84 2.70 1.10 1.42 1.16 0.93 2.52 0.73 0.82 1.34 0.41 4.12 0.65
96 121 25 25 25 38 25 154 139 25 25 83 25 25 25 25 25 25 25 25 98 116 25 26 247 109 25 272 235 254 155 25 174 131 155 136 276 181 222 213 162 240 223 255 173 262 278 212 190 203 166 129 156 228
2.22 2.28 0.40 0.92 0.70 0.47 2.12 1.77 1.74 0.82 0.10 4.60 0.76 0.38 0.38 0.45 0.36 0.38 0.51 0.83 2.25 2.12 1.30 1.45 5.27 0.72 1.97 1.39 0.88 3.28 1.52 1.33 4.19 4.42 4.02 3.45 3.82 3.24 3.11 3.09 4.00 3.18 4.88 3.96 5.03 3.59 1.74 1.23 2.40 2.15 2.39 2.39 2.66 2.77
2.64 2.54 0.79 1.06 0.88 0.78 2.55 1.02 1.06 1.03 0.15 4.47 0.04 0.74 0.68 0.70 0.69 0.81 0.87 0.90 2.17 2.53 1.88 1.80 3.87 0.44 1.62 0.21 0.45 2.38 2.28 1.65 4.15 4.02 4.08 3.98 4.24 4.04 3.29 4.93 4.34 5.20 4.69 4.07 4.39 5.35 0.20 0.36 0.96 1.49 1.97 2.54 2.54 2.00
2.86 3.11 0.60 0.91 0.69 0.52 2.03 1.54 1.44 0.82 0.17 4.17 0.14 1.09 1.14 1.14 1.09 1.14 1.17 1.17 2.80 1.73 1.53 1.33 5.24 0.54 0.91 1.91 1.54 2.38 1.78 1.29 6.03 4.33 4.02 3.86 5.16 3.38 2.77 3.08 4.61 3.03 3.71 5.18 4.76 3.62 1.63 1.50 1.81 2.33 2.49 2.65 2.92 2.98
1.68 1.78 1.69 1.65 2.30 1.83 2.03 2.08 3.48 0.23 0.86 0.02 0.07 0.76 1.14 1.89 4.44 3.87 3.32 2.88 3.17 1.94 1.47 1.61 3.36 1.62 2.19 3.13 3.86 2.01 0.44 0.08 0.65 1.10 1.65 2.10 2.07 1.56
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APPENDIX (Continued) Compound 5-Allyl-5-methylbarbital 5-Allyl-5-ethylbarbital 5-Allyl-5-isopropylbarbital Secobarbital 5,5-Diallylbarbital 5-(3-Methyl-2-butenyl)-5-ethylbarbital 5-(3-Methyl-2-butenyl)-5-isoprbarbital 5-Ethyl-5-phenylbarbital 5-Allyl-5-phenylbarbital Cyclobutyl-5-spirobarbituric acid Cyclopentyl-5-spirobarbituric acid Cyclohexyl-5-spirobarbituric acid Cycloheptyl-5-spirobarbituric acid Cyclooctyl-5-spirobarbituric acid Amitrole Carbaryl Carbofuran Chlorfenac Coumatetralyl 2,4-DB DDT Desmedipham Dichlorophen Dichlorprop Diuron DNOC Etofenprox Fenoxycarb Fenuron Fluometuron Isoprocarb Isoproturon Linuron Methyldymron Metolcarb Metoxuron Monolinuron Propoxur Warfarin XMC Cyclopropyl-5-spirobarbituric acid Uracil Chlorpheniramine Fentanyl Adenine
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
0.17 0.70 1.37 2.16 0.75 1.63 2.23 1.37 1.41 0.57 0.01 0.55 1.11 1.67 0.53 2.38 2.47 3.43 4.83 3.42 6.76 3.40 4.89 3.26 2.68 2.29 7.36 4.46 0.98 2.39 2.29 2.40 3.00 3.24 1.71 1.78 2.31 1.65 2.89 2.21 1.13 1.06 3.15 3.62 0.29
0.36 0.87 1.37 1.97 1.15 1.73 2.23 1.47 1.69 0.27 0.24 0.91 1.36 1.79 0.87 2.36 1.63 3.20
166 160 143 132 174 155 131 174 133 256 270 289 266 228 159 142 152 161 180 117 109 120 178 118 159 86 37 54 133 163 93 158 93 60 76 125 80 91 161 99 325 335 25 83 363
1.16 1.61 1.71 2.36 2.08 2.25 2.59 2.32 2.37 1.66 2.35 3.06 3.17 2.98 0.52 3.22 2.80 3.08 2.84 3.73 7.15 4.63 3.95 2.83 3.05 1.46 8.60 4.70 1.60 3.43 2.86 3.54 3.59 3.35 1.80 2.56 2.57 2.05 4.26 2.58 1.89 1.49 0.24 1.13 2.43
0.68 1.24 1.70 2.82 1.73 2.34 2.87 2.88 3.28 0.12 0.73 1.33 1.94 2.56 0.86 2.74 1.77 3.10 4.77 3.60 7.46 5.10 4.58 3.35 2.98 2.40 7.84 4.82 1.64 2.11 2.21 3.00 3.39 3.74 1.57 2.18 2.36 1.62 4.07 2.08 0.36 1.19 3.06 4.22 0.19
1.08 1.55 2.05 2.73 1.74 2.43 2.80 2.36 1.99 1.24 1.94 2.69 3.02 3.20 0.31 3.05 3.24 4.29 5.88 3.84 7.10 3.85 5.92 3.69 3.52 2.40 6.98 4.25 1.56 3.27 2.47 3.23 3.18 3.09 1.72 2.28 2.36 1.81 3.75 2.45 1.37 1.54 2.65 3.70 2.59
3.53 6.91 3.39 3.43 2.68 2.13 7.05 4.30 0.98 2.42 2.31 2.50 3.20 3.01 1.70 1.64 2.30 1.52 2.70 2.23 0.53 1.07 3.17 3.89 0.09
REFERENCES 1. Hansch C, Quninlan JE, Lawrence GL. 1968. The linear free-energy relationship between partition coef®cient and the aqueous solubility of organic liquids. J Org Chem 33:347±350. JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 91, NO. 2, FEBRUARY 2002
2. Yalkowsky SH, Valvani SC. 1980. Solubility and partitioning I: Solubility of nonelectrolytes in water. J Pharm Sci 69(8):912±922. 3. Yalkowsky SH, Sinkula AA, Valvani SC. 1980. Physical chemical properties of drugs. New York: Marcel Dekker, Inc.
COMPARISON OF ASER AND THE GSE
4. Klopman G, Wang S, Balthasar DM. 1992. Estimation of aqueous solubility of organic molecules by the group contribution approach. Application to the study of biodegradation. J Chem Inf Comput Sci 32:474±482. 5. Yalkowsky SH, Pinal R. 1993. Estimation of the aqueous solubility of complex organic molecules. Chemosphere 26(7):1239±1261. 6. KuÈhne R, Ebert RU, Kleint F, Scmidt G, SchuÈ uÈrmann G. 1995. Group contribution methods to estimate water solubility of organic chemicals. Chemosphere 30:2061±2077 7. Meylan WM, Howard PH, Boethling RS. 1996. Improved method of estimating water solubility from octanol±water partition coef®cient. Environ Toxicol Chem 15(2):100±106. 8. Mitchell BE, Jurs PC. 1998. Prediction of aqueous solubility of organic compounds from molecular structure. J Chem Inf Comput Sci 38:489±496. 9. Katritzky AR, Wang Y, Sild S, Tamm T. 1998. QSPR studies on vapor pressure, aqueous solubility, and the prediction of water-air partition coef®cients. J Chem Inf Comput Sci 38:720±725. 10. Huuskonen J. 2000. Estimation of aqueous solubility for a diverse set of organic compounds based on molecular topology. J Chem Inf Comput Sci 40: 773±777. 11. Jorgensen WL, Duffy EM. 2000. Prediction of drug solubility from Monte Carlo simulations. Bioorga Med Chem Lett 10:1155±1158. 12. Klopman G, Zhu H. 2001. Estimation of the aqueous solubility of organic molecules by the group contribution approach. J Chem Inf Comput Sci 41:439±445.
