Aqueous solubility prediction of organic compounds

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Authors Yang, Gang

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Link to Item http://hdl.handle.net/10150/298795 AQUEOUS SOLUBILITY PREDICTION OF ORGANIC COMPOUNDS

by

Gang Yang

A Dissertation Submitted to the Faculty of the

DEPARTMENT OF PHARMACEUTICAL SCIENCES

In Partial Fulfillment of the Requirements

For the Degree of

DOCTOR OF PHILOSOPHY

In the Graduate College

THE UNIVERSITY OF ARIZONA

2005 UMI Number: 3158221

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As members of the Final Examination Committee, we certify that we have read the dissertation prepared by Gang Yang entitled Aqueous Solubility Prediction of Organic Compounds

and recommend that it be acceptable as fulfilling the dissertation requirement for the

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Samuel HTy alkowsky, Ph.D. date /'QC Michael Mayersohn, Prf®. date

Paul B. Myrdal, Ph.Dr^ date

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Final approval and acceptance of this dissertation is contigent upon the candidate's submission of the final copies of the dissertation to the Graduate College. I hereby certify that I have read this dissertation prepared under my direction and recommend that it be accepted as fi^filling the disseration requirement.

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SIGNED: 4

ACKNOWLEDGEMENTS

I would like to express my sincere gratitude to my advisor, Dr. Samuel Yalkowsky, for giving me the opportunity and financial support to study in the field of Pharmaceutical

Sciences, for his expert guidance and mentorship, and for his constant support and encouragement over the years at Arizona. He has made it a challenging and fun experience that I will cherish for years to come.

I would like to thank members of my major committee. Dr. Michael Mayersohn and Dr.

Paul Myrdal, for reviewing drafts of the dissertation on a very short notice and providing helpful comments on the dissertation. My appreciations also go to the members of my minor committee. Dr. Srini Raghavan and Dr. Scott Saavedra, for dedicating their time to serve on my committee.

During the years at Arizona, I had the pleasure to work with many friends and colleagues including Neera, Jeff, Debra, Yingqing, Tapan, Ahbi, Yan, Jenny, Akash, Kia, Stephen,

Ritesh, Yvonne, Huadong, Abhi, Kelly, Phil, Julie, Eric and Will. I would like to thank all of them for being there for me when I needed help.

My special thanks go to Dr. Wolf-Dietrich Dilenfeldt for his fragmentation program.

I am greatly indebted to many teachers back in China, in particularly, Xinfang Liu and

Manguo Tao for keeping me interested in science and helping me excel.

At last, I would like to thank my family: my fiancee Hui for her love and encouragement throughout my study; my parents and sister for their years of loving support and understanding. 5

DEDICATION

To my parents and Hui 6

TABLE OF CONTENTS

LIST OF FIGURES 10 LIST OF TABLES 11 ABSTRACT 12 CHAPTER 1: INTRODUCTION 14 CHAPTER 2: AQUEOUS SOLUBILITY PREDICTION METHODS 21 INTRODUCTION 21 THE IDEAL SOLUTION AND REGULAR SOLUTION THEORY 21 Ideal Solution 21 Regular Solution 22 Aqueous Solution 22 Crystalline Solute 23 REVIEW OF LITERATURE 24 Group Contribution Approach 24 Mobile Order Theory 25 Linear Solvation Energy Relationship (LSER) 26 Atom Type Electrotopological State Indices 27 MODEL DEVELOPMENT 28 General Solubility Equation 28 The AQUAFAC Method 29 A New Model 30 CHAPTER 3: DATA COLLECTION AND ANALYSIS 32 INTRODUCTION 32 DATA 33 Solubility Data 33 Melting Point (MP) 36 Octanol-Water Partition Coefficient (P) 36 RELATIONSHIPS 40 7

TABLE OF CONTENTS - Continued

Regression Analysis 40 CLOGP Prediction Evaluation 41 Predicted versus Experimental Octanol-Water Partition Coefficient 42 Solubility and Octanol-Water Partition Coefficient 44 Solubility and Melting Point 50 CHAPTER 4: STRUCTURAL FRAGMENTATION 52 INTRODUCTION 52 SMILES 54 SMARTS 57 STRUCTURAL FRAGMENTATION PROGRAM 57 FRAGMENTATION SCHEME 59 CHAPTER 5: EVALUATION OF SOLUBILITY PREDICTION BY THE GENERAL SOLUBILITY EQUATION ON A SET OF DIVERSE COMPOUNDS 64 INTRODUCTION 64 METHODS 65 Data Set 65 Evaluation 66 Regression Analysis 68 RESULTS AND DISCUSSION 69 Overall Performance 69 Solid Versus Liquid 76 Non-electrolyte Versus Weak Electrolyte 78 Regression Analysis 82 SUMMARY 83 CHAPTER 6: COMPARISON OF THE GENERAL SOLUBILITY EQUATION AND THE METHOD USING AN AMENDED SOLVATION ENERGY RELATIONSHIP. 84 INTRODUCTION 84 METHODS 86 8

TABLE OF CONTENTS - Continued

RESULTS 87 Octanol-Water Partition Coefficients 87 Melting Point 89 Solubility 90 DISCUSSION 93 SUMMARY 98 CHAPTER 7: DEVELOPMENT OF THE EXTENDED AQUAFAC MODEL 99 INTRODUCTION 99 METHODS 101 Data Set 101 Aqueous Activity Coefficient 101 Structural Fragmentation 102 Regression Analysis 102 RESULTS 103 Fragmentation Performance 103 Regression Analysis 103 Group Contribution Values qi 103 Aqueous Solubility Prediction 107 CHAPTER 8: DEVELOPMENT OF A NEW GROUP CONTRIBUTION MODEL FOR AQUEOUS SOLUBILITY PREDICTION 108 INTRODUCTION 108 METHODS 110 Data Set 110 Structural Fragmentation 110 Regression Analysis 110 RESULTS Ill Fragmentation Performance Ill Regression Analysis Ill 9

TABLE OF CONTENTS - Continued

Group Contribution Values mi 112 CHAPTER 9: COMPARISON OF AQUEOUS SOLUBILITY PREDICTION MODELS 116 PREDICTION COMPARISON 117 SUMMARY 121 APPENDIX A. Experimental Solubility Collection with Melting Point, log P and Predicted Solubility Using the General Solubility Equation 122 APPENDIX B. Comparison of Predicted Solubility Using the General Solubility Equation and the Amended Solvation Energy Relationship 161 APPENDIX C. Predicted Solubility for Test Set 1 175 APPENDIX D. Predicted Solubility for Test Set 2 176 APPENDIX E. Predicted Solubility for Test Set 3 177 REFERENCES 179 10

LIST OF FIGURES

Figure 3.1: Log solubility (log Sw) distribution of 1804 compounds in the data set 35 Figure 3.2: Melting point (MP) distribution of 1037 solids in the data set 37 Figure 3.3: Calculated log octanol-water partition coefficient (Clog?) distribution of 1804 compounds in the data set 38 Figure 3.4: Experimental log octanol-water partition coefficient (MlogP) distribution of 1226 compounds in the data set 39 Figure 3.5: Plot of calculated log octanol-water partition coefficients (ClogP) versus experimental log octanol-water partition coefficients (MlogP) 43 Figure 3.6: Scatterplot of log versus calculated log octanol-water partition coefficients (ClogP) for 597 liquids or gases in the data set 46 Figure 3.7: Scatterplot of log Sw versus experimental log octanol-water partition coefficients (MlogP) for 393 liquids or gases with available experimental log P in the data set 47 Figure 3.8: Scatterplot of log aqueous solubilities (log Sw) versus calculated log octanol-water partition coefficients (ClogP) for all 1804 compounds in the data set 48 Figure 3.9: Scatterplot of log aqueous solubilities (log Sw) versus experimental log octanol-water partition coefficients (MlogP) for 1225 compounds with available experimental log P in the data set 49 Figure 3.10: Scatterplot of log Sw versus experimental melting point for 1525 compounds with available melting point information in the data set 51 Figure 4.1: An example illustrating the expression of Benzocaine structure in SMILES 56 Figure 4.2: Fragmentation of benzocaine structure according to the AQUAFAC Scheme 63 Figure 5.1: Plot of predicted log Sw versus experimental log Sw 71 Figure 5.2: Absolute prediction error distribution 72 Figure 5.3: Plot of prediction error against experimental log Sw 73 Figure 5.4: Plot of prediction error against calculated log P (ClogP) 74 Figure 5.5: Plot of prediction error against melting point for 1037 solids 75 Figure 6.1: Plot of measured logP (MlogP) versus ClogP (n = 530) 88 Figure 6.2: Experimental log Sw versus predicted log Sw using the ASER method (n = 664). The diagonal line is the line of identity 91 Figure 6.3: Experimental log Sw versus predicted log Sw using the GSE method (n = 664). The diagonal line is the line of identity 92 Figure 6.4: Experimental log Sw versus predicted log Sw using the average of the ASER prediction and the GSE prediction (n = 664). The diagonal line is the line of identity 97 11

LIST OF TABLES

Table 3.1: Literature sources of the current data collection 34 Table 4.1: Examples illustrating the SMARTS expressions for substructural fragments 58 Table 4.2: Fragment list in the extended AQUAFAC fragmentation scheme 61 Table 5.1: Statistical analysis of predicted log Sw values compared with experimental log Sw values 77 Table 5.2: Statistical analysis of prediction performance of different classes of Compounds 80 Table 6.1: Statistical analysis of predicted log Sw values compared with experimental log Sw values 94 Table 7.1: Fragments in the extended AQUAFAC scheme: The number of occurrences (N), group contribution values (qi) and statistical significance 104 Table 8.1: Fragments for the GClogP model: The number of occurrences (N), group contribution values (mO and statistical significance 113 Table 9.1: Comparison of prediction results of test set 1 119 Table 9.2: Comparison of prediction results of test set 2 119 Table 9.3: Comparison of prediction results of test set 3 120 Table 9.4: Comparison of prediction results of test sets 1 and 2 120 12

ABSTRACT

Aqueous solubility is one of the most important physical properties to consider in drug discovery and development. Drug candidates with poor solubility often have poor bioavailability, which leads to increased developmental cost and efforts. Therefore, there is a strong trend to perform solubility screening of drug candidates as early as possible in the drug discovery and development process. While experimental methods are being developed to increase the throughput of solubility measurement, the development of aqueous solubility prediction methods can be a powerful complementary tool.

This dissertation starts by compiling a large collection of aqueous solubility data for organic compounds covering diverse classes of structures. The data set is first used to critically evaluate the General Solubility Equation (Yalkowsky et al., 1980, 1999), one of the most widely used methods for aqueous solubility prediction. The General Solubility

Equation performs very well overall as measured by the average absolute error (AAE) of

0.56 log unit. Detailed analyses indicate that it gives better predictions for non- electrolytes than some classes of weak electrolytes. This method is then compared with a method based on an amended solvation energy relationship, which considers the hydrogen bonding potentials of functional groups. It is shown that averaging the prediction results from the two methods gives better prediction than either method alone. Following the concept of the AQUAFAC model developed by Myrdal et al. (1992, 1993,

1995), an extended version of the original structural fragmentation scheme is developed.

The model is trained on the data set and has an value of 0.881 and a standard error of estimation of 0.819 log unit. Group contribution parameters for a set of 104 fragments are obtained.

A new group contribution model is developed to suit the needs in the early drug discovery stage, when melting information is generally not available. Calculated octanol- water partition coefficient is included in the model. The model has a standard error of estimation of 0.814 log unit. When evaluated on independent test sets, the new model provides comparable prediction results with the other two models. The independence of the new model of experimental melting information makes it a suitable tool for aqueous solubility screening in early drug discovery. 14

CHAPTER 1: INTRODUCTION

Aqueous solubility is a crucial physical property to consider in pharmaceutical discovery and development process. It is a major driving force for drug dissolution, which, along with drug permeability, determines the absorption rate of an orally delivered drug from the gastrointestinal tract. The lack of adequate solubility may render a good drug candidate orally inactive due to poor bioavailability. To a significant degree, aqueous solubility also determines the ease of development of a drug candidate for parenteral and ophthalmic formulations.

Recent developments in combinatorial synthesis and high-throughput screening technology have greatly enhanced the structural diversity available for biological activity testing and the efficiency in lead compound generation. These technologies have become the major drug lead source. However, it has been noted that drug leads from combinatorial libraries and high-throughput screening tend to have poorer solubility profiles than leads generated before these technologies became common (Lipinski et al.,

2001).

A poor solubility problem may be fixed by formulation in some cases but it does pose a burden on the development process. Developing poorly soluble drugs is often time consuming and expensive, and it is more difficult to bring them to market and to repay the development costs compared to more soluble compounds. According to Pfizer's profiling of marketed drugs, only about 11% of drugs with very low solubility ever reach the market (Lipinski et al., 2001). Therefore, it is not surprising to see strong motivation in performing solubility studies as early as possible in the drug discovery process.

Solubility is an equilibrium property and the equilibrium involved in solubility measurement can take days or even weeks to reach. Generation of quality solubility information can be time consuming and labor intensive. In the drug discovery stage, compounds from combinatorial sjmthesis are never crystallized and are generally stored as concentrates in DMSO. They have purity in the range of 80-90%. These conditions preclude the possibility of using the reliable traditional shake-flask method to measure solubilities of thousands of discovery compounds in a reasonable time frame. To meet the needs at this stage, several novel methods have been developed to increase the throughput of solubility data generation at the expense of quality. Once a compound enters the development stage, quality solubility measurements are required for the

Biopharmaceutics Classification system and the traditional shake-flask method is recommended by the FDA.

Development of aqueous solubility prediction methods can be a complementary tool to experimental measurements. Prediction of aqueous solubility can help the design and evaluation of combinatorial library before its synthesis. Such methods can provide useful tools for medicinal chemists to guide their synthesis efforts towards chemicals with the desired properties in the lead optimization process. They can also provide scientists estimated solubility information before they perform the experimental solubility measurement. Thus, such predictions can avoid the unnecessary waste of a limited supply of sample in early development.

Before developing a solubility prediction method, it is important for the developer to know the needs of the users of the services. Different users may have different requirements of the method. Combinatorial chemists want to have a tool to estimate the solubilities of thousands of compounds in the library before synthesis. The method needs to be fast, based only on parameters that can be calculated from molecular structure, and preferably easily implemented into a spreadsheet or computer program. Medicinal chemists doing lead optimization want to have something to tell them how the solubility and lipophilicity change if they add, delete or substitute a functional group in the molecule. The method needs to be simple and straightforward. Something similar to an atomic weight table would be ideal. Preformulation scientists need to perform solubility measurements sooner or later. However, with a limited amount of sample in early development, an estimation of solubility before carrying out the measurement can help avoid wasting the precious sample. Some physical properties (melting point is a common one) may be available at this stage. It is easy to use simple semiempirical methods like the General Solubility Equation. Another factor to consider is that it is desirable for the prediction model to start from a thermodynamically sound relationship. Methods that physically make sense are more likely to be acceptable to the users. Based on the ideal solution and regular solution theory, two solubility prediction methods have been developed by this research group (Yalkowsky and Valvani, 1980; Jain and

Yalkowsky, 1999; Myrdal et al., 1992; Myrdal et al., 1993; Myrdal et al., 1995). These two approaches have become the recommended methods for the prediction of aqueous solubility when melting point information is available (Mackay, 2000).

The General Solubility Equation relates aqueous solubility of an organic non-electrolj^e compound with its melting point and octanol-water partition coefficient. The method has been shown to give a reasonable estimation of aqueous solubility for a wide range of organic compounds (Peterson et al., 2001; Ran et al., 2002). The overall prediction performances were reported in the studies but little analysis was done to look at the performance in more details. Considering that the derivation of the relationship was based on assumptions that may be true only for non-electrolytes, residual error analyses against different classes of compounds could provide insights into the evaluation of the assumptions.

Myrdal et al. developed the AQUAFAC group contribution method to predict the aqueous activity coefficient Yw, which was used together with a crystallinity term to give aqueous solubility prediction. One of the advantages of this approach is its independence of partition data. Only aqueous phase data and melting point information is need for the development of the model. The AQUAFAC approach was shown to be slightly superior to the General Solubility Equation when applied to a test set of 97 compounds (Myrdal et 18 al., 1995). The study clearly demonstrated the potential applicability of the AQUAFAC approach. Two subsequent studies extended the applicability to a wider range of functional groups (Lee et al., 1996; Pinsuwan et al., 1997). However, due to the lack of computational tools to break down the molecular structures at the time of development, the applicability of the approach is still limited to molecules containing a limited number of groups, whose group counting can be handled manually.

Both of the above methods require melting point information for solubility prediction, which can be easily measured with a small amount of drug substance at the early drug development stage. However, the melting point information is generally not available at the drug discovery stage as the compounds have low purity and they are not crystallized.

While research on the prediction of the melting point of organic compounds from molecular structures is ongoing, it is generally conceived that melting point prediction itself is at least as challenging as aqueous solubility prediction. Development of an aqueous solubility prediction method without the need of melting point information, therefore, would be more applicable in the drug discovery stage.

With the development of chemical languages to represent chemical structures and substructural patterns in a computer as well as related computational tools, the classification and molecular structure fragmentation (group counting) of a large number of molecules become possible in a reasonable time frame. Taking advantage of these 19 developments, this dissertation intends to address the issues discussed above. The specific objectives are as follows

1. To critically evaluate the applicability of the General Solubility Equation against

a variety of classes of compounds;

2. To extend the applicability of the AQUAFAC approach and obtain the group

contribution parameters;

3. To develop a new model of aqueous solubility prediction from molecular

structures without the requirement of melting point information.

Chapter 2 reviews the various prediction models and computational methods available in the literature. It is followed by an introduction of the ideal solution and regular solution theory as well as the aqueous solubility parameter, which serves as the theoretical basis of the General Solubility Equation, the AQUAFAC method and a new model developed.

The development and evaluation of any prediction model cannot be separated from reliable experimental data. A large collection of compounds with solubility, partition coefficient and melting point information is introduced in Chapter 3. This data set is used in later chapters for the evaluation of the General Solubility Equation as well as the development of an extended AQUAFAC model and a new model without the need for experimental melting point information. 20

Chapter 4 introduces the SMILES language for chemical structure representation, the

SMARTS language for substructural pattern (fragment) representation, the automatic structural fragmentation program, and the structural fragmentation scheme used in this study.

The General Solubility Equation is a well accepted and referenced method of solubility prediction when melting point information is available. The performance of the General

Solubility Equation is carefully evaluated for different classes of compounds in Chapter

5.

Chapter 6 compares the General Solubility Equation with another successful solubility prediction method based on an amended solvation energy relationship.

Chapter 7 extends the AQUAFAC (AQUeous Functional group Activity Coefficient) method to include a much wider range of functional groups.

Chapter 8 develops a new method by modeling the crystallinity term using the same set of structural parameters as used in AQUAFAC.

Chapter 9 evaluates the performances of the different models on an independent set of compounds. The accuracy of different methods is compared. 21

CHAPTER 2: AQUEOUS SOLUBILITY PREDICTION METHODS

INTRODUCTION

Attempts to predict aqueous solubility with other physical properties started as early as

1965 (Irmann, 1965). Thereafter, various aqueous solubility prediction models have been developed. Excellent reviews on these methods can be found in the literature (Yalkowsky and Banerjee, 1982; Huuskonen, 2001; Jorgensen and Duffy, 2002). This chapter gives a discussion of the underlying theories of different models.

THE IDEAL SOLUTION AND REGULAR SOLUTION THEORY

Ideal Solution

An ideal gas is one in which the intermolecular interactions are negligible. An ideal solution, on the other hand, is one in which interactions between different kinds of molecules have the same magnitude as those between molecules of the same kind. There is no change in heat and volume associated with the formation of an ideal solution. Since the heat of mixing for an ideal solution is zero and the entropy of mixing is always positive, the free energy of mixing is always negative. Therefore, two liquids are miscible in all proportions if they form an ideal solution. 22

Regular Solution

To form regular solutions, the solute and solvent usually have similar molecular volumes and similar intermolecular interactions. A regular solution has ideal entropy of mixing and no change in volume of mixing. However, there is enthalpy change associated with the formation of a regular solution. The deviation of a regular solution from ideality is exclusively due to an energetic effect. The regular solution concept is a useful model for a wide range of mixtures formed by non-hydrogen bonding components. Regular solutions often have upper critical solution temperatures (Tcrit), temperatures above which two partially immiscible liquids become completely miscible in all proportions. The upper critical solution temperature can be calculated using a simplified form of the relationship described by Hildebrand and Scott (1955) r V.fe-

Tcrit is lower than 25 °C.

Aqueous Solution

Water, as a solvent, strongly associates with other water molecules by the formation of hydrogen bonds. Aqueous solutions of organic compounds do not follow the ideal 23 solution or the regular solution theory. The deviation from ideality can be described with the aqueous activity coefficient yw in

log = log - log (2-2) where Xw is the molar fractional solubility in water and Xj is the ideal molar fractional solubility.

The aqueous activity coefficient accounts for the differences in solute-ideal solvent interactions and solute-water interactions. Similar to octanol-water partition coefficient, its logarithm can be modeled using group contribution approaches.

Crystalline Solute

It takes additional energy to overcome the cohesive interactions in crystalline solutes. A hypothetical supercooled liquid (SCL) of the solute is usually used as a reference state.

According to Hildebrand and Scott (1962), the ideal solubility of a crystalline solute (Xj'^) can be expressed as

X' ri n logX; =log -log- (2.3) X SCL 2.303/? [T TJ 2.303/? [ T where AHm is the melting enthalpy of the crystalline solute; T and T^ are the temperature of interest and the melting temperature of the solute, respectively; ACp is the difference in heat capacity of the crystalline and the hypothetical supercooled liquid form of the solute. 24

The second term on the right hand side of the equation can be ignored since ACp is quite small. The equation can be simplified as

-AH., -T logx; = (2.4) 2303RTm \ which can be transformed as logj; =— (2.5) ' 2303RT

For a crystalline solute whose hypothetical supercooled liquid can form a mutually miscible regular solution with a solvent, its solubility in the solvent can be described using the same equation.

The aqueous solubility of a crystalline solute (Xw") can also be related to the ideal solubility by considering its deviation from ideality

REVIEW OF LITERATURE

Group Contribution Approach

Adding or removing a fragment from a molecule will change its physical properties.

Group contribution approach is conceptually the most straightforward method. In this approach, each molecular fragment is assigned a contribution value towards a certain property. The property of a molecule can be estimated by summing the frequency (ni) of each fragment occurring in the molecule times its contribution (Ci). logS.=2;",C,+C„ (2.7) i

Different structural fragmentation schemes have been proposed in the literature (Wakita et al., 1986; Klopman et al., 1992; Kuhne et al., 1995; Klopman and Zhu, 2001; Marrero and Gani, 2002). The aqueous solubility (Sw) was correlated with the group contributions either directly or with the inclusion of other properties.

Mobile Order Theory

The mobile order theory (Huyskens and Siegel, 1988; Huyskens, 1992) states that "in hydrogen bonded liquids, a proton donor group follows for most of the time a proton acceptor group of one or another neighboring molecule in its walk through the liquid.

Both the correlation in the motions of the interacting groups and the mobility of the H- bonds on a very short timescale bring to the system a particular kinds of order which does not exist in H-bonded crystals: the mobile order." (Ruelle and Kesselring, 1997b) The dissolution of nonpolar or weakly polar solutes in H-bonded solvent can further increase the mobile order because of the hindrance of movement of H-bonded solvent molecules.

The negative entropy explains the origin of the hydrophobic effect. 26

Based on the theory, Ruelle and Kesselring (1997a, b) developed the following equation to predict aqueous solubility of nonpolar or slightly polar compounds: log Sb = A/2.3 + 2.154 - 0.036Vb - 0.2171nVB (2.8) where Sb is the molar solubility; Vb is the molar volume of the solute calculated by a group contribution approach; and A = -0.02278(Tni - 298.15).

Linear Solvation Energy Relationship (LSER)

The linear solvation energy relationship was initially developed to correlate solvent effects with various free energy properties (Kamlet and Taft, 1981; Taft et al., 1985a).

The approach was then generalized to correlate physicochemical properties (Taft et al.,

1985b; Kamlet et al., 1987; Abraham et al., 1994). The following equation was used to relate a physicochemical property SP to solvation descriptors characteristic of the solute: log SP = c + rR2 + sTCa" + aEai" + bSpa" + vV^ (2.9) where

R2 is the excess molar refractivity (MR) index defined as the MR difference over an

alkane of the same molecular volume;

7C2" is the dipolarity/polarizability, a Gibbs-energy related parameter back calculated

from GLPC result and is equivalent to a gas-liquid partition coefficient;

Etta" is a hydrogen bond acidity parameter;

is a hydrogen bond basicity parameter;

Vx is a molecular volume parameter. 27

These parameters, initially derived from experimental measurements, can now be calculated from compound structure using a computer program (Platts et al., 1999).

The equation cannot account for intermolecular interaction in the crystal lattice when applied to solubility prediction. An extra Zai" X ZP2" term was added to deal with hydrogen bond interactions between acid and basic sites in the solid or liquid (Abraham andLe, 1999).

Atom Type Electrotopological State Indices

Hall and Kier introduced the atom type electrotopological state (E-state for short) indices

(1995). The approach has both similarity to and difference from the group contribution approach. It fragments molecular structure to the atomic level instead of functional group level, which reduces the number of parameters needed. The atom classification is based on atom (element) identity, valence state, number of bonded hydrogen atoms, and the identity of other bonded atoms. Not all counts of a certain atom class are treated to have the same contribution. An E-state index (a) is calculated for each atom by consider the intrinsic electronic state and the perturbation by the electronic influence of all other atoms in the molecule within the context of the topological character of the molecule.

The sum index value (A) for each atom class was used in the correlation with aqueous solubility and a contribution value (Ci) is assigned to each atom class i.

A = (2-10) j 28 log5.=2;AC,+C„ (2.11)

MODEL DEVELOPMENT

The General Solubility Equation and the AQUAFAC approach were developed based on the ideal solution and regular solution theory. Assuming the entropy of melting follows

Walden's Rule, the ideal solubility of crystalline solute can be estimated at 25 °C using

Eq (2.10) logX; = -O.Ol(r„, -298) = -0.01(MP-25) (2.12) where Tm and MP are melting point in K and °C respectively.

General Solubility Equation

Octanol-water partition coefficient has been used widely as a measure of the lipophilicity of a compound. For a crystalline solute whose hypothetical supercooled liquid can form a mutually miscible regular solution with octanol, its solubility in octanol can be described using eq. (2.12). According to the regular solution theory, liquid compounds with a solubility parameter between 15.1 and 27.1 are completely miscible with octanol. Most organic non-electrolytes have solubility parameters within the range. Assuming the solubility ratio in octanol and water is approximately equal to the octanol-water partition coefficient (P) 29

C S P = -2- = -iL (2.13) C,.,W 5„^ W

The aqueous solubility Sw can be related to octanol solubility So with octanol-water partition coefficient in log5^ =log5„-logP (2.14)

The molar octanol solubility can be calculated with eq. (2.12) after conversion from mole fractional solubility, which introduces the correction term "0.5". It gives the General

Solubility Equation in the following form log5„ =0.5-0.01(MP-25)-logP (2.15)

For all liquid solutes, there is no crystallinity effect on solubility and the MP is set as 25

°C.

The AQUAFAC Method

Instead of using octanol as a reference solvent, the AQUAFAC method uses a group contribution approach to estimate the deviation of aqueous solubility from ideal solubility, the aqueous activity coefficient. logs, =C„-0m(MP-25)-logr„ (2.16) logs, =C„ -0.01(M/'-25)-2]n,^, (2.17) 30 where the constant Co is expected due to conversion from mole fraction solubility to molar solubility; ni is the counts for a specific group i; and qi is the group contribution value for group i.

A New Model

The development of a new model aims to eliminate the melting point term from the prediction equation. Eq. (2.6) can be rearranged to the following form logX;= (2.18) ' 2.303RT 2.303R

The enthalpy of melting of an organic compound is assumed to be dependent upon the interactions between its molecular fragments and therefore can be estimated using group contribution approach (Zhao and Yalkowsky, 1999). The entropy of melting can be either assumed to follow Walden's Rule or estimated by the semiempirical equation of

Dannenfelser and Yalkowsky (1996)

AS,„=56.5-R\n(T+R\n^ (2.19) where a is the symmetry number of the molecule and O is a measure of the molecular flexibility. The majority of pharmaceutical compounds are expected to have no symmetry and have a value of 1. 0 can be calculated by

^ 5/'3+0.55P2+0.5/?/A'G-l ^2

Insertion of Eq. (2.20) into Eq. (2.19) gives 31

=56.5 + C(SP3 + 0.5^P2 + 0.5i?/iVG-l) (2.21) which indicates that the entropy of melting can also be estimated by group contribution approach.

Therefore, it is theoretically reasonable to attempt the use of group contribution approach to estimate the ideal solubility. logX;=^n,m, (2.22) i

The molar aqueous solubility can then be estimated using log5,=C„+^n,m,-logP (2.23) 32

CHAPTER 3: DATA COLLECTION AND ANALYSIS

INTRODUCTION

Development and validation of prediction models rely on the availability of quality experimental data collection. In order to accomplish the three objectives stated in Chapter

1, it is of great importance to have aqueous solubility data for a set of structurally diverse compounds. This chapter describes a collection of 1804 organic compounds with aqueous solubility data. Their melting points were collected, as they are required for the solubility prediction using the General Solubility Equation and the AQUAFAC method. The octanol-water partition coefficients were calculated using CLOGP software and available experimental values were also reported. The representative feature of this data set is demonstrated by the wide distributions of these properties. Regression analyses were done to examine the relationship between aqueous solubility and octanol-water partition coefficient as well as the relationship between aqueous solubility and melting point. 33

DATA

Solubility Data

The aqueous solubility data of organic compounds were collected from several data sets with relatively large number of compounds used in the recent literature. The literature sources are listed in Table 3.1. These data sets were merged to allow only one appearance for each compound in the final data set. Significant overlap in compound coverage was observed and many compounds appeared in two or more data sets. When multiple solubility values were reported for the same compound, the solubility data were evaluated by comparing with the data in AQUASOL database and the most reliable one was selected.

The merged data set contains solubility data for 1804 compounds with diverse structures.

All the solubility data are reported in logarithm (log Sw) values, where Sw has a unit of

"mole per liter". The log Sw values range from -12.95 (decachlorodiphenyl ether) to 2.06

(ethylamine) with the distribution graph shown in Figure 3.1. The average log Sw is -2.93 for the compounds in the data set, 77.7 % of which has log Sw in the range of -5 to 0 and

88.4% of which in the range of -6 to 1. 34

Table 3.1; Literature sources of the current data collection.

Reference N Description Yalkowsky and Banerjee (1982) 21 Compounds of environmental or pharmaceutical interests, complex structures, often with multiple functionalities Mitchell and Jurs (1998) 332 Diverse classes of compounds; hydrocarbon, halocarbons, sugar, steroids, PCBs, organic acids, barbiturates Abraham and Le (1999) 664 Hydrocarbons, halocarbons, PCBs, monofunctional organic compounds, and a small percentage of barbiturates, steroids Huuskonen (2000) 1297 Large collection of structurally diverse compounds Huuskonen et al. (2000) 38 Pharmaceutical compounds Chen et al. (2002) 267(train) Drug or drug-like solid compounds 54(test) Ran et al. (2003) 1026 Mostly non-electrolytes 35

400

350

300

250

E 200

*5 150

100

50

\

log S„

Figure 3.1: log solubility (log Sw) distribution of 1804 compounds in the data set. 36

Melting Point (MP)

Melting point information was collected from Merck Index, ChemFinder database,

Beilstein database and CRC Handbook of Chemistry and Physics. Within the data set,

1037 compounds were found to have a melting point higher than 25 °C, 488 compounds to have a melting point lower than or equal to 25 °C, 109 compounds to be liquid at 25 °C but without reported melting point information, and 170 compounds to have no information on melting point or physical state at 25 °C. Figure 3.2 shows the melting point distribution of the compounds with melting point higher than 25 °C. These compounds have an average melting point of 143 °C.

Octanol-Water Partition Coefficient (P)

The logarithms of octanol-water partition coefficients (log P) of these compounds were calculated using CLOGP software Version 4.0 (BioByte Corp., Claremont, CA). The software also provides experimental octanol-water partition coefficients (MlogP) of a compound if it is included in the database attached with the software. Experimental values for 1226 compounds in the data set were reported. The distribution graphs for calculated and experimental log P are shown in Figure 3.3 and Figure 3.4. The ClogP average is 2.51 for all the compounds in the data set and the MlogP average is 2.44 for the 1226 compounds with measured values reported. 37

300

» 200

P 150

"5 « 100

MP ("C)

Figure 3.2: Melting point (MP) distribution of 1037 solids in the data set. 38

400

350

300 - w 1 250 - 3 §• 200 - o u "5 150 - *

100 -

50

A -N \ <0 A o> ClogP

Figure 3.3: Calculated log octanol-water partition coefficient (ClogP) distribution of 1804 compounds in the data set. 39

300 1

250

M 200

E 150

* 100

50

A ,N \ MlogP

Figure 3.4: Experimental log octanol-water partition coefficient (MlogP) distribution of

1226 compounds in the data set. 40

RELATIONSHIPS

Regression Analysis

Regression analysis can be used to explore the relationship between a dependent variable and one or more independent variables or covariables. In this study, we looked at the relationship between aqueous solubility and octanol-water partition coefficient as well as the relationship between aqueous solubility and melting point. For each model, the R^, regression coefficient and standard error of estimation were obtained to evaluate the relationship. SPSS version 10.0 (SPSS Inc., Chicago, IL) was used to perform the regression analyses. Data can be read into the software directly from an Excel spreadsheet file. 41

CLOGP Prediction Evaluation

The prediction performance of CLOGP was evaluated by calculating the average error

(AE)

AE = [ S ( Clog? - MlogP )] / n the average absolute error (AAE) is determined as

AAE = ( S I ClogP - MlogP I) / n and the root mean square error (RMSE) as

RMSE = [ I (ClogP - MlogP)^ I where ClogP and MlogP are the logarithms of the predicted and experimental octanol- water partition coefficient respectively, and n is the number of compounds. 42

Predicted versus Experimental Octanol-Water Partition Coefficient

The log octanol-water partition coefficients can be estimated using a number of software packages either freely available (e.g., KOWWIN) or commercially available (e.g., ClogP,

ACDlogP, i.a.). In this study, the ClogP version 4.0 was used. It gave a prediction with average error (AE) of 0.00, average absolute error (AAE) of 0.18 and root mean sqare error (RMSE) of 0.29 for the 1225 compounds with experimental log P data reported.

Figure 5 shows a plot of the calculated log P values against the measured log P data.

Regression analysis gave the following correlation relationship.

ClogP = l.OHMlogP - 0.0304 N = 1225, R^ = 0.981, SE = 0.290 MIogP

Figure 3.5: Plot of calculated log octanol-water partition coefficients (ClogP) experimental(measured) log octanol-water partition coefficients (MlogP). 44

Solubility and Octanol-Water Partition Coefficient

The aqueous solubility of an organic compound has an inverse relationship with its lipophilicity as measured by the octanol-water partition coefficient. Hansch et al. showed that the relationship between log Sw and log P for a group of liquids can be described by

log Sw = -1.339 log P + 0.978 N = 156, = 0.874, SE = 0.472

The relationship can be seen in the plots of log Sw versus either ClogP (Figure 6) or

MlogP (Figure 3.7) for the liquids in the current set of compounds. The equations and results obtained from regression analyses underline the strong relationship as indicated by the high for the correlation.

log Sw = -1.073 ClogP + 0.597 N = 597, R^ = 0.894, SE = 0.559 log Sw = -1.112 MlogP + 0.690 N = 393, R^ = 0.905, SE = 0.531

With the bigger data set we used, the coefficients for ClogP and MlogP and the constant were slightly different from those obtained in Hansch's study. At the same time, the standard error of estimation grew bigger.

A similar relationship can still be observed when solids were included in the plots (Figure

3.8 and Figure 3.9). However, the correlation seemed to be not as strong as shown by liquid solutes only. R decreased significantly while the SE increased one fold. The coefficients for log P were still close to "-1" but their magnitude decreased, indicating that the log decreases less with log P for solids than for liquids. It is also interesting to note that the constant terms changed from positive numbers to negative numbers, which translates into that, in general, a solid solute has a lower solubility than a liquid solute when they have similar octanol-water partition coefficients.

log Sw = -0.843 ClogP - 0.809 N = 1804, = 0.714, SE = 1.212 log Sw = -0.906 MlogP - 0.602 N = 1225, R^ = 0.723, SE = 1.141 46

Figure 3.6: Scatterplot of log Sw versus calculated log octanol-water partition coefficients

(ClogP) for 597 liquids or gases in the data set. 47

Figure 3.7: Scatterplot of log Sw versus experimental log octanol-water partition coefficients (MlogP) for 393 liquids or gases with available experimental log P in the data set. 48

4 n

-14 T 1 1 1 1 1 -8 -4 0 4 8 12 ClogP

Figure 3.8: Scatterplot of log aqueous solubilities (log Sw) versus calculated log octanol- water partition coefficients (ClogP) for all 1804 compounds in the data set. 49

Figure 3.9: Scatterplot of log aqueous solubilities (log Sw) versus experimental log octanol-water partition coefficients (MlogP) for 1225 compounds with available experimental log P in the data set. 50

Solubility and Melting Point

Scatterplot of experimental log against melting point reveals a negative correlation

(Figure 3.10). However, the correlation between the two variables is very weak as indicated in the results of regression analyses. The first equation is for 1525 compounds with available melting point information. The second equation is for 1037 solid compounds with available melting point information.

log Sw = -0.0050 MP - 2.645 N = 1525, = 0.0614, SE = 2.276 log Sw = -0.0007 MP - 3.408 N = 1037, = 0.0004, SE = 2.455 -14 i ^ 1 1 1 1 1 1 -200 -100 0 100 200 300 400 500 MP (°C)

Figure 3.10: Scatterplot of log Sw versus experimental melting point for 1525 compounds with available melting point information in the data set. 52

CHAPTER 4: STRUCTURAL FRAGMENTATION

INTRODUCTION

Group contribution approaches have been used for the prediction of physical properties such as octanol-water partition coefficient, enthalpy of melting, entropy of melting, etc.

They start by breaking down the molecular structures into a predefined set of substructural fragments. Regression analysis is then performed to assign a group contribution value towards the property of interest for each substructural fragment.

Property of a new molecule can be predicted by summing up the number of occurrences of each fragment in the molecule times its group contribution value.

The structure breakdown process is generally called structural fragmentation. The substructural fragments can be defined in a variety of ways. The different ways of defining the substructural fragments are called fragmentation schemes. Early group contribution works were done "manually" by looking at the molecular structures and counting the number of presences of defined fragments. Small data sets can be manageable with the "manual" approach. However, it will take enormous amounts of time when large data sets need to be processed.

The recent developments in chemical information system and computational chemistry have greatly enhanced the productivity in processing structural information in chemistry. Various chemical languages and file formats have been developed to represent and communicate chemical structures, reactions and data (Weininger, 1988; Bebak et al.,

1989; Barnard, 1990; Dalby et al., 1992; Allen et al., 1995). Efficient processing and storage of the chemical information are now possible with the development of ancillary computer programs. 54

SMILES

SMILES (Simplified Molecular Input Line Entry Specifications) is a language used for chemical structure representation in computer systems (Weininger, 1988). It allows the representation of molecular structure by a linear string of symbols. Compared with other chemical notation languages, one of the major advantages of SMILES is its user- friendliness. Good chemical notation systems need to give a unique notation for a molecular structure to serve as the identifier of the structure for storage and processing.

To achieve that, many rules need to be followed to generate a unique notation for a structure. SMILES is designed to avoid putting the burden on users. Users are given great flexibility in following only a small set of rules that are easy and natural to learn. This can lead to various equally valid notations of a structure. The conversion of them into a unique notation is handled by a build-in algorithm in the system.

The five basic rules of SMILES language are as follows:

1. Atoms are represented by atomic symbols;

2. Double and triple bonds are represented by = and # respectively;

3. Branching is indicated by parentheses;

4. Ring closures are indicated by matching digits appended to symbols;

5. Aromaticity may be indicated by writing atomic symbols in lower cases. 55

An example is given in Figure 4.1 to illustrate these rules. More details about the

SMILES language can be found in the literature (Weininger, 1988; Weininger et al.;

1989) and the Daylight web site. 56

o

NHc

CC0C(=0)clccc(N)ccl

Nc(ccl)ccclC(=0)0CC

NC(C=C1 )=CC=C 1 C(=0)0CC

Figure 4.1: An example illustrating the expression of Benzocaine structure in SMILES. 57

SMARTS

Structural fragmentation is an important step in group contribution methods. SMARTS

(Smiles Arbitrary Target Specification) was developed by Daylight Chemical

Information System, Inc. to allow the representation of substructural fragments. It uses rules that are straightforward extensions of the SMILES language. Logical operators and a few new symbols were included to allow precise specification of the fragments and their bonding environments. Table 4.1 gives some examples to illustrate the expression of substructural fragments in SMARTS.

STRUCTURAL FRAGMENTATION PROGRAM

Structural fragmentations in this study were performed using an online service freely accessible at the University of Erlangen. Users are allowed to define and implement their own fragmentation schemes in SMARTS language. Input of molecular structures in

SMILES format can be processed in batch mode. Fragmentation results can be given in a number of formats, which facilitate the transport of data to different software. 58

Table 4.1: Examples illustrating the SMARTS expressions for substructural fragments. cc Any pair of attached aliphatic carbons c-c Any pair of aromatic carbons joined by a single bond

(e.g. biphenyl)

[0;H1] Hydroxy group

[F,CI,Br,I] Any one of the four halogen atoms

[!C;R] Atom that is NOT an aliphatic carbon AND is in a ring

[C;H0;X{2-3}] Any carbon atom that has no bonded hydrogen and is

connected to two or three atoms (e.g. -C=, =C=, >C=)

F[$([a]),$([C;A;X{2-3}])] Any fluorine atom that is connected to an aromatic

atom or an carbon atom that has no bonded hydrogen

and is connected to two or three atoms

[0;Hl][$([c])] Phenol group

[0;Hl][c] A group composed of a phenol group with the attached

aromatic carbon 59

FRAGMENTATION SCHEME

The current fragmentation scheme is developed on the basis of the AQUAFAC scheme described previously (Myrdal et al. 1992, 1993,1995). It can be considered an extended version of the AQUAFAC fragmentation scheme. Sulfur and phosphorus containing fragments are now included to extend the applicability to a wide range of compounds.

As in the original AQUAFAC scheme, fragmentation is based on fundamental groups and the hybrid state of the atom(s) to which they are bonded. The fundamental groups are listed in the first column of Table 4.2. Depending on the types of neighboring atom(s) they are bonded to, some commonly encountered ones are further classified. Two types of neighboring atoms are defined. An atom is designated by an "X" if it is a sp carbon, amine nitrogen, ether oxygen, divalent sulfur or any of the four common halogens. The neighboring atoms that are designated by a "Y" include sp and sp carbons, aromatic atoms, nitrogens in nitro groups, pentavalent phosphorus atoms, and sulfur atoms in sulfoxide or sulfonyl group. Fundamental groups are given a prefix to indicate the neighboring connection(s). A prefix of "X" indicates all neighboring atoms are "X" type while a prefix of "Y" indicates one neighboring atom is "Y" type. "YY" is used as prefix when two or more neighboring atoms of a fragment are "Y" type. 60

The classification system does not apply to aromatic fragments. For aromatic carbons, they are differentiated as normal aromatic carbons, biphenyl carbons and bridgehead carbons (as in fused aromatic rings).

Fragments such as -C(=0)0-, -C(=0)N< and -C(=0)NH-, have more than one atom for neighbor bonding. Myrdal et al. indicated that consideration of only the neighbor which is bonded to the carbonyl group is necessary for the classification of these fragments

(1995).

To keep the number of fragments to a reasonable range, the less commonly encountered fragments are not differentiated. Three atomic fragments are included to minimize the possibility of missing fragments.

Figure 4.2 shows an example of structure fragmentation using the AQUAFAC scheme.

The benzocaine structure is broken into 10 fragments according to the scheme. 61

Table 4.2: Fragment list in the extended AQUAFAC fragmentation scheme.

Neighboring Group Fragment X Y YY -CH3 XCH3 YCH3 * -CH2- XCH2 YCH2 YYCH2 >CH- XCH YCH YYCH >C< XC YC YYC CH2= CH2dbl * * -CH= XCHdbl YCHdbl >C= XCdbl YCdbl YYCdbi CH= CHtri * * -C= XCtri YCtri * =C= Callenic * * -F XF YF * -CI XCl YCl * -Br XBr YBr * -I XI YI * -OH XOH YOH * -0- XO YO YYO -NH2 XNH2 YNH2 * >NH XNH YNH YYNH >N- XN YN YYN NH= NHdbl * * -N= XNdbl YNdbl * -SH XSH YSH * >S XS YS YYS -C(=0)H XCHO YCHO * >C=0 XCO YCO YYCO -C(=0)0H XCOOH YCOOH YYCOOH -C(=0)0- XCOO YCOO YYCOO HC(=0)0- HCOO * * -C(=0)NH2 XC0NH2 YC0NH2 YYC0NH2 -C(=0)NH- XCONH YCONH YYCONH -C(=0)N< XCON YCON YYCON -C=N XCN YCN YYCON HC(=0)N< HCON * * -N(=0)=0 XN02 YN02 * Non-existent fragment Table 4.2: (Continued).

Fragment Name Fragment Name C aromatic Car >S=0 SO C biphenyl Cbp >S(=0)=0 S02 CH aromatic CHar -S(=0)(=0)NH2 S02NH2 C bridgehead Cbr -S(=0)(=0)NH- S02NH 0 aromatic Oar -S(=0)(=0)N< S02N N aromatic Nar -SC(=0)NH- SCONH S aromatic Sar -SC(=0)N< SCON Car=0 Car=0 -SC=N SCN -0C(=0)NH- OCONH -N=C=S NCS -0C(=0)N< OCON PO4 P04 -C(=0)0C(=0)- COOCO P(=0)02S P03S -NHC(=0)NH2 NHC0NH2 P(=0)0S2 P02S2 -NHC(=0)NH- NHCONH P(=S)03 PS03 >NC(=0)NH2 NC0NH2 P(=S)02S PS02S >NC(=0)NH- NCONH -P(=0)02 P03 >NC(=0)N< NCON -P(=0)0S P02S -C(=0)NHC(=0)- CONHCO -P(=S)02 PS02 -C(=0)NC(=0)- CONCO -P(=S)OS PSOS -CH=N- CH=N 0= Odbl_other >C=N- C=N >P(<)- Pv5_other -CH=NOH CH=NOH s= Sdbl_other >C=NOH C=:NOH 63

XCH2

XCH

YCOO NH

YNH2

Figure 4.2: Fragmentation of benzocaine structure according to the AQUAFAC scheme. 64

CHAPTER 5: EVALUATION OF SOLUBILITY PREDICTION BY

THE GENERAL SOLUBILITY EQUATION ON A SET OF DIVERSE

COMPOUNDS

INTRODUCTION

The General Solubility Equation (GSE) was originally proposed by Yalkowsky et al.

(1980) and recently revised by Jain and Yalkowsky (2001). It relates the molar aqueous solubility (Sw) to the melting point (MP) in Celsius and the octanol-water partition coefficient (P) by the following simple equation: log Sw = 0.5 - 0.01(MP - 25) - log P

The General Solubility Equation has been shown to produce reasonable predictions for a wide variety of organic non-electrolyte compounds (Peterson et al., 2001; Ran et al.,

2002). In this study, we intend to test the GSE on an even more diverse data set including non-electrolytes and weak electrolytes. The performance of GSE on different classes of compounds is evaluated. 65

METHODS

Data Set

Since the coefficients in the General Solubility Equation were not obtained by regression on a particular training set of compounds, any compounds in the data set described in

Chapter 3 can be used to test the performance of the General Solubility Equation. For the

1804 compounds in the data set, melting information were not found for 170 of them.

The remaining 1604 compounds were used as a test set for the study. 66

Evaluation

The General Solubility Equation was used to estimate the 1634 compounds with melting point or physical state information. The prediction performance was evaluated by calculating the average error (AE)

AE = [ S (log Scale - log Sw)] / n

, the average absolute error (AAE) is determined as

AAE = ( Z I log Scale - log Sw I ) / n and the root mean square error (RMSE) as

RMSE = [ Z (log Scale - log Sw )^ / n ] where log Scale and log Sw are the logarithms of the predicted and experimental aqueous solubility respectively, and n is the number of compounds.

The AE indicates whether the predictions are biased. The AAE and RMSE are representative of the size of a "typical" error of prediction. They are generally used to compare the prediction performance of different models. The RMSE is more sensitive than the AAE to the occasional large errors because the squaring process gives much more weight to very large errors. Therefore, the RMSE is usually slightly bigger than the

AAE.

Residual diagnostics was performed by analysis of the residual distribution plot; plots of residuals against experimental log Sw, MP and ClogP; residual comparisons of liquids versus solids, non-electrolytes versus weak electrolytes, zwitterions and compounds with specific functional groups. 68

Regression Analysis

Regression analysis can be used to explore the relationship between a dependent variable and one or more independent variables or covariables. In this study, we looked at the relationship between aqueous solubility and octanol-water partition coefficient, the relationship between aqueous solubility and melting point, and the relationship between aqueous solubility and both octanol-water partition coefficient and melting point. For each model, the R^, regression coefficient and standard error of estimation were obtained to evaluate the relationship. SPSS version 10.0 (SPSS Inc., Chicago, IL) was used to perform the regression analyses. Data can be read into the program directly from an

Excel spreadsheet file. 69

RESULTS AND DISCUSSION

Overall Performance

For the 1634 compounds with known melting point or known to be liquid at 25 °C, the

General Solubility Equation gave a good prediction of the aqueous solubility as shown in

Figure 5.1. The average absolute error of estimation of 0.56 log unit corresponds to a factor of about 3.6 normal units. The error distribution plot (Figure 5.2) indicates that the

GSE predicted the solubilities of about 60 % of the compounds with errors below 0.5 log unit and about 85 % with errors below 1 log unit.

The prediction error was plotted against experimental log Sw, ClogP and melting point in

Figures 5.3, 5.4 and 5.5 respectively. No trends were observed in the plots of prediction error against the experimental log Sw or the melting point, indicating that there is little systemic deviation in the prediction. However, there was a slight trend in the plot with respect to ClogP. It can be seen that aqueous solubilities of compounds with low ClogP tend to be overestimated. There is no definite explanation for this trend currently. Two factors may be considered as part of the reason. One is that a significant portion of this group of compounds are zwitterionic in nature. The other is the prediction error associated with log P estimation for this group of compounds using CLOGP. For example, the two compounds with the largest prediction error are cephaloridine and natamycin. CLOGP gives warning messages "error uncertain for charged structure"

"possible low due to hydrophilic overlap" for the calculation of their log P values. 8 n 6 -

-12 - o' o

-14 I ^ ! I ^ ^ 1 I I I I I -14 -12 -10 -8 -6 -4 -2 0 2 4 6 8 Experimental log Sw

Figure 5.1: Plot of predicted log Sw versus experimental log Sw 72

70

60

50 - in E I 40 E o O 30 . o s? 20

10 -

0 ! 1 t , r— O <0'<0 N- 1/ 'b ^

Figure 5.2: Absolute prediction error distribution. ~n -14 -12 -10 -8 -6 -4 -2 0 4 Experimental log Sw

Figure 5.3: Plot of prediction error against experimental log Sw. -8 -4 0 4 12 ClogP

Figure 5.4: Plot of prediction error against calculated log P (ClogP). O oOoo o o OOO - •oO

O nB ^*^0^ 0 ODO •^o^O " o o","

1 1 1 1 0 50 100 150 200 250 300 350 400 450

MP f0/ C)

Figure 5.5: Plot of prediction error against melting point for 1037 solids. 76

Solid Versus Liquid

It is apparent from Table 5.1 that the General Solubility Equation provided better prediction for liquids than for solids. Part of the reason might be that liquids tend to have simpler structures than solids. Most of the liquids in the data set are hydrocarbons, halogen substituted hydrocarbons, or simple alcohols. As a result of the simplicity in structure, less complicated intramolecular and intermolecular interactions are expected, which always makes the modeling more accurate.

It should be noted that compounds exist in gas state at 25 °C are not separeated from the liquids in the current study. The treatment did not result in significantly larger prediction errors for gases than for liquids. 77

Table 5.1: Statistical analysis of predicted log Sw values compared with experimental log

Sw values.

N AE AAE RMSE

All 1634 0.07 0.56 0.82

Liquids/Gases 597 0.08 0.40 0.57

Solids 1037 0.06 0.66 0.93 78

Non-electrolyte Versus Weak Electrolyte

The General Solubility Equation was derived based on assumptions applicable for organic non-electrolytes. Strictly speaking, it is only applicable for non-electrolytes. The fact that it performs so well on non-electrolytes has led to its extended use in predicting solubilities of organic weak electrolytes. When applied to organic weak electrolytes, the predicted solubilities by GSE refer to the solubilities of the neutral or unionized species, i.e. intrinsic solubilities. Solubilities of weak electrolytes can be affected by solution pH and the relevant equations describing the variation have been given in the literature

(Grant and Higuchi, 1990). An acidic solute with pKa of 4 is expected to have a solubility about 1000 fold of its intrinsic solubility at pH 7 due to ionization (assuming Ksp is not reached). However, an acidic solute with pKa of greater than 8 is expected to have a solubility no more than 10 % deviated from its intrinsic solubility at pH 7. Dissolved weak electrolyte in water can affect the pH of the solution depending on the pKa and the concentration of the solute. The relationship has been evaluated in recent studies

(Abraham and Le, 1999; Sanghvi et al., 2003). Upon dissolving in water, a weakly acidic solute is expected to lower the pH of the solution and minimize the deviation from intrinsic solubility due to ionization. For compounds with the same or similar pKa's, the higher its intrinsic solubility, the more it lowers the solution pH and the less the deviation. Therefore, significant deviation of solubility from intrinsic solubility is expected for acidic compounds with low pKa's or low intrinsic solubilities, or basic compounds with high pKa's or low intrinsic solubilities. 79

Dissociation constant (pKa) information is not as widely available as the aqueous solubility information. It will be very hard to collect pKa data for so many compounds in the current data set. However, pKa can be roughly estimated for compounds with certain functional groups. For example, conjugative acids of amines have pKa's of about 10-11 while those of anilines have pKa's of about 4-5.

In this study, the prediction performance was evaluated on three groups of compounds, carboxylic acids, amines and zwitterions. Zwitterions were identified by the presence of both a carboxylic acid functional group and an amine functional group. The prediction results are summarized in Table 3. As can be seen from the table, the General Solubility

Equation tends to underestimate the solubilities for carboxylic acids and amines, which may be partially explained by the pH effect due to ionization of the solute itself.

According to the theoretical calculations (Abraham and Le, 1999; Sanghvi et al., 2003), little effect is expected for high solubility compounds and the more negative deviation is expected for low solubility compounds. However, residual analyses on the different classes of compounds indicate that ionization is not the only factor. Residual plots of compounds containing an XCOOH group is shown to illustrate this point (Figure 5.6). It is supprising to see that the solubilities of zwitterionic compounds are overestimated by the GSE. The GSE gives solubility prediction for the hypothetical charge-free form of a zwitterionic compounds which, in theory, should be less soluble than the charged form. 80

Table 5.2: Statistical analysis of prediction performance of different classes of compounds.

N AE AAE RMSE

(Pred - Exp)

Carboxylic acids 47 -0.60 0.74 0.87

YCOOH

Carboxylic acids 77 -0.47 0.78 1.03

XCOOH

Primary amines 18 -0.21 1.04 1.28

Secondary amines 22 -0.49 0.70 0.93

Ternary amines 59 -0.23 0.99 1.28

Zwitterions 29 1.32 1.34 1.96

Others 1383 0.12 0.50 0.72

All 1634 0.07 0.56 0.82 y = -0.0154x-0.5103 = 0.001

o 9 O O ^ O o CO Ul ° S O? OO O o •^ f U "lA'O W o_ o^ OOo o 0 O O tf>

^^ 1__ I

-10 -8 -6 -4 -2 0 4

log SW

Figure 5.6: Residue plot of compounds containing XCOOH group. 82

Regression Analysis

Regression analysis using ClogP and (MP - 25) as the independent variables to correlate with log Sw gave the following equation and results.

log Sw = 0.304 - 0.947 ClogP - 0.0101 (MP - 25)

N = 1634, = 0.880, SE = 0.8067

Comparing with the correlation between log Sw and ClogP alone, it is obvious that the correlation improved significantly with the inclusion of (MP - 25). The fact that the coefficients for ClogP and (MP - 25) obtained from regression are very close to those in the General Solubility Equation lends support to the validity of the assumption made in the derivation of GSE. 83

SUMMARY

The prediction performance of the General Solubility Equation is evaluated on a large collection of structurally diverse environmental and pharmaceutical compounds. The data set contains a total of 1634 non-electrolytes and weak electrolytes. The GSE gives an overall prediction with AAE of 0.56 and RMSE of 0.82 log unit. Predictions are generally more accuate for liquids than for solids. The GSE also provides better predictions for non-electrolytes than for weak electrolytes. Solubilities of carboxylic acids and amines are generally underestimated while those of zwitterionic compounds are overestimated by the GSE. 84

CHAPTER 6: COMPARISON OF THE GENERAL SOLUBILITY

EQUATION AND THE METHOD USING AN AMENDED

SOLVATION ENERGY RELATIONSHIP

INTRODUCTION

An Amended Solvation Energy Relationship (ASER) was recently proposed to predict the aqueous solubility of organic compounds. (Abraham and Le, 1999) The method starts with an equation that relates a solvation property (SP) to a sum of the following specific interaction terms: the excess molar refraction (R2), a combined dipolarity/polarizability

TT U descriptor (K2 ), the overall solute hydrogen bond acidity (Sa2 ), the overall solute hydrogen bond basicity (SP2"), and the McGowan's characteristic molecular volume

(Vx). In view of the influence of intermolecular interactions on melting points and solubilities, a product term "Za2" x EP2"" was incorporated to partly account for the absence of a solid correction term. This leads to the amended solvation energy relationship as follows

log Sw = c + rR2 + sTiz" + ai:a2" + bipz" + ld:a2" x IP2" + vV^ (6.1) where each term is determined by a separate formula and/or a set of group contribution values. Multiple linear regression analysis was used to construct the prediction equation.

This method was applied to a diverse set of 664 organic liquids and solids with 85 satisfactory results. In this chapter, the General Solubility Equation is applied to the same set of compounds and the prediction results are compared. 86

METHODS

The melting point data for the 664 compounds were obtained from the Merck Index,

AQUASOL dATAbASE and several internet databases. The octanol-water partition coefficients were calculated with CLOGP software (Version 4.0, BioByte Corp.,

Claremont, CA). Experimental octanol-water partition coefficients are listed if available.

The experimental aqueous solubilities and the ASER predicted solubilities are those reported by Abraham and Le (1999). The aqueous solubilities were also calculated using the General Solubility Equation (GSE) of Jain and Yalkowsky (2001). For each calculation the average absolute error (AAE) is determined as

AAE = ( 2 I log Scale - log Sw I) / n and the root mean square error (RMSE) as

RMSE = [ E (log Scale -log S^f/n where logScaic and log Sw are the logarithms of the predicted and experimental aqueous solubility respectively, and n is the number of compounds. 87

RESULTS

Octanol-Water Partition Coefficients

Experimental partition coefficients were found for 530 of the 664 compounds. As shown in Figure 6.1, the calculated partition coefficients using CLOGP® are in very good agreement with the available measured values (MLOGP), with an AAE of only 0.121 log units. CLOGP version 4.0 seems to give more accurate estimations of octanol-water partition coefficients than the previous version. Partition coefficients calculated with

CLOGP are used in the solubility calculations since 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 II. MLOGP

Figure 6.1: Plot of measured logP (MlogP) versus ClogP (n = 530). Melting Point

Melting points were found for 662 of the 664 compounds. The other two compounds

(hydrocortisone 21-acetate and morphine) decompose upon melting and thus may not have true melting points. (Note that the use of a decomposition temperature in the GSE gives the maximum solubility estimation. The predicted solubility would be lower if the true melting point were higher than the decomposition temperature.) If polymorphs or hydrates of the compound exist, the melting point of the most stable form in equilibrium with the solution should be used. The melting points used in the GSE are listed in the fourth column of the APPENDIX II. Note that an MP of 25°C is used for all liquids so that the crystal term vanishes. 90

Solubility

The solubility values used by Abraham for the 664 compounds studied are listed in the

5th column of the APPENDIX II. All of these values were confirmed 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 column 6 and 7 of the APPENDIX II, respectively.

They are also plotted against the experimental solubility values in Figures 6.2 and 6.3 respectively. The average absolute prediction error for the 662 compounds is 0.446 log units and the root mean square error 0.622 log units, which are consistent with the results of previous studies (Jain and Yalkowsky, 2001; Ran and Yalkowsky, 2001; Ran et al.,

2001). As shown in Table 6.1, the results are similar when the two compounds which decompose before melting are included. 91

3

1

1

3

5

•7

9

11 11 9 7 •5 •3 1 1 3

Experimental log Sw

Figure 6.2: Experimental log Sw versus predicted log Sw using the ASER method (n =

664). The diagonal line is the line of identity. 92

3

1

1

•3

•5

•7

•9

11 11 9 7 5 3 1 1 3

Experimental log Sw

Figure 6.3; Experimental log Sw versus predicted log Sw using the GSE method (n = 664).

The diagonal line is the line of identity. 93

DISCUSSION

In spite of the fact that the General Solubility Equation uses only two input variables and does not use any training set or fitted parameters, it gives quite reasonable predictions.

The ASER method produces only marginally better predictions (Table 6.1). However it uses seven coefficients, six variables derived from a very large number of structural descriptor values, and multiple linear regression analysis.