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13. Jain N, Yalkowsky SH. 2001. Estimation of the aqueous solubility I: Application to organic nonelectrolytes. J Pharm Sci 90(2):234±252. 14. Abraham MH, Le J. 1999. The correlation and prediction of the solubility of compounds in water using an amended solvation energy relationship. J Pharm Sci 88(9):868±880. 15. Ran Y, Yalkowsky SH. 2001. Prediction of drug solubility by the General Solubility Equation (GSE). J Chem Inf Comput Sci 41:354±357. 16. Ran Y, Jain N, Yalkowsky SH. 2001. Prediction of aqueous solubility of organic compounds by the general solubility equation (GSE). J Chem Inf Comput Sci 41:1208±1217. 17. Joback KG. 1984. A uni®ed approach to physical property estimation using multivariate statistical techniques. Ph.D. Thesis, Massachusetts Institute of Technology, Boston, MA. 18. Boethling RS, Campbell SE, Lynch DG, LaVeck GD. 1988. Validation of CHEMEST, an on-line system for the estimation of chemical properties. Ecotoxicol Environ Safety 15(1):21±30. 19. Dearden JC. 1991 The QSAR prediction of melting point, a property of environmental relevance. Sci Total Environ 109±110:59±68. 20. Simamora P, Yalkowsky SH. 1994. Group contribution methods for predicting the melting points and boiling points of aromatic compounds. Ind Eng Chem Res 33:1405±1409. 21. Krzyzaniak JF, Myrdal PB, Simamora P, Yalkowsky SH. 1995. Boiling point and melting point prediction for non-hydrogen bonding compounds. Ind Eng Chem Res 34:2531±2535.
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ABSTRACT: An Amended Solvation Energy Relationship (ASER) was recently reported to successfully predict the aqueous solubilities of a set of 664 organic compounds. The average absolute error and root mean square error are 0.43 and 0.62 log units, respectively. When the General Solubility Equation (GSE) is applied to the same set of compounds, it gives an average absolute error of 0.45 log units and a root mean square error of 0.62 log units. These results are similar to those of the ASER method. The advantages and disadvantages of each method are discussed. It is shown that when the two methods agree with each other, they also agree with the experimentally determined values. ß 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:517±533, 2002
Keywords:
aqueous solubility; estimation; Kow; melting point
INTRODUCTION Aqueous solubility is a crucial physical property in pharmaceutical and environmental research. Several methods for the prediction of the aqueous solubility have been published in recent years.1±13 The General Solubility Equation (GSE), as initially proposed by Yalkowsky and Valvani in 1980,2 and recently revised by Jain and Yalkowsky,13 has been used widely. The GSE relates the molar aqueous solubility (Sw) to the Celsius melting point (mp) and the octanol±water partition coef®cient (Kow) by the following simple equation: log Sw 0:5
0:01 mp
25
log Kow
1
The GSE has been shown to produce reasonable predictions for a wide variety of compounds.
An Amended Solvation Energy Relationship (ASER) was recently proposed to predict the aqueous solubility of organic compounds.14 The method starts with an equation that relates a solvation property (SP) to a sum of the following speci®c interaction terms: the excess molar refraction (R2), a combined dipolarity/polarizability H descriptor P (pH2 ), the overall solute hydrogen bond acidity ( Pa2 ), the overall solute hydrogen bond basicity ( bH 2 ), and the McGowan's characteristic molecular volume (Vx). In view of the in¯uence of intermolecular interactions on melting points and P P solubilities, a product term `` aH bH 2 2 '' was incorporated to partly account for the absence of a solid correction term, leading to the ASER as follows: X log Sw c rR2 sH aH 2 a 2 X X X H b bH k a bH 2 2 vVx 2 2
Correspondence to: Gang Yang (Telephone: 520-626-4308; Fax: 520-626-4063; E-mail: [email protected]) Journal of Pharmaceutical Sciences, Vol. 91, 517±533 (2002) ß 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association
where each term is determined by a separate formula and/or a set of group contribution values. Multiple linear regression analysis was used to
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construct the prediction equation. This method was applied to a diverse set of 664 organic liquids and solids with satisfactory results. In this study, the GSE is applied to the same set of compounds and the prediction results are compared.
METHODS The melting point data for the 664 compounds were obtained from the AQUASOL dATAbASE, Merck Index, and several Internet databases. The octanol±water partition coef®cients were calculated with CLOGP1 software (Version 4.0, BioByte Corp., Claremont, CA). Experimental octanol±water partition coef®cients are listed if available. The experimental aqueous solubilities and the ASER predicted solubilities are those reported by Abraham and Le.14 The aqueous solubilities were also calculated using the GSE of Jain and Yalkowsky.13 For each calculation, the average absolute error (AAE) is determined as X . 3 AAE jlog Scalc log Sobs j n and the root mean square error (RMSE) as hX i1=2 RMSE log Scalc log Sobs 2 =n
4
where log Scalc and log Sobs are the logarithms of the predicted and experimental aqueous solubility, respectively, and n is the number of compounds.
RESULTS Octanol±Water Partition Coef®cient Experimental partition coef®cients were found for 530 of the 664 compounds. As shown in Figure 1, the calculated partition coef®cients using CLOGP1 are in very good agreement with the available measured values (MLOGP), with an AAE of only 0.121 log units. CLOGP1 version 4.0 seems to give more accurate estimations of octanol±water partition coef®cients than the previous version. Partition coef®cients calculated with CLOGP1 are used in the solubility calculations because they are easily determined and are available for compounds with no available experimental values. The CLOGP and the available MLOGP values for Abraham's data set are listed in the second and third column of the Appendix. JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 91, NO. 2, FEBRUARY 2002
Figure 1. Measured log P (MlogP) versus ClogP (n 530).
Melting Point Melting points (mps) were found for 662 of the 664 compounds. The other two compounds (hydrocortisone 21-acetate and morphine) decompose on melting and thus may not have true mps. (Note that the use of a decomposition temperature in the GSE gives a maximum solubility estimation. The predicted solubility would be lower if the true mp were higher than the decomposition temperature.) If polymorphs or hydrates of the compound exist, the mp of the most stable form in equilibrium with the solution should be used. The mps used in the GSE are listed in the fourth column of the Appendix. Note that an mp of 258C is used for all liquids so that the crystal term vanishes. Solubility The solubility values used by Abraham for the 664 compounds studied are listed in the 5th column of the Appendix. All of these values were con®rmed to be in agreement with the values in the AQUASOL dATAbASE. The solubilities predicted by Abraham's ASER and by the GSE are listed in columns 6 and 7 of the Appendix, respectively. They are also plotted against the experimental solubility values in Figure 2. The AAE for the 662 compounds is 0.446 log units and the RMSE is 0.622 log units using the GSE method; these values are consistent with the results of previous studies.13,15,16 As shown in Table 1, the results are
COMPARISON OF ASER AND THE GSE
519
similar when the two compounds that decompose before melting are included.
DISCUSSION In spite of the fact that the GSE uses only two input variables and does not use any training set or ®tted parameters, it gives quite reasonable predictions. The ASER method produces only marginally better predictions (Table 1). However, the ASER method uses seven coef®cients, six variables derived from a very large number of structural descriptor values, and multiple linear regression analysis. As can be seen in Table 1, both methods give better prediction for the 408 liquids than for the 256 solids. The AAE of the GSE prediction is 0.358 for liquids and 0.588 for solids. The ASER method gives an AAE of 0.338 for liquids and 0.575 for solids. The success of the GSE for liquid nonelectrolytes is based on the relationship between the octanol±water partition coef®cient and the water solubility originally proposed by Hansch et al.1 and validated by Yalkowsky and Valvani.2 When applied to solid compounds, the GSE assumes that the entropy of melting of organic nonelectrolytes obeys Walden's rule (i.e., DSm 56.6 J K 1 mol 1) and that the solid± liquid heat capacity difference is negligible (i.e., DCpm 0). (Note: CLOGP1 alone gives better prediction for liquids than solids.) the ASER P In P method, the product term `` aH bH 2 2 ''deals with hydrogen-bond interactions between acid and basic sites in the solid or liquid. The addition H of a term ``pH 2 p2 '' to deal with dipole±dipole interactions did not improve the prediction. The ASER method predicts aqueous solubilities from compound structures without the need of experimental mp values. However, it is limited by the availability of descriptors for the contribution of speci®c groups present in a compound to the six
Figure 2. Experimental log Sw versus predicted log Sw using (a) the ASER method and (b) the GSE method (n 664).