As can be seen in Table 6.1, both methods give better predictions for the 408 liquids than for the 256 solids. The average absolute error 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 non-electrolytes is based upon the relationship between the octanol-water partition coefficient and the water solubility originally proposed by Hansch et al. (1968) and validated by Yalkowsky and Valvani (1980).

When applied to solid compounds, the General Solubility Equation assumes that the entropy of melting of organic non-electrolytes obeys Walden's rule (i.e. ASm = 56.6 JK"

'mole ') and that the solid-liquid heat capacity difference is negligible (i.e. ACpm = 0).

(Note: CLOGP alone gives better prediction for liquids than solids.) In the ASER method, the product term "Za2" x i;p2""deals with hydrogen-bond interactions between acid and basic sites in the solid or liquid. The addition of a term "Tta" x 712"" to deal with dipole/dipole interactions did not improve the prediction. 94

Table 6.1: Statistical analysis of predicted log Sw values compared with experimental log

Sw values.

All All - 2" Liquids Solids n = 664 n = 662 n = 408 n = 256 ASER 0.430 0.431 0.338 0.575 AAE GSE 0.447 0.446 0.358 0.588 AVG 0.377 0.376 0.309 0.486 ASER 0.615 0.615 0.490 0.774 RMSE GSE 0.623 0.622 0.505 0.775 AVG 0.534 0.533 0.453 0.642

''All compounds except two which decompose before melting. 95

The ASER method predicts aqueous solubilities from compound structures without the need of experimental melting point values. However, it is limited by the availability of descriptors for the contribution of specific groups present in a compound to the six parameters used. For example, dicarboxylic acids are not included in the ASER study because descriptors for these compounds have not yet been finalized.

The applicability of the General Solubility Equation depends on the availability of melting point and octanol-water partition coefficient data. As shown in previous studies, octanol-water partition coefficients can be reliably predicted using CLOGP or other software (Jain and Yalkowsky, 2001; Ran and Yalkowsky, 2001; Ran et al., 2001). On the other hand, melting point data are not always available and a reliable general method of predicting melting point from compound structures is not available currently. Most attempts to predict melting point are either unsatisfactory or applicable to only a very small group of compounds (Joback, 1984; Boethling et al., 1988; Dearden, 1991;

Simamora and Yalkowsky, 1994; Krzyzaniak et al., 1995). However, if melting points can be predicted with a 30 °C error it would correspond to only a two-fold error in solubility.

It is interesting to note that the average (AVG) of the predicted log values using the two independent methods gives a better prediction than either method used alone (Figure

6.4). Table 6.1 shows that the AAE and RMSE are generally reduced when the average values are used. Furthermore, the two predictions differ by less than a factor of 2 (0.30 96 log units) from each other for about half of the compounds. For more than 60% of these

331 compounds the average of the two calculations is within a factor of 2 of the observed value. 97

3

1

o O -3 d) (0W -5c k. V > < -7

-9

-11 -11 -9 -7 -5 -3-113

Experimental log Sw

Figure 6.4: Experimental log Sw versus predicted log Sw using the average of the ASER prediction and the GSE prediction (n = 664). The diagonal line is the line of identity. 98

SUMMARY

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 while the GSE is simpler and user- friendlier. However the latter requires knowledge of either an experimentally determined or an estimated melting point of the solute. This study provides support for the reliability of the GSE in estimating the aqueous solubilities of organic compounds. It can be used alone or in combination with the ASER calculation to provide confirmatory results. 99

CHAPTER 7: DEVELOPMENT OF THE EXTENDED AQUAFAC

MODEL

INTRODUCTION

As discussed in Chapter 2, the deviation of aqueous solubility from ideal solubility is generally described by the aqueous activity coefficient Yw Myrdal et al. developed the

AQUAFAC group contribution method to estimate the molar aqueous activity coefficient, log^^=C +(7.1) i where C is a constant; n; is the counts for a specific group i; and qj is the group contribution value for group i.

Estimation of the aqueous activity coefficient allows the development of a solubility prediction model from aqueous phase data and avoids the use of octanol as a reference solvent. Together with melting point (MP) information, the aqueous solubility can be predicted using

= -0.01(MP-25)-log;/, (7.2)

When tested on a set of 97 compounds, the AQUAFAC approach was shown to be slightly superior to the General Solubility Equation (Myrdal et al., 1995). The study 100 clearly demonstrated the potential applicability of the AQUAFAC approach. Two subsequent studies extended the applicability to a wider range of functional groups (Lee et al, 1996; Pinsuwan et al., 1997). However, due to the lack of computational tools to break down the molecular structures at the time of development, the applicability of the approach is still limited to molecules containing a limited number of groups, whose group counting can be handled "manually".

This chapter intends to take advantage of the computational tools described in Chapter 4.

The AQUAFAC scheme is extended to a set of 114 fragments covering a diverse range of functional groups. Group contribution values for 104 fragments are obtained from multiple linear regression analysis. 101

METHODS

Data Set

Aqueous solubility and melting point information contained in the data set described in

Chapter 3 was used for the development of the extended AQUAFAC model. Part of the data set was taken out and reserved as test set for the comparison of the prediction performances using different methods. It includes a set of 21 environmental and pharmaceutical compounds compiled by Yalkowsky and Banerjee (1982), a test set of 38 pharmaceutical compounds used by Huuskonen et al. (2000), and a set of 54 drug or drug-like compounds tested in a study by Chen et al. (2002). Compounds with no melting information (no melting point found or not known as liquid at 25 °C) were excluded, as melting information is required for the development of the AQUAFAC model. As a result, the final training set contains 1574 compounds.

Aqueous Activity Coefficient

The aqueous activity coefficient Yw was calculated from the aqueous solubility Sw, through the following equations as previously described (Myrdal et al., 1993)

^ogr„=-\ogS„ (7.5) for liquid solute, and

logr„=-O.Ol(MP-25)-logS^ (7.6) 102 for solid solute.

The calculated aqueous activity coefficients were used in the regression analysis to generate the group contribution values for different fragments.

Structural Fragmentation

The structural fragmentation program, developed by Dr. Ihlenfeldt at the University of

Erlangen, was used to count the occurrence of each fragment in the molecules. The program takes SMILES names as structure input and has two build-in fragmentation schemes. It also allows users to customize the fragmentation schemes according to their own need or preference. The extended AQUAFAC scheme described in Chapter 4, was implemented in SMARTS language and used for this study.

Regression Analysis

The regression analyses were performed using SPSS for Windows version 10.0 (SPSS

Inc., Chicago, IL). The data set containing the aqueous activity coefficients and group counts was prepared in Excel and used as input for SPSS. The multiple linear regression analysis function of SPSS was used to generate group contribution values qi. Regression analyses with or without a constant term were both performed. 103

RESULTS

Fragmentation Performance

With the extended AQUAFAC scheme, the molecular structures of all 1574 compounds in the training set were fragmented. Out of the 114 defined fragments, 104 fragments were found in those structures.

Regression Analysis

Although the original studies found that the inclusion of a constant term in the regression equation was not necessary, the result of the regression analysis performed on a large data set in this study indicates that the constant term is significant. The constant term has a value of -0.742. The model with a constant term has an of 0.881 and a standard error of estimation of 0.819 for the training set. Without the constant term, the model gives a standard error of estimation of 0.838.

Group Contribution Values qi

Table 7.1 lists the group contribution values for 104 fragments encountered in the training set. These parameters constitute the basis for the estimation of aqueous activity coefficients of new compounds. 104

Table 7.1: Fragments in the extended AQUAFAC scheme: The number of occurrences (N), group contribution values (qi) and statistical significance.

Code Name N Qi Sig. 0 Const. -0.742 0.000 1 YCH3 365 0.588 0.000 2 XCH3 1476 0.696 0.000 3 YYCH2 37 0.338 0.036 4 YCH2 470 0.267 0.000 5 XCH2 2214 0.476 0.000 6 YYCH 34 0.096 0.610 7 YCH 187 0.060 0.408 8 XCH 731 0.144 0.000 9 YYC 59 -0.170 0.347 10 YC 187 -0.483 0.000 11 XC 136 -0.653 0.000 12 CH2dbl 72 0.758 0.000 13 YCHdbl 133 0.106 0.100 14 XCHdbl 155 0.425 0.000 15 YYCdbl 30 0.596 0.000 16 YCdbl 72 0.650 0.001 17 XCdbl 141 0.013 0.894 18 CHtri 14 0.288 0.309 19 YCtri 0 20 XCtri 16 0.601 0.019 21 Callenic 1 0.859 0.305 22 Car 2522 0.145 0.004 23 Cbp 194 0.427 0.000 24 CHar 4387 0.337 0.000 25 Cbr 416 0.333 0.000 26 Nar 239 -0.497 0.000 27 Sar 20 0.829 0.000 28 Oar 1 0.214 0.794 29 YF 29 0.517 0.000 30 XF 87 0.670 0.000 31 YCI 900 0.834 0.000 32 XCI 213 0.762 0.000 33 YBr 56 1.190 0.000 34 XBr 42 0.843 0.000 35 YI 25 1.197 0.000 36 XI 10 1.146 0.000 37 YOH 173 -0.624 0.000 38 XOH 361 -0.482 0.000 Table 7.1: Continued.

Code Name N Qi Sig. 39 YYO 76 0.849 0.000 40 YO 136 -0.275 0.000 41 XO 94 -0.447 0.000 A1 YSH 4 1.188 0.005 43 XSH 3 0.323 0.499 44 YYS 13 0.519 0.125 45 YS 20 0.945 0.000 46 XS 19 0.046 0.798 A1 YCHO 15 -0.030 0.890 48 XCHO 9 -0.242 0.393 49 YYCO 40 -0.215 0.182 50 YCO 50 -0.213 0.136 51 XCO 81 -0.627 0.000 52 YCOOH 53 -0.559 0.000 53 XCOOH 111 -0.876 0.000 54 YCOO 64 -0.194 0.077 55 XCOO 86 -0.666 0.000 56 HCOO 6 -0.363 0.286 57 CarO 20 0.648 0.001 58 YNH2 106 -0.359 0.000 59 XNH2 46 -0.800 0.000 60 YYNH 19 -0.401 0.099 61 YNH 42 -0.192 0.111 62 XNH 25 -1.783 0.000 63 YYN 23 -0.597 0.027 64 YN 28 -0.831 0.000 65 XN 57 -2.008 0.000 66 NHdbl 0 67 YNdbl 2 -0.304 0.463 68 XNdbl 4 0.423 0.682 69 YCN 12 -0.099 0.642 70 XCN 7 -0.090 0.782 71 YCONH2 13 0.384 0.109 72 XCONH2 5 -0.675 0.073 73 YCONH 27 -0.458 0.011 74 XCONH 67 -0.820 0.000 75 HCONH 3 1.151 0.004 76 YCON 9 -1.183 0.000 Table 7.1: Continued.

Code Name N Qi Sig. 77 XCON 28 -1.453 0.000 78 HCON 0 79 YN02 74 0.443 0.000 80 XN02 6 0.259 0.454 81 OCON 4 -0.757 0.076 82 OCONH 22 -0.632 0.000 83 NHCONH2 5 -1.017 0.006 84 NHCONH 8 -0.873 0.008 85 NCONH2 2 -0.358 0.668 86 NCONH 14 -1.558 0.000 87 NCON 1 -2.981 0.000 88 CONHCO 42 -0.540 0.003 89 CONGO 11 -0.492 0.084 90 COOCO 1 -0.566 0.493 91 SO 6 -0.858 0.023 92 S02 13 -0.403 0.120 93 S02NH2 17 -1.102 0.000 94 S02NH 31 -0.781 0.000 95 SCON 8 -0.646 0.031 96 SCONH 0 97 CH=N 14 0.211 0.349 98 C=N 26 0.021 0.898 99 CH=NOH 1 -0.308 0.716 100 C=NOH 0 101 SCN 0 102 NCS 2 1.474 0.011 103 P04 2 -1.564 0.008 104 P03S 0 105 P02S2 0 106 PS03 10 0.397 0.149 107 PS02S 8 0.417 0.122 108 P03 1 -2.221 0.008 109 P02S 0 110 PS02 2 -0.277 0.648 111 PSOS 0 112 Odbl_other 6 -0.236 0.783 113 Pv5_other 1 -3.087 0.027 114 Sdbl_other 16 0.051 0.837 * Refer to Chapter 4 for the descriptions of the fragments. 107

Aqueous Solubility Prediction

The predictive ability of the extended AQUAFAC model will be evaluated in Chapter 9 on an independent set of compounds not included in the training set. The prediction performance will be compared with other models. 108

CHAPTER 8: DEVELOPMENT OF A NEW GROUP

CONTRIBUTION MODEL FOR AQUEOUS SOLUBILITY

PREDICTION

INTRODUCTION

Both of the General Solubility Equation and the AQUAFAC approach require melting point information for solubility prediction, which can be easily measured with a small amount of drug substance at the early drug development stage. However, the melting point information is generally not available at the drug discovery stage as the compounds have low purity and they are not crystallized. While research on the prediction of the melting point of organic compounds from molecular structures is ongoing, it is generally conceived that melting point prediction itself is at least as challenging as aqueous solubility prediction. Development of aqueous solubility prediction method without the need of melting point information therefore would be more applicable at the drug discovery stage.

The purpose of this Chapter is to develop such a model for predicting aqueous solubility based on the theory of ideal solution and regular solution.

As discussed in Chapter 2, it is theoretically reasonable to attempt the use of group contribution approach to estimate the ideal solubility 109

logX,^ (8.1) i where iii is the counts of fragment i and mi is the group conribution of fragment i.

The molar aqueous solubility can then be estimated using

log5.=C„+2;'i,'n,-log/' (8.2) i

The log octanol-water partition coefficient can be either calculated using commercial software or modeled using the same set of fragments. The second approach will have the form of

log5„ = C„ (8.3) / /

The two group contribution terms can be combined to give

logi.=C,+j;n,s, (8.4) i

Equation (8.4) is essentially the basis of a pure group contribution approach for aqueous solubility prediction. Both Equation (8.2) and Equation (8.4) will be explored to model aqueous solubility in this chapter. 110

METHODS

Data Set

Development of the new model requires only aqueous solubility and calculated log P value. Therefore, all the compounds contained in the data set described in Chapter 3 can be used. For comparison of prediction performance, part of the data set was taken out and reserved as a test set as described in Chapter 7. The final training set contains 1691 compounds.

Structural Fragmentation

The structural fragmentation procedure is the same as described in Chapter 7.

Regression Analysis

The regression analyses were performed using SPSS for Windows version 10.0 (SPSS

Inc., Chicago, IL). The data set containing the aqueous solubility, ClogP information and group counts was prepared in Excel and used as input for SPSS. The multiple linear regression analysis function of SPSS was used to generate group contribution values Sj. Ill

RESULTS

Fragmentation Performance

All the molecular structures of the training set compounds were break down successfully using the extended AQUAFAC fragmentation scheme and no missing fragment was found.

Regression Analysis

Two independent regression analyses, based on Equation (8.2) and Equation (8.4) respectively, were conducted in SPSS. The first regression gives an R of 0.595 and standard error of estimation of 0.814. The second regression considers the contribution of each fragment towards log solubility. The model has an R of 0.865 and a standard error of estimation of 0.873 for the training set. The two R^ are not comparable because the variables are different in the two regressions. The first regression analysis is with regard to the part of solubility variance that cannot be explained by the lipophilicity of a compound, while, the second is about all the solubility variance. Since log P is a major variable in determining aqueous solubility and can be modeled using group contribution approach, it is not surprising to see that the second analysis has a much higher R . The standard error of estimation is a better indication of the "fitness" of the two models. The first model has a smaller standard error of estimation and is selected for further 112 development and evaluation. This model is referred as GClogP model since it is a Group

Contribution model with Clog? as a parameter.

Group Contribution Values nii

Table 8.1 lists the group contribution values for 104 fragments encountered in the training set. Together with calculated octanol-water partition coefficients, these parameters can be used for the estimation of aqueous solubility of new compounds. Table 8.1: Fragments for the GClogP model: The number of occurrences (N), group contribution values (mi) and statistical significance.

Code Name N m Sis. 0 Const. 0.148 0.077 1 YCH3 399 0.331 0.000 2 XCH3 1603 0.232 0.000 3 YYCH2 46 -0.217 0.138 4 YCH2 524 0.105 0.057 5 XCH2 2412 0.049 0.000 6 YYCH 43 -0.272 0.096 7 YCH 217 -0.246 0.000 8 XCH 783 -0.097 0.000 9 YYC 80 -0.010 0.952 10 YC 204 -0.286 0.001 11 XC 146 -0.227 0.005 12 CH2dbl 77 0.249 0.011 13 YCHdbl 146 0.013 0.833 14 XCHdbl 175 -0.069 0.367 15 YYCdbl 35 -0.284 0.036 16 YCdbl 76 -0.435 0.015 17 XCdbl 166 -0.134 0.119 18 CHtri 15 -0.092 0.742 19 YCtri 0 20 XCtri 17 -0.300 0.236 21 Callenic 1 -0.629 0.449 22 Car 2736 -0.210 0.000 23 Cbp 201 -0.449 0.000 24 CHar 4709 0.084 0.000 25 Cbr 458 -0.366 0.000 26 Nar 339 -0.228 0.000 27 Sar 24 -0.217 0.227 28 Oar 1 0.014 0.986 29 YF 35 0.142 0.188 30 XF 96 0.082 0.158 31 YCl 916 0.168 0.001 32 XCI 221 0.056 0.215 33 YBr 56 -0.082 0.365 34 XBr 42 0.008 0.935 35 YI 34 0.116 0.302 36 XI 10 0.000 0.999 37 YOH 188 0.360 0.000 38 XOH 391 -0.167 0.000 Table 8.1: Continued.

Code Name N nii Sig. 39 YYO 79 -0.343 0.004 40 YO 155 -0.029 0.678 41 XO 98 -0.120 0.080 42 YSH 5 -0.931 0.014 43 XSH 3 -0.280 0.555 44 YYS 16 0.866 0.004 45 YS 24 -0.049 0.808 46 XS 23 -0.371 0.029 47 YCHO 15 0.013 0.952 48 XCHO 9 -0.068 0.809 49 YYCO 45 -0.632 0.000 50 YCO 54 -0.480 0.000 51 XCO 87 -0.478 0.000 52 YCOOH 61 -0.226 0.036 53 XCOOH 120 -0.502 0.000 54 YCOO 67 -0.524 0.000 55 XCOO 93 -0.223 0.017 56 HCOO 6 -0.272 0.420 57 CarO 20 -0.535 0.006 58 YNH2 119 -0.462 0.000 59 XNH2 49 -0.994 0.000 60 YYNH 23 -0.970 0.000 61 YNH 52 -0.319 0.003 62 XNH 30 -0.086 0.532 63 YYN 29 -0.609 0.009 64 YN 36 -0.490 0.002 65 XN 66 0.193 0.101 66 NHdbl 0 67 YNdbl 3 -0.173 0.643 68 XNdbl 4 -0.971 0.209 69 YCN 14 -0.482 0.016 70 XCN 8 -0.636 0.035 71 YCONH2 13 -1.545 0.000 72 XCONH2 5 -0.878 0.019 73 YCONH 31 -1.035 0.000 74 XCONH 97 -0.640 0.000 75 HCONH 3 -1.147 0.003 76 YCON 10 -0.224 0.435 Table 8.1: Continued.

Code Name N mi Sig. 77 XCON 35 -0.578 0.000 78 HCON 0 79 YN02 76 -0.233 0.010 80 XN02 7 -0.809 0.011 81 OCON 4 -0.341 0.418 82 OCONH 26 -0.706 0.000 83 NHCONH2 5 -1.005 0.007 84 NHCONH 9 -1.144 0.000 85 NCONH2 4 -1.213 0.012 86 NCONH 18 -1.462 0.000 87 NCON 3 1.109 0.003 88 CONHCO 69 -1.294 0.000 89 CONCO 20 -0.450 0.033 90 COOCO 1 0.145 0.860 91 SO 6 -0.692 0.062 92 S02 17 -0.642 0.003 93 S02NH2 21 -1.073 0.000 94 S02NH 32 -0.848 0.000 95 SCON 8 -0.910 0.002 96 SCONH 0 97 CH=N 20 -0.586 0.003 98 C=N 37 -0.430 0.002 99 CH=NOH 1 -0.428 0.611 100 C=NOH 0 101 SCN 0 102 NCS 2 -0.112 0.846 103 P04 2 -0.618 0.289 104 P03S 0 105 P02S2 0 106 PS03 10 -0.810 0.003 107 PS02S 8 -0.755 0.005 108 P03 1 0.319 0.699 109 P02S 0 110 PS02 2 0.254 0.669 111 PSOS 0 112 Odbl_other 7 0.908 0.134 113 Pv5_other 1 -2.940 0.014 114 SdbI_other 16 -0.449 0.059 116

CHAPTER 9: COMPARISON OF AQUEOUS SOLUBILITY

PREDICTION MODELS

Comparison of different aqueous solubility prediction methods is challenging in that there are no objective criteria for evaluation. The following aspects are generally considered in choosing a suitable prediction method: accuracy, applicability and ease of use.

In this chapter, the accuracy of different aqueous solubility prediction models are evaluated and compared using three independent test sets from the literature. These include a set of 21 environmental and pharmaceutical compounds compiled by

Yalkowsky and Banerjee (1982), a test set of 38 pharmaceutical compounds used by

Huuskonen et al. (2000), and a set of 54 drug or drug-like compounds tested in a study by

Chen et al. (2002). One compound in test set 3, zidovudine, contains an azide group that is not defined in the AQUAFAC fragmentation scheme. This compound was therefore excluded from the evaluation. 117

PREDICTION COMPARISON

The predicted aqueous solubility for the three test sets of compounds is listed in

Appendices C, D and E respectively. Since melting point information was not found for a large portion of test set 3, it was not used for the evaluation of the General Solubility

Equation and the AQUAFAC approach. In Tables 9.1-9.4, the prediction results from the three models are compared to those of recently published methods and the General

Solubility Equation (GSE). H_MLR refers to Huuskonen's E-state indices with multiple linear regression model and H_ANN refers to his artificial neural network (ANN) model.

The models of both Klopman et al. and Kuhne et al. are group contribution methods. A recently published method by a group from Bristol-Myers Squibb (BMS) uses similar descriptors to those in the linear solvation energy relationship (LSER).

Although average absolute error is

The GClogP method provides surprisingly good results on test set 1, even better than

Huuskonen's ANN model. Prediction performance of the new method is comparable to that of Huuskonen's MLR model but not as good as his ANN model. The GClogP method did not do as well as the BMS model on test set 3, but still better than Klopman's group contribution model. Compared with the AQUAFAC method, the GSE method provides slightly better predictions on test set 1 but worse on test set 2. Overall, the AQUAFAC gives better predictions on combined data sets of 1 and 2 than both the GSE and the GClogP method.

One point that needs to be noted here is that, when evaluating the performance of a prediction method or comparing different methods, it is possible for a small test set to give a misleading result as quite different prediction errors are observed on the three test sets.

For possible future improvement of the AQUAFAC and the GClogP methods, some correction factors can be considered. Proximity takes into account the effects of halogen substitution on the same atom or neighboring atoms. Secondary substructural units take into account the connection of several functional groups. Formation of intramolecular hydrogen bond may change the contribution of individual functional groups. 119

Table 9.1: Comparison of prediction results of test set 1.

GClogP AQUAFAC GSE H_MLR H_ANN Klopman Kuhne

AAE 0.55 0.77 0.59 0.79 0.62 0.76 0.86

RMSE 0.68 0.93 0.83 1.05 0.81 0.99 1.09

Table 9.2: Comparison of prediction results of test set 2.

GCIogP AQUAFAC GSE H_MLR H_ANN

AAE 0.70 0.65 0.78 0.62 0.54

RMSE 1.05 0.81 1.08 0.74 0.62 Table 9.3: Comparison of prediction results of test set 3.

GClogP BMS Klopman

AAE 0.86 0.66 1.16

RMSE 1.14 0.79 1.58

Table 9.4: Comparison of prediction results of test sets 1 and 2.

GClogP AQUAFAC GSE H_MLR H_ANN

AAE 0.65 0.69 0.71 0.68 0.57

RMSE 0.94 0.85 1.00 0.86 0.69 121

SUMMARY

Three models for aqueous solubility prediction are evaluated. Overall, they provide similar prediction performances. The General Solubility Equation has the simplest form and relates the aqueous solubility to its two most critical determinants: octanol-water partition coefficient and melting point. Prediction by the GSE is most accurate on non- electrolytes and slightly worse on weak electrolytes. The extended AQUAFAC method provides an alternative to the GSE when melting point information is available. It gives slightly better predictions than the GSE. The GClogP method predicts aqueous solubility from compound structure alone and provides comparable prediction performances to the

GSE and the AQUAFAC methods. It can be a valuable tool for early drug discovery scientists. Inclusion of CLOG? as a parameter in the model provides better prediction than other group contribution methods. 122

APPENDIX A. Experimental Solubility Collection with Melting Point, log P and Predicted Solubility Using the General Solubility Equation.

Name CASRN CLOGP MLOGP MP("C) log logS„ Error Expt GSE Pred-Obs (4-chIoro-2-methylphenoxy) 94-74-6 2.70 2.75 118 -2.23 -3.13 -0.90 acetic acid (d,l)-alanine 302-72-7 -3.12 -2.96 289 0.243 0.98 0.74 (dl)-leucine 328-39-2 -1.67 -1.52 294.5 -1.1 -0.53 0.58 (l)-alanine 56-41-7 -3.12 -2.98 316 0.25 0.72 0.47 (l)-aspartic acid 56-84-8 -2.41 270 -1.41 0.46 1.87 (l)-leucine 61-90-5 -1.67 -1.52 294 -0.75 -0.52 0.23 (l)-norleucine 327-57-1 -1.54 -1.54 327 -0.975 -0.98 -0.01 (l)-phenylalanine 63-91-2 -1.56 -1.52 283 -0.804 -0.52 0.28 1,1,1,2-tetrachloroethane 630-20-6 3.03 2.62 -42 -2.18 -2.53 -0.35 1,1,1-trichloroethane 71-55-6 2.48 2.49 -33 -2.00 -1.98 0.02 1,1,1-trifluoro-2-propanol 374-01-6 0.83 0.71 -52 0.30 -0.33 -0.63 1,1,2,2-tetrabromoethane 79-27-6 3.20 -1 -2.72 -2.70 0.02 1,1,2,2-tetrachloroethane 79-34-5 2.64 2.62 -43 -1.76 -2.14 -0.38 1,1,2-trichloroethane 79-00-5 2.05 2.07 -36 -1.48 -1.55 -0.07 1,1,2-trichlorofluoroethane 811-95-0 2.59 -105 -3.04 -2.09 0.95 1,1,2-trichlorotrilluoroethane 76-13-1 3.29 3.16 -36 -3.04 -2.79 0.25 1,1,3,4,4-pentachloro-1,2- 112042-51-0 3.85 <25 -4.23 -3.35 0.88 butadiene 1,1,3-trimethylcyclohexane 3073-66-3 4.91 -66 -4.85 -4.41 0.44 1,1,3-trimethylcyclopentane 4516-69-2 4.35 -142 -4.48 -3.85 0.63 1,1-dichlorobutane 541-33-3 2.84 <25 -2.40 -2.34 0.06 1,1-dichloroethane 75-34-3 1.78 1.79 -97 -1.29 -1.28 0.01 1,1-dichloroethylene 75-35-4 2.37 2.13 -122 -1.64 -1.87 -0.23 1,1-diethoxyethane 105-57-7 0.93 0.84 -100 -0.43 -0.43 0.00 1,1-dimethoxyethane 25154-53-4 0.93 0.84 <25 -0.43 -0.43 0.00 1,1'-ethylidenebis(4-chloro- 3424-82-6 6.74 80 -6.36 -6.79 -0.43 benzene) 1,1'-iminobis-2-propanol 110-97-4 -0.85 -0.82 33 0.81 1.27 0.46 1,2,3,4,6,7,8- 67562-39-4 8.60 236 -11.48 -10.21 1.27 heptachlorodibenzofuran 1,2,3,4,6,7,8- 35822-46-9 9.21 265 -11.25 -11.11 0.14 heptachlorodibenzo-p-dioxin 1,2,3,4,7,8- 70648-26-9 8.48 226 -10.66 -9.99 0.67 hexachlorodibenzofuran 1,2,3,4,7,8-hexachlorodibenzo- 39227-28-6 8.61 273 -9.95 -10.59 -0.64 p-dioxin 1,2,3,4,7-pentachlorodibenzo-p- 39227-61-7 8.02 7.79 195 -9.48 -9.22 0.26 dioxin 1,2,3,4-tetrachlorobenzene 634-66-2 4.75 4.55 46 -4.38 -4.46 -0.08 1,2,3,4-tetrachlorodibenzo-p- 30746-58-8 7.31 7.18 185 -8.77 -8.4] 0.36 dioxin 1,2,3,4-tetrahydronaphthalene 119-64-2 3.71 3.49 -35 -3.47 -3.21 0.26 123

1,2,3,5-tetrachlorobenzene 634-90-2 4.75 4.66 54 -4.63 -4.54 0.09 1,2,3,5-tetrafluorobenzene 2367-82-0 2.57 -48 -2.31 -2.07 0.24 1,2,3,6,7,8- 57117-44-9 7.88 233 -10.33 -9.46 0.87 hexachlorodibenzofuran 1,2,3,6,7,8-hexahydropyrene 1732-13-4 5.34 133 -5.96 -5.92 0.04 1,2,3,7-tetrachlorodibenzo-p- 67028-18-6 7.05 175 -8.65 -8.05 0.60 dioxin 1,2,3,-trichlorobenzene 87-61-6 4.04 4.11 53 -4.08 -3.82 0.26 1,2,3,-trimethylbenzene 526-73-8 3.54 3.59 -25 -3.20 -3.04 0.16 1,2,3-tribromobenzene 608-21-9 4.33 87 -5.04 -4.45 0.59 1,2,3-trichloropropane 96-18-4 1.98 -15 -1.92 -1.48 0.44 1,2,4,5-tetrabromobenzene 636-28-2 5.19 5.13 182 -6.98 -6.26 0.72 1,2,4,5-tetrachlorobenzene 95-94-3 4.75 4.60 139 -5.47 -5.39 0.08 1,2,4,5-tetrafluorobenzene 327-54-8 2.57 4 -2.38 -2.07 0.31 1,2,4,5-tetramethylbenzene 95-93-2 4.04 4.00 80 -4.59 -4.09 0.50 1,2,4-tribromobenzene 615-54-3 4.53 41 -4.50 -4.19 0.31 1,2,4-trichlorobeiizene 120-82-1 4.16 3.97 16 -3.64 -3.66 -0.02 1,2,4-trichlorodibenzo-p-dioxin 39227-58-2 6.71 7.47 129 -7.53 -7.25 0.28 1,2,4-trimethylbenzene 95-63-6 3.59 3.63 -44 -3.33 -3.09 0.24 1,2-benzanthracene 56-55-3 5.66 5.44 160 -7.19 -6.51 0.68 1,2-benzenediamine 95-54-5 -0.31 0.15 101 -0.42 0.05 0.47 1,2-benzenediol 120-80-9 0.88 0.88 104 0.62 -1.17 -1.79 1,2-dibromo-3-chlorpropane 96-12-8 2.26 <25 -2.38 -1.76 0.62 1,2-dibromobenzene 583-53-9 3.67 3.64 4 -3.50 -3.17 0.33 1,2-dibromoethane 106-93-4 1.74 1.96 10 -1.68 -1.24 0.44 1,2-dibronioethylene 540-49-8 1.95 <25 -1.32 -1.45 -0.13 1,2-dibromopropane 78-75-1 2.27 -55 -2.15 -1.77 0.38 1,2-dichlorobenzene 95-50-1 3.45 3.43 -15 -3.05 -2.95 0.10 1,2-dichloroethane 107-06-2 1.46 1.47 -35 -1.06 -0.96 0.10 1,2-dichloroethylene 540-59-0 1.77 1.86 -57 -1.30 -1.27 0.03 1,2-dichloropropane 78-87-5 1.99 1.99 -100 -1.60 -1.49 0.11 1,2-dichlorotetrafluoroethane 76-14-2 2.85 2.82 -94 -2.74 -2.35 0.39 1,2-diethoxyethane 629-14-1 0.93 0.66 -74 -0.77 -0.43 0.34 1,2-diethylbenzene 135-01-3 4.15 3.72 -31 -3.28 -3.65 -0.37 1,2-diiodoethylene 590-27-2 2.51 -11 -3.22 -2.01 1.21 1,2-dimethoxydiethyl ether 24424-51-9 -0.06 <25 0.88 0.56 -0.32 1,2-dimethoxyethane 110-71-4 0.93 0.66 -58 -0.77 -0.43 0.34 1,2-dimethylcyclohexane 583-57-3 4.39 <25 -4.30 -3.89 0.41 1,2-dinitrobenzene 528-29-0 1.63 1.69 118 -3.10 -2.06 1.04 1,2-propylene oxide 75-56-9 0.18 0.03 -112 -0.59 0.32 0.91 1,3,5-tribromobenzene 626-39-1 4.73 4.51 121 -5.60 -5.19 0.41 1,3,5-trichlorobenzene 108-70-3 4.28 4.19 -4.44 1,3,5-trimethylbenzene 108-67-8 3.64 3.58 -45 -3.40 -3.14 0.26 1,3,5-trinitrobenzene 99-35-4 1.37 1.18 123 -2.89 -1.85 1.04 1,3,6,8-tetrachlorodibenzo-p- 33423-92-6 7.55 6.29 219 -9.00 -8.99 0.01 dioxin 1,3-benzenediol 108-46-3 0.81 0.80 110 0.81 -1.16 -1.97 1,3-butadiene 106-99-0 1.90 1.99 -109 -1.87 -1.40 0.47 1,3-dibromobenzene 108-36-1 3.87 3.75 -7 -3.54 -3.37 0.17 124

1,3-dibromopropane 109-64-8 1.99 2.37 -34 -2.08 -1.49 0.59 1,3-dichloro-2-propanol 96-23-1 0.20 -4 -0.11 0.30 0.41 l,3-dichloro-5,5- 118-52-5 0.47 145 -2.6 -1.17 1.43 dimethylhydantoin 1,3-dichlorobenzene 541-73-1 3.57 3.53 -25 -3.04 -3.07 -0.03 1,3-dichloropropane 142-28-9 1.71 2.00 -99 -1.62 -1.21 0.41 1,3-difluorobenzene 372-18-9 2.43 2.21 -59 -2.00 -1.93 0.07 1,3-dimethylnaphthalene 575-41-7 4.31 4.42 -5 -4.29 -3.81 0.48 1,3-dinitrobenzene 99-65-0 1.63 1.49 90.02 -2.29 -1.78 0.51 1,4,5-tritnethylnaphthalene 2131-41-1 4.81 4.90 62 -4.92 -4.68 0.24 1,4-benzenediamine 106-50-3 1.08 141 -0.38 -1.74 -1.36 1,4-benzenediol 123-31-9 0.81 0.59 170 -0.17 -1.76 -1.59 1,4-cyclohexadiene 628-41-1 2.39 2.30 -49 -1.97 -1.89 0.08 1,4-dibromobenzene 106-37-6 3.87 3.79 87 -4.07 -3.99 0.08 1,4-diethylbenzene 105-05-5 4.20 -43 -3.75 -3.70 0.05 1,4-difluorobenzene 540-36-3 2.43 -13 -1.97 -1.93 0.04 1,4-diiodobenzene 624-38-4 4.39 4.11 131 -5.37 -4.95 0.42 1,4-dimethylcyclohexane 589-90-2 4.39 -87 -4.47 -3.89 0.58 1,4-dimethylnaphthalene 571-58-4 4.31 4.37 8 -4.14 -3.81 0.33 1,4-dinitrobenzene 100-25-4 1.63 1.47 173 -3.39 -2.61 0.78 1,4-pentadiene 591-93-5 2.37 2.47 -148 -2.09 -1.87 0.22 1,5-dimethylnaphthalene 571-61-9 4.31 4.38 81 -4.69 -4.37 0.32 1,5-hexadiene 592-42-7 2.90 2.87 -141 -2.68 -2.40 0.28 1,7-phenanthroline 230-46-6 2.05 2.51 79 -2.68 -2.09 0.59 11-alpha-hydroxyprogesterone 80-75-1 2.85 2.36 165 -3.82 -3.75 0.07 11-aminoundecanoic acid 2432-99-7 0.41 188 -2.7 -1.54 1.16 13h-dibenzo(a,i)carbazole 239-64-5 5.51 216 -7.41 -6.92 0.49 17-methyl testosterone 58-18-4 3.74 3.36 164 -3.97 -4.63 -0.66 1-acetylurea 591-07-1 -1.03 218 -0.9 -0.40 0.50 1-aminoacridine 578-06-3 2.86 2.47 180 -4.22 -3.91 0.31 l-anthranol 529-86-2 3.82 158 -4.73 -4.65 0.08 1-bromo-2-chlorobenzene 694-80-4 3.58 -12 -3.19 -3.08 0.11 1 -bromo-2-methylpropane 78-77-3 2.53 -118 -2.43 -2.03 0.40 1-bromo-3-chloropropane 109-70-6 1.85 -59 -1.85 -1.35 0.50 1-bromo-3-methylbutane 107-82-4 3.06 -112 -2.89 -2.56 0.33 1-bromo-4-chlorobenzene 106-39-8 3.72 3.54 67 -3.63 -3.64 -0.01 1 -bromobutane 109-65-9 2.66 2.75 -112 -2.37 -2.16 0.21 l-bromoheptane 629-04-9 4.25 4.36 -58 -4.43 -3.75 0.68 l-bromohexane 111-25-1 3.72 3.80 -85 -3.81 -3.22 0.59 1-bromonaphthalene 90-11-9 4.18 -1 -4.19 -3.68 0.51 1-bromooctane 111-83-1 4.78 4.89 -55 -5.06 -4.28 0.78 1-bromopentane 110-53-2 3.19 3.37 -95 -3.07 -2.69 0.38 1 -bromopropane 106-94-5 2.13 2.10 -108 -1.73 -1.63 0.10 l-butanol 71-36-3 0.82 0.88 -90 0.00 -0.32 -0.32 1-butene 106-98-9 2.33 2.40 -185 -1.94 -1.83 0.11 1 -butyltheobromine 1.53 -1.63 1 -butyne 107-00-6 1.45 1.46 -126 -1.24 -0.95 0.29 1 -chloro-2-bronioethane 107-04-0 1.60 -16 -1.32 -1.10 0.22 1 -chloro-2-methylpropane 513-36-0 2.39 -131 -2.00 -1.89 0.11 125 l-chlorobutane 109-69-3 2.52 2.64 -123 -2.03 -2.02 0.01 1-chlorodibenzo-p-dioxin 39227-53-7 5.15 5.05 98 -5.72 -5.38 0.34 1-chloroheptane 629-06-1 4.11 4.15 -70 -3.99 -3.61 0.38 1-chlorohexane 544-10-5 3.58 3.66 -94 -3.12 -3.08 0.04 1-chloronaphthalene 90-13-1 4.03 4.10 -20 -3.93 -3.53 0.40 1-chloropentane 543-59-9 3.05 3.11 -99 -2.73 -2.55 0.18 1-chloropropane 540-54-5 1.99 2.04 -122 -1.47 -1.49 -0.02 1 -decanol 112-30-1 4.00 4.57 6 -3.63 -3.50 0.13 1-decene 872-05-9 5.50 -66 -5.51 -5.00 0.51 1-ethylnaphthalene 1127-76-0 4.34 4.39 -14 -4.16 -3.84 0.32 1 -ethyltheobromine 39832-36-5 -0.15 -0.15 165 -0.72 -0.75 -0.03 1-fluoro-4-iodobenzene 352-34-1 3.41 -20 -3.13 -2.91 0.22 1-heptanol 111-70-6 2.41 2.72 -36 -1.81 -1.91 -0.10 1-heptene 592-76-7 3.91 3.99 -119 -3.73 -3.41 0.32 1-heptyne 628-71-7 3.04 3.32 -81 -3.01 -2.54 0.47 1-hexadecanol 124-29-8 7.17 56 -7.00 -6.98 0.02 1-hexanol 111-27-3 1.88 2.03 -52 -1.23 -1.38 -0.15 l-hexen-3-one 1629-60-3 1.04 <25 -0.83 -0.54 0.29 1-hexene 592-41-6 3.38 3.39 -140 -3.23 -2.88 0.35 l-hexene-3-ol 4798-44-1 1.38 <25 -0.59 -0.88 -0.29 1-hexyne 693-02-7 2.51 2.73 -132 -2.20 -2.01 0.19 1-hydroxychlordene 2597-11-7 3.36 201 -5.46 -4.62 0.84 1 -iodobutane 542-69-8 3.05 3.08 -103 -2.96 -2.55 0.41 1 -iodoheptane 4282-40-0 4.64 4.70 -48 -4.81 -4.14 0.67 1-iodonaphthalene 90-14-2 4.44 5 -4.55 -3.94 0.61 1-iodopropane 107-08-4 2.52 2.54 -101 -2.29 -2.02 0.27 1-methyl fluorene 1730-37-6 4.57 4.97 87 -5.22 -4.69 0.53 1-methyl uric acid 708-79-2 -0.61 -0.57 400 -1.56 -2.64 -1.08 1-methylcyclohexene 591-49-1 3.39 -120 -3.27 -2.89 0.38 1-methylnaphthalene 90-12-0 3.81 3.87 -22 -3.69 -3.31 0.38 1 -methylphenanthrene 832-69-9 4.99 5.08 123 -5.85 -5.47 0.38 1 -methyluracil 615-77-0 -1.20 -1.2 238 -0.8 -0.43 0.37 1-naphthaleneacetic acid 86-87-3 2.59 132 -2.65 -3.16 -0.51 1-naphthol 90-15-3 2.65 2.84 96 -2.22 -2.86 -0.64 1-naphthyl isothiocyanate 551-06-4 4.48 4.34 58 -4.6 -4.31 0.29 1 -naphthylamine 134-32-7 2.09 2.25 49 -1.92 -1.83 0.09 1-nitronaphthalene 86-57-7 3.06 3.19 59 -3.54 -2.90 0.64 1 -nitropropane 108-03-2 0.77 0.87 <25 -0.80 -0.27 0.53 1 -nitroso-1-ethy lurea 759-73-9 0.32 0.23 103 -0.96 -0.60 0.36 1 -nitroso-1 -methylurea 684-93-5 -0.20 -0.03 124 -0.85 -0.29 0.56 1 -nonanol 143-08-8 3.47 3.67 -7 -3.01 -2.97 0.04 1 -nonene 124-11-8 4.97 5.15 -81 -5.05 -4.47 0.58 1-nonyne 3452-09-3 4.10 4.51 -50 -4.24 -3.60 0.64 1-octadecanol 112-92-5 8.43 61 -8.40 -8.29 0.11 1 -octanol 111-87-5 2.94 3.00 -15 -2.39 -2.44 -0.05 1-octene 111-66-0 4.44 4.57 -102 -4.44 -3.94 0.50 1-octyne 629-05-0 3.57 3.92 -80 -3.66 -3.07 0.59 1-pentadecanol 629-76-5 6.64 46 -6.35 -6.35 0.00 1-pentanol 71-41-0 1.35 1.56 -108 -0.61 -0.85 -0.24 126

1-pentene 109-67-1 2.86 2.80 -165 -2.68 -2.36 0.32 1-phenylethanol 98-85-1 1.41 1.42 20 -0.92 -0.91 0.01 1-propanol 71-23-8 0.29 0.25 -126 0.62 0.21 -0.41 1-propene 115-07-1 1.80 1.77 -185 -2.20 -1.30 0.90 1-propyltheobromine 63906-63-8 1.00 -1.21 1-tetradecanol 112-72-1 6.11 6.36 40 -5.84 -5.76 0.08 2-(lh)quinolinone 59-31-4 2.32 199 -2.14 -3.56 -1.42 2-(2,4,5- 93-72-1 3.86 3.8 176 -3.31 -4.87 -1.56 trichlorophenoxy)propionic acid 2-(4-aminophenyl)-6-methyl- 92-36-4 3.64 191 -3.68 -4.80 -1.12 benzothiazole 2,2,2,o,p'- 789-02-6 6.76 74 -6.80 -6.75 0.05 pentachloroethylidenebisbenzene 2,2,2-trichloro-1,1-ethanediol 302-17-0 0.71 0.99 57 0.72 -0.53 -1.25 2,2',3,3',4,4',5,5' 6'- 83992-73-8 10.26 158 -10.55 -11.09 -0.54 nonachlorodiphenyl ether 2,2',3,3',4,4',5,5',6- 40186-72-9 9.34 9.14 205 -10.26 -10.64 -0.38 nonachlorobiphenyl 2,2',3,3',4,4',5,5'- 35694-08-7 8.99 7.40 156 -9.47 -9.80 -0.33 octachlorobiphenyl 2,2',3,3',4,4',5,5'- 57379-40-5 9.00 126 -10.13 -9.51 0.62 octachlorodiphenyl ether 2,2',3,3',4,4',5- 71585-40-5 8.29 104 -9.12 -8.58 0.54 heptachlorodiphenyl ether 2,2',3,3',4,4',6- 52663-71-5 7.91 122 -8.30 -8.38 -0.08 heptachlorobiphenyl 2,2',3,3',4,4'-hexachlorobiphenyl 38380-07-3 7.33 7.32 152 -7.79 -8.10 -0.31 2,2',3,3',4,4'-hexachlorodiphenyl 71585-39-2 7.58 138 -8.14 -8.21 -0.07 ether 2,2',3,3',4,5,5',6,6'- 52663-77-1 9.21 204 -10.41 -10.50 -0.09 nonachlorobiphenyl 2,2',3,3',4,5,5'6'- 85918-38-3 8.89 205 -10.10 -10.19 -0.09 octachlorodiphenyl ether 2,2',3,3',4',5,6- 83992-71-6 8.83 81 -9.09 -8.89 0.20 heptachlorodiphenyl ether 2,2',3,3',4,5-hexachlorobiphenyl 55215-18-4 7.45 7.32 101 -7.79 -7.71 0.08 2,2',3,3',4-pentachlorobiphenyl 52663-62-4 6.73 119 -7.05 -7.17 -0.12 2,2',3,3',5,5',6,6'- 2136-99-4 8.73 7.73 160 -9.15 -9.58 -0.43 octachlorobiphenyl 2,2',3,3',5,5'-hexachlorobiphenyl 35694-04-3 7.69 7.07 65 -6.96 -7.59 -0.63 2,2',3,3',5',6-hexachlorobiphenyl 52704-70-8 7.32 7.25 132 -7.90 -7.89 0.01 2,2',3,3',6,6'-hexachlorobiphenyl 38411-22-2 7.07 7.12 114 -8.09 -7.46 0.63 2,2',3,3'-tetrachlorobiphenyl 38444-93-8 6.26 5.60 121 -7.28 -6.72 0.56 2,2',3,4,4',5,5'6- 83992-75-0 8.83 168 -10.14 -9.76 0.38 octachlorodiphenyl ether 2,2',3,4,4',5,5'- 83992-69-2 8.91 89 -9.50 -9.05 0.45 heptachlorodiphenyl ether 2,2',3,4,4',5',6- 52663-69-1 8.27 7.30 83 -7.92 -8.35 -0.43 heptachlorobiphenyl 2,2',3,4,4',5'-hexachlorobiphenyl 35065-28-2 7.69 7.25 80 -7.69 -7.74 -0.05 2,2',3',4,4',5-hexachlorodiphenyl 71585-38-1 7.82 79 -8.44 -7.86 0.58 ether 127

2,2',3,4,4',5'-hexachlorodiphenyl 71585-36-9 7.70 69 -8.31 -7.64 0.67 ether 2,2',3,4,4',6'-hexachlorodiphenyl 106220-83-1 7.59 121 -8.10 -8.05 0.05 ether 2,2',3,4,4'-pentachlorodiphenyl 71585-37-0 7.11 66 -7.44 -7.02 0.42 ether 2,2',3,4,5,5',6- 52712-05-7 8.27 7.00 147 -8.94 -8.99 -0.05 heptachlorobiphenyl 2,2',3,4',5,5',6- 52663-68-0 8.27 7.00 147 -8.94 -8.99 -0.05 heptachlorobiphenyl 2,2',3,4',5,5',6- 109828-23-1 8.83 118 -9.05 -9.26 -0.21 heptachlorodiphenyl ether 2,2',3,4,5,5 '-hexachlorobiphenyl 52712-04-6 7.69 7.19 85 -7.68 -7.79 -0.11 2,2',3,4,5 '-hexachlorobiphenyl 38380-02-8 6.85 6.85 112 -6.97 -7.22 -0.25 2,2',3,4,5-pentachlorobiphenyl 55312-69-1 6.97 100 -7.21 -7.22 -0.01 2,2',3,4,6-pentachlorobiphenyl 55215-17-3 6.84 100 -7.43 -7.09 0.34 2,2',3,5,5 ',6-hexachlorobipheny 1 52663-63-5 7.56 6.85 100 -7.42 -7.81 -0.39 2,2',3,5'-tetrachlorobiphenyl 41464-39-5 6.26 6.00 47 -6.47 -5.98 0.49 2,2,3-trimethyl-3-pentanol 7294-05-5 2.33 -6 -1.27 -1.83 -0.56 2,2,3-trimethylbutane 464-06-2 4.01 <25 -4.36 -3.51 0.85 2,2',4,4',5,5 '-hexachlorobiphenyl 35065-27-1 7.69 6.90 103 -7.63 -7.97 -0.34 2,2',4,4',5,5'-hexachlorodiphenyl 71859-30-8 8.16 114 -8.36 -8.55 -0.19 ether 2,2',4,4',5,6'-hexachlorodiphenyl 106220-81-9 7.71 95 -8.04 -7.91 0.13 ether 2,2',4,4',6,6'-hexachlorobiphenyl 33979-03-2 7.31 7.00 113 -8.20 -7.69 0.52 2,2',4,4'-tetrachlorobiphenyl 2437-79-8 6.38 6.29 83 -6.51 -6.46 0.05 2,2',4,4'-tetrachlorodiphenyl 28076-73-5 6.97 69 -6.82 -6.91 -0.09 ether 2,2',4,5,5'-pcb 37680-73-2 6.97 6.85 77 -6.77 -6.99 -0.22 2,2',4,5'-tetrachlorobiphenyl 41464-40-8 6.38 6.10 64 -6.57 -6.27 0.30 2,2',4,6,6'-pentachlorobiphenyl 56558-16-8 6.59 5.81 85 -7.32 -6.69 0.63 2,2,4-trimethylpentane 540-84-1 4.54 -107 -4.67 -4.04 0.63 2,2',5,5'-tetrabromobiphenyl 59080-37-4 6.88 143 -8.06 -7.56 0.50 2,2',5,5'-tetrachlorobiphenyl 35693-99-3 6.38 6.26 87 -6.23 -6.50 -0.27 2,2',5,6'-tetrachlorobiphenyl 41464-41-9 6.13 5.50 103 -6.80 -6.41 0.39 2,2',5-trichlorobiphenyl 37680-65-2 5.67 5.60 44 -5.65 -5.36 0.29 2,2,5-trimethylhexane 3522-94-9 5.06 -106 -5.05 -4.56 0.49 2,2',6,6'-tetrachlorobiphenyl 15968-05-5 5.88 5.94 198 -7.39 -7.11 0.28 2,2'-bipyridine 366-18-7 1.56 1.73 72 -1.42 -1.53 -0.11 2,2'-dichlorobiphenyl 13029-08-8 4.96 4,90 61 -5.27 -4.82 0.45 2,2-dimethyl- 1-butanol 1185-33-7 1.62 -35 -1.04 -1.12 -0.08 2,2-dimethyl-1-pentanol 2370-12-9 2.15 <25 -1.52 -1.65 -0.13 2,2-dimethyl-1-propanol 75-84-3 1.09 1.31 50 -0.40 -0.84 -0.44 2,2-dimethyl-3-pentanol 3970-62-5 1.93 -5 -1.15 -1.43 -0.28 2,2-diinethylbutane 75-83-2 3.61 3.82 -100 -3.55 -3.11 0.44 2,2-diinethylpentane 590-35-2 4.14 -124 -4.36 -3.64 0.72 2,3,3',4,4',5-hexachlorobiphenyl 38380-08-4 7.82 7.57 129 -7.82 -8.36 -0.54 2,3,3',4,4',5-hexachlorodiphenyl 109828-22-0 8.32 135 -8.78 -8.92 -0.14 ether 128

2,3,3',4,4',6-hexachlorobiphenyl 74472-42-7 7.69 7.25 107 -7.66 -8.01 -0.35 2,3,3',4,4'-pentachlorodiphenyl 85918-31-6 7.45 65 -7.67 -7.35 0.32 ether 2,3,3',4',5,6-hexachlorobiphenyl 74472-44-9 7.57 122 -7.83 -8.04 -0.21 2,3,3'4,4',5,6- 83992-70-5 8.99 169 -9.46 -9.93 -0.47 heptachlorodiphenyl ether 2,3,3-trimethyl-2-butanol 594-83-2 1.80 17 -0.72 -1.30 -0.58 2,3 ',4,4',5,5 '-hexachlorodiphenyl 131138-20-0 8.20 84 -8.72 -8.29 0.43 ether 2,3,4,4',5,6-hexachlorodiphenyl 63646-56-0 7.34 146 -8.94 -8.05 0.89 ether 2,3',4,4',5-pentachlorobiphenyl 31508-00-6 7.10 7.12 109 -7.39 -7.44 -0.05 2,3',4,4'-tetrachlorobiphenyl 32598-10-0 6.51 5.90 128 -6.89 -7.04 -0.15 2,3,4,5,6-pentachlorobiphenyl 18259-05-7 7.09 6.74 124 -7.78 -7.58 0.20 2,3,4,5-tetrachloroanisole 938-86-3 4.64 4.50 88 -5.26 -4.77 0.49 2,3,4,5-tetrachlorobiphenyl 33284-53-6 6.51 6.41 91 -7.16 -6.67 0.49 2,3',4',5-tetrachlorobiphenyl 32598-11-1 6.51 6.39 104 -7.25 -6.80 0.45 2,3,4,5-tetrachlorophenol 4901-51-3 4.18 4.21 116 -3.15 -4.59 -1.44 2,3,4,5-tetraiodopyrrol 87-58-1 4.30 140 -3.46 -4.95 -1.49 2,3,4,6-tetrachlorophenol 58-90-2 4.09 4.12 70 -3.10 -4.04 -0.94 2,3,4,7,8- 57117-31-4 7.29 6.92 196 -9.16 -8.50 0.66 pentachlorodibenzofuran 2,3,4-trichloroanisole 54135-80-7 4.11 4.03 70 -4.29 -4.06 0.23 2',3,4-trichlorobipheny1 38444-86-9 5.80 5.87 60 -6.29 -5.65 0.64 2,3,4'-trichlorobiphenyl 38444-85-8 5.80 5.42 69 -6.26 -5.74 0.52 2,3,4-trichlorophenol 15950-66-0 3.58 79 -2.67 -3.62 -0.95 2,3,4-trimethylpentane 565-75-3 4.54 -109 -4.80 -4.04 0.76 2,3,5,6-tetrachlorophenol 935-95-5 3.97 3.88 114 -3.37 -4.36 -0.99 2,3',5-trichlorobiphenyl 38444-81-4 5.92 5.76 40 -6.01 -5.57 0.44 2,3,5-trichlorophenol 933-78-8 3.58 57 -2.67 -3.40 -0.73 2,3,6-trichlorobiphenyl 55702-45-9 5.67 5.67 56 -6.29 -5.48 0.81 2,3,6-trichlorophenol 933-75-5 3.37 3.77 56 -2.64 -3.18 -0.54 2,3,7,8-tetrachlorodibenzofuran 51207-31-9 6.70 6.53 227 -8.86 -8.22 0.64 2,3,7,8-tetrachlorodibenzo-p- 1746-01-6 7.31 6.42 305 -10.22 -9.61 0.61 dioxin 2,3-benzofluorene 243-17-4 5.25 5.77 208 -7.73 -6.58 1.15 (benzo[b]fluorene) 2,3-dichloro-2-methylbutane 507-45-9 2.91 <25 -2.69 -2.41 0.28 2,3-dichloroanisole 1984-59-4 3.32 3.24 32 -3.31 -2.89 0.42 2,3-dichlorobutane 7581-97-7 2.52 <25 -2.35 -2.02 0.33 2,3-dichlorodibenzo-p-dioxin 29446-15-9 5.74 160 -7.23 -6.59 0.64 2,3-dichloronitrobenzene 3209-22-1 3.11 3.05 61 -3.48 -2.97 0.51 2,3-dichlorophenol 576-24-9 2.84 2.84 59 -1.30 -2.68 -1.38 2,3-dimethyl-1,3-butadiene 513-81-5 2.70 -76 -2.40 -2.20 0.20 2,3-dimethyl-1-butanol 594-60-5 1.40 1.48 -14 -0.39 -0.90 -0.51 2,3-dimethyl-2-pentanol 4911-70-0 1.93 <25 -0.89 -1.43 -0.54 2,3-diinethyl-3-pentanol 595-41-5 1.93 <25 -0.85 -1.43 -0.58 2,3-ditnethylbutane 79-29-8 3.61 3.42 -129 -3.63 -3.11 0.52 2,3-dimethylbutanol 19550-30-2 1.62 <25 -0.39 -1.12 -0.73 2,3-diniethylnaphthalene 581-40-8 4.26 4.40 102 -4.72 -4.53 0.19 129

2,3-diinethylpentane 565-59-3 4.14 <25 -4.28 -3.64 0.64 2,3-dimethylpyridine 583-61-9 1.59 -17 0.38 -1.09 -1.47 2,3-xylenol 526-75-0 2.42 2.48 75 -1.43 -2.42 -0.99 2,4,4',6-tetrachlorobiphenyl 32598-12-2 6.38 93 -6.94 -6.56 0.38 2,4,4'-trichlorobiphenyl 7012-37-5 5.92 5.62 57 -6.21 -5.74 0.47 2,4,4'-trichlorodiphenyl ether 59039-21-3 6.41 50 -6.22 -6.16 0.06 2,4,5,6-tetrachloroanisole 938-22-7 4.53 5.75 64 -5.13 -4.42 0.71 2,4,5-t 93-76-5 3.33 3.31 158 -2.96 -4.16 -1.20 2,4,5-trichlorobiphenyl 15862-07-4 5.92 5.90 76 -6.27 -5.93 0.34 2,4',5-trichlorobiphenyl 16606-02-3 5.92 5.79 67 -6.25 -5.84 0.41 2,4,5-trichlorodiphenyl ether 52322-80-2 6.29 61 -6.58 -6.15 0.43 2,4,5-trichlorophenoI 95-95-4 3.58 3.72 68 -2.21 -3.51 -1.30 2,4,6-tribromobiphenyl 59080-33-0 6.02 66 -7.30 -5.93 1.37 2,4,6-trichloroanisole 87-40-1 3.93 4.04 61 -4.20 -3.79 0.41 2,4,6-trichlorobiphenyl 35693-92-6 5.67 5.60 63 -6.00 -5.55 0.46 2,4,6-trichlorophenol 88-06-2 3.37 3.69 69.5 -2.34 -3.32 -0.98 2,4,6-trimethylphenol 527-60-6 2.97 71 -2.05 -2.93 -0.88 2,4,6-trinitrotoluene 118-96-7 1.71 1.60 80.9 -3.22 -1.77 1.45 2,4-d 94-75-7 2.73 2.81 138 -2.51 -3.36 -0.85 2,4-db 94-82-6 3.42 3.53 117 -3.73 -3.84 -0.11 2,4'-dichlorobiphenyl 34883-43-7 5.21 5.10 43 -5.28 -4.89 0.39 2,4-dichlorobiphenyl 33284-50-3 5.21 5.10 24 -5.25 -4.71 0.54 2,4'-dichlorodiphenyl ether 6903-65-7 5.69 31 -5.52 -5.25 0.27 2,4-dichlorophenol 120-83-2 2.96 3.06 45 -1.55 -2.66 -1.11 2,4-diinethyl-1-pentanol 6305-71-1 2.15 <25 -1.60 -1.65 -0.05 2,4-dimethyl-2-pentanol 625-06-9 1.93 <25 -0.92 -1.43 -0.51 2,4-dimethyl-3-pentanol 600-36-2 1.93 -70 -1.22 -1.43 -0.21 2,4-dimethylpentane 108-08-7 4.14 -119 -4.26 -3.64 0.62 2,4-dimethylphenol 105-67-9 2.47 2.30 27.5 -1.19 -2.00 -0.81 2,4-diinethylpyridine 108-47-4 1.64 -60 0.38 -1.14 -1.52 2,4-diniethyIquinoline 1198-37-4 3.03 <25 -1.94 -2.53 -0.59 2,4-dinitrotoluene 121-14-2 2.05 1.98 69 -2.82 -1.99 0.83 2,4-octadione 14090-87-0 1.13 -35 -1.56 -0.63 0.93 2,4-pentanedione 123-54-6 -0.46 0.40 -23 0.22 0.96 0.74 2,5-dichlorobiphenyl 34883-39-1 5.21 5.16 23 -5.27 -4.71 0.56 2,5-dimethoxybenzaldehyde 93-02-7 1.79 1.91 52 -2.32 -1.56 0.76 2,5-dimethylpiperazine 106-55-8 -0.45 102 0.49 0.18 -0.31 2,5-dimethylpyridine 589-93-5 1.64 -15 0.4 -1.14 -1.54 2,5-piperazinedione 106-57-0 -1.72 233 -0.83 0.14 0.97 2,5-xylenol 95-87-4 2.47 2.33 74 -1.54 -2.46 -0.92 2,6-dichloroanisole 1984-65-2 3.21 3.14 31 -3.10 -2.77 0.33 2,6-dichlorobenzonitrile 1194-65-6 2.74 2.74 144 -3.98 -3.43 0.55 2,6-dichlorobenzyl alcohol 15258-73-8 1.79 97 -2.10 -2.01 0.09 2,6-dichlorobiphenyl 33146-45-1 4.96 5.00 35 -4.97 -4.56 0.41 2,6-dichlorodiphenyl ether 28419-69-4 5.69 39 -5.06 -5.33 -0.27 2,6-dichlorophenol 87-65-0 2.63 2.75 67 -1.79 -2.55 -0.76 2,6-diethylaniline 579-66-8 2.87 3 -2.35 -2.37 -0.02 2,6-dimethyl-4-pyrimidinamine 461-98-3 0.63 0.39 180 -1.28 -1.68 -0.40 2,6-dimethylnaphthalene 581-42-0 4.31 4.31 109 -4.89 -4.65 0.24 130