Table 1 Statistical Analysis of Predicted Log Sw Values Compared With Experimental Log Sw Values Parameter AAE RMSE
Method
All n 664
All 2a n 662
Liquids n 408
Solids n 256
ASER GSE AVG ASER GSE AVG
0.430 0.447 0.377 0.615 0.623 0.534
0.431 0.446 0.376 0.615 0.622 0.533
0.338 0.358 0.309 0.490 0.505 0.453
0.575 0.588 0.486 0.774 0.775 0.642
a
All compounds except two, which decompose before melting. JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 91, NO. 2, FEBRUARY 2002
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parameters used. For example, dicarboxylic acids are not included in the ASER study because descriptors for these compounds have not yet been ®nalized. The applicability of the GSE depends on the availability of mp and octanol±water partition coef®cient data. As shown in previous studies, octanol±water partition coef®cients can be reliably predicted using CLOGP1 or other software.13,15,16 On the other hand, mp data are not always available, and a reliable general method of predicting mp from compound structures is not available currently. Most attempts to predict mp are either unsatisfactory or applicable to only a very small group of compounds.17±21 However, if mps can be predicted with a 308C error, it would correspond to only a twofold error in solubility. Fortunately, mps are available for most characterized compounds that do not decompose before melting. It is interesting to note that the average (AVG) of the predicted log Sw values using the two independent methods gives a better prediction than either method used alone. The results in Table 1 indicate that AAE and RMSE are
generally reduced when the average values are used. Furthermore, the two predictions differ by a factor of < 2 (0.30 log units) from each other for about half of the compounds. For > 60% of these 331 compounds, the average of the two calculations is within a factor of 2 of the observed value.
CONCLUSIONS Both the ASER and the GSE methods give satisfactory prediction for the compound set. The ASER is based on multiple linear regression analysis of a large training set that may or may not contain the required structural fragments, whereas the GSE is simpler and more userfriendly. However, the latter requires knowledge of either an experimentally determined or an estimated mp of the solute. This study provides support for the reliability of the GSE in estimating the aqueous solubilities of organic compounds. The GSE method can be used alone or in combination with the ASER calculation to provide con®rmatory results.
APPENDIX Compound Methane Ethane Propane Butane 2-Methylpropane Pentane 2-Methylbutane Hexane 2-Methylpentane 3-Methylpentane 2,2-Dimethylbutane 2,3-Dimethylbutane Heptane 2,2-Dimethylpentane 2,3-Dimethylpentane 2,4-Dimethylpentane 3,3-Dimethylpentane 2,2,3-Trimethylbutane Octane 2-Methylheptane 3-Methylheptane 4-Methyloctane 2,2,4-Trimethylpentane 2,3,4-Trimethylpentane Nonane
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
1.10 1.75 2.28 2.81 2.68 3.34 3.21 3.87 3.74 3.74 3.61 3.61 4.40 4.14 4.14 4.14 4.14 4.01 4.93 4.80 4.80 5.32 4.54 4.54 5.65
1.09 1.81 2.36 2.89 2.76 3.39
25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25
0.90 1.36 1.94 2.57 2.55 3.18 3.18 3.84 3.74 3.68 3.55 3.65 4.53 4.36 4.28 4.26 4.23 4.36 5.24 5.08 5.16 6.05 4.74 4.80 5.88
0.48 1.04 1.60 2.16 2.16 2.72 2.72 3.29 3.29 3.29 3.29 3.29 3.85 3.85 3.85 3.85 3.85 3.85 4.41 4.41 4.41 4.41 4.41 4.41 4.97
0.60 1.25 1.78 2.31 2.18 2.84 2.71 3.37 3.24 3.24 3.11 3.11 3.90 3.64 3.64 3.64 3.64 3.51 4.43 4.30 4.30 4.82 4.04 4.04 5.15
3.90 3.82 3.42 4.66
5.18 4.69 5.45
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APPENDIX (Continued) Compound 2,2,5-Trimethylhexane Decane Undecane Dodecane Tetradecane Hexadecane Cyclopentane Methylcyclopentane Propylcyclopentane Pentylcyclopentane Cyclohexane Methylcyclohexane cis-1,2-Dimethylcyclohexane trans-1,4-Dimethylcyclohexane Ethylcyclohexane Cycloheptane Cyclooctane Decalin Ethylene Propylene 1-Butene 2-Methylpropene 1-Pentene cis-2-Pentene trans-2-Pentene 2-Methyl-1-butene 3-Methyl-1-butene 2-Methyl-2-butene 1-Hexene 2-Methyl-1-pentene 1-Heptene trans-2-Heptene 1-Octene 1-Nonene 1-Decene 1,3-Butadiene 2-Methyl-1,3-butadiene 2,3-Dimethyl-1,3-butadiene 1,4-Pentadiene 1,5-Hexadiene Cyclopentene Cyclohexene 1-Methylcyclohexene Cycloheptene 1,4-Cyclohexadiene Ethyne Propyne 1-Butyne 1-Pentyne 1-Hexyne 3-Hexyne 1-Heptyne 1-Octyne 1-Nonyne
CLOGP 5.06 5.98 6.51 7.04 8.10 9.16 2.79 3.31 4.37 5.43 3.35 3.87 4.39 4.39 4.40 3.91 4.47 4.79 1.27 1.80 2.33 2.20 2.86 2.86 2.86 2.73 2.73 2.73 3.38 3.25 3.91 3.91 4.44 4.97 5.50 1.90 2.30 2.70 2.37 2.90 2.31 2.87 3.39 3.43 2.39 0.39 0.92 1.45 1.98 2.51 2.51 3.04 3.57 4.10
MLOGP 5.01 6.50 6.10 8.00 3.00 3.37 3.44 3.61
4.00 4.45 1.13 1.77 2.40 2.34 2.80
2.67 3.39 3.99 4.57 5.15 1.99 2.47 2.87 2.86 2.30 0.37 0.94 1.46 1.98 2.73 3.32 3.92 4.51
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25
5.05 6.98 7.59 7.67 7.96 8.40 2.64 3.30 4.74 6.08 3.10 3.85 4.30 4.47 4.25 3.51 4.15 5.19 0.40 1.08 1.94 2.33 2.68 2.54 2.54 2.73 2.73 2.56 3.23 3.03 3.73 3.82 4.44 5.05 5.51 1.87 2.03 2.40 2.09 2.68 2.10 2.59 3.27 3.18 2.06 0.29 0.41 1.24 1.64 2.36 1.99 3.01 3.66 4.24
4.97 5.53 6.09 6.66 7.78 8.90 2.48 3.00 4.12 5.24 3.08 3.61 4.18 4.10 4.16 3.69 4.31 4.98 0.60 1.17 1.73 1.73 2.29 2.34 2.32 2.31 2.26 2.35 2.83 2.85 3.41 3.44 3.97 4.53 5.10 1.54 2.09 2.53 1.99 2.56 1.87 2.50 3.07 3.07 2.02 0.13 0.45 1.16 1.66 2.25 2.30 2.91 3.46 4.02