2,6-dimethylphenol 576-26-1 2.47 2.36 49 -1.29 -2.21 -0.92 2,6-dimethylpyridine 108-48-5 1.64 1.68 -6.1 0.45 -1.14 -1.59 2,6-dinitrotoluene 606-20-2 1.97 2.10 65 -3.00 -1.87 1.13 2,7-dichlorodibenzo-p-dioxin 33857-26-0 5.86 201 -7.83 -7.12 0.71 2,7-dimethylquinoline 93-37-8 3.03 61 -1.94 -2.89 -0.95 2,8-dichlorodibenzofuran 5409-83-6 5.51 5.65 184 -7.21 -6.60 0.61 2,8-dichlorodibenzo-p-dioxin 38964-22-6 5.86 6.38 151 -7.18 -6.62 0.56 2-aminiopteridine 700-81-2 -0.83 -2.3 2-aniinoanthracene 613-13-8 3.26 239 -5.17 -4.90 0.27 2-aminothiazole 96-50-4 0.22 0.38 93 -0.36 -0.40 -0.04 2-bromobenzoic acid 88-65-3 2.20 2.20 149 -2.28 -2.94 -0.66 2-bromofluorobenzene 1072-85-1 3.15 14 -2.70 -2.65 0.05 2-bronionaphthalene 580-13-2 4.18 54 -4.40 -3.97 0.43 2-bromopropane 75-26-3 2.13 2.14 -89 -1.59 -1.63 -0.04 2-broniotoluene 95-46-5 3.50 -26 -2.23 -3.00 -0.77 2-butoxyethanol 111-76-2 0.84 0.83 -74 -0.42 -0.34 0.08 2-butyl benzene 135-98-8 4.10 -78 -3.89 -3.60 0.29 2-chloro-2-methylbutane 594-36-5 2.92 2.52 -74 -2.51 -2.42 0.09 2-chloroacetanilide 533-17-5 1.28 1.28 88 -1.40 -1.41 -0.01 2-chloroanisole 766-51-8 2.75 2.68 -27 -2.46 -2.25 0.21 2-chlorobutane 78-86-4 2.52 2.33 -140 -1.96 -2.02 -0.06 2-chlorodibenzo-p-dioxin 39227-54-8 5.15 5.45 89 -5.82 -5.29 0.53 2-chlorodiphenyl ether 2689-07-8 5.09 45 -4.78 -4.79 -0.01 2-chloronaphthalene 91-58-7 4.03 4.14 60 -4.14 -3.88 0.26 2-chloropentane 625-29-6 3.05 -138 -2.63 -2.55 0.08 2-chlorophenol 95-57-8 2.15 2.15 <25 -1.06 -1.65 -0.59 2-chlorophenoxyacetic acid 614-61-9 1.97 1.86 146 -2.16 -2.68 -0.52 2-chloropropane 75-29-6 1.99 1.90 -117 -1.41 -1.49 -0.08 2-chlorpteridine -0.14 -0.7 2-cyanoguanidine 461-58-5 -1.15 -1.15 209 -0.31 -0.19 0.12 2-decanone 693-54-9 3.49 3.73 4 -3.31 -2.99 0.32 2-dimethylaminopteridine 41047-52-3 0.07 0.36 2-ethyl pyridine 100-71-0 1.67 1.69 -63 0.51 -1.17 -1.68 2-ethyl-1,3-hexanediol 94-96-2 1.26 -40 -0.54 -0.76 -0.22 2-ethyl-1-butanol 97-95-0 1.75 <25 -1.17 -1.25 -0.08 2-ethyl-1-hexanol 104-76-7 2.81 -76 -2.11 -2.31 -0.20 2-ethyl-2-propanol 75-85-4 1.00 0.89 -12 -0.20 -0.50 -0.30 2-ethylanthracene 52251-71-5 5.52 5.85 150 -6.89 -6.27 0.62 2-ethylbutyric acid 88-09-5 1.92 1.68 -14 -0.81 -1.42 -0.61 2-ethylhexylaniine 104-75-6 2.91 2.82 -76 -1.71 -2.41 -0.70 2-ethylnaphthalene 939-27-5 4.34 4.38 -7 -4.29 -3.84 0.45 2-ethylthiophene 872-55-9 2.82 3.01 <25 -2.59 -2.32 0.27 2-ethyltoluene 611-14-3 3.62 3.53 -17 -3.21 -3.12 0.09 2-furoic acid 88-14-2 1.01 129 -0.48 -1.55 -1.07 2-heptanol 543-49-7 2.19 2.31 <25 -1.55 -1.69 -0.14 2-heptanone 110-43-0 1.91 1.98 -31 -1.42 -1.41 0.01 2-hexanol 626-93-7 1.66 1.76 <25 -0.89 -1.16 -0.27 2-hydroxyacetanilide 614-80-2 0.72 0.72 208 -2.24 -2.05 0.19 2-hydroxypteridine -0.20 -1.95 131

2-hydroxypyridine 72762-00-6 0.93 106 1.02 -1.24 -2.26 2-imidazolidinethione 96-45-7 -0.66 -0.66 203 -0.71 -0.62 0.09 2-iodopropane 75-30-9 2.52 2.89 -90 -2.09 -2.02 0.07 2-isopropyltoluene 527-84-4 4.02 -71 -3.76 -3.52 0.24 2-niercaptobenzothiazole 149-30-4 2.95 2.41 179 -3.18 -3.99 -0.81 2-mercaptopteridine 16878-76-5 0.16 205 -2.36 -1.46 0.90 2-methoxypteridine 102170-44-5 0.09 150 -1.11 -0.84 0.27 2-methyl pentane 107-83-5 3.74 -154 -3.74 -3.24 0.50 2-methyl tetrahydrofuran 96-47-9 1.04 -136 0.11 -0.54 -0.65 2-methyl-1,3-butadiene 78-79-5 2.30 -120 -2.03 -1.80 0.23 2-methyl-1-butanol 137-32-6 1.22 -70 -0.47 -0.72 -0.25 2-methyl-1-butene 563-46-2 2.73 -138 -2.73 -2.23 0.50 2-methyl-1-pentanol 105-30-6 1.75 <25 -1.11 -1.25 -0.14 2-methyl-1-pentene 763-29-1 3.25 -136 -3.03 -2.75 0.28 2-methyl-2-butene 513-35-9 2.73 2.67 -134 -2.56 -2.23 0.33 2-methyl-2-heptanol 625-25-2 2.59 -50 -1.72 -2.09 -0.37 2-methyl-2-hexanol 625-23-0 2.06 <25 -1.08 -1.56 -0.48 2-methyl-2-pentanol 590-36-3 1.53 -107 -0.49 -1.03 -0.54 2-methyl-2-propanol 75-65-0 0.47 0.35 26 0.63 0.02 -0.61 2-methyl-3-pentanol 565-67-3 1.53 <25 -0.70 -1.03 -0.33 2-methylaniline 95-53-4 1.36 1.32 -15 -0.85 -0.86 -0.01 2-methylanthracene 613-12-7 4.99 205 -6.69 -6.29 0.40 2-methylbenzimidazole 615-15-6 1.83 176 -1.96 -2.84 -0.88 2-methylbutane 78-78-4 3.21 -160 -3.18 -2.71 0.47 2-methylcyclohexanone 583-60-8 1.38 -14 -0.94 -0.88 0.06 2-methylheptane 592-27-8 4.80 -109 -4.48 -4.30 0.18 2-methylhexane 591-76-4 4.27 -118 -4.60 -3.77 0.83 2-methylnaphthalene 91-57-6 3.81 3.86 34 -3.75 -3.40 0.35 2-methyl-nevirapine 135794-77-3 2.85 235 -4.27 -4.45 -0.18 2-methylphenanthrene 2531-84-2 4.99 4.86 57 -5.84 -4.81 1.03 2-methylphenol 95-48-7 1.97 1.95 30.9 -0.62 -1.53 -0.91 2-methylpiperazine 109-07-9 -0.97 66 0.74 1.06 0.32 2-methylpropane 75-28-5 2.68 2.76 -159 -2.55 -2.18 0.37 2-methylpropene 115-11-7 2.20 2.34 -140 -2.33 -1.70 0.63 2-methylpteridine 2432-20-4 -0.36 <25 -0.12 0.86 0.98 2-methylthiopteridine 16878-77-6 0.35 136 -1.76 -0.96 0.80 2-naphthol 135-19-3 2.65 2.70 121 -2.28 -3.11 -0.83 2-nitroacetanilide 552-32-9 1.00 1 93 -1.91 -1.18 0.73 2-nitropropane 79-46-9 0.55 0.80 <25 -0.62 -0.05 0.57 2-nonanol 628-99-9 3.25 -35 -2.74 -2.75 -0.01 2-nonanone 821-55-6 2.94 3.14 -21 -2.58 -2.44 0.14 2-octanol 123-96-6 2.72 2.90 -39 -2.09 -2.22 -0.13 2-octanone 111-13-7 2.44 2.37 -16 -2.05 -1.94 0.11 2-pentanol 6032-29-7 1.13 1.19 -50 -0.29 -0.63 -0.34 2-pentanone 107-87-9 0.85 0.91 -78 -0.19 -0.35 -0.16 2-pentene 109-68-2 2.86 -140 -2.54 -2.36 0.18 2-phenoxyethanol 122-99-6 1.19 1.16 14 -0.70 -0.69 0.01 2-phenyl-3,1-benzoxazin-4-one 1022-46-4 2.55 124 -4.61 -3.04 1.57 2-phenylethanol 60-12-8 1.33 1.36 -14 -0.74 -0.83 -0.09 132

2-phenylphenol 90-43-7 3.36 3.09 57 -2.39 -3.18 -0.79 2-propanol 67-63-0 0.07 0.05 -89 0.43 0.43 0.00 2-propenamide 79-06-1 -0.61 -0.67 85 0.95 0.51 -0.44 2-pyrazinecarboxaniide 98-96-4 -0.71 -0.6 190 -0.91 -0.44 0.47 2-thiouracil 141-90-2 -0.37 -0.28 340 -2.26 -2.28 -0.02 2-toluenesulfonatnide 88-19-7 0.80 0.84 156 -2.02 -1.61 0.41 2-undecanol 1653-30-1 4.31 -11 -2.94 -3.81 -0.87 3,3',4,4'-tetrachlorobiphenyl 32598-13-3 6.64 6.63 180 -8.68 -7.69 0.99 3,3'!4,4'-tetrachlorodiphenyl 56348-72-2 6.85 70 -6.98 -6.80 0.18 ether 3,3 ',5,5'-tetrachlorobipheny1 33284-52-5 6.88 6.85 164 -8.54 -7.77 0.77 3,3'-dichlorobenzidine 91-94-1 3.57 3.51 133 -4.92 -4.15 0.77 3,3'-dichlorobiphenyl 2050-67-1 5.46 5.30 29 -5.80 -5.00 0.80 3,3-dimethyl-1-butanol 624-95-3 1.62 -62 -0.50 -1.12 -0.62 3,3-dimethyl-2-butanol 464-07-3 1.40 1.47 5 -0.62 -0.90 -0.28 3,3-dimethyl-2-butanone 75-97-8 1.25 1.20 -53 -0.73 -0.75 -0.02 3,3-dimethylpentane 562-49-2 4.14 -134 -4.23 -3.64 0.59 3,4,4'-trichlorobipheny1 38444-90-5 6.05 5.90 88 -7.06 -6.18 0.88 3,4,5,6-tetrachloro veratrole 944-61-6 4.38 90 -5.24 -4.53 0.71 3,4,5-trichlorodiphenyl ether 63646-53-7 6.14 54 -6.77 -5.93 0.84 3,4,5 -trichloro veratrole 16766-29-3 3.67 66 -4.37 -3.58 0.79 3,4-benzopyrene 50-32-8 6.12 6.13 -7.82 3,4-dichloroaniline 95-76-1 2.59 2.69 72 -3.24 -2.56 0.68 3,4-dichlorobiphenyl 2974-92-7 5.34 5.29 50 -7.44 -5.09 2.35 3,4-dichloronitrobenzene 99-54-7 3.19 3.12 41 -3.20 -2.85 0.35 3,4-dichloropheno 1 95-77-2 3.17 3.33 67 -1.25 -3.09 -1.84 3,4-dimethyIphenol 95-65-8 2.42 2.23 62.5 -1.38 -2.30 -0.92 3,4-dimethylpyridine 583-58-4 1.59 -12 0.36 -1.09 -1.45 3,5-dichlorophenol 591-35-5 3.29 3.52 68 -1.34 -3.22 -1.88 3,5-diiodosalicylic acid 133-91-5 4.24 4.56 233 -3.31 -5.82 -2.51 3,5 -diiodotyrosine 66-02-4 -0.29 204 -2.86 -1.00 1.86 3,5 -dimethyIphenol 108-68-9 2.47 2.35 64 -1.40 -2.36 -0.96 3,5-dimethylphenyl 2655-14-3 2.21 2.23 99 -2.58 -2.45 0.13 methylcarbamate 3,5-dimethylpyridine 591-22-0 1.64 1.78 -6.6 0.38 -1.14 -1.52 3-bromo-4- 2973-78-6 2.15 1.83 124 -2.18 -2.64 -0.46 hydroxybenzaldehyde 3-bromopropylene 106-95-6 1.65 1.79 -50 -1.50 -1.15 0.35 3-chloroanisole 2845-89-8 2.91 2.98 <25 -2.78 -2.41 0.37 3-chlorobiphenyl 2051-61-8 4.74 4.71 18 -4.88 -4.24 0.64 3-chloropentane 616-20-6 3.05 -106 -2.63 -2.55 0.08 3-chlorophenol 108-43-0 2.48 2.50 34 -0.70 -2.07 -1.37 3-chloropropionitrile 542-76-7 0.20 0.18 -51 -0.29 0.30 0.59 3-chloropropylene 107-05-1 1.51 -135 -1.36 -1.01 0.35 3-ethoxy-4- 121-32-4 1.80 1.61 78 -1.77 -1.83 -0.06 hydroxybenzaldehyde 3-ethyl-3-pentanol 597-49-9 2.06 -12 -0.85 -1.56 -0.71 3-heptanol 589-82-2 2.19 2.24 -70 -1.47 -1.69 -0.22 3-hexanol 623-37-0 1.66 1.65 <25 -0.80 -1.16 -0.36 3-hexanone 589-38-8 1.38 -56 -0.83 -0.88 -0.05 133

3-hexyne 928-49-4 2.51 -103 -1.99 -2.01 -0.02 3-hydroxy-5-methylisoxazole 10004-44-1 0.62 0.47 85 -0.07 -0.72 -0.65 3-hydroxypyridine 109-00-2 0.93 0.52 129 -0.46 -1.47 -1.01 3-hydroxytetrahydrofuran 453-20-3 -0.78 <25 1.05 1.28 0.23 3-methyl cholanthrene 56-49-5 6.62 6.42 179 -7.92 -7.66 0.26 3-methyl-l-butanol acetate 123-92-2 2.17 2.25 -79 -1.92 -1.67 0.25 3-niethyl-l-butene 563-45-1 2.73 -168 -2.73 -2.23 0.50 3-methyl-2-butanol 598-75-4 1.00 1.28 <25 -0.20 -0.50 -0.30 3-inethyl-2-butanone 563-80-4 0.85 0.84 -92 -0.12 -0.35 -0.23 3-methyl-2-heptanol 31367-46-1 2.59 -114 -1.72 -2.09 -0.37 3-methyl-2-pentanol 565-60-6 1.53 <25 -0.72 -1.03 -0.31 3-methyl-2-pentanone 565-61-7 1.38 <25 -0.67 -0.88 -0.21 3-methyl-3-heptanol 5582-82-1 2.59 -83 -1.60 -2.09 -0.49 3-methyl-3-hexanol 597-96-6 2.06 <25 -1.00 -1.56 -0.56 3-methyl-3-pentanol 77-74-7 1.53 -24 -0.38 -1.03 -0.65 3-methyl-4-chlorophenol 59-50-7 2.98 3.1 67 -1.57 -2.90 -1.33 3-methylacetanilide 537-92-8 1.66 1.68 66 -2.09 -1.57 0.52 3-methylcyclohexanone 591-24-2 1.38 -75 -1.87 -0.88 0.99 3-methylheptane 589-81-1 4.80 -121 -5.16 -4.30 0.86 3-methylhexane 589-34-4 4.27 -119 -4.47 -3.77 0.70 3-methylindole 83-34-1 2.63 2.60 95 -2.42 -2.83 -0.41 3-methylpentane 96-14-0 3.74 3.60 -118 -3.68 -3.24 0.44 3-methylphenol 108-39-4 1.97 1.96 11.5 -0.68 -1.47 -0.79 3-methylthiophene 616-44-4 2.29 2.45 -69 -2.39 -1.79 0.60 3-octanol 589-98-0 2.72 -45 -1.98 -2.22 -0.24 3-pentanol 584-02-1 1.13 1.21 <25 -0.24 -0.63 -0.39 3-pentanone 96-22-0 0.85 0.82 -39 -0.28 -0.35 -0.07 3-pentenenitrile 16529-66-1 0.82 <25 -0.96 -0.32 0.64 3-phenylpropanol 122-97-4 1.71 1.68 0 -1.38 -1.21 0.17 3-propyl-2,4-pentadione 1540-35-8 1.13 <25 -0.88 -0.63 0.25 3-pyridinemethanol 100-55-0 -0.39 -0.02 -8 0.96 0.89 -0.07 3-trifluoromethylaniline 98-16-8 2.29 2.29 5 -1.47 -1.79 -0.32 4(3h)-pyridone 51953-17-4 -1.29 -1.38 164 0.59 0.40 -0.19 4,4'-bipyridine 553-26-4 1.14 112 -1.54 -1.51 0.03 4,4'-dibromobiphenyl 92-86-4 5.76 5.72 170 -7.74 -6.71 1.03 4,4'-dichlorobiphenyl 2050-68-2 5.46 5.30 149 -6.56 -6.20 0.36 4,4-dimethyl-1-pentanol 3121-79-7 2.15 <25 -1.55 -1.65 -0.10 4,5,7-trichloro-2,l,3- 1982-55-4 4.25 122 -4.98 -4.72 0.26 benzothiadiazole 4,5-dichloroquiaiacol 2460-49-3 2.91 3.26 72 -2.53 -2.88 -0.35 4,5-dichloroveratrole 2772-46-5 3.19 83 -3.46 -3.27 0.19 4,7-dimethyl-l,10- 3248-05-3 3.05 193 -3.97 -4.23 -0.26 phenanthroline 4-aminoacetanilide 122-80-5 -0.07 0.08 165 -0.98 -0.83 0.15 4-aminobenzoic acid 150-13-0 0.98 0.83 -1.37 4-aminopteridine 6973-01-9 -0.83 -2.31 4-bromobenzoic acid 586-76-5 2.85 2.86 245.5 -3.54 -4.56 -1.02 4-bromophenol 106-41-2 2.63 2.59 66 -1.09 -2.54 -1.45 4-bromotoluene 106-38-7 3.50 3.42 29 -3.19 -3.04 0.16 134

4-chloro-3,5-dimethylphenol 88-04-0 3.48 3.27 115 -2.8 -3.88 -1.08 4-chloroanisole 623-12-1 2.91 2.78 -18 -2.78 -2.41 0.37 4-chlorophenol 106-48-9 2.48 2.39 43.2 -0.70 -2.16 -1.46 4-chlorophenoxyacetic acid 122-88-3 2.20 2.25 157 -2.29 -3.02 -0.73 4-dimethylaminopteridine 0.07 -1.02 4-ethoxy-3- 120-25-2 1.97 65 -2.19 -1.87 0.32 methoxybenzaldehyde 4-ethyl pyridine 536-75-4 1.67 1.65 -91 0.83 -1.17 -2.00 4-ethyltoluene 622-96-8 3.67 -62 -3.11 -3.17 -0.06 4-formy1 acetanil ide 122-85-0 1.05 154 -1.58 -1.84 -0.26 4-heptanol 589-55-9 2.19 2.22 -42 -1.40 -1.69 -0.29 4-heptanone 123-19-3 1.91 2.04 -33 -1.30 -1.41 -0.11 4-hexylresorcinol 136-77-6 3.95 3.45 65 -2.59 -3.85 -1.26 4-hydroxy-2-methylquinoline 607-67-0 2.81 235 -1.2 -4.41 -3.21 4-hydroxypteridine -0.20 -1.47 4-hydroxypyridine 626-64-2 0.93 148 1.02 -1.66 -2.68 4-iodoacetanilide 622-50-4 2.54 2.71 184 -3.25 -3.63 -0.38 4-isopropyltoluene 99-87-6 4.07 4.10 -67 -3.77 -3.57 0.20 4-mercaptopteridine 65882-61-3 0.16 176 -2.77 -1.17 1.60 4-methoxypteridine 30564-38-6 0.09 193 -1.11 -1.27 -0.16 4-methyl-1-pentanol 626-89-1 1.75 <25 -1.14 -1.25 -0.11 4-methyl-1-pentene 691-37-2 3.25 -154 -3.24 -2.75 0.49 4-methyl-2-pentanol 108-11-2 1.53 -90 -0.80 -1.03 -0.23 4-niethyl-2-pentanone 108-10-1 1.25 1.31 -80 -0.74 -0.75 -0.01 4-methylbiphenyl 644-08-6 4.53 4.63 45 -4.62 -4.23 0.39 4-methylcyciohexanol 589-91-3 1.79 1.79 -41 -0.88 -1.29 -0.41 4-inethylinorphoHne 109-02-4 0.20 -66 1.00 0.30 -0.70 4-niethyloctane 2216-34-4 5.32 -113 -6.05 -4.82 1.23 4-methylpentanol 106-67-2 1.75 <25 -1.14 -1.25 -0.11 4-methylpteridine 2432-21-5 -0.36 152 -0.47 -0.41 0.06 4-inethylthiopteridine 6966-78-5 0.35 191 -2.36 -1.51 0.85 4-methyoxyacetanilide 51-66-1 0.86 131 -1.30 -1.42 -0.12 4-nitroacetanilide 104-04-1 1.46 1.66 215 -2.69 -2.86 -0.17 4-nitroaniline 100-01-6 1.26 1.39 146 -2.37 -1.97 0.40 4-pentene-l-ol 821-09-0 0.87 <25 -0.15 -0.37 -0.22 4-phenylsemicarbazide 537-47-3 -0.22 123 -2.33 -0.26 2.07 5-(3-methyl-2-butenyl)-5- 21149-88-2 1.63 1.73 155 -2.25 -2.43 -0.18 ethylbarbital 5-(3-methyl-2-butenyl)-5- 2.23 2.23 131.3 -2.59 -2.80 -0.20 isoprbarbital 5,5-diallylbarbital (allobarbital) 52-43-7 0.75 1.15 174 -2.08 -1.74 0.34 5,5-diisopropylbarbital 99167-69-8 1.45 1.56 228 -2.77 -2.98 -0.21 5,5-dimethyl-2,4-hexadione 7307-04-2 1.00 -1.63 5,5-dimethylbarbituric acid 24448-94-0 -0.40 -0.44 278 -1.74 -1.63 0.11 5,5-diphenylbarbiturate 21914-07-8 1.88 1.96 -4.2 5,5-dipropylbarbiturate 2217-08-5 1.71 1.75 -2.53 5,6,7,8-tetrahydro-2-naphthol 1125-78-6 3.05 2.9 57 -1.99 -2.87 -0.88 5,6-dehydroisoandrosterone 853-23-6 4.13 166 -4.46 -5.04 -0.58 acetate 5,6-diitiethyIchry sene 3697-27-6 6.61 128 -7.01 -7.14 -0.13 135