4.56 5.48 6.01 6.54 7.60 8.66 2.29 2.81 3.87 4.93 2.85 3.37 3.89 3.89 3.90 3.41 3.97 4.29 0.77 1.30 1.83 1.70 2.36 2.36 2.36 2.23 2.23 2.23 2.88 2.75 3.41 3.41 3.94 4.47 5.00 1.40 1.80 2.20 1.87 2.40 1.81 2.37 2.89 2.93 1.89 0.11 0.42 0.95 1.48 2.01 2.01 2.54 3.07 3.60
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APPENDIX (Continued) Compound Dichloromethane Trichloromethane Tetrachloromethane Chloroethane 1,1-Dichloroethane 1,2-Dichloroethane 1,1,1-Trichloroethane 1,1,2-Trichloroethane 1,1,2,2-Tetrachloroethane 1,1,1,2-Tetrachloroethane Pentachloroethane Hexachloroethane 1-Chloropropane 2-Chloropropane 1,2-Dichloropropane 1,3-Dichloropropane 1-Chlorobutane 1-Chloro-2-methylpropane 2-Chlorobutane 1-Chloropentane 2-Chloro-2-methylbutane 1-Chlorohexane 1-Chloroheptane Chloroethylene 1,1-Dichloroethylene cis-1,2-Dichloroethylene Trichloroethylene Tetrachloroethylene Hexachloro-1,3-butadiene Bromomethane Dibromomethane Tribromomethane Tetrabromomethane Bromoethane 1,2-dibromoethane 1-Bromopropane 2-Bromopropane 1-Bromobutane 1-Bromo-2-methylpropane 1-Bromopentane 1-Bromohexane 1-Bromoheptane 1-Bromooctane Iodomethane Diiodomethane Iodoethane 1-Iodopropane 2-Iodopropane 1-Iodobutane 1-Iodoheptane Bromochloromethane Bromodichloromethane Chlorodibromethane 1-Chloro-2-bromoethane
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
1.25 1.95 2.88 1.47 1.78 1.46 2.48 2.05 2.64 3.03 3.63 4.61 1.99 1.99 1.99 1.71 2.52 2.39 2.52 3.05 2.92 3.58 4.11 1.52 2.37 1.77 2.63 3.48 4.90 1.08 1.53 2.37 3.43 1.60 1.74 2.13 2.13 2.66 2.53 3.19 3.72 4.25 4.78 1.47 2.31 2.00 2.52 2.52 3.05 4.64 1.39 2.09 2.23 1.60
1.25 1.97 2.83 1.43 1.79 1.47 2.49 2.07 2.62 2.62 3.22 4.14 2.04 1.90 1.99 2.00 2.64
25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 90 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25
0.63 1.17 2.31 1.06 1.29 1.06 2.00 1.48 1.74 2.18 2.60 3.67 1.47 1.41 1.60 1.62 2.03 2.00 1.96 2.73 2.51 3.12 4.00 1.75 1.64 1.30 1.96 2.54 4.92 0.79 1.17 1.91 3.14 1.09 1.68 1.73 1.59 2.37 2.43 3.08 3.81 4.43 5.06 1.00 2.34 1.60 2.29 2.09 2.96 4.81 0.89 1.54 1.90 1.32
0.99 1.59 2.60 1.02 1.35 1.29 2.18 1.70 2.21 2.52 3.03 4.23 1.57 1.49 1.81 1.84 2.12 2.05 2.06 2.69 2.85 3.24 3.80 1.11 1.73 1.38 2.28 3.12 5.12 0.82 1.56 2.47 3.74 1.29 1.72 1.85 1.77 2.40 2.40 2.96 3.52 4.07 4.63 1.30 2.42 1.77 2.32 2.26 2.88 4.54 1.32 1.84 2.12 1.69
0.75 1.45 2.38 0.97 1.28 0.96 1.98 1.55 2.14 2.53 3.13 4.11 1.49 1.49 1.49 1.21 2.02 1.89 2.02 2.55 2.42 3.08 3.61 1.02 1.87 1.27 2.13 2.98 4.40 0.58 1.03 1.87 3.58 1.10 1.24 1.63 1.63 2.16 2.03 2.69 3.22 3.75 4.28 0.97 1.81 1.50 2.02 2.02 2.55 4.14 0.89 1.59 1.73 1.10
2.33 3.11 2.52 3.66 4.15 2.13 1.86 2.61 3.40 4.78 1.19 1.88 2.67 3.42 1.61 1.96 2.10 2.14 2.75 3.37 3.80 4.36 4.89 1.51 2.30 2.00 2.54 2.89 3.08 4.70 1.41 2.10 2.24
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APPENDIX (Continued) Compound 1,1,2-Trichlorotri¯uoroethane 1,2-Dichlorotetra¯uoroethane Diethyl ether Dipropyl ether Diisopropyl ether Dibutyl ether Methyl propyl ether Methyl butyl ether Methyl tert-butyl ether Ethyl propyl ether Propyl isopropyl ether Ethyl vinyl ether Dimethoxymethane 1,1-Diethoxyethane 1,2-Diethoxyethane 1,2-Propylene oxide Tetrahydrofuran 2-Methyltetrahydrofuran Tetrahydropyran Propionaldehyde Butyraldehyde Valeraldehyde Caproaldehyde 2-Ethylbutanol 2-Ethylhexanol trans-Crotonaldehyde 2-Ethyl-2-hexanol 2-Butanone 2-Pentanone 3-Pentanone 3-Methyl-2-butanone 2-Hexanone 3-Hexanone 3-Methyl-2-pentanone 4-Methyl-2-pentanone 3,3-Dimethyl-2-butanone 2-Heptanone 4-Heptanone 2,4-Dimethyl-3-pentanone 2-Octanone 2-Nonanone 5-Nonanone 2-Decanone Cyclohexanone Carvone Camphor Menthone Methyl formate Ethyl formate Propyl formate Isopropyl formate Butyl acetate Isobutyl formate Isopentyl formate
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
3.29 2.85 0.87 1.93 1.49 2.91 0.87 1.40 1.05 1.40 1.71 1.01 0.43 0.93 0.93 0.25 0.53 1.04 0.95 0.30 0.83 1.36 1.89 1.75 2.81 0.52 2.59 0.32 0.85 0.85 0.85 1.38 1.38 1.38 1.25 1.25 1.91 1.91 1.91 2.44 2.97 2.97 3.49 0.86 2.01 2.18 2.83 0.26 0.26 0.79 0.57 1.77 1.19 1.72
3.16 2.82 0.89 2.03 1.52 3.22 1.21 1.66 0.94
25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 177 25 25 25 25 25 25 25 25
3.04 2.74 0.09 1.10 1.10 1.85 0.39 0.99 0.24 0.66 1.34 0.85 0.48 0.43 0.77 0.59 0.49 0.11 0.03 0.58 0.01 0.85 1.30 1.52 2.13 0.32 2.46 0.52 0.19 0.28 0.12 0.80 0.83 0.67 0.74 0.72 1.45 1.30 1.30 2.05 2.58 2.58 3.30 0.60 2.06 1.96 2.35 0.58 0.15 0.49 0.63 1.37 1.01 1.52
2.62 2.41 0.34 1.43 1.64 2.54 0.44 0.95 0.23 0.86 1.44 0.39 0.79 0.59 0.15 0.70 0.18 0.15 0.37 0.55 0.00 0.54 1.09 1.10 2.24 0.29 2.04 0.31 0.24 0.27 0.26 0.80 0.81 0.80 0.80 0.82 1.35 1.35 1.36 1.89 2.47 2.47 3.02 0.28 2.70 2.15 2.63 0.61 0.08 0.50 0.39 1.05 0.96 1.52
2.79 2.35 0.37 1.43 0.99 2.41 0.37 0.90 0.55 0.90 1.21 0.51 0.93 0.43 0.43 0.25 0.03 0.54 0.45 0.20 0.33 0.86 1.39 1.25 2.31 0.02 2.09 0.18 0.35 0.35 0.35 0.88 0.88 0.88 0.75 0.75 1.41 1.41 1.41 1.94 2.47 2.47 2.99 0.36 1.51 3.20 2.33 0.76 0.24 0.29 0.07 1.27 0.69 1.22
1.04 0.18 0.84 0.66 0.13 0.47 0.95 0.59 0.88 1.78
0.29 0.91 0.82 0.84 1.38 1.31 1.20 1.98 2.04 1.86 2.37 3.14 2.88 3.73 0.81 2.38 0.03 0.83 1.78