5-allyl-5-ethylbarbital 2373-84-4 0.70 0.87 160 -1.61 -1.55 0.06 5 -ally1-5 -isopropylbarbital 77-02-1 1.37 1.37 143 -1.71 -2.05 -0.34 (aprobarbital) 5 -ally1-5 -methylbarbital 0.17 0.36 166 -1.16 -1.08 0.08 5-allyl-5-phenylbarbital 115-43-5 1.41 1.69 158 -2.18 -2.24 -0.06 (phenallymal) 5-aminosalicylic acid 89-57-6 1.06 -2.26 5-ethyl-5-(3-methylbut-2- 1.63 1.73 -2.25 enyl)barbiturate 5-ethyl-5-(3- 57-43-2 2.11 2.07 156 -2.66 -2.92 -0.26 methylbutyObarbital (amobarbital) 5-ethyl-5-heptylbarbiturate 3.30 -3.22 5-ethyl-5-isopropylbarbituric 76-76-6 1.05 1.10 203 -2.15 -2.33 -0.18 acid (probarbital) 5-ethyl-5-nonylbarbiturate 4.36 -4.46 5-ethyl-5-octylbarbiturate 3.83 -3.94 5-ethyl-5-pentylbarbiturate 115-58-2 2.24 2.24 -2.34 5-ethyl-5-propylbarbiturate 33376-25-9 1.18 -1.49 5-ethyl-barbiturate 2518-72-1 -0.39 -0.35 -1.43 5-ethylhydantoin 15414-82-1 -0.64 120 -0.06 0.19 0.25 5-fluorouracil 51-21-8 -0.58 -1 281 -1.07 -1.48 -0.41 5-hydroxyquinoline 578-67-6 2.08 2.1 224 -2.54 -3.57 -1.03 5-(-propyl-5-(3-methylbut-2- 2.03 2.23 -2.59 enyl)barbiturate 5-isopropylbarbiturate 7391-69-7 0.01 -0.02 -1.46 5-methyl barbiturate -0.92 -1.13 5-methyl-2-hexanol 627-59-8 2.06 <25 -1.38 -1.56 -0.18 5-methyl-2-hexanone 110-12-3 1.78 1.88 -74 -1.33 -1.28 0.05 5-methyl-2-thiouracil 636-26-0 -1.39 284 -2.45 -0.70 1.75 5-methyl-5-(3-methylbut-2- 1.10 1.17 -2.6 enyl)barbiturate 5-methyl-5-allylbarbiturate 0.17 0.36 -1.16 5-methyl-5-ethylbarbiturate 0.13 0.08 -1.16 5-methylchrysene 3697-24-3 6.16 117 -6.59 -6.58 0.01 5-niethylcytosine 58366-64-6 -1.40 -0.56 5-methyluracil 65-71-4 -0.56 -0.62 316 -1.52 -1.85 -0.33 5-nitrobarbituric acid 28176-10-5 -1.72 -2.28 5-nonanone 502-56-7 2.97 2.88 -50 -2.59 -2.47 0.12 5-f-butyl-5-(3-methylbut-2- 2.43 2.56 -3.55 enyl)barbiturate 6-aminochrysene 2642-98-0 4.44 4.98 210 -6.2 -5.79 0.41 6-aminopteridine -0.83 -2.34 6-chlorpteridine -0.14 -1.12 6-hydroxypteridine -0.20 -2.71 6-hydroxyquinoline 580-16-5 2.08 1.8 192 -2,16 -3.25 -1.09 6-methoxypteridine 0.09 -1.14 6-methyl-2,4-heptadione 3002-23-1 1.00 <25 -1.60 -0.50 1.10 6-methylchrysene 1705-85-7 6.16 160 -6.57 -7.01 -0.44 6-methylprednisolone 83-43-2 1.70 228 -2.99 -3.23 -0.24 6-methyluracil 626-48-2 -0.56 -0.77 318 -1.26 -1.87 -0.61 7,12-dimethylbenz[a]anthracene 57-97-6 6.66 5.80 122 -7.02 -7.13 -0.11 7-aminopteridine 769-66-4 -0.83 -2.31 7-butyltheophylline 1.53 -1.81 7-chlorpteridine 1125-84-4 -0.14 -0.88 7-dimethylaminopteridine 0.07 -0.02 7-ethyltheophylline 0.47 -0.76 7-hydroxypteridine -0.20 -2.12 7-isobutyltheophylline 1.40 -0.94 7-mercaptopteridine -0.21 -2.71 7-methoxypteridine 204443-27-6 0.09 -0.91 7-methoxypteridine 0.09 -0.91 7-methylpteridine -0.36 -0.85 7-methylthiopteridine 204443-30-1 0.35 -1.55 8-quinolinol 148-24-3 2.08 2.02 72 -2.42 -2.05 0.37 9,10-dimethyl-l,2- 56-56-4 6.66 123 -6.83 -7.14 -0.31 benzanthracene 9,10-dimethylanthracene 781-43-1 5.49 5.69 183 -6.57 -6.57 0.00 9-methylanthracene 779-02-2 4.99 5.07 79 -5.89 -5.03 0.86 a-aminoisobutyric acid 62-57-7 -2.62 335 0.21 0.02 -0.19 abietic acid 514-10-3 6.28 173 -3.8 -7.26 -3.46 acenaphthalene 83-32-9 3.62 90 -3.96 -3.77 0.19 acenaphthylene 208-96-8 3.77 3.92 95 -3.96 -3.97 -0.01 acetamide 60-35-5 -1.11 -1.09 81 1.58 1.05 -0.53 acetanilide 103-84-4 1.16 1.16 114 -1.33 -1.55 -0.22 acetazolamide 59-66-5 -1.25 -0.26 -2.49 acetic acid 64-19-7 -0.19 -0.17 16.6 2.00 0.69 -1.31 acetohexamide 968-81-0 2.25 2.44 189 -2.06 -3.39 -1.33 acetonitrile 75-05-8 -0.39 -0.34 -48 0.26 0.89 0.63 acetophenone 98-86-2 1.58 1.58 20 -1.28 -1.08 0.20 acetylsalicylicacid 50-78-2 1.02 1.19 135 -1.61 -1.62 -0.01 acridine 260-94-6 3.41 3.4 107 -3.67 -3.73 -0.06 acrolein 107-02-8 -0.01 -0.01 -88 0.57 0.51 -0.06 acrylonitrile 107-13-1 0.29 0.25 -84 0.15 0.21 0.06 adenine 73-24-5 -0.29 -0.09 363 -2.43 -2.59 -0.16 adenosine 58-61-7 -2.27 -1.05 -1.73 adipic acid 124-04-9 -0.02 0.08 152 -0.82 -0.75 0.07 adrenosterone 382-45-6 2.04 185 -3.48 -3.14 0.34 a-endosulfan 959-98-8 3.95 3.83 109 -5.89 -4.29 1.60 ajmaline 4360-12-7 2.17 160 -2.82 -3.02 -0.20 alachlor 15972-60-8 3.19 3.52 40 -3.17 -2.84 0.33 alclofenac 22131-79-9 2.73 2.47 -3.13 aldicarb 116-06-3 1.12 1.13 100 -1.50 -1.37 0.13 aldosterone 52-39-1 1.57 164 -3.85 -2.46 1.39 aldrin 309-00-2 5.41 6.50 104 -6.31 -5.70 0.61 alizarin 72-48-0 2.38 287 -2.78 -4.50 -1.72 allantoin 97-59-6 -2.23 238 -1.6 0.60 2.20 allicin 539-86-6 1.90 <25 -0.83 -1.40 -0.57 allopurinol 315-30-0 -0.88 -0.55 360 -2.26 -1.97 0.29 137 alloxan 50-71-5 -1.84 -1.84 256 -1.25 0.03 1.28 alloxantin(uroxine) 76-24-4 -4.88 -1.99 alpha-aminobutyric acid 80-60-4 -2.60 -2.53 285 0.31 0.50 0.19 alpha-chlorotoluene 100-44-7 2.70 -39 -2.39 -2.20 0.19 amertryn 834-12-8 2.98 2.98 84 -3.04 -3.07 -0.03 amikacin 37517-28-5 -4.12 203 -0.5 2.84 3.34 aminocarb 2032-59-9 1.98 1.9 93 -2.36 -2.16 0.20 aminopyrine 58-15-1 0.57 1 108 -0.36 -0.90 -0.54 amitraz 33089-61-1 5.50 86 -5.47 -5.61 -0.14 amitriptyline 50-48-6 4.85 4.92 193 -4.46 -6.03 -1.57 amitrole 61-82-5 -0.53 -0.87 159 0.52 -0.31 -0.83 ampicillin 800-79-3 -1.20 -1.13 200 -1.54 -0.05 1.49 ampyrone 83-07-8 -0.75 108 -0.62 0.42 1.04 amygdalin 29883-15-6 -2.19 224 -0.77 0.70 1.47 amylacetate 628-63-7 2.30 2.29 -71 -1.89 -1.80 0.09 ancymidol 12771-68-5 0.76 110 -2.6 -1.11 1.49 androstane-17-one 36378-49-1 5.08 119 -5.70 -5.52 0.18 androstanedione 846-46-8 3.15 3.60 142 -3.76 -3.82 -0.06 androstenedione 63-05-8 3.15 3.6 142 -3.69 -3.82 -0.13 androsterone 53-41-8 3.55 3.69 185 -4.40 -4.65 -0.25 anethole 104-46-1 3.31 22 -3.13 -2.81 0.32 aniline 62-53-3 0.91 0.90 <25 -0.41 -0.41 0.00 anisole 100-66-3 2.06 2.11 -37 -1.85 -1.56 0.29 anisomycin 22862-76-6 1.48 142 -1.61 -2.15 -0.54 antazoline 91-75-8 4.11 122 -2.6 -4.58 -1.98 anthracene 120-12-7 4.49 4.45 216 -6.35 -5.90 0.45 anthraquinone 84-65-1 2.62 3.39 284 -5.19 -4.71 0.48 antipyrine 60-80-0 0.20 0.23 111 0.39 -0.56 -0.95 arecoline 63-75-2 0.90 <25 0.81 -0.40 -1.21 ascorbic acid 50-81-7 -1.76 -1.64 191 0.28 0.60 0.32 asulam 3337-71-1 -0.31 -0.27 153 -1.66 -0.47 1.19 atrazine 1912-24-9 2.50 2.61 175 -3.55 -3.50 0.05 atrazine 1912-24-9 2.50 2.61 -3.49 atropic acid 492-38-6 1.90 1.84 107 -2.06 -2.22 -0.16 atropine 51-55-8 1.32 1.83 116 -2.2 -1.73 0.47 azathioprine 446-86-6 0.01 0.1 -3.44 azelaic acid 123-99-9 1.56 1.57 100 -1.89 -1.81 0.08 azintamide 1830-32-6 0.99 -1.72 azobenzene 103-33-3 3.85 3.82 69 -2.75 -3.79 -1.04 aztreonam 78110-38-0 0.66 227 -1.64 -2.18 -0.54 baclofen 1134-47-0 -0.62 -0.96 -1.7 barban 101-27-9 3.98 75 -4.37 -3.98 0.39 barbital 57-44-3 0.66 0.65 190 -2.4 -1.81 0.59 benazolin 3813-05-6 1.34 1.30 192 -2.61 -2.51 0.10 bendroflumethiazide 73-48-3 1.69 1.19 224 -3.59 -3.18 0.41 benfluralin 1861-40-1 5.29 5.29 65 -5.53 -5.19 0.34 benodanil 15310-01-7 2.92 137 -4.21 -3.54 0.67 benperidol 2062-84-2 3.82 -4.28 bensulide 741-58-2 4.37 4.22 34 -4.20 -3.96 0.24 138 bentazon 25057-89-0 2.80 2.8 138 -2.68 -3.43 -0.75 benzaldehyde 100-52-7 1.50 1.47 -55 -1.19 -1.00 0.19 benzamide 55-21-0 0.65 0.64 129 -0.96 -1.19 -0.23 benzanthracene 5.66 5.54 -7.21 (benzo [a] anthracene) benzene 71-43-2 2.14 2.13 6 -1.64 -1.64 0.00 benzenesulfonamide 98-10-2 0.30 0.31 151 -1.56 -1.06 0.50 benzhydrol 91-01-0 2.45 2.67 66 -2.55 -2.36 0.19 benzilic acid 76-93-7 1.85 2.3 151 -2.21 -2.61 -0.40 benznidazole 22994-85-0 0.89 0.91 190 -2.81 -2.04 0.77 benzo(a)fluorene 238-84-6 5.25 5.68 187 -6.68 -6.37 0.31 benzo(a)pyrene 50-32-8 6.12 6.13 178 -8.25 -7.15 1.10 benzo(b)fluoranthene 205-99-2 6.12 167 -7.79 -7.04 0.75 benzo(b)fluorene 243-17-4 5.25 5.77 212 -8.04 -6.62 1.42 benzo(e)pyrene 192-97-2 6.12 6.44 178 -7.80 -7.15 0.65 benzo(f)quinoline 85-02-9 3.20 3.4 93 -3.36 -3.38 -0.02 benzo(g,h,i)perylene 191-24-2 6.58 6.63 278 -9.02 -8.61 0.41 benzo(j)fluoranthene 205-82-3 6.12 165 -8.00 -7.02 0.98 benzo(k)fluoranthene 207-08-9 6.12 6.11 216 -8.49 -7.53 0.96 benzocaine 94-09-7 1.92 1.86 89 -2.32 -2.06 0.26 benzoic acid 65-85-0 1.88 1.87 122 -1.55 -2.35 -0.80 benzoin 579-44-2 2.38 2.13 134 -2.85 -2.97 -0.12 benzonitrile 100-47-0 1.57 1.56 -13 -1.00 -1.07 -0.07 benzophenone 119-61-9 3.18 3.18 49 -3.12 -2.92 0.20 benzothiazole 95-16-9 2.08 2.01 2 -1.50 -1.58 -0.08 benzotriazole 95-14-7 1.41 1.44 99 -0.78 -1.65 -0.87 benzoxazole 273-53-0 1.41 1.59 28 -1.16 -0.94 0.22 benzyl butyl phthalate 85-68-7 3.88 4.91 -35 -5.64 -3.38 2.26 benzylamine 100-46-9 1.09 1.09 10 -1.54 -0.59 0.95 benzylurea 538-32-9 0.73 0.73 148 -0.95 -1.46 -0.51 beta-aminobutyric acid 2835-82-7 -2.83 190 1.08 1.68 0.60 beta-endosulfan 33213-65-9 3.95 3.83 209 -6.08 -5.29 0.79 beta-estradiol 50-28-2 3.78 3.86 173 -4.85 -4.76 0.09 beta-iodopropionic acid 141-76-4 0.93 81 -0.43 -0.99 -0.56 betamethasone 378-44-9 1.75 2.01 230 -3.77 -3.30 0.47 betamethasone-17-valerate 2152-44-5 3.87 3.60 196 -4.71 -5.08 -0.37 bibenzyl 103-29-7 4.59 4.79 50 -4.62 -4.34 0.28 bifonazole 60628-96-8 4.77 4.99 142 -5.95 -5.44 0.51 biphenyl 92-52-4 4.03 4.01 70 -4.30 -3.98 0.32 biquinoline 119-91-5 5.10 5.02 71 -5.4 -5.06 0.34 bis-(2-chloroethyl)-ether 111-44-4 1.00 1.29 -45 -1.12 -0.50 0.62 bis-(2-chloroethyl)-sulfone 471-03-4 -0.31 56 -1.50 0.50 2.00 bis-(2-chloroethyl)-sulfoxide 5819-08-9 -0.19 110 -1.16 -0.16 1.00 bis-(p-aminophenyl)-methane 101-77-9 1.75 1.59 93 -2.3 -1.93 0.37 borneol(sp) 507-70-0 2.58 2.72 206 -2.32 -3.89 -1.57 brinzolamide 138890-62-7 0.18 -2.95 bromacil 314-40-9 2.69 2.11 158 -2.52 -3.52 -1.00 bromazepam 1812-30-2 1.69 1.69 238 -3.48 -3.32 0.17 bromobenzene 108-86-1 3.01 2.99 -31 -2.55 -2.51 0.04 139 bromochloromethane 74-97-5 1.39 1.41 -87 -0.89 -0.89 0.00 bromocyclohexane 108-85-0 3.33 3.20 -57 -2.30 -2.83 -0.53 bromodichloromethane 75-27-4 2.09 2.10 -57 -1.54 -1.59 -0.05 bromoethane 74-96-4 1.60 1.61 -118 -1.09 -1.10 -0.01 bromomethane 74-83-9 1.08 1.19 -94 -0.85 -0.58 0.27 bromophos 2104-96-3 5.09 5.21 51 -6.09 -4.85 1.24 bromopropylate 18181-80-1 4.97 5.40 76 -4.93 -4.98 -0.05 bromoxynil 1689-84-5 2.88 2.8 190 -3.33 -4.03 -0.70 brompyrazone 3042-84-0 1.40 220 -3.12 -2.85 0.27 brucine 357-57-3 1.31 0.98 177 -2.09 -2.33 -0.24 bumetanide 28395-03-1 3.35 230 -3.56 -4.90 -1.34 bupirimate 41483-43-6 2.70 2.7 -4.16 busulfan 55-98-1 -0.59 -0.52 -2.27 butabarbital 125-40-6 1.58 1.65 166 -2.39 -2.49 -0.10 butacarb 2655-19-8 4.86 100 -4.24 -5.11 -0.87 butachlor 23184-66-9 4.78 4.50 <25 -4.19 -4.28 -0.09 butalbital 77-26-9 1.63 -2.12 butamben 94-25-7 3.08 2.87 58 -3.08 -2.91 0.17 butan-2-ol 78-92-2 0.60 0.61 -115 0.18 -0.10 -0.28 butane 106-97-8 2.81 2.89 -138 -2.95 -2.31 0.64 butanethiol 109-79-5 2.23 2.28 -116 -2.18 -1.73 0.45 butethal 77-28-1 1.71 1.73 127 -1.83 -2.23 -0.40 buturon 3766-60-7 2.66 3.00 143 -3.90 -3.34 0.56 butyl acetate 123-86-4 1.77 1.78 -106 -1.24 -1.27 -0.03 butyl benzene 104-51-8 4.23 4.38 -88 -4.06 -3.73 0.33 butyl benzoate 136-60-7 3.70 3.84 -22 -3.48 -3.20 0.28 butylamine 109-73-9 0.92 0.97 -50 0,96 -0.42 -1.38 butylate 2008-41-5 4.01 4.15 <25 -3.68 -3.51 0.17 butyl-p-hydroxybenzoate 94-26-8 3.57 3.57 68 -2.72 -3.50 -0.78 butyltoluene 27458-20-4 4.68 <25 -4.06 -4.18 -0.12 butyraldehyde 123-72-8 0.83 0.88 -96 -0.01 -0.33 -0.32 butyric acid 107-92-6 0.86 0.79 -8 -0.19 -0.36 -0.17 caffeine 58-08-2 -0.06 -0.07 235 -0.88 -1.54 -0.66 camphor(sp) 76-22-2 2.18 2.38 177 -1.99 -3.20 -1.21 caproaldehyde 66-25-1 1.89 1.78 -56 -1.30 -1.39 -0.09 caprylaldehyde 124-13-0 2.95 14 -2.36 -2.45 -0.09 caprylic acid 124-07-2 2.98 3.05 17 -2.3 -2.48 -0.18 captafol 2939-80-2 3.74 3.83 162 -5.4 -4.61 0.79 carbamazepine 298-46-4 1.98 2.19 -3.29 carbanilide 102-07-8 3.01 3 238 -3.15 -4.64 -1.49 carbaryl 63-25-2 2.38 2.36 142 -3.28 -3.05 0.23 carbazole 86-74-8 3.52 3.48 247 -5.27 -5.24 0.03 carbetamide 16118-49-3 1.35 -1.83 carbofuran 1563-66-2 2.47 1.63 152 -2.80 -3.24 -0.44 carbophenothion 786-19-6 5.94 5.33 <25 -5.74 -5.44 0.30 carboxin 5234-68-4 2.10 2.14 92 -3.14 -2.27 0.87 carbromal 77-65-6 1.62 1.54 118 -2.68 -2.05 0.63 carbutamide 339-43-5 1.02 1.01 144 -2.18 -1.71 0.47 carvacrol 499-75-2 3.40 3 -2.08 -2.90 -0.82 140 carvone 99-49-0 2.01 2.01 <25 -2.06 -1.51 0.55 cefamandole 34444-01-4 0.31 0.25 -0.14 cefazolin 26970-89-8 -1.16 -0.58 -2.62 ceftazidime 78439-06-2 -6.22 -2.04 cephaloridine 50-59-9 -6.63 184 -1.32 5.54 6.86 cephradine 38821-53-3 -1.53 -1.22 cetyl alcohol 6653-82-4 7.17 56 -7.26 -6.98 0.28 chenodeoxycholic acid 474-25-9 4.51 166 -3.64 -5.42 -1.78 chloral hydrate 302-17-0 0.71 0.99 1.7 chloralose 15879-93-3 0.41 1.02 183 -1.84 -1.49 0.35 chloramben 133-90-4 1.95 195 -2.47 -3.15 -0.68 chloramben methyl ester 7286-84-2 2.49 57 -3.26 -2.31 0.95 chloramphenicol 56-75-7 1.28 1.14 151 -2.11 -2.04 0.07 chlordane 57-74-9 5.80 6 <25 -5.35 -5.30 0.05 chlordene 3734-48-3 5.09 5.44 -62 -5.39 -4.59 0.80 chlordiazepoxide 58-25-3 2.46 2.44 -2.18 chlordimeform 6164-98-3 2.79 2.89 32 -2.86 -2.36 0.50 chlorfenac 85-34-7 3.43 3.2 161 -3.08 -4.29 -1.21 chlorfenprop-methyl 14437-17-3 3.40 <25 -3.77 -2.90 0.87 chlorflurecol 2464-37-1 2.67 194 -4.18 -3.86 0.32 chloroacetamide 79-07-2 -0.50 -0.53 117 -0.02 0.08 0.10 chloroacetic acid 79-11-8 -0.08 0.22 61 1.81 0.22 -1.59 chlorobenzene 108-90-7 2.86 2.89 -46 -2.38 -2.36 0.02 chlorodibromomethane 124-48-1 2.23 2.24 -22 -1.90 -1.73 0.17 chloroethane 75-00-3 1.47 1.43 -136 -1.06 -0.97 0.09 chloroethylene 75-01-4 1.52 -154 -1.36 -1.02 0.34 chloroform 67-66-3 1.95 1.97 -64 -1.17 -1.45 -0.28 chloroneb 2675-77-6 3.20 134 -4.41 -3.79 0.62 chloropham 101-21-3 3.37 3.51 41 -3.38 -3.03 0.35 chloropicrin 76-06-2 1.60 2.09 <25 -2.00 -1.10 0.90 chloropropylate 5836-10-2 4.87 73 -4.53 -4.85 -0.32 chlorothalonil 1897-45-6 3.47 2.90 250 -5.64 -5.22 0.42 chlorothiazide 58-94-6 -0.31 -0.24 342 -3.05 -2.36 0.69 chloroxuron 1982-47-4 3.79 151 -4.89 -4.55 0.34 chlorpheniramine 132-22-9 3.15 3.17 <25 -0.24 -2.65 -2.42 chlorpromazine 50-53-3 5.80 5.35 57 -5.1 -5.62 -0.52 chlorpropamide 94-20-2 2.35 2.27 127 -3.03 -2.87 0.16 chlorpyrifos methyl 5598-13-0 3.81 4.31 46 -4.82 -3.52 1.30 chlorpyriphos 2921-88-2 4.49 4.82 43 -5.67 -4.17 1.50 chlorquinox 3495-42-9 3.81 190 -5.43 -4.96 0.47 chlortetracycline 57-62-5 -0.09 168 -2.88 -0.84 2.04 chlorthalidone 77-36-1 0.45 -3.45 chlorzoxazone 95-25-0 1.87 -2.83 cholanthrene 479-23-2 6.12 173 -7.85 -7.10 0.75 cholic acid 81-25-4 2.43 200 -3.37 -3.68 -0.31 chrysene 218-01-9 5.66 5.81 256 -7.58 -7.47 0.11 cimetidine 51481-61-9 0.35 0.40 142 -1.35 -1.02 0.33 cinchomeronicacid 490-11-9 -0.25 262 -1.86 -1.62 0.24 cinchonidine 485-71-2 2.49 2.82 201 -3.07 -3.75 -0.68 141 cinchonine 118-10-5 2.49 2.82 259 -3.09 -4.33 -1.24 cinmetacin 20168-99-4 3.95 170 -5.54 -4.90 0.64 cinnamic acid 621-82-9 2.24 2.13 133 -2.48 -2.82 -0.34 cis-1,2-dichloroethylene 156-59-2 1.77 1.86 -81 -1.30 -1.27 0.03 cis-1,2-dimethyIcyclohexane 2207-01-4 4.39 -50 -4.27 -3.89 0.38 cis-2-pentene 627-20-3 2.86 -151 -2.54 -2.36 0.18 citral 5392-40-5 2.95 <25 -2.06 -2.45 -0.39 citric acid 77-92-9 -1.56 -1.72 153 0.51 0.78 0.27 clofazimine 2030-63-9 6.69 7.48 -5.8 cocaine 50-36-2 2.57 2.3 98 -2.25 -2.80 -0.55 codeine 76-57-3 0.98 1.14 155 -1.52 -1.78 -0.26 colchicine 64-86-8 1.19 1.3 -0.94 coronene 191-07-1 7.04 438 -9.38 -10.67 -1.29 corticosterone 50-22-6 2.32 1.94 181 -3.24 -3.38 -0.14 cortisone 53-06-5 1.30 1.47 -3.27 cortisone-acetate 50-04-4 1.83 2.10 235 -4.00 -3.43 0.57 coumaphos 56-72-4 4.33 4.13 91 -5.38 -4.49 0.89 coumarin 91-64-5 1.41 1.39 70 -1.73 -1.36 0.37 coumatetralyl 5836-29-3 4.83 180 -2.84 -5.88 -3.04 crotonaldehyde (2-butenal) 4170-30-3 0.52 -77 0.32 -0.02 -0.34 cyanazine 21725-46-2 1.39 2.22 167 -3.15 -2.31 0.84 cycloate 1134-23-2 3.66 3.97 12 -3.40 -3.16 0.24 cyclobarbital 52-31-3 1.87 1.77 171 -2.02 -2.83 -0.81 cyclobutyl-5-spirobarbituric acid 6128-03-6 -0.57 -0.27 256 -1.66 -1.24 0.42 cycloheptane 291-64-5 3.91 4.00 -12 -3.51 -3.41 0.10 cycloheptanol 502-41-0 1.83 2 -0.88 -1.33 -0.45 cycloheptatriene 544-25-2 2.55 2.63 -80 -2.15 -2.05 0.10 cycloheptene 628-92-2 3.43 -56 -3.18 -2.93 0.25 cyclohexane 110-82-7 3.35 3.44 7 -3.10 -2.85 0.25 cyclohexanecarboxylic acid 98-89-5 1.84 30 -1.45 -1.39 0.06 cyclohexane-spirobarbiturate 1.11 1.36 266 -3.17 -3.02 0.15 cyclohexanol 108-93-0 1.27 1.23 23 -0.44 -0.77 -0.33 cyclohexanol acetate 622-45-7 2.21 <25 -1.67 -1.71 -0.04 cyclohexanone 108-94-1 0.86 0.81 -47 -0.60 -0.36 0.24 cyclohexene 110-83-8 2.87 2.86 -104 -2.59 -2.37 0.22 cycloheximide 66-81-9 0.23 0.55 120 -1.13 -0.68 0.45 cyclohexyl-5-spirobarbituric 52-44-8 0.55 0.91 289 -3.06 -2.69 0.37 acid cyclooctane 292-64-8 4.47 4.45 15 -4.15 -3.97 0.18 cyclooctanol 696-71-9 2.38 15 -1.29 -1.88 -0.59 cyclooctyl-5-spirobarbituric acid 1.67 1.79 228 -2.98 -3.20 -0.22 cyclopentane 287-92-3 2.79 3.00 -94 -2.64 -2.29 0.35 cyclopentene 142-29-0 2.31 -135 -1.73 -1.81 -0.08 cyclopentyl-5-spirobarbituric 56209-30-4 -0.01 0.24 270 -2.35 -1.94 0.41 acid cyclopropyl-5-spirobarbituric 6947-77-9 -1.13 -0.53 325 -1.89 -1.37 0.52 acid cycloserine 68-41-7 -1.19 156 -0.01 0.38 0.39 cycluron 2163-69-1 2.58 130 -2.36 -3.13 -0.77 142 cyproheptadine 129-03-3 4.92 4.69 -1.9 cytisine 485-35-8 0.01 155 0.36 -0.81 -1.17 cytosine 71-30-7 -1.85 -1.73 320 -1.14 -0.60 0.54 d,l-mepivacaine 96-88-8 2.12 1.95 150 -1.55 -2.87 -1.32 daminozide 1596-84-5 -1.03 -1.5 163 -0.2 0.15 0.35 danazol 17230-88-5 3.93 3.93 225 -5.51 -5.43 0.08 danthron 117-10-2 2.84 -5.19 dapsone 80-08-0 0.89 0.97 175 -2.82 -1.89 0.93 dazomet 533-74-4 0.86 104 -2.13 -1.15 0.98 d-camphoric acid 124-83-4 1.75 184 -1.42 -2.84 -1.42 decachlorobiphenyl 2051-24-3 9.92 8.27 304 -11.89 -12.21 -0.32 decachlorodiphenyl ether 31710-30-2 10.93 221 -12.95 -12.39 0.56 decalin 91-17-8 4.79 -31 -4.35 -4.29 0.06 decane 124-18-5 5.98 -30 -6.44 -5.48 0.96 decanoic acid 334-48-5 4.04 4.09 31 -3.44 -3.60 -0.16 delmadinone acetate 13698-49-2 4.11 169 -4.95 -5.05 -0.10 delta-hexachlorocyclohexane 319-86-8 3.75 3.72 142 -4.51 -4.42 0.09 demeclocycline 127-33-3 -0.61 176 -2.52 -0.40 2.12 deoxycholic acid 83-44-3 4.51 174 -3.95 -5.50 -1.55 deoxycorticosterone 64-85-7 3.25 2.88 136 -3.45 -3.86 -0.41 deoxycorticosterone acetate 56-47-3 3.79 3.08 -136 -4.63 -3.29 1.34 des 56-53-1 4.96 5.07 169 -4.35 -5.90 -1.55 desipramine 50-47-5 4.47 4.9 212 -3.66 -5.84 -2.18 desmedipham 13684-56-5 3.40 3.39 120 -4.63 -3.85 0.78 dexamethasone 50-02-2 1.75 2.01 263 -3.61 -3.63 -0.02 dexamethasone-17-acetate 1177-87-3 2.28 2.91 263 -4.90 -4.16 0.74 d-fenchone 4695-62-9 2.18 6 -1.85 -1.68 0.17 di(2-ethylhexyl)-phthalate 117-81-7 8.71 7.45 -50 -6.96 -8.21 -1.25 dialifos 10311-84-9 4.36 68 -6.34 -4.29 2.05 diallate 2303-16-4 3.67 25 -4.08 -3.17 0.91 diallyl phthalate 131-17-9 3.11 3.23 -70 -3.13 -2.61 0.52 diatrizoic acid 117-96-4 0.65 -2.79 diazepam 439-14-5 3.16 2.99 125 -3.76 -3.66 0.10 diazinon 333-41-5 3.50 3.3 120 -3.76 -3.95 -0.19 dibenz(a,h)anthracene 53-70-3 6.84 6.50 266 -8.74 -8.75 -0.01 dibenzofurane 132-64-9 4.09 4.12 82 -4.60 -4.16 0.44 dibenzo-p-dioxin 262-12-4 4.62 4.38 123 -5.31 -5.10 0.21 dibenzothiophene 132-65-0 4.56 4.49 97 -5.21 -4.78 0.43 dibromomethane 74-95-3 1.53 1.88 -53 -1.17 -1.03 0.14 dibucaine 85-79-0 5.34 4.4 64 -3.7 -5.23 -1.53 dibutyl ether 142-96-1 2.91 3.22 -95 -1.99 -2.41 -0.42 dibutylamine 111-92-2 2.66 2.83 -59 -1.44 -2.16 -0.72 dibutylphthalate 84-74-2 4.65 4.72 -35 -4.40 -4.15 0.25 dicamba 1918-00-9 2.23 2.21 115 -1.7 -2.63 -0.93 dicapthon 2463-84-5 3.55 3.88 53 -4.31 -3.33 0.98 dichlormid 37764-25-3 1.92 1.64 5 -1.62 -1.42 0.20 dichlorodifluoromethane 75-71-8 2.00 2.16 -155 -1.99 -1.50 0.49 dichlorodiphenyldichloroethane 72-54-8 6.06 6.22 110 -6.55 -6.41 0.15 (ddd) 143 dichlorodiphenyldichloroethylen 72-55-9 6.74 6.96 89 -6.90 -6.88 0.02 e (p,p'-dde) dichloromethane 75-09-2 1.25 1.25 -97 -0.74 -0.75 -0.01 dichlorophen 97-23-4 4.89 177.5 -3.95 -5.92 -1.96 dichlorprop 120-36-5 3.26 3.43 118 -2.83 -3.69 -0.86 diclofenac 15307-86-5 4.32 4.4 -5.1 diclofopmethyl 51338-27-3 5.50 4.80 40 -3.82 -5.15 -1.33 didanosine 69655-05-6 -1.98 -1.24 -0.94 dieldrin 60-57-1 3.70 4.55 175 -6.29 -4.70 1.59 dienestrol 84-17-3 4.50 227 -4.95 -6.02 -1.07 diethyl disulfide 110-81-6 2.80 -102 -2.42 -2.30 0.12 diethyl ether 60-29-7 0.87 0.89 -116 -0.09 -0.37 -0.28 diethyl phthalate 84-66-2 2.62 2.47 -33 -2.35 -2.12 0.23 diethyl succinate 123-25-1 1.48 1.19 -20 -0.96 -0.98 -0.02 diethyl sulfide 352-93-2 1.90 1.95 -104 -1.34 -1.40 -0.06 diethyl sulfone 597-35-3 -0.44 -0.59 73 0.04 0.46 0.42 diethylamine 109-89-7 0.54 0.58 -50 1.03 -0.04 -1.07 difenoxuron 14214-32-5 2.99 -4.16 diflunisal 22494-42-4 4.39 4.44 -4.48 difluron 35367-38-5 3.95 3.88 231 -6.02 -5.51 0.51 digitoxin 71-63-6 3.05 2.83 256 -5.28 -4.86 0.42 digoxin 20830-75-5 2.27 1.26 260 -4.16 -4.12 0.04 dihydroequilenin 3.53 -4.64 dihydroequilin 3.30 -4.4 diiodomethane 75-11-6 2.31 2.30 5 -2.34 -1.81 0.53 diisobutylphthalate 84-69-5 4.39 4.11 -58 -4.66 -3.89 0.77 diisopropyl ether 108-20-3 1.49 1.52 -87 -1.10 -0.99 0.11 diisopropyl sulfide 625-80-9 2.52 2.84 -78 -2.24 -2.02 0.22 diisopropylketone 565-80-0 1.91 1.86 -80 -1.30 -1.41 -0.11 dimetan 122-15-6 1.83 46 -0.85 -1.54 -0.69 dimethirimol 5221-53-4 2.05 1.9 102 -2.24 -2.32 -0.08 dimethoate 60-51-5 0.75 0.78 52 -0.74 -0.52 0.22 dimethoxymethane 109-87-5 -0.43 0.18 -105 0.48 0.93 0.45 dimethyl carbate 5826-73-3 1.10 38 -1.20 -0.73 0.47 dimethyl disulfide 624-92-0 1.74 1.77 -85 -1.44 -1.24 0.20 dimethyl phthalate 131-11-3 1.56 1.56 2 -1.66 -1.06 0.60 dimethylsulfide 75-18-3 0.84 1.05 -98 -0.45 -0.34 0.11 dimethylterephthalate 120-61-6 2.08 2.25 141 -4.01 -2.74 1.27 dimorpholamine 119-48-2 3.96 0.1 dinitramine 29091-05-2 4.02 98 -5.47 -4.25 1.22 dinoseb 88-85-7 3.54 3.56 56 -3.38 -3.35 0.03 d-inositol 643-12-9 -0.12 224 0.35 -1.37 -1.72 diosgenin 512-04-9 5.91 195 -7.32 -7.11 0.21 dioxacarb 6988-21-2 0.28 114 -1.57 -0.67 0.90 diphenamid 957-51-7 2.31 135 -2.98 -2.91 0.07 diphenic acid 482-05-3 1.80 2.07 227 -2.28 -3.32 -1.04 diphenyl ether 101-84-8 4.24 4.21 27 -3.91 -3.76 0.15 diphenylacetic acid 117-34-0 2.76 3.09 147 -3.22 -3.48 -0.26 diphenylamine 122-39-4 3.62 3.50 52 -3.50 -3.39 0.11 144 diphenylmethane 101-81-5 4.21 4.14 26 -4.08 -3.72 0.36 diphenylnitrosamine 86-30-6 3.16 3.13 67 -3.75 -3.08 0.67 diphenylolpropane 80-05-7 3.67 3.32 150 -2.82 -4.42 -1.60 dipropyl ether 111-43-3 1.93 2.03 -123 -1.62 -1.43 0.19 dipropyl sulfide 111-47-7 2.96 -103 -2.58 -2.46 0.12 dipropylamine 142-84-7 1.60 1.67 <25 -0.46 -1.10 -0.64 disopyramide 3737-09-5 2.58 2.71 -1.7 disulfiram 97-77-8 3.88 3.88 70 -4.86 -3.83 1.03 disulfoton 298-04-4 4.17 4.02 108 -4.23 -4.50 -0.27 ditalimfos 5131-24-8 3.48 3.47 82 -3.35 -3.55 -0.20 ditolyl ether 28299-41-4 5.24 <25 -4.85 -4.74 0.11 diuron 330-54-1 2.68 2.68 159 -3.76 -3.52 0.24 dl-1,2-diphenylethanol 614-29-9 2.98 67 -2.52 -2.90 -0.38 dl-2-(2-chlorophenoxy)propionic 76466-16-5 2.50 114 -2.22 -2.89 -0.67 acid dl-coniine 458-88-8 2.51 -18 -1.5 -2.01 -0.51 d-limonene 5989-27-5 4.35 -74 -4.00 -3.85 0.15 dl-tartaric acid 133-37-9 -2.78 205 0.767 1.48 0.71 dl-tropic acid 552-63-6 0.43 0.77 119 -0.93 -0.87 0.06 d-mandelic acid 611-71-2 0.50 0.62 131 0.0414 -1.06 -1.10 d-mannitol 69-65-8 -2.05 -2.65 168 0.07 1.12 1.05 dnoc 534-52-1 2.29 2.13 85.8 -1.46 -2.40 -0.94 dodecane 112-40-3 7.04 6.10 -10 -7.67 -6.54 1.13 dodecanol 112-53-8 5.06 5.13 24 -4.67 -4.56 0.11 doxepin 1668-19-5 4.09 120 -3.4 -4.54 -1.14 doxycycline 564-25-0 -0.51 201 -2.87 -0.75 2.12 d-querticol 488-73-3 -1.05 234 -0.17 -0.54 -0.37 d-tartaric acid 147-71-7 -2.78 173 0.837 1.80 0.96 dulcin 150-69-6 1.48 173 -2.17 -2.46 -0.29 dyphylline 479-18-5 -1.30 161.5 -0.17 0.44 0.61 ecgonine 481-37-8 -2.71 <25 -0.02 3.21 3.23 endosulfan 115-29-7 3.95 3.83 106 -6.15 -4.26 1.89 endothall 145-73-3 -0.34 144 -0.27 -0.35 -0.08 endrin 72-20-8 3.70 4.55 200 -6.18 -4.95 1.23 ephedrine 299-42-3 0.89 0.93 38 -0.47 -0.52 -0.05 epiandrosterone 481-29-8 3.55 3.69 162 -4.16 -4.42 -0.26 epichlorohydrin 106-89-8 0.46 0.45 -57 -0.15 0.04 0.19 epinephrine 51-43-4 0.89 0.93 -2.74 epitiostanol 2363-58-8 4.45 127 -5.41 -4.97 0.44 equilenin 517-09-9 3.27 258 -5.24 -5.10 0.14 equilin 474-86-2 2.90 238 -5.28 -4.53 0.75 eriodictyol 552-58-9 1.84 2.02 257 -3.62 -3.66 -0.04 erythritol 149-32-6 -1.71 -2.29 122 0.70 1.24 0.54 estradiol 57-91-0 3.78 3.86 220 -5.03 -5.23 -0.20 estragole 140-67-0 3.13 <25 -2.92 -2.63 0.29 estriol 50-27-1 3.20 2.45 -4.96 estrone 53-16-7 3.38 3.13 255 -5.53 -5.18 0.35 ethambutol 74-55-5 0.12 88 -0.57 -0.25 0.32 ethane 74-84-0 1.75 1.81 -183 -2.73 -1.25 1.48 145 ethanethiol 75-08-1 1.17 -148 -0.60 -0.67 -0.07 ethanol 64-17-5 -0.24 -0.31 -114 1.10 0.74 -0.36 ethinyl-estradiol 57-63-6 3.86 3.67 142 -4.30 -4.53 -0.23 ethiofencarb 29973-13-5 2.20 2.04 <25 -2.09 -1.70 0.39 ethion 563-12-2 5.57 5.07 -25 -5.54 -5.07 0.47 ethirimol 23947-60-6 2.41 2.20 158 -3.02 -3.24 -0.22 ethisterone 434-03-7 3.30 269 -5.66 -5.24 0.42 ethofumesate 26225-79-6 2.32 2.70 70 -3.42 -2.27 1.15 ethoxyzolamide 452-35-7 2.02 2.01 189 -3.81 -3.16 0.65 ethyl acrylate 140-88-5 1.33 1.32 -72 -0.74 -0.83 -0.09 ethyl caprinate 110-38-3 4.94 <25 -4.10 -4.44 -0.34 ethyl cinnamate 103-36-6 3.14 2.99 7 -3.00 -2.64 0.36 ethyl dipropylthiocarbamate 759-94-4 3.21 3.21 <25 -2.70 -2.71 -0.01 ethyl formate 109-94-4 0.26 -113 0.15 0.24 0.09 ethyl heptanoate 106-30-9 3.36 -87 -2.74 -2.86 -0.12 ethyl pelargonate 123-29-5 4.41 -36 -3.80 -3.91 -0.11 ethyl propionate 105-37-3 1.24 1.21 -99 -0.66 -0.74 -0.08 ethyl propyl ether 628-32-0 1.40 -127 -0.66 -0.90 -0.24 ethyl valerate 539-82-2 2.30 -91 -1.75 -1.80 -0.05 ethyl vinyl ether 109-92-2 1.01 1.04 -116 -0.85 -0.51 0.34 ethyl-4-aminobenzoate 94-09-7 1.92 1.86 -2.62 (benzocaine) ethylacetate 141-78-6 0.71 0.73 -84 -0.02 -0.21 -0.19 ethylamine 75-04-7 -0.13 -0.13 -81 2.06 0.63 -1.43 ethylbenzene 100-41-4 3.17 3.15 -95 -2.77 -2.67 0.10 ethylbenzoate 93-89-0 2.64 2.64 -31 -2.32 -2.14 0.18 ethyl-biscoumacetate 548-00-5 3.21 177 -3.66 -4.23 -0.57 ethylbutyrate 105-54-4 1.77 1.71 -135 -1.28 -1.27 0.01 ethyl-caproate 123-66-0 2.83 -68 -2.31 -2.33 -0.02 ethyl-caprylate 106-32-1 3.88 -47 -3.39 -3.38 0.01 ethylcyclohexane 1678-91-7 4.40 -111 -4.25 -3.90 0.35 ethylene 74-85-1 1.27 1.13 -169 -0.40 -0.77 -0.37 ethylene glycol 107-21-1 -1.37 -1.36 -13 1.06 1.87 0.81 ethyl-isopropyl-ether 625-54-7 1.18 <25 -0.55 -0.68 -0.13 ethyl-p-hydroxybenzoate 120-47-8 2.51 2.47 117 -2.35 -2.93 -0.58 ethyne 74-86-2 0.39 0.37 -81 0.29 0.11 -0.18 etofenprox 80844-07-1 7.36 7.05 37 -8.60 -6.98 1.62 etomidate 33125-97-2 2.66 3.05 -6.74 etryptamine 2235-90-7 2.26 97 -2.57 -2.48 0.09 eucalyptol 470-82-6 2.76 2.50 36 -2.49 -2.37 0.12 eugenol 97-53-0 2.40 15 -1.56 -1.90 -0.34 fenarimol 60168-88-9 2.86 3.6 117 -4.38 -3.28 1.10 fenbuconazole 114369-43-6 4.01 3.23 -6.23 fenbufen 36330-85-5 3.14 3.20 186 -5.06 -4.25 0.81 fenchlorphos 299-84-3 4.96 5.07 -4.1 fenclofenac 34645-84-6 4.71 4.80 136 -3.85 -5.32 -1.47 fenfuram 24691-80-3 1.93 110 -3.30 -2.28 1.02 fenitrothion 122-14-5 3.21 3.3 3.4 -4.04 -2.71 1.33 fenoxycarb 72490-01-8 4.46 4.30 54 -4.70 -4.25 0.46 146 fenpiclonil 74738-17-3 3.66 3.86 -5.07 fensulfothion 115-90-2 2.24 2.23 <25 -2.30 -1.74 0.56 fentanyl 437-38-7 3.62 3.89 83 -1.13 -3.70 -2.57 fenthion 55-38-9 3.84 4.09 8 -4.57 -3.34 1.23 fenuron 101-42-8 0.98 0.98 133 -1.6 -1.56 0.04 fluconazole 86386-73-4 0.47 0.47 139 -1.80 -1.11 0.69 flucytosine 2022-85-7 -1.65 -0.96 fludioxonil 131341-86-1 4.15 4.12 -5.21 fludrocortisone 127-31-1 1.54 1.67 -3.43 flufenamic acid 530-78-9 4.88 5.25 134 -4.36 -5.47 -1.11 fluometuron 2164-17-2 2.39 2.42 163 -3.43 -3.27 0.16 fluoranthene 206-44-0 4.95 5.16 110 -5.89 -5.30 0.59 fluorene 86-73-7 4.07 4.18 116 -4.91 -4.48 0.43 fluorodifen 15457-05-3 4.74 3.65 90 -5.22 -4.89 0.33 fluoromethalone 426-13-1 2.07 2.00 296 -4.10 -4.28 -0.18 fluotrimazole 31251-03-3 5.15 164 -8.4 -6.04 2.36 fluphenazine 69-23-8 4.63 4.36 165 -4.15 -5.53 -1.38 flurbiprofen 5104-49-4 3.75 4.16 -3.74 fluridone 59756-60-4 2.80 2.93 213 -4.44 -4.18 0.26 flurobenzene 462-06-6 2.28 2.27 -42 -1.80 -1.78 0.02 flutriafol 76674-21-0 2.32 2.3 130 -3.37 -2.87 0.50 folic acid 59-30-3 -2.17 -5.44 formanilide 103-70-8 1.16 1.15 47 -0.68 -0.88 -0.20 formetanate 22259-30-9 0.56 -2.34 fructose 57-48-7 -2.06 129 0.64 1.52 0.88 furan 110-00-9 1.32 1.34 -86 -0.82 -0.82 0.00 furfural 98-01-1 0.67 0.41 -37 -0.10 -0.17 -0.07 furosemide 54-31-9 1.87 2.03 206 -3.66 -3.18 0.48 gallic acid 149-91-7 0.43 0.7 222 -1.16 -1.90 -0.74 gamma-butyrolatone 96-48-0 -0.39 -45 1.07 0.89 -0.18 gentisin(sp) 437-50-3 3.05 266 -2.93 -4.96 -2.03 gibberellic acid 77-06-5 -0.57 0.24 227 -1.84 -0.95 0.89 glafenine 3820-67-5 3.04 -4.57 glucose 50-99-7 -2.21 -2.41 146 0.74 1.50 0.76 glutamine 56-85-9 -3.37 -3.64 185 -0.55 2.27 2.82 glutaric acid 110-94-1 -0.13 -0.29 97.5 1 -0.10 -1.10 glutethimide 77-21-4 1.99 1.9 -2.34 glyburide 10238-21-8 4.23 170 -5.09 -5.18 -0.09 glybuthiazole 535-65-9 1.54 221 -3.74 -3.00 0.74 glycerol 56-81-5 -1.54 -1.96 18 1.12 2.04 0.92 glyceryl triacetate 102-76-1 0.67 0.25 3 -0.60 -0.17 0.43 glycine 56-40-6 -3.21 -3.21 233 0.493 1.63 1.14 glycocholic acid 475-31-0 1.71 166 -5.15 -2.62 2.53 griseofulvin 126-07-8 1.75 2.18 220 -4.60 -3.20 1.40 guaiacol 90-05-1 1.32 1.32 28 -1.96 -0.85 1.11 guaifenesin 93-14-1 0.10 -0.6 guanidinoacetic acid 352-97-6 -2.54 300 -1.51 0.29 1.80 guanine 73-40-5 -1.28 -0.96 -3.58 haloperidol 52-86-8 3.85 4.28 148 -4.43 -4.58 -0.15 147 halothane 151-67-7 2.45 2.30 <25 -1.71 -1.95 -0.24 hematein 475-25-2 -0.18 250 -2.7 -1.57 1.13 heptabarbital 509-86-4 2.43 2.03 -3 heptachlor 76-44-8 4.92 6.10 95 -6.32 -5.12 1.20 heptachlor-epoxide 1024-57-3 3.87 4.98 160 -6.05 -4.72 1.33 heptanal 111-71-7 2.42 -43 -1.70 -1.92 -0.22 heptane 142-82-5 4.40 4.66 -91 -4.53 -3.90 0.63 heptobarbital (5-methyl-5- 76-94-8 0.84 0.91 -2.38 phenylbarbital) heptyl-4-aminobenzoate 14309-40-1 4.57 4.5 75 -4.6 -4.57 0.03 heptylamine 111-68-2 2.51 2.57 -23 -0.90 -2.01 -1.11 heroin 561-27-3 1.50 1.58 -2.8 hexabarital 56-29-1 1.63 1.49 145 -2.74 -2.33 0.41 hexachloro-1,3-butadiene 87-68-3 4.90 4.78 -21 -4.92 -4.40 0.52 hexachlorobenzene 118-74-1 6.06 5.73 227 -7.56 -7.58 -0.02 hexachlorocyclopentadiene 77-47-4 5.05 5.04 -10 -5.18 -4.55 0.63 hexachloroethane(sp) 67-72-1 4.61 4.14 187 -3.67 -5.73 -2.06 hexachlorophene 70-30-4 7.08 7.54 165 -3.71 -7.98 -4.27 hexadecane 544-76-3 9.16 18 -8.40 -8.66 -0.26 hexamethylbenzene 87-85-4 4.99 4.61 164 -5.23 -5.88 -0.65 hexanoic acid 142-62-1 1.92 1.92 -3 -1.06 -1.42 -0.36 hexestrol 5635-50-7 5.11 185 -4.43 -6.21 -1.78 hexethal ((5-ethyl-5- 77-30-5 2.77 2.47 -3.05 hexylbarbituric acid) hexyl acetate 142-92-7 2.83 2.96 -112 -2.46 -2.33 0.13 hexyl-4-aniinobenzoate 13476-55-6 4.04 3.95 62 -3.95 -3.91 0.04 hexylamine 111-26-2 1.98 2.06 -23 -0.25 -1.48 -1.23 hexylbenzene 1077-16-3 5.29 5.52 -61 -5.21 -4.79 0.42 hippuric acid 495-69-2 0.65 0.31 189 -1.68 -1.79 -0.11 histidine 71-00-1 -3.73 -3.56 282 -0.53 1.66 2.19 hydantoin 461-72-3 -1.69 -1.69 222 -0.4 0.22 0.62 hydrastine 118-08-1 2.08 132 -4.11 -2.65 1.46 hydrazobenzene 122-66-7 2.97 2.94 131 -2.92 -3.53 -0.61 hydrobenzoin 27134-24-3 1.77 1.91 120 -1.93 -2.22 -0.29 hydrochlorothiazide 58-93-5 -0.40 -0.07 -2.69 hydrocinnamic acid 501-52-0 1.90 1.84 49 -1.41 -1.64 -0.23 hydrocortisone 50-23-7 1.70 1.61 218 -3.08 -3.13 -0.05 hydrocortisone 21-acetate 50-03-3 2.23 2.19 223 -4.88 -3.71 1.17 hydrocortisone tebutate 508-96-3 3.69 230 -5.51 -5.24 0.27 hydroflumethiazide 135-09-1 -0.25 0.36 -3.04 hydroxyisoandrosterone 514-17-0 2.63 193 -3.59 -3.81 -0.22 hydroxyprogesterone-17a 68-96-2 3.15 3.17 276 -3.82 -5.16 -1.34 hydroxyurea 127-07-1 -1.80 -1.80 145 1.12 1.10 -0.02 hyocholic acid 547-75-1 2.43 261 -4.35 -4.29 0.06 hyodeoxycholic acid 83-49-8 4.51 198 -3.82 -5.74 -1.92 hyoscyamine 101-31-5 1.62 1.83 116 -1.91 -2.03 -0.12 hypoxanthine 68-94-0 -1.20 -1.11 150 -2.29 0.45 2.74 ibuprofen 15687-27-1 3.68 3.5 76 -3.76 -3.69 0.07 ibuproxam 53648-05-8 2.61 123 -3.04 -3.09 -0.05 148 idobutal (5-butyl-5- 3146-66-5 1.76 -2.17 allylbarbiturate) imipramine 50-49-7 5.04 4.44 174 -4.19 -6.03 -1.84 indane 496-11-7 3.15 3.18 -51 -3.03 -2.65 0.38 indapamide 26807-65-8 2.94 -3.79 indazole 271-44-3 1.63 1.77 147 -2.16 -2.35 -0.19 indole 120-72-9 2.13 2.14 52 -1.52 -1.90 -0.38 indole-3-acetic acid 87-51-4 1.40 1.41 168 -2.07 -2.33 -0.26 indoline 496-15-1 1.78 <25 -1.04 -1.28 -0.24 indomethacine 53-86-1 4.18 4.27 159 -4.62 -5.02 -0.40 indoprofen 31842-01-0 2.74 2.77 -4.82 inosine 58-63-9 -3.16 -2.1 212 -1.23 1.79 3.02 iodamide 440-58-4 0.69 -2.32 iodobenzene 591-50-4 3.27 3.25 -29 -2.78 -2.77 0.01 iodoethane 75-03-6 2.00 2.00 -108 -1.60 -1.50 0.10 iodofenphos 18181-70-9 5.49 5.51 72 -5.31 -5.46 -0.15 iodomethane 74-88-4 1.47 1.51 -67 -1.00 -0.97 0.03 iopanoic acid 96-83-3 4.89 -4.58 ioxynil 1689-83-4 3.26 3.43 200 -3.61 -4.51 -0.90 iprodione 36734-19-7 3.12 3.1 -4.41 isoamyl salicylate 87-20-7 4.32 <25 -3.16 -3.82 -0.66 isobutanol 78-83-1 0.69 0.76 -108 0.03 -0.19 -0.22 isobutyl acetate 110-19-0 1.64 1.76 -99 -1.21 -1.14 0.07 isobutylacetate 106-63-8 2.25 2.22 <25 -1.21 -1.75 -0.54 isobutylbenzene 538-93-2 4.63 -51 -4.12 -4.13 -0.01 isobutylformate 542-55-2 1.19 -95 -1.01 -0.69 0.32 isobutyltoluene 28517-37-5 4.55 <25 -4.12 -4.05 0.07 isobutyric acid 79-31-2 0.86 -46 0.28 -0.36 -0.64 isocarbamid 30979-48-7 1.03 -2.15 isocarboxazid 59-63-2 0.97 1.49 -2.46 isocinchomeronicacid 100-26-5 1.29 156 -2.14 -2.10 0.04 isoguanine 492-32-0 0.35 -3.4 isoniazid 54-85-3 -0.67 -0.7 171.4 0.01 -0.29 -0.30 isopentanol 123-51-3 1.22 1.16 -117 -0.52 -0.72 -0.20 isopentyl formate 110-45-2 1.72 -93 -1.52 -1.22 0.30 isophorone 78-59-1 2.09 -8 -1.06 -1.59 -0.53 isoprocarb 2631-40-5 2.29 2.31 93 -2.86 -2.47 0.39 isopropyl formate 625-55-8 0.57 -108 -0.63 -0.07 0.56 isopropyl tert-butyl ether 17348-59-3 1.89 1.52 -88 -2.37 -1.39 0.98 isopropylacetate 108-21-4 1.24 1.22 -73 -0.60 -0.74 -0.14 isopropylbenzene 98-82-8 3.57 3.66 -96 -3.27 -3.07 0.20 isoproturon 34123-59-6 2.40 2.50 158 -3.54 -3.23 0.31 isoquinoline 119-65-3 1.82 2.08 26 -1.45 -1.33 0.12 karbutilate 4849-32-5 1.47 1.66 169 -2.93 -2.41 0.52 kebuzone 853-34-9 0.90 128 -3.27 -1.43 1.84 ketoprofen 22071-15-4 2.76 3.12 94 -3.25 -2.95 0.30 khellin 82-02-0 2.57 154 -2.40 -3.36 -0.96 1-arabinose 87-72-9 -2.18 -2.32 162 0.39 1.32 0.93 1-asparagine 70-47-3 -1.42 -1.9 290 -0.74 -0.73 0.01 149