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APPENDIX (Continued) Compound Methyl acetate Ethyl acetate Propyl acetate Isopropyl acetate Isobutyl acetate Pentyl acetate Isopentyl acetate Methyl propionate Ethyl propionate Methyl butyrate Ethyl butyrate Propyl butyrate Methyl pentanoate Ethyl pentanoate Propyl propanoate Pentyl propanoate Methyl hexanoate Ethyl hexanoate Ethyl heptanoate Methyl octanoate Ethyl octanoate Methyl nonanoate Ethyl nonanoate Methyl decanoate Ethyl decanoate Methyl acrylate Glyceryl triacetate Malonic acid diethyl ester Acetonitrile Propionitrile Acrylonitrile Ethylamine Propylamine Butylamine Pentylamine Hexylamine Heptylamine Octylamine Diethylamine Dipropylamine Dibutylamine Trimethylamine Triethylamine Tripropylamine Nitromethane Nitroethane 1-Nitropropane 2-Nitropropane Chloropicrin Acetamide N,N-Dimethylacetamide Urea o-Ethyl carbamate Acetic acid
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
0.18 0.71 1.24 1.24 1.64 2.30 2.17 0.71 1.24 1.24 1.77 2.30 1.77 2.30 1.77 2.83 2.30 2.83 3.36 3.36 3.88 3.88 4.41 4.41 4.94 0.80 0.67 1.13 0.39 0.13 0.29 0.13 0.39 0.92 1.45 1.98 2.51 3.04 0.54 1.60 2.66 0.02 1.40 2.98 0.28 0.25 0.77 0.55 1.60 1.11 0.80 1.66 0.18 0.19
0.18 0.73 1.24 1.22 1.76 2.29 2.25 0.82 1.21 1.29 1.71 2.15 1.96
25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 81 25 132 25 25
0.46 0.04 0.72 0.55 1.21 1.89 1.92 0.14 0.66 0.82 1.28 1.92 1.36 1.75 1.34 2.25 1.87 2.35 2.74 3.17 3.39 3.38 3.80 4.69 4.10 0.22 0.60 0.82 0.26 0.28 0.15 2.06 1.52 0.96 0.27 0.25 0.90 1.46 1.03 0.46 1.44 1.32 0.14 2.28 0.26 0.22 0.80 0.62 2.00 1.58 1.11 0.96 0.85 2.00
0.36 0.18 0.74 0.64 1.20 1.84 1.76 0.22 0.75 0.76 1.30 1.86 1.32 1.84 1.30 2.42 1.85 2.39 2.94 2.96 3.50 3.52 4.06 4.07 4.61 0.25 0.73 0.53 0.80 0.42 0.35 1.20 0.65 0.09 0.46 1.01 1.57 2.12 0.43 0.67 1.77 0.86 0.32 1.85 0.63 0.15 0.49 0.40 2.07 1.86 1.34 2.32 0.79 1.18
0.32 0.21 0.74 0.74 1.14 1.80 1.67 0.21 0.74 0.74 1.27 1.80 1.27 1.80 1.27 2.33 1.80 2.33 2.86 2.86 3.38 3.38 3.91 3.91 4.44 0.30 0.17 0.63 0.89 0.37 0.21 0.63 0.11 0.42 0.95 1.48 2.01 2.54 0.04 1.10 2.16 0.48 0.90 2.48 0.78 0.25 0.27 0.05 1.10 1.05 1.30 1.09 0.68 0.69
2.67 2.42
3.87 4.41 0.80 0.25 0.96 0.34 0.16 0.25 0.13 0.47 0.97 1.49 2.06 2.57 3.09 0.58 1.67 2.83 0.16 1.45 2.79 0.35 0.18 0.87 0.80 2.09 1.09 0.77 1.66 0.15 0.17
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APPENDIX (Continued) Compound Hexanoic acid Decanoic acid Methacrylic acid Chloroacetic acid Trichloroacetic acid Methanol Ethanol 1-Propanol 2-Propanol 1-Butanol 2-Methylpropan-1-ol Butan-2-ol 1-Pentanol 2-Pentanol 3-Pentanol 2-Methylbutanol 3-Methylbutan-1-ol 2-Methylbutan-2-ol 3-Methyl-2-butanol 2,2-Dimethylpropanol 1-Hexanol 2-Hexanol 3-Hexanol 2-Methylpentanol 3-Methyl-2-Pentanol 4-Methylpentanol 2-Methyl-2-pentanol 3-Methyl-2-pentanol 4-Methyl-2-pentanol 2-Methyl-3-pentanol 3-Methyl-3-pentanol 2-Ethyl-1-butanol 2,2-Dimethyl-1-butanol 3,3-Dimethyl-1-butanol 3,3-Dimethyl-2-butanol 1-Heptanol 2-Heptanol 3-Heptanol 4-Heptanol 2-Methyl-2-hexanol 3-Methyl-3-hexanol 3-Ethyl-3-pentanol 2,2-Dimethylpentanol 2,4-Dimethyl-2-pentanol 2,4-Dimethyl-3-pentanol 1-Octanol 2-Octanol 3-Octanol 2-Methyl-2-heptanol 3-Methyl-3-heptanol 2-Ethyl-1-hexanol 1-Nonanol 2-Nonanol 1-Decanol
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
1.92 4.04 0.66 0.08 1.68 0.76 0.24 0.29 0.07 0.82 0.69 0.60 1.35 1.13 1.13 1.22 1.22 1.00 1.00 1.09 1.88 1.66 1.66 1.75 1.53 1.75 1.53 1.53 1.53 1.53 1.53 1.75 1.62 1.62 1.40 2.41 2.19 2.19 2.19 2.06 2.06 2.06 2.15 1.93 1.93 2.94 2.72 2.72 2.59 2.59 2.81 3.47 3.25 4.00
1.92 4.09 0.93 0.22 1.33 0.77 0.31 0.25 0.05 0.88 0.76 0.61 1.56 1.19 1.21 1.29 1.16 0.89 1.28 1.31 2.03 1.76 1.65
25 31 25 61 57 25 25 25 25 25 25 25 25 25 25 25 25 25 25 53 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25
1.06 3.44 0.00 1.81 0.60 1.56 1.10 0.62 0.43 0.00 0.10 0.47 0.60 0.29 0.24 0.47 0.51 0.15 0.18 0.40 1.24 0.89 0.80 1.11 0.72 1.14 0.49 0.71 0.80 0.70 0.36 1.17 1.04 0.50 0.62 1.81 1.55 1.47 1.40 1.08 0.98 0.85 1.52 0.92 1.22 2.39 2.09 1.98 1.72 1.60 2.11 3.01 2.74 3.63
0.99 3.19 0.05 0.87 0.01 1.59 1.04 0.49 0.70 0.06 0.07 0.07 0.62 0.41 0.43 0.64 0.61 0.33 0.43 0.51 1.17 0.96 0.98 1.19 1.19 1.18 0.87 0.97 0.97 1.01 0.91 1.21 1.23 1.19 1.02 1.73 1.53 1.52 1.52 1.42 1.46 1.50 1.79 1.45 1.59 2.28 2.06 2.08 1.99 2.01 2.32 2.84 2.63 3.40
1.42 3.60 0.16 0.22 1.50 1.26 0.74 0.21 0.43 0.32 0.19 0.10 0.85 0.63 0.63 0.72 0.72 0.50 0.50 0.87 1.38 1.16 1.16 1.25 1.03 1.25 1.03 1.03 1.03 1.03 1.03 1.25 1.12 1.12 0.90 1.91 1.69 1.69 1.69 1.56 1.56 1.56 1.65 1.43 1.43 2.44 2.22 2.22 2.09 2.09 2.31 2.97 2.75 3.50
1.47 2.72 2.31 2.24 2.22
3.00 2.90
3.67 4.57
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APPENDIX (Continued) Compound 2-Undecanol 1-Dodecanol 1-Tetradecanol 1-Pentadecanol 1-Hexadecanol 1-Octadecanol Cyclohexanol Cycloheptanol Cyclooctanol 4-Pentene-1-ol 1-Hexene-3-ol 2-Butoxyethanol Ethanethiol Butanethiol Dimethyl sul®de Diethyl sul®de Di-n-propyl sul®de Diisopropl sul®de Dimethyl disul®de Diethyl disul®de Thiourea Triethyl phosphate Benzene Toluene Ethylbenzene o-Xylene m-Xylene p-Xylene Propylbenzene Isopropylbenzene 1,2,3-Trimethylbenzene 1,2,4-Trimethylbenzene 1,3,5-Trimethylbenzene 2-Ethyltoluene 4-Ethyltoluene Butyltoluene Isobutyltoluene tert-Butylbenzene 1,2-Diethylbenzene 1,4-Diethylbenzene 1,2,4,5-Tetramethylbenzene 2-Isopropyltoluene 4-Isopropyltoluene Pentylbenzene tert-Pentylbenzene Pentamethylbenzene Hexylbenzene Hexamethylbenzene Styrene Diphenylmethane Bibenzyl Biphenyl 4-Methylbiphenyl Naphthalene
CLOGP 4.31 5.06 6.11 6.64 7.17 7.70 1.27 1.83 2.38 0.87 1.38 0.84 1.17 2.23 0.84 1.90 2.96 2.52 1.74 2.80 1.02 0.28 2.14 2.64 3.17 3.09 3.14 3.14 3.70 3.57 3.54 3.59 3.64 3.62 3.67 4.68 4.55 3.97 4.15 4.20 4.04 4.02 4.07 4.76 4.50 4.49 5.29 4.99 2.87 4.21 4.59 4.03 4.53 3.32
MLOGP 5.13 6.36
1.23
0.83 2.28 1.05 1.95 2.84 1.77 1.02 0.80 2.13 2.73 3.15 3.12 3.20 3.15 3.72 3.66 3.59 3.63 3.58 3.53
4.11 3.72 4.00 4.10 4.90 4.56 5.52 4.61 2.95 4.14 4.79 4.01 4.63 3.30
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MP
log Sw Obsvd
log Sw ASER
log Sw GSE
25 25 40 46 56 61 25 25 25 25 25 25 25 25 25 25 25 25 25 25 176 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 25 80 25 25 25 25 50 25 164 25 26 52 70 45 80
2.94 4.80 5.84 6.35 7.00 8.40 0.44 0.88 1.29 0.15 0.59 0.42 0.60 2.18 0.45 1.34 2.58 2.24 1.44 2.42 0.32 0.43 1.64 2.21 2.77 2.80 2.82 2.77 3.37 3.27 3.20 3.31 3.40 3.21 3.11 4.06 4.12 3.66 3.28 3.75 4.59 3.76 3.77 4.64 4.15 4.00 5.21 5.23 2.82 4.08 4.62 4.35 4.62 3.60
3.75 4.50 5.61 6.17 6.73 7.84 0.64 1.22 1.83 0.28 0.88 0.24 0.80 1.91 0.57 1.54 2.65 2.45 1.51 2.58 1.14 0.23 1.96 2.51 3.05 3.02 3.01 3.00 3.61 3.57 3.48 3.47 3.47 3.52 3.50 4.16 4.17 4.07 4.10 4.08 4.06 4.04 4.01 4.71 4.71 4.60 5.28 4.92 2.96 4.35 4.91 4.26 4.83 3.60
3.81 4.56 5.76 6.35 6.98 7.56 0.77 1.33 1.88 0.37 0.88 0.34 0.67 1.73 0.34 1.40 2.46 2.02 1.24 2.30 0.01 0.22 1.64 2.14 2.67 2.59 2.64 2.64 3.20 3.07 3.04 3.09 3.14 3.12 3.17 4.18 4.05 3.47 3.65 3.70 4.09 3.52 3.57 4.26 4.00 4.24 4.79 5.88 2.37 3.72 4.36 3.98 4.23 3.37
COMPARISON OF ASER AND THE GSE
527
APPENDIX (Continued) Compound 1-Methylnaphthalene 2-Methylnaphthalene 1,3-Dimethylnaphthalene 1,4-Dimethylnaphthalene 1,5-Dimethylnaphthalene 2,3-Dimethylnaphthalene 2,6-Dimethylnaphthalene 1-Ethylnaphthalene 2-Ethylnaphthalene 1,2,3,4-Tetrahydronaphthalene Indan Acenaphthene Acenaphthylene Fluorene 1-Methyl¯uorene Anthracene 2-Methylanthracene 9-Methylanthracene 9,10-Dimethylanthracene Phenanthrene 1-Methylphenanthrene 2-Methylphenanthrene Fluoranthene Benzo[a]¯uorene Benzo[b]¯uorene Pyrene 7,12-Dimethylbenz[a]anthracene Naphthacene Chrysene 5-Methylchrysene 6-Methylchrysene 5,6-Dimethylchrysene Triphenylene Perylene Benzo[b]¯uoranthene Benzo[ j]¯uoranthene Benzo[k]¯uoranthene Cholanthrene 3-Methylcholanthrene Benzo[a]pyrene Benzo[e]pyrene Benzo[ghi]perylene Picene Fluorobenzene 1,3-Di¯uorobenzene 1,4-Di¯uorobenzene Benzyl tri¯uoride Chlorobenzene 1,2-Dichlorobenzene 1,3-Dichlorobenzene 1,4-Dichlorobenzene 1,2,3-Trichlorobenzene 1,2,4-Trichlorobenzene 1,3,5-Trichlorobenzene
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
3.81 3.81 4.31 4.31 4.31 4.26 4.31 4.34 4.34 3.71 3.15 3.77 3.62 4.07 4.57 4.49 4.99 4.99 5.49 4.49 4.99 4.99 4.95 5.25 5.25 4.95 6.66 5.66 5.66 6.16 6.16 6.61 5.66 6.12 6.12 6.12 6.12 6.12 6.62 6.12 6.12 6.58 6.84 2.28 2.43 2.43 3.03 2.86 3.45 3.57 3.57 4.04 4.16 4.28
3.87 3.86 4.42 4.37 4.38 4.40 4.31 4.39 4.38 3.49 3.18 3.92
25 35 25 25 82 103 109 25 25 25 25 95 90 116 87 216 205 79 183 100 123 57 110 187 212 150 122 357 255 117 160 128 199 278 167 165 216 173 179 179 178 278 366 25 25 25 25 25 25 25 54 25 25 63
3.70 3.77 4.29 4.14 4.68 4.72 4.89 4.17 4.29 4.37 3.04 4.63 3.96 5.00 5.22 6.35 6.96 5.89 6.57 5.26 5.85 5.84 6.00 6.68 8.04 6.18 7.02 8.60 8.06 6.59 6.57 7.01 6.73 8.80 8.23 8.00 8.49 7.85 7.92 8.70 7.80 9.02 7.87 1.80 2.00 1.97 2.51 2.38 3.05 3.04 3.27 4.00 3.59 4.48
4.16 4.12 4.77 4.79 4.79 4.79 4.72 4.78 4.73 3.83 3.31 4.37 4.11 4.61 5.17 5.36 5.83 5.87 6.35 5.12 5.71 5.71 5.98 6.79 6.77 6.12 8.13 7.07 6.93 7.49 7.49 8.06 6.67 7.40 7.38 7.52 7.60 7.45 8.04 7.83 7.92 8.51 8.80 2.02 2.15 1.98 2.50 2.75 3.42 3.52 3.48 4.17 4.16 4.22
3.31 3.41 3.81 3.81 4.38 4.54 4.65 3.84 3.84 3.21 2.65 3.97 3.77 4.48 4.69 5.90 6.29 5.03 6.57 4.74 5.47 4.81 5.30 6.37 6.62 5.70 7.13 8.48 7.46 6.58 7.01 7.14 6.90 8.15 7.04 7.02 7.53 7.10 7.66 7.16 7.15 8.61 9.75 1.78 1.93 1.93 2.53 2.36 2.95 3.07 3.36 3.54 3.66 4.16
4.18 4.97 4.45 5.07 5.69 4.47 5.08 4.86 5.16 5.68 5.77 4.88 5.80 5.90 5.81
5.49 5.82 6.11 6.42 6.13 6.44 6.63 7.11 2.27 3.01 2.89 3.43 3.53 3.44 4.14 4.05 4.19
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APPENDIX (Continued) Compound 1,2,3,4-Tetrachlorobenzene 1,2,3,5-Tetrachlorobenzene 1,2,4,5-Tetrachlorobenzene Pentachlorobenzene Hexachlorobenzene 2-Chlorotoluene 4-Chlorotoluene Benzyl chloride 1-Chloronaphthalene 2-Chloronaphthalene 2-Chlorobiphenyl 3-Chlorobiphenyl Bromobenzene 1,2-Dibromobenzene 1,3-Dibromobenzene 1,4-Dibromobenzene 1,3,5-Tribromobenzene 1,2,4,5-Tetrabromobenzene 2-Bromotoluene 4-Bromotoluene 1-Bromonaphthalene 2-Bromonaphthalene Iodobenzene 1-Iodonaphthalene o-Fluorobromobenzene m-Fluorobromobenzene o-Chlorobromobenzene m-Chlorobromobenzene p-Chlorobromobenzene o-Chloroiodobenzene m-Chloroiodobenzene p-Chloroiodobenzene p-Bromoiodobenzene Anisole 2-Chloroanisole 3-Chloroanisole 4-Chloroanisole Diphenyl ether Benzaldehyde p-Methoxybenzaldehyde Acetophenone Benzophenone Anthraquinone Methyl benzoate Ethyl benzoate Dimethyl phthalate Diethyl phthalate Di(2-ethylthexyl)phthalate Benzonitrile Phthalonitrile Aniline o-Toluidine m-Methylaniline p-Methylaniline
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
4.63 4.75 4.75 5.35 6.06 3.35 3.35 2.70 4.03 4.03 4.49 4.49 3.01 3.67 3.87 3.87 4.73 5.19 3.50 3.50 4.18 4.18 3.27 4.44 3.15 3.15 3.44 3.72 3.72 3.98 3.98 3.98 4.13 2.06 2.75 2.91 2.91 4.24 1.50 1.78 1.58 3.18 2.62 2.11 2.64 1.56 2.62 8.71 1.57 1.01 0.91 1.36 1.36 1.41
4.64 4.66 4.60 5.18 5.73 3.42 3.33
46 54 139 50 227 25 25 25 25 60 32 25 25 25 25 87 121 182 25 29 25 54 25 25 25 25 25 25 67 25 55 53 90 37 25 25 25 28 25 25 25 49 284 25 25 25 25 25 25 140 25 25 25 43