1-carvone 6485-40-1 2.01 <25 -2.06 -1.51 0.55 l-dihydrocarvone 619-02-3 2.35 -2.18 l-dopa 63-84-3 -2.82 -2.74 -1.82 lenacil 2164-08-1 2.83 2.31 290 -4.59 -4.98 -0.39 leptophos 21609-90-5 6.39 6.31 60 -5.66 -6.24 -0.58 levodopa 59-92-7 -2.82 -2.74 295 -1.6 0.62 2.22 lidocaine 137-58-6 1.95 2.26 -1.77 limonene 138-86-3 4.35 4.35 -95 -4.00 -3.85 0.15 linalool 78-70-6 2.75 <25 -1.99 -2.25 -0.26 lindane 58-89-9 3.75 3.72 113 -4.6 -4.13 0.47 linuron 330-55-2 3.00 3.2 -3.52 liothyronine 6893-02-3 2.63 -5.22 1-mandelic acid 17199-29-0 0.50 0.62 131 -0.185 -1.06 -0.88 1-menthone 14073-97-3 2.83 -6 -2.49 -2.33 0.16 lomefloxacin 98079-51-7 -0.32 -0.8 -2.53 lorazepain 846-49-1 2.36 2.39 167 -3.6 -3.28 0.32 lovastatin 75330-75-5 4.30 4.26 174 -6 -5.29 0.71 1-tryptophan 73-22-3 -1.57 -1.06 282 -1.23 -0.50 0.73 l-tyrosine 60-18-4 -2.22 -2.26 342 -2.57 -0.45 2.12 lutidinic acid 499-80-9 1.29 247 -1.83 -3.01 -1.18 malathion 121-75-5 2.70 2.38 <25 -3.36 -2.20 1.16 malonic acid 141-82-2 -0.71 -0.81 135 0.762 0.11 -0.65 malonic acid diethyl ester 105-53-3 1.13 0.96 -50 -0.82 -0.63 0.19 m-aminoacetophenone 99-03-6 0.86 97 -1.28 -1.08 0.20 mannitol 87-78-5 -2.05 -2.65 167 0.06 1.13 1.07 m-bromotoluene 591-17-3 3.50 3.41 -40 -3.52 -3.00 0.52 m-chloroaniline 108-42-9 1.96 1.88 -10.3 -1.37 -1.46 -0.09 m-chlorobenzoic acid 535-80-8 2.70 2.68 158 -2.59 -3.53 -0.94 m-chlorobromobenzene 108-37-2 3.72 3.70 -21 -3.21 -3.22 -0.01 m-chloroiodobenzene 625-99-0 3.98 55 -3.55 -3.78 -0.23 m-chloronitrobenzene 121-73-3 2.60 2.47 43 -2.77 -2.28 0.49 m-chlorotoluene 108-41-8 3.35 3.28 -48 -3.52 -2.85 0.67 mebandazole 31431-39-7 3.06 2.83 289 -3.88 -5.20 -1.32 meconin 569-31-3 0.72 102 -1.89 -0.99 0.90 mecoprop 93-65-2 3.13 3.23 93 -2.55 -3.31 -0.76 medinoterb acetate 2487-01-6 3.25 86 -4.47 -3.36 1.11 medrogestone 977-79-7 4.19 138 -5.27 -4.82 0.45 mefenamic acid 61-68-7 4.94 5.12 -3.77 mefluidide 53780-34-0 1.87 2.02 184 -3.24 -2.96 0.28 megestrol acetate 595-33-5 3.58 214 -5.35 -4.97 0.38 melphalan 148-82-3 -0.21 -3.49 menadione 58-27-5 2.45 2.20 105 -3.03 -2.75 0.28 menthol 89-78-1 3.23 3.23 42 -2.54 -2.90 -0.36 menthone 10458-14-7 2.83 -6 -2.35 -2.33 0.02 meperidine 57-42-1 2.23 2.45 30 -1.89 -1.78 0.11 meprobamate 57-53-4 0.91 0.7 -1.81 metalaxyl 57837-19-1 2.71 1.65 72 -1.6 -2.68 -1.08 methacrylic acid 79-41-4 0.66 0.93 <25 0.00 -0.16 -0.16 methanol 67-56-1 -0.76 -0.77 -98 1.56 1.26 -0.30 150 methapyrilene 91-80-5 2.95 <25 -2.64 -2.45 0.19 methaqualone 72-44-6 2.93 2.5 -2.92 metharbital 50-11-3 1.14 1.15 154 -2.23 -1.93 0.30 methazolamide 554-57-4 0.09 0.13 213 -1.83 -1.47 0.36 methazole 20354-26-1 2.59 123 -2.82 -3.07 -0.25 methionine 63-68-3 -1.73 -1.87 280 -0.42 -0.32 0.10 methocarbamol 532-03-6 0.15 -0.99 methoprene 40596-69-8 5.54 5.50 164 -5.34 -6.43 -1.09 methotrimeprazine 60-99-1 5.33 4.68 117 -4.22 -5.75 -1.53 methoxsalen 298-81-7 2.30 1.93 143 -3.66 -2.98 0.68 methoxychlor 72-43-5 5.17 5.08 78 -6.54 -5.20 1.34 methoxychlor 72-43-5 5.17 5.08 89 -6.89 -5.31 1.58 methyclothiazide 135-07-9 0.90 -3.78 methyl acetate 79-20-9 0.18 0.18 -98 0.46 0.32 -0.14 methyl acrylate 96-33-3 0.80 0.80 -77 -0.22 -0.30 -0.08 methyl benzoate 93-58-3 2.11 2.12 <25 -1.85 -1.61 0.24 methyl butyl ether 628-28-4 1.40 1.66 -116 -0.99 -0.90 0.09 methyl butylketone 591-78-6 1.38 1.38 -57 -0.80 -0.88 -0.08 methyl butyrate 623-42-7 1.24 1.29 -95 -0.82 -0.74 0.08 methyl caprate 110-42-9 4.41 4.41 -13 -4.63 -3.91 0.72 methyl caprylate 111-11-5 3.36 -37 -2.88 -2.86 0.02 methyl chloride 74-87-3 1.25 1.25 -97 -0.88 -0.75 0.13 methyl ethyl ketone 78-93-3 0.32 0.29 -86 0.52 0.18 -0.34 methyl formate 107-31-3 -0.26 0.03 -100 0.58 0.76 0.18 methyl gallate 99-24-1 0.93 200 -1.24 -2.18 -0.94 methyl hydrazine 60-34-4 -1.06 -1.05 -20.09 1.34 1.56 0.22 methyl isopropyl ether 598-53-8 0.65 <25 -0.06 -0.15 -0.09 methyl isothiocyanate 556-61-6 1.17 0.94 30 -1.00 -0.72 0.28 methyl laurate 111-82-0 4.94 41 -4.69 -4.60 0.09 methyl methacrylate 80-62-6 1.11 1.38 -48 -0.80 -0.61 0.19 methyl nicotinate 93-60-7 0.77 0.83 43 -0.46 -0.45 0.02 methyl nonanoate 1731-84-6 3.88 3.87 -34 -3.38 -3.38 0.00 methyl propionate 554-12-1 0.71 0.82 -88 -0.14 -0.21 -0.07 methyl propyl ether 557-17-5 0.87 1.21 <25 -0.39 -0.37 0.02 methyl salicylate 119-36-8 2.33 2.34 20 -2.34 -1.83 0.51 methyl valerate 624-24-8 1.77 1.96 -91 -1.36 -1.27 0.09 methyl-2-chloro-9- 2536-31-4 2.67 194 -4.18 -3.86 0.32 hydroxyfluorene-9-carboxylate methyl-4-aminobenzoate 619-45-4 1.39 1.35 110 -1.59 -1.74 -0.15 methyl-4-methoxybenzoate 121-98-2 2.28 2.27 50 -2.41 -2.03 0.38 methyl-capronate 106-70-7 2.30 2.42 -71 -2.00 -1.80 0.20 methylcyclohexane 108-87-2 3.87 3.61 -126 -3.81 -3.37 0.44 methylcyclopentane 96-37-7 3.31 3.37 -142 -3.30 -2.81 0.49 methyldymron 42609-73-4 3.24 3.01 60 -3.35 -3.09 0.26 methylparaben 99-76-3 1.98 1.96 128 -1.83 -2.51 -0.68 methyl-/>-hydroxybenzoate 99-76-3 1.98 1.96 -1.71 methyl-t-butyl ether 1634-04-4 1.05 0.94 -109 -0.24 -0.55 -0.31 methyltestosterone 58-18-4 3.74 3.36 -3.99 methylthiouracil 56-04-2 -1.39 330 -2.43 -1.16 1.27 151