4.57 4.63 5.56 5.65 7.68 3.52 3.08 2.39 3.93 4.14 4.54 4.88 2.55 3.50 3.54 4.07 5.60 6.98 2.23 3.19 4.35 4.40 3.01 4.55 2.70 2.67 3.19 3.21 3.63 3.54 3.55 4.03 4.56 1.85 2.46 2.78 2.78 3.96 1.19 1.49 1.28 3.12 5.19 1.85 2.32 1.66 2.35 6.96 1.00 2.38 0.41 2.21 0.85 1.21
4.77 4.80 4.79 5.37 6.00 3.36 3.31 2.18 4.36 4.36 4.99 4.96 2.98 4.02 4.06 4.06 5.13 5.88 3.59 3.53 4.69 4.62 3.42 5.16 3.29 3.25 3.90 3.92 3.88 4.43 4.42 4.42 4.64 2.04 2.92 2.90 2.78 4.58 1.36 1.53 1.53 3.56 3.73 1.89 2.41 1.32 2.31 8.94 1.45 1.10 1.01 1.50 1.46 1.44
4.34 4.54 5.39 5.10 7.58 2.85 2.85 2.20 3.53 3.88 4.06 3.99 2.51 3.17 3.37 3.99 5.19 6.26 3.00 3.04 3.68 3.97 2.77 3.94 2.65 2.65 2.94 3.22 3.64 3.48 3.78 3.76 4.28 1.68 2.25 2.41 2.41 3.77 1.00 1.28 1.08 2.92 4.71 1.61 2.14 1.06 2.12 8.21 1.07 1.66 0.41 0.86 0.86 1.09
4.10 4.14 4.53 2.99 3.64 3.75 3.79 4.51 5.13
3.25
2.11 2.68 2.98 2.78 4.21 1.47 1.76 1.58 3.18 3.39 2.12 2.64 1.56 2.47 7.45 1.56 0.99 0.90 1.32 1.32 1.39
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APPENDIX (Continued) Compound o-Chloroaniline m-Chloroaniline p-Choroaniline o-Nitroaniline m-Nitroaniline p-Nitroaniline Ethyl-p-aminobenzoate Risocaine Butamben N-Methylaniline N-Ethylaniline N,N-Dimethylaniline N,N-Diethylaniline 1-Naphthylamine p, p-Biphenyldiamine Benzylamine Procaine Diphenylamine Azobenzene Nitrobenzene o-Nitrotoluene m-Nitrotoluene p-Nitrotoluene o-Chloronitrobenzene m-Chloronitrobenzene p-Chloronitrobenzene o-Nitroanisole p-Nitroanisole 1,2-Dinitrobenzene 1,3-Dinitrobenzene 1,4-Dinitrobenzene 2,4-Dinitrotoluene 2,6-Dinitrotoluene 2,4,6-Trinitrotoluene 1,3,5-Trinitrobenzene 1-Nitronaphthalene 2,3-Dichloronitrobenzene 3,4-Dichloronitrobenzene Benzamide Acetanilide p-Fluoroacetanilide p-Chloroacetanilide p-Bromoacetanilide 4-Nitroacetanilide Phenacetin Lidocain Benzoic acid o-Toluic acid m-Toluic acid p-Toluic acid o-Chlorobenzoic acid m-Chlorobenzoic acid p-Chlorobenzoic acid 2-Bromobenzoic acid
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
1.96 1.96 1.96 1.92 1.38 1.38 2.03 2.55 3.08 1.64 2.17 2.34 3.23 2.09 1.58 1.09 2.54 3.62 3.85 1.88 2.30 2.38 2.38 2.40 2.60 2.60 1.82 2.10 1.63 1.63 1.63 2.05 2.05 1.71 1.37 3.06 3.11 3.19 0.65 1.16 1.56 2.13 2.28 1.46 1.77 1.95 1.88 2.38 2.38 2.38 2.10 2.70 2.70 2.20
1.90 1.88 1.88 1.85 1.37 1.39 1.86 2.43 2.87 1.66 2.16 2.31 3.31 2.25 1.34 1.09 2.14 3.50 3.82 1.85 2.30 2.42 2.37 2.52 2.47 2.39 1.73 2.03 1.69 1.49 1.47 1.98 2.10 1.60 1.18 3.19 3.05 3.12 0.64 1.16 1.47 2.12 2.29 1.66 1.58 2.26 1.87 2.40 2.37 2.27 2.05 2.68 2.65 2.20
25 25 73 72 114 146 89 75 58 25 25 25 25 49 128 25 61 52 69 25 25 25 55 34 43 84 25 54 118 90 173 69 65 81 123 59 61 41 128 114 153 178 165 215 135 68 122 105 112 182 142 158 243 149
1.52 1.37 1.66 1.96 2.19 2.37 2.10 2.45 3.08 1.28 1.70 1.92 3.03 1.92 2.70 1.54 1.78 3.50 2.75 1.80 2.33 2.44 2.49 2.55 2.77 2.92 1.96 2.41 3.10 2.29 3.39 2.82 3.00 3.22 2.89 3.54 3.48 3.20 0.96 1.33 1.78 2.84 3.08 2.69 2.35 1.71 1.55 2.06 2.14 2.60 1.89 2.59 3.31 2.28
1.96 1.82 1.77 1.75 1.44 1.23 2.03 2.60 3.17 1.61 2.21 2.46 3.59 2.45 2.74 0.43 2.23 3.63 4.28 1.87 2.42 2.57 2.43 2.61 2.59 2.75 2.16 2.11 1.98 1.66 1.66 2.22 2.30 2.12 1.55 3.72 3.37 3.44 0.40 0.89 1.11 1.81 2.09 1.83 1.74 2.41 1.06 1.74 1.66 1.61 1.52 1.77 1.85 1.74
1.46 1.46 1.94 1.89 1.77 2.09 2.17 2.55 2.91 1.14 1.67 1.84 2.73 1.83 2.11 0.59 2.40 3.39 3.79 1.38 1.80 1.88 2.18 1.99 2.28 2.69 1.32 1.89 2.06 1.78 2.61 1.99 1.95 1.77 1.85 2.90 2.97 2.85 1.18 1.55 2.34 3.16 3.18 2.86 2.37 1.88 2.35 2.68 2.75 3.45 2.77 3.53 4.38 2.94
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APPENDIX (Continued) Compound 4-Bromobenzoic acid m-Nitrobenzoic acid p-Nitrobenzoic acid o-Aminobenzoic acid Aspirin Phenylacetic acid Ibuprofen Naproxen Phenol 2-Methylphenol 3-Methylphenol p-Cresol 2,4-Dimethylphenol 2,6-Dimethylphenol 3,4-Dimethylphenol 3,5-Dimethylphenol 2,4,6-Trimethylphenol p-tert-Butylphenol Thymol p-Phenylphenol 2-Chlorophenol 3-Chlorophenol 4-Chlorophenol 4-Bromophenol 2,3-Dichlorophenol 2,4-Dichlorophenol 2,6-Dichlorophenol 3,4-Dichlorophenol 3,5-Dichlorophenol 2,3,4-Trichlorophenol 2,3,5-Trichlorophenol 2,3,6-Trichlorophenol 2,4,5-Trichlorophenol 2,4,6-Trichlorophenol 2,3,4,5-Tetrachlorophenol 2,3,4,6-Tetrachlorophenol 2,3,5,6-Tetrachlorophenol Pentachlorophenol o-Methoxyphenol p-Hydroxybenzaldehyde o-Aminophenol p-Aminophenol o-Nitrophenol m-Nitrophenol p-Nitrophenol Salicyclic acid p-Hydroxybenzoic acid 1,2-Benzenediol 1,3-Benzenediol 1,4-Benzenediol Methylparaben Ethyl-p-hydroxybenzoate o-Hydroxybenzamide p-Hydroxyacetanilide
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
2.85 1.84 1.84 1.21 1.02 1.41 3.68 2.82 1.47 1.97 1.97 1.97 2.47 2.47 2.42 2.47 2.97 3.30 3.20 3.36 2.15 2.48 2.48 2.63 2.84 2.96 2.63 3.17 3.29 3.58 3.58 3.37 3.58 3.37 4.30 4.09 4.09 4.68 1.32 1.44 0.62 0.25 1.85 1.85 1.85 2.19 1.56 0.88 0.81 0.81 1.98 2.51 1.28 0.49
2.86 1.83 1.89 1.21 1.19 1.41 3.50 3.34 1.47 1.95 1.96 1.94 2.30 2.36 2.23 2.35
246 142 242 145 135 77 76 153 41 31 25 33 28 49 63 64 71 98 48 167 25 34 43 66 59 45 67 67 68 79 57 56 68 70 116 70 114 174 28 25 175 189 44 97 113 159 217 104 110 170 128 117 140 169
3.54 1.68 2.80 1.52 1.72 0.89 3.76 4.20 0.00 0.62 0.68 0.73 1.19 1.29 1.38 1.40 2.05 2.41 2.22 3.48 1.06 0.70 0.70 1.09 1.30 1.55 1.79 1.25 1.34 2.67 2.67 2.64 2.21 2.34 3.15 3.10 3.37 4.28 1.96 0.96 0.72 0.80 1.74 1.01 0.74 1.82 1.41 0.62 0.81 0.17 1.83 2.35 1.82 1.03
2.16 1.53 1.55 1.02 1.13 1.09 3.93 3.89 0.73 1.44 1.26 1.33 1.82 1.96 1.73 1.80 2.39 2.77 2.81 3.18 1.56 1.37 1.30 1.60 2.22 2.25 2.22 1.81 1.83 2.57 2.60 2.71 2.64 2.67 3.26 3.49 3.39 3.48 1.21 0.67 0.47 0.13 1.86 1.04 0.85 1.48 1.07 0.42 0.27 0.32 1.48 2.02 1.11 1.02
4.56 2.51 3.51 1.91 1.62 1.43 3.69 3.60 1.13 1.53 1.47 1.55 2.00 2.21 2.30 2.36 2.93 3.53 2.93 4.28 1.65 2.07 2.16 2.54 2.68 2.66 2.55 3.09 3.22 3.62 3.40 3.18 3.51 3.32 4.71 4.04 4.48 5.67 0.85 0.94 1.62 1.39 1.54 2.07 2.23 3.03 2.98 1.17 1.16 1.76 2.51 2.93 1.93 1.43
3.31 3.30 3.20 2.15 2.50 2.39 2.59 2.84 3.06 2.75 3.33 3.52 3.77 3.72 3.69 4.21 4.12 3.88 5.12 1.32 1.35 0.62 0.04 1.79 2.00 1.91 2.26 1.58 0.88 0.80 0.59 1.96 2.47 1.28 0.51
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APPENDIX (Continued) Compound 1-Naphthol 2-Naphthol Phenylmethanol 1-Phenylethanol 2-Phenoxyethanol Ephedrine Thiophenol Phenylthiourea p-Toluenesulfonamide Furane Furfural Dibenzofurane Pyridine 2,3-Dimethylpyridine 2,4-Dimethylpyridine 2,6-Dimethylpyridine 3,4-Dimethylpyridine 3,5-Dimethylpyridine 2-Ethyl pyridine 4-Ethyl pyridine Cocaine Atropine Quinoline Isoquinoline Carbazole Antipyrene Morpholine Theophylline Caffeine Morphine Codeine Thiophene Imipramine Progesterone Testosterone Deoxycorticosterone Hydroxyprogesterone-17a Corticosterone Cortisone Hydrocortisone 17a-Methyltestosterone Prednisolone Hydrocortisone 21-acetate Estrone Estradiol Dexamethasone 5,5-Dimethylbarbituric acid 5-Methyl-5-ethylbarbituric acid Barbital 5-Ethyl-5-isopropylbarbituric acid Butabarbital Pentobarbital 5-Ethyl-5-(3-methylbutyl)barbital 5,5-Diisopropylbarbital
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
2.65 2.65 1.10 1.41 1.19 0.89 2.53 0.75 0.80 1.32 0.67 4.09 0.64 1.59 1.64 1.64 1.59 1.64 1.67 1.67 2.57 1.32 2.03 1.82 3.52 0.20 0.41 0.06 0.06 0.59 0.98 1.79 5.04 3.77 3.22 3.25 3.15 2.32 1.30 1.70 3.74 1.38 2.23 3.38 3.78 1.75 0.40 0.13 0.66 1.05 1.58 2.11 2.11 1.45
2.84 2.70 1.10 1.42 1.16 0.93 2.52 0.73 0.82 1.34 0.41 4.12 0.65
96 121 25 25 25 38 25 154 139 25 25 83 25 25 25 25 25 25 25 25 98 116 25 26 247 109 25 272 235 254 155 25 174 131 155 136 276 181 222 213 162 240 223 255 173 262 278 212 190 203 166 129 156 228
2.22 2.28 0.40 0.92 0.70 0.47 2.12 1.77 1.74 0.82 0.10 4.60 0.76 0.38 0.38 0.45 0.36 0.38 0.51 0.83 2.25 2.12 1.30 1.45 5.27 0.72 1.97 1.39 0.88 3.28 1.52 1.33 4.19 4.42 4.02 3.45 3.82 3.24 3.11 3.09 4.00 3.18 4.88 3.96 5.03 3.59 1.74 1.23 2.40 2.15 2.39 2.39 2.66 2.77
2.64 2.54 0.79 1.06 0.88 0.78 2.55 1.02 1.06 1.03 0.15 4.47 0.04 0.74 0.68 0.70 0.69 0.81 0.87 0.90 2.17 2.53 1.88 1.80 3.87 0.44 1.62 0.21 0.45 2.38 2.28 1.65 4.15 4.02 4.08 3.98 4.24 4.04 3.29 4.93 4.34 5.20 4.69 4.07 4.39 5.35 0.20 0.36 0.96 1.49 1.97 2.54 2.54 2.00
2.86 3.11 0.60 0.91 0.69 0.52 2.03 1.54 1.44 0.82 0.17 4.17 0.14 1.09 1.14 1.14 1.09 1.14 1.17 1.17 2.80 1.73 1.53 1.33 5.24 0.54 0.91 1.91 1.54 2.38 1.78 1.29 6.03 4.33 4.02 3.86 5.16 3.38 2.77 3.08 4.61 3.03 3.71 5.18 4.76 3.62 1.63 1.50 1.81 2.33 2.49 2.65 2.92 2.98
1.68 1.78 1.69 1.65 2.30 1.83 2.03 2.08 3.48 0.23 0.86 0.02 0.07 0.76 1.14 1.89 4.44 3.87 3.32 2.88 3.17 1.94 1.47 1.61 3.36 1.62 2.19 3.13 3.86 2.01 0.44 0.08 0.65 1.10 1.65 2.10 2.07 1.56
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APPENDIX (Continued) Compound 5-Allyl-5-methylbarbital 5-Allyl-5-ethylbarbital 5-Allyl-5-isopropylbarbital Secobarbital 5,5-Diallylbarbital 5-(3-Methyl-2-butenyl)-5-ethylbarbital 5-(3-Methyl-2-butenyl)-5-isoprbarbital 5-Ethyl-5-phenylbarbital 5-Allyl-5-phenylbarbital Cyclobutyl-5-spirobarbituric acid Cyclopentyl-5-spirobarbituric acid Cyclohexyl-5-spirobarbituric acid Cycloheptyl-5-spirobarbituric acid Cyclooctyl-5-spirobarbituric acid Amitrole Carbaryl Carbofuran Chlorfenac Coumatetralyl 2,4-DB DDT Desmedipham Dichlorophen Dichlorprop Diuron DNOC Etofenprox Fenoxycarb Fenuron Fluometuron Isoprocarb Isoproturon Linuron Methyldymron Metolcarb Metoxuron Monolinuron Propoxur Warfarin XMC Cyclopropyl-5-spirobarbituric acid Uracil Chlorpheniramine Fentanyl Adenine
CLOGP
MLOGP
MP
log Sw Obsvd
log Sw ASER
log Sw GSE
0.17 0.70 1.37 2.16 0.75 1.63 2.23 1.37 1.41 0.57 0.01 0.55 1.11 1.67 0.53 2.38 2.47 3.43 4.83 3.42 6.76 3.40 4.89 3.26 2.68 2.29 7.36 4.46 0.98 2.39 2.29 2.40 3.00 3.24 1.71 1.78 2.31 1.65 2.89 2.21 1.13 1.06 3.15 3.62 0.29
0.36 0.87 1.37 1.97 1.15 1.73 2.23 1.47 1.69 0.27 0.24 0.91 1.36 1.79 0.87 2.36 1.63 3.20
166 160 143 132 174 155 131 174 133 256 270 289 266 228 159 142 152 161 180 117 109 120 178 118 159 86 37 54 133 163 93 158 93 60 76 125 80 91 161 99 325 335 25 83 363
1.16 1.61 1.71 2.36 2.08 2.25 2.59 2.32 2.37 1.66 2.35 3.06 3.17 2.98 0.52 3.22 2.80 3.08 2.84 3.73 7.15 4.63 3.95 2.83 3.05 1.46 8.60 4.70 1.60 3.43 2.86 3.54 3.59 3.35 1.80 2.56 2.57 2.05 4.26 2.58 1.89 1.49 0.24 1.13 2.43
0.68 1.24 1.70 2.82 1.73 2.34 2.87 2.88 3.28 0.12 0.73 1.33 1.94 2.56 0.86 2.74 1.77 3.10 4.77 3.60 7.46 5.10 4.58 3.35 2.98 2.40 7.84 4.82 1.64 2.11 2.21 3.00 3.39 3.74 1.57 2.18 2.36 1.62 4.07 2.08 0.36 1.19 3.06 4.22 0.19
1.08 1.55 2.05 2.73 1.74 2.43 2.80 2.36 1.99 1.24 1.94 2.69 3.02 3.20 0.31 3.05 3.24 4.29 5.88 3.84 7.10 3.85 5.92 3.69 3.52 2.40 6.98 4.25 1.56 3.27 2.47 3.23 3.18 3.09 1.72 2.28 2.36 1.81 3.75 2.45 1.37 1.54 2.65 3.70 2.59
3.53 6.91 3.39 3.43 2.68 2.13 7.05 4.30 0.98 2.42 2.31 2.50 3.20 3.01 1.70 1.64 2.30 1.52 2.70 2.23 0.53 1.07 3.17 3.89 0.09
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COMPARISON OF ASER AND THE GSE
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