methyprylon 125-64-4 1.78 0.78 -0.38 metiazinic acid 13993-65-2 3.90 146 -3.94 -4.61 -0.67 metoclopramide 364-62-5 2.21 2.62 146 -3.18 -2.92 0.26 metolachlor 51218-45-2 3.25 3.13 <25 -2.73 -2.75 -0.02 metolazone 17560-51-9 2.42 252 -3.78 -4.19 -0.41 metolcarb 1129-41-5 1.71 1.70 75 -1.80 -1.71 0.09 metoxuron 19937-59-8 1.78 1.64 125 -2.56 -2.28 0.28 metronidazole 443-48-1 -0.46 -0.02 160 -1.22 -0.39 0.83 m-flourobenzoic acid 455-38-9 2.13 2.15 123 -1.97 -2.61 -0.64 m-fluorobromobenzene 1073-06-9 3.15 <25 -2.67 -2.65 0.02 mininoxidil 38304-91-5 0.48 1.24 260 -1.98 -2.33 -0.35 minocycline 10118-90-8 0.19 -0.94 m-iodobenzoic acid 618-51-9 3.11 3.13 187 -3.27 -4.23 -0.96 mitomycin c 50-07-7 -2.55 -0.4 -2.56 m-methylaniline 108-44-1 1.36 1.32 -30 -0.85 -0.86 -0.01 m-nitroaniline 99-09-2 1.38 1.37 114 -2.19 -1.77 0.42 m-nitrobenzoic acid 121-92-6 1.84 1.83 142 -1.68 -2.51 -0.83 m-nitrophenol 554-84-7 1.85 2.00 97 -1.01 -2.07 -1.06 m-nitrotoluene 99-08-1 2.38 2.42 <25 -2.44 -1.88 0.56 monolinuron 1746-81-2 2.31 2.30 80 -2.57 -2.36 0.21 monuron 150-68-5 1.99 1.94 171 -2.92 -2.95 -0.03 morin 480-16-0 1.54 1.73 299 -3.08 -3.78 -0.70 morphine 57-27-2 0.59 0.76 254 -3.28 -2.38 0.90 morpholine 110-91-8 -0.41 -0.86 <25 1.97 0.91 -1.06 m-toluic acid 99-04-7 2.38 2.37 112 -2.14 -2.75 -0.61 m-xylene 108-38-3 3.14 3.20 -48 -2.82 -2.64 0.18 n, n'-diethylthiourea 105-55-5 0.79 0.57 76 -1.46 -0.80 0.66 n,n-diethylaniline 91-66-7 3.23 3.31 -38.8 -3.03 -2.73 0.30 n,n-dimethylacetamide 127-19-5 -0.80 -0.77 <25 1.11 1.30 0.19 n,n-dimethylaniline 121-69-7 2.34 2.31 2.45 -1.92 -1.84 0.08 n-[4-(aminosulfonyl)phenyl]- 121-61-9 -0.35 -0.21 218 -1.61 -1.08 0.53 acetamide nadolol 42200-33-9 0.38 0.71 130 -1.01 -0.93 0.08 naepaine 2188-67-2 3.00 66 -3.27 -2.91 0.36 nalidixic acid 389-08-2 1.32 1.59 227 -3.37 -2.84 0.53 nalidixic acid 389-08-2 1.32 1.59 -3.37 n-amyl-carbamate 638-42-6 1.41 1.35 94 -1.47 -1.60 -0.13 naphthacene 92-24-0 5.66 5.90 341 -8.19 -8.32 -0.13 naphthalene 91-20-3 3.32 3.30 80 -3.58 -3.37 0.21 naphthalene-1,5-did 83-56-7 1.98 1.82 260 -2.92 -3.83 -0.91 napropamide 15299-99-7 3.79 3.36 75 -3.57 -3.79 -0.22 naproxen 22204-53-1 2.82 3.34 153 -4.2 -3.60 0.60 natamycin 7681-93-8 -4.55 200 -3.21 3.30 6.51 n-benzoylbenzamide 614-28-8 3.17 -2.27 neburon 555-37-3 4.02 4.10 102 -4.76 -4.29 0.47 n-ethylaniline 103-69-5 2.17 2.16 -64 -1.70 -1.67 0.03 nevirapine 129618-40-2 2.35 1.81 248 -3.19 -4.08 -0.89 n-heptyl carbamate 4248-20-8 2.47 2.36 66 -2.62 -2.38 0.24 n-hexane 110-54-3 3.87 3.90 -95 -3.84 -3.37 0.47 152 n-hexyl carbamate 2114-20-7 1.94 1.85 62 -1.92 -1.81 0.11 niclosamide 50-65-7 4.31 223 -4.7 -5.79 -1.09 nicotinamide 98-92-0 -0.21 -0.37 132 0.61 -0.36 -0.97 nicotine 54-11-5 0.90 1.17 -7.9 0.79 -0.40 -1.19 nicotinic acid 59-67-6 0.80 -0.85 nifedipine 21829-25-4 3.41 2.86 173 -4.76 -4.39 0.37 niflumic acid 4394-00-7 3.79 4.43 198 -4.17 -5.02 -0.85 nifuroxime 6236-05-1 1.10 0.3 158 -2.19 -1.93 0.26 nimetazepam 2011-67-8 2.34 2.16 156 -3.8 -3.15 0.65 niridazole 61-57-4 0.77 0.95 260 -3.22 -2.62 0.60 nitrapyrin 1929-82-4 3.42 3.41 63 -3.76 -3.30 0.46 nitrazipam 146-22-5 2.31 2.13 224 -3.8 -3.80 0.00 nitrobenzene 98-95-3 1.88 1.85 5 -1.80 -1.38 0.42 nitroethane 79-24-3 0.25 0.18 <25 -0.22 0.25 0.47 nitrofen 1836-75-5 5.60 4.64 70.5 -5.46 -5.56 -0.09 nitrofurantoin 67-20-9 -0.47 -0.47 272 -3.38 -1.50 1.88 nitrofurantoin 67-20-9 -0.47 -0.47 -3.48 nitroguanidine 556-88-7 -1.68 239 -1.37 0.04 1.41 nitromethane 75-52-5 -0.28 -0.35 <25 0.26 0.78 0.52 n-methyl-2-pyridone 694-85-9 -0.09 -0.23 31 0.96 0.53 -0.43 n-methylacetanilide 579-10-2 1.11 1.12 102 -0.95 -1.38 -0.43 n-methylaniline 100-61-8 1.64 1.66 <25 -1.28 -1.14 0.14 n-methylanthranilic acid 119-68-6 2.36 172 -2.88 -3.33 -0.45 n-methylpiperidine 626-67-5 1.40 1.3 -18 0.23 -0.90 -1.13 n-methylpyrrolidone 872-50-4 -0.40 -0.54 -24 1.00 0.90 -0.10 n-methylurea 598-50-5 -1.30 -1.40 130 1.13 0.75 -0.38 n-nitrosopiperidine 100-75-4 0.45 0.36 <25 -0.17 0.05 0.22 nonanal 124-19-6 3.48 63 -3.17 -3.36 -0.19 nonane 111-84-2 5.65 5.45 -53 -5.88 -5.15 0.73 norethindrone 68-22-4 2.78 2.97 203 -4.63 -4.06 0.57 norethisterone 1236-00-6 1.39 -4.63 norethisterone-acetate 51-98-9 3.74 161 -4.79 -4.60 0.19 norfloxacin 70458-96-7 -0.99 -1.03 228 -3.06 -0.54 2.52 norflurazon 27314-13-2 2.89 2.45 177 -4.04 -3.91 0.13 norleucine 616-06-8 -1.54 -1.54 327 -1.06 -0.98 0.08 noscapine 128-62-1 2.06 175 -3.14 -3.06 0.08 n-phenyldiethanolamine 120-07-0 0.83 57 -0.73 -0.65 0.08 o,p'-ddt 789-02-6 6.76 74 -6.62 -6.75 -0.13 o,p'- 53-19-0 6.06 76 -6.51 -6.07 0.44 dichlorodiphenyldichloroethane (o,p'-ddd) o-aminobenzoic acid 118-92-3 1.21 1.21 145 -1.52 -1.91 -0.39 o-aminophenol 95-55-6 0.62 0.62 175 -0.72 -1.62 -0.90 o-benzyl carbamate 621-84-1 1.20 1.2 88 -0.35 -1.33 -0.98 o-butyl carbamate 592-35-8 0.88 0.85 54 -0.66 -0.67 -0.01 o-chloroaniline 95-51-2 1.96 1.90 -1.94 -1.52 -1.46 0.06 o-chlorobenzoic acid 118-91-2 2.10 2.05 142 -1.89 -2.77 -0.88 o-chlorobiphenyl 2051-60-7 4.49 4.30 34 -4.54 -4.08 0.46 o-chloroiodobenzene 615-41-8 3.98 1 -3.54 -3.48 0.06 153 o-chloronitrobenzene 88-73-3 2.40 2.52 34 -2.55 -1.99 0.56 o-chlorotoluene 95-49-8 3.35 3.42 -35 -3.52 -2.85 0.67 octachlorodibenzofuran 39001-02-0 9.31 258 -11.59 -11.14 0.45 octachlorodibenzo-p-dioxin 3268-87-9 9.42 9.22 322 -12.79 -11.89 0.90 octafluorocyclobutane 115-25-3 1.74 -41 -3.92 -1.24 2.68 octane 111-65-9 4.93 5.18 -56 -5.24 -4.43 0.81 octyl-4-aminobenzoate 14309-41-2 4.33 4.31 194 -5.4 -5.52 -0.12 octylamine 111-86-4 3.04 3.09 1 -1.46 -2.54 -1.08 o-ethylphenol 90-00-6 2.50 2.47 -18 -1.36 -2.00 -0.64 o-fluorobenzoic acid 445-29-4 1.77 1.77 124 -1.29 -2.26 -0.97 o-hydroxybenzamide 65-45-2 1.28 1.28 140 -1.82 -1.93 -0.11 o-iodobenzoic acid 88-67-5 2.40 2.4 162 -2.73 -3.27 -0.54 o-isobutyl carbamate 2114-15-0 0.75 0.65 63 -0.30 -0.63 -0.33 o-methyl carbamate 598-55-0 -0.70 -0.66 57 0.97 0.88 -0.09 o-nitroaniline 88-74-4 1.92 1.85 71.5 -1.96 -1.89 0.08 o-nitroanisole 91-23-6 1.82 1.73 <25 -1.96 -1.32 0.64 o-nitrobenzoicacid 552-16-9 1.47 1.27 148 -1.35 -2.20 -0.85 o-nitrophenol 88-75-5 1.85 1.79 44 -1.74 -1.54 0.20 o-nitrotoluene 88-72-2 2.30 2.30 <25 -2.33 -1.80 0.53 o-octyl carbamate 2029-64-3 3.00 2.84 67 -3.30 -2.92 0.38 o-phenanthroline 66-71-7 2.05 1.78 115 -1.82 -2.45 -0.63 o-phthalic acid 88-99-3 0.73 0.73 230 -2.11 -2.28 -0.17 orotic acid 65-86-1 -0.75 345 -1.93 -1.95 -0.02 oryzalin 19044-88-3 2.92 141 -3.61 -3.58 0.03 osthole 484-12-8 4.27 83 -4.31 -4.35 -0.04 o-t-butyl carbamate 4248-19-5 0.53 0.47 110 0.1 -0.88 -0.98 o-toluic acid 118-90-1 2.38 2.40 105 -2.06 -2.68 -0.62 o-toluidine 95-53-4 1.36 1.32 -14.7 -2.21 -0.86 1.35 oxadiazon 19666-30-9 4.80 4.80 89 -5.69 -4.94 0.75 oxalic acid 144-62-7 -3.03 189 0.38 1.89 1.51 oxamniquine 21738-42-1 1.81 2.24 -2.97 oxazepam 604-75-1 2.29 2.24 205 -3.95 -3.59 0.36 oxycarboxin 5259-88-1 0.65 0.74 120 -2.43 -1.10 1.33 o-xylene 95-47-6 3.09 3.12 -25 -2.77 -2.59 0.18 oxyphenbutazone 129-20-4 2.72 2.72 124 -3.73 -3.21 0.52 oxytetracycline 79-57-2 -1.28 184 -3.14 0.19 3.33 p,p'-biphenyldiamine 92-87-5 1.58 1.34 128 -2.70 -2.11 0.59 p,p'-ddt 50-29-3 6.76 6.91 109 -8.08 -7.10 0.98 p-acetoxy-acetanilide 2623-33-8 0.67 0.80 153 -1.91 -1.45 0.46 palmitic acid 57-10-3 7.21 62 -6.81 -7.08 -0.27 p-aminoacetophenone 99-92-3 0.86 0.83 106 -1.61 -1.17 0.44 p-aminophenol 123-30-8 0.25 0.04 189 -0.80 -1.39 -0.59 p-aminopropiophenone 70-69-9 1.39 142 -2.63 -2.06 0.57 /7-aminosalicylic acid 65-49-6 1.06 1.32 -1.96 parabanic acid 120-89-8 -2.54 230 -0.4 0.99 1.39 paracetamol 103-90-2 0.49 0.51 169 -0.99 -1.43 -0.44 parathion 56-38-2 3.47 3.83 <25 -4.29 -2.97 1.32 parathion methyl 298-00-0 2.79 2.86 36 -3.68 -2.40 1.28 parethoxycaine 94-23-5 3.96 <25 -2.71 -3.46 -0.75 154 p-bromoacetanilide 103-88-8 2.28 2.29 165 -3.08 -3.18 -0.10 p-bromoiodobenzene 589-87-7 4.13 90 -4.56 -4.28 0.28 p-chloroacetanilide 539-03-7 2.13 2.12 178 -2.84 -3.16 -0.32 p-chloroaniline 106-47-8 1.96 1.88 72.5 -1.66 -1.94 -0.28 p-chlorobenzoic acid 74-11-3 2.70 2.65 243 -3.31 -4.38 -1.07 p-chiorobiphenyl 2051-62-9 4.74 4.61 78 -5.20 -4.77 0.43 p-chloroiodobenzene 637-87-6 3.98 53 -4.03 -3.76 0.27 p-chloronitrobenzene 100-00-5 2.60 2.39 84 -2.92 -2.69 0.23 p-chlorotoluene 106-43-4 3.35 3.33 8 -3.08 -2.85 0.23 p-cresol 106-44-5 1.97 1.94 33 -0.73 -1.55 -0.82 p-dichlorobenzene 106-46-7 3.57 3.44 54 -3.31 -3.35 -0.04 pebulate 1114-71-2 3.74 3.84 <25 -3.35 -3.24 0.11 pecazine 60-89-9 5.59 80 -4.74 -5.64 -0.90 pelargonic acid 112-05-0 3.51 3.45 12 -2.75 -3.01 -0.26 pelletierine 4396-01-4 0.85 <25 -0.45 -0.35 0.10 penicillamine 52-67-5 -1.73 200 -0.13 0.48 0.61 pent-l-yne 627-19-0 1.98 1.98 -106 -1.64 -1.48 0.16 pentachlorobenzene 608-93-5 5.35 5.18 84 -5.66 -5.44 0.22 pentachlorobutadiene 55880-77-8 4.05 <25 -4.23 -3.55 0.68 pentachloroethane 76-01-7 3.63 3.22 -28 -2.60 -3.13 -0.53 pentachlorophenol 87-86-5 4.68 5.12 174 -4.28 -5.67 -1.39 pentadecanoic acid 1002-84-2 6.68 52 -4.31 -6.45 -2.14 pentaerythritol 115-77-5 -0.93 260 -0.44 -0.92 -0.48 pentamethylbenzene 700-12-9 4.49 4.56 54 -4.00 -4.28 -0.28 pentane 109-66-0 3.34 3.39 -130 -3.18 -2.84 0.34 pentanoic acid 109-52-4 1.39 1.39 -21 -0.51 -0.89 -0.38 pentazocin 359-83-1 4.67 4.64 -3.8 pentobarbital 76-74-4 2.11 2.10 129 -2.39 -2.65 -0.26 pentoxifylline 6493-05-6 0.10 0.29 -0.56 pentyl propanoate 624-54-4 2.83 2.67 -73 -2.25 -2.33 -0.08 pentyl-4-aminobenzoate 13110-37-7 3.51 3.47 52 -3.26 -3.28 -0.02 pentylamine 110-58-7 1.45 1.49 -50 0.27 -0.95 -1.22 pentylbenzene 538-68-1 4.76 4.90 -75 -4,64 -4.26 0.38 pentylcyclopentane 3741-00-2 5.43 -83 -6.08 -4.93 1.15 perfluidone 37924-13-3 3.78 142 -3.8 -4.45 -0.65 pericyazine 2622-26-6 3.74 3.65 116 -3.98 -4.15 -0.17 permethrin 52645-53-1 7.38 6.50 36 -6.29 -6.99 -0.70 perphenazine 58-39-9 4.32 4.2 97 -4.16 -4.54 -0.38 perthane 72-56-0 6.69 60 -7.04 -6.54 0.50 perylene 198-55-0 6.12 5.82 278 -8.80 -8.15 0.65 p-fluoroacetanilide 351-83-7 1.56 1.47 153 -1.78 -2.34 -0.56 p-fluorobenzyl chloride 352-11-4 2.85 -18 -2.54 -2.35 0.19 phenacetin 62-44-2 1.77 1.58 135 -2.35 -2.37 -0.02 phenanthrene 85-01-8 4.49 4.47 100 -5.21 -4.74 0.47 phenanthridine 229-87-8 3.20 3.47 106 -2.78 -3.51 -0.73 phenbutamide 3149-00-6 2.00 130 -3.05 -2.55 0.50 phenetole 103-73-1 2.59 2.51 -30 -2.33 -2.09 0.24 phenmedipham 13684-63-4 3.37 3.59 143 -4.78 -4.05 0.73 phenobarbital 50-06-6 1.37 1.47 176 -2.34 -2.38 -0.04 155 phenol 108-95-2 1.47 1.47 40.5 0.00 -1.13 -1.13 phenolphthalein 77-09-8 2.63 264 -2.9 -4.52 -1.62 phenothrin 26002-80-2 7.20 <25 -5.24 -6.70 -1.46 phenoxyacetic acid 122-59-8 1.35 1.34 100 -1.1 -1.60 -0.50 phenyl hydrazine 100-63-0 1.26 1.25 19 0.07 -0.76 -0.83 phenyl salicylate 118-55-8 3.84 42 -3.15 -3.51 -0.36 phenylacetic acid 103-82-2 1.41 1.41 77 -0.89 -1.43 -0.54 phenylbutazone 50-33-9 3.38 3.16 105 -3.81 -3.68 0.13 phenylethanolamine 7568-93-6 0.27 58 -0.48 -0.10 0.38 phenylhydroxylamine 100-65-2 0.80 0.79 83 -0.74 -0.88 -0.14 phenylmethanol 100-51-6 1.10 1.10 -15 -0.40 -0.60 -0.20 phenylthiourea 103-85-5 0.75 0.73 154 -1.77 -1.54 0.23 phenytoin 57-41-0 2.08 2.26 295 -3.99 -4.28 -0.29 phorate 298-02-2 3.84 3.83 -43 -4.11 -3.34 0.77 phthalamide 88-96-0 -1.81 -1.73 228 -2.92 0.28 3.20 phthalic-anhydride 85-44-9 1.60 1.60 131 -1.39 -2.16 -0.77 phthalimide 85-41-6 1.15 1.15 238 -2.61 -2.78 -0.17 phthalonitrile 91-15-6 1.01 0.99 139 -2.38 -1.65 0.73 p-hydroxybenzaldehyde 123-08-0 1.44 1.35 <25 -0.96 -0.94 0.02 p-hydroxybenzoic acid 99-96-7 1.56 1.58 217 -1.41 -2.98 -1.57 picene 213-46-7 6.84 7.11 366 -8.05 -9.75 -1.70 picloram 1918-02-1 2.39 2.3 215 -2.75 -3.79 -1.04 picric acid 88-89-1 1.59 0.89 122 -1.26 -2.06 -0.80 pindone 83-26-1 2.05 110 -4.11 -2.40 1.71 pipemedic acid 51940-44-4 -2.73 253 -2.98 0.95 3.93 piperazine 110-85-0 -1.48 -1.5 106 1.07 1.17 0.10 piperidine 110-89-4 0.93 0.84 -13 1.07 -0.43 -1.50 piperine 94-62-2 2.91 132 -3.46 -3.48 -0.02 piperonal 120-57-0 1.35 1.05 38 -1.63 -0.98 0.65 pirimicarb 23103-98-2 1.15 1.7 91 -1.95 -1.31 0.64 piroxicam 36322-90-4 1.89 1.98 210 -4.16 -3.24 0.92 p-methoxybenzaldehyde 123-11-5 1.78 1.76 -1 -1.49 -1.28 0.21 p-methylbenzyl alcohol 589-18-4 1.60 1.58 60 -1.20 -1.45 -0.25 p-nitroanisole 100-17-4 2.10 2.03 54 -2.41 -1.89 0.52 p-nitrobenzoic acid 62-23-7 1.84 1.89 242 -2.80 -3.51 -0.71 p-nitrophenol 100-02-7 1.85 1.91 113 -0.74 -2.23 -1.49 p-nitrotoluene 99-99-0 2.38 2.37 54.5 -2.49 -2.18 0.32 p-phenylphenol 92-69-3 3.36 3.20 167 -3.48 -4.28 -0.80 prasterone 53-43-0 3.07 3.23 150 -4.06 -3.82 0.24 praziquantel 55268-74-1 3.36 137 -2.89 -3.98 -1.09 prednisolone 50-24-8 1.38 1.62 240 -3.18 -3.03 0.15 prednisolone acetate 52-21-1 1.92 2.40 232 -4.37 -3.49 0.88 prednisone 53-03-2 1.62 1.47 234 -3.48 -3.21 0.27 prednisonone-21- 1107-99-9 3.78 233 -4.58 -5.36 -0.78 trimethylacetate pregnenolone 145-13-1 4.03 4.22 193 -4.65 -5.21 -0.56 primidone 125-33-7 0.88 0.91 281 -2.64 -2.94 -0.30 procaine 59-46-1 2.54 2.14 61 -1.78 -2.40 -0.62 prochlorperazine 58-38-8 4.90 4.6 197 -4.4 -6.12 -1.72 156 progesterone 57-83-0 3.77 3.87 127 -4.42 -4.29 0.13 proline 147-85-3 -2.41 -2.5 1.15 promazine 58-40-2 4.90 4.55 30 -4.3 -4.45 -0.15 promethazine 60-87-7 4.90 4.81 60 -4.26 -4.75 -0.49 prometryn 7287-19-6 3.29 3.51 118 -4.10 -3.72 0.38 propachlor 1918-16-7 2.06 2.18 72 -2.48 -2.03 0.45 propane 74-98-6 2.28 2.36 -188 -2.84 -1.78 1.06 propanil 709-98-8 3.33 3.07 92 -3.22 -3.50 -0.28 propazine 139-40-2 2.80 2.93 213 -4.43 -4.18 0.25 propionaldehyde (propanal) 123-38-6 0.30 0.59 -81 0.58 0.20 -0.38 propionanilide 620-71-3 1.69 1.61 106 -1.92 -2.00 -0.08 propionitrile 107-12-0 0.13 0.16 -93 0.28 0.37 0.09 propiophenone 93-55-0 2.11 2.19 19 -1.83 -1.61 0.22 propoxur 114-26-1 1.65 1.52 91 -2.05 -1.81 0.24 propranolol 525-66-6 2.75 2.98 96 -0.71 -2.96 -2.25 propyl acetate 109-60-4 1.24 1.24 -96 -0.72 -0.74 -0.02 propyl benzoate 2315-68-6 3.17 3.01 -51 -2.67 -2.67 0.00 propyl butyrate 105-66-8 2.30 2.15 -95 -1.92 -1.80 0.12 propyl formate 110-74-7 0.79 0.83 -93 -0.49 -0.29 0.20 propyl gallate 121-79-9 1.99 150 -1.78 -2.74 -0.96 propyl isopropyl ether 627-08-7 1.71 <25 -1.34 -1.21 0.13 propyl propanoate 106-36-5 1.77 -76 -1.34 -1.27 0.07 propylamine 107-10-8 0.39 0.47 -83 1.52 0.11 -1.41 propylbenzene 103-65-1 3.70 3.72 -102 -3.25 -3.20 0.05 propylcyclopentane 2040-96-2 4.37 -117 -4.74 -3.87 0.87 propylparaben 94-13-3 3.04 3.04 -2.56 propylthiouracil 51-52-5 -0.33 -2.19 propyne 74-99-7 0.92 0.94 -103 -0.41 -0.42 -0.01 prostaglandin e2 363-24-6 2.01 2.82 67 -2.47 -1.93 0.54 proxyphylline 603-00-9 -0.58 -0.77 0.62 pteridine 91-18-9 -0.86 -0.58 140 0.02 0.21 0.19 p-terphenyl 92-94-4 5.92 6.03 213 -7.11 -7.30 -0.19 p-tert-butylphenol 98-54-4 3.30 3.31 98 -2.41 -3.53 -1.12 p-toluenesulfonamide 70-55-3 0.80 0.82 139 -1.74 -1.44 0.30 p-toluic acid 99-94-5 2.38 2.27 182 -2.60 -3.45 -0.85 p-xylene 106-42-3 3.14 3.15 13 -2.77 -2.64 0.13 pyracarbolid 24691-76-7 2.13 109 -2.56 -2.47 0.09 pyrazon 1698-60-8 1.20 1.19 205 -2.87 -2.50 0.37 pyrene 129-00-0 4.95 4.88 156 -6.18 -5.76 0.42 pyridazine 289-80-5 -0.73 -0.72 -8 1.10 1.23 0.13 pyridine 110-86-1 0.64 0.65 <25 0.76 -0.14 -0.90 pyrimidine 289-95-2 -0.31 -0.4 21 1.1 0.81 -0.29 pyrolan 87-47-8 2.10 50 -2.09 -1.85 0.24 pyrrole 109-97-7 0.75 0.75 -23 -0.17 -0.25 -0.08 pyrrolidine 123-75-1 0.38 0.47 -60 1.15 0.12 -1.03 pyrrolidone 616-45-5 -0.97 -0.85 24 1.07 1.47 0.40 quinethazone 73-49-4 0.55 250 -3.29 -2.30 0.99 quinidine 56-54-2 2.79 2.64 167 -3.37 -3.71 -0.34 quinine 130-95-0 2.79 2.64 177 -2.76 -3.8! -1.05 157 quinoline 91-22-5 2.03 2.03 <25 -1.30 -1.53 -0.23 quinolinic acid 89-00-9 0.17 189 -1.19 -1.31 -0.12 quinonamid 27541-88-4 2.99 212 -5.03 -4.36 0.67 quinone 106-51-4 0.13 0.20 116 -0.56 -0.54 0.02 quintozene 82-68-8 5.05 4.64 144 -5.82 -5.74 0.08 reposal 3625-25-0 2.19 213 -2.64 -3.57 -0.93 rhodanine 141-84-4 4.77 169 -1.77 -5.71 -3.94 riboflavin 83-88-5 -0.73 290 -3.68 -1.42 2.26 risocaine 94-12-2 2.55 2.43 75 -2.45 -2.55 -0.10 rolitetracycline 751-97-3 0.48 162 -1.42 -1.35 0.07 ronnel 299-84-3 4.96 5.07 35 -3.90 -4.56 -0.66 rotenone 83-79-4 4.19 4.10 165 -4.42 -5.09 -0.67 saccharin 81-07-2 0.72 0.91 229 -1.64 -2.26 -0.62 salbutamol 18559-94-9 0.11 150 -1.22 -0.86 0.36 salicin 138-52-3 -1.06 -1.22 198 -0.85 -0.17 0.68 salicyl alcohol 90-01-7 0.44 0.73 84 -0.29 -0.53 -0.24 salicylaldehyde 90-02-8 1.81 1.81 1 -0.86 -1.31 -0.45 salicylanilide 87-17-2 3.27 3.27 137 -3.59 -3.89 -0.30 salicylic acid 69-72-7 2.19 2.26 -1.8 santonin 481-06-1 1.65 171 -3.09 -2.61 0.48 scopolamine 51-34-3 0.30 59 -0.48 -0.14 0.34 secbutabarbital 143-81-7 1.58 1.65 -2.33 secobarbital 76-73-3 2.16 1.97 132 -2.36 -2.73 -0.37 siduron 1982-49-6 3.65 3.80 137 -4.11 -4.27 -0.16 simazine 122-34-9 2.19 2.18 225 -4.12 -3.69 0.43 simvastatin 79902-63-9 4.70 4.68 -4.15 sorbic acid 110-44-1 1.51 1.33 135 -1.77 -2.11 -0.34 sorbitol 50-70-4 -2.05 -2.65 111 1.09 1.69 0.60 sparteine 90-39-1 2.72 32 -1.89 -2.29 -0.40 spironolactone 52-01-7 2.25 2.26 201 -4.28 -3.51 0.77 stadacaine 3772-43-8 5.79 <25 -3.84 -5.29 -1.45 stanolone 521-18-6 3.55 3.66 -4.74 stearic acid 57-11-4 8.27 70 -5.68 -8.22 -2.54 strychnine 57-24-9 1.66 1.93 -3.33 styphnic acid 82-71-3 1.19 180 -1.66 -2.24 -0.58 styrene 100-42-5 2.87 2.95 -30 -2.82 -2.37 0.45 styrene oxide 96-09-3 1.29 1.61 -37 -1.60 -0.79 0.81 subericacid 505-48-6 1.03 142 -1.29 -1.70 -0.41 succinic acid 110-15-6 -0.53 -0.59 184 -0.2 -0.56 -0.36 succinimide 123-56-8 -1.17 124 0.3 0.68 0.38 sucrose 57-50-1 -3.09 -3.01 191 0.0719 1.93 1.86 sufentanil 56030-54-7 3.45 3.95 97 -3.71 -3.67 0.04 sulfadiazine 68-35-9 0.07 -0.09 258 -3.51 -1.90 1.61 sulfadimethoxine 122-11-2 1.90 1.63 202 -2.96 -3.17 -0.21 sulfaethidole 94-19-9 0.75 1.01 188 -1.94 -1.88 0.06 sulfaguanidine 57-67-0 -1.24 -1.22 190 -1.99 0.09 2.08 sulfallate 95-06-7 3.42 <25 -3.39 -2.92 0.47 sulfamerazine 127-79-7 0.57 0.14 235 -2.85 -2.17 0.68 sulfameter 651-06-9 0.59 0.41 213 -2.58 -1.97 0.61 158 sulfamethazine 57-68-1 1.07 0.28 198 -2.27 -2.30 -0.03 sulfamethiazole 144-82-1 0.22 0.54 208 -2.41 -1.55 0.86 sulfamethomidine 3772-76-7 1.49 0.61 146 -2.54 -2.20 0.34 sulfamethoxazole 723-46-6 0.55 0.89 -2.71 sulfamethoxypyridazine 80-35-3 0.35 0.32 182 -3.28 -1.42 1.86 sulfamoxole 729-99-7 0.50 193 -2.44 -1.68 0.76 sulfanilacetamide 144-80-9 -0.98 -0.96 183 -1.23 -0.10 1.13 sulfanilamide 63-74-1 -0.57 -0.62 165 -1.36 -0.33 1.03 sulfaperine 599-88-2 0.57 0.34 262 -2.82 -2.44 0.38 sulfaphenazole 526-08-9 2.06 2.72 206 -2.32 -3.37 -1.05 sulfapyridine 144-83-2 0.84 0 191 -2.7 -2.00 0.70 sulfathiozole 72-14-0 0.70 203 -2.43 -1.98 0.45 sulfisomidine 515-64-0 1.07 243 -2.24 -2.75 -0.51 sulfisoxazole 127-69-5 0.20 1.01 195 -2.91 -1.40 1.51 sulindac 38194-50-2 3.16 3.05 184 -5 -4.25 0.76 sulpiride 15676-16-1 1.11 179 -2.88 -2.15 0.73 talbutal 115-44-6 1.63 1.47 -2.02 t-amylbenzene 2049-95-8 4.50 -58 -4.15 -4.00 0.15 tenoxicam 59804-37-4 1.61 0.81 -3.88 terbacil 5902-51-2 2.41 1.91 176 -2.48 -3.42 -0.94 terbutryne 886-50-0 3.38 3.38 104 -4.00 -3.67 0.33 terfenadine 50679-08-8 6.09 5.69 -4.67 tert-amyl carbamate 590-60-3 1.06 85 -0.80 -1.16 -0.36 tert-butylbenzene 98-06-6 3.97 4.11 -58 -3.66 -3.47 0.19 testosterone 58-22-0 3.22 3.32 155 -4.07 -4.02 0.05 testosterone acetate 1045-69-8 4.16 4.16 141 -5.18 -4.82 0.36 testosterone propionate 57-85-2 4.69 118 -5.37 -5.12 0.25 tetrabromomethane 558-13-4 3.43 3.42 90 -3.14 -3.58 -0.44 tetrachloroethylene 127-18-4 3.48 3.40 -22 -2.74 -2.98 -0.24 tetrachloroguaiacol 2539-17-5 3.92 122 -4.02 -4.39 -0.37 tetrachloromethane 56-23-5 2.88 2.83 -22 -2.31 -2.38 -0.07 tetracycline 60-54-8 -0.91 -1.47 176 -3.12 -0.10 3.02 tetradecane 629-59-4 8.10 8.00 6 -7.96 -7.60 0.36 tetradecanoic acid 544-63-8 6.15 6.1 54 -5.33 -5.94 -0.61 tetrafluoromethane 75-73-0 1.11 1.18 -185 -3.68 -0.61 3.07 tetrahydrofuran 109-99-9 0.53 0.47 -108 0.49 -0.03 -0.52 tetrahydropyran 142-68-7 0.95 0.95 -45 -0.03 -0.45 -0.42 tetramethylurea 632-22-4 -0.11 0.19 -1 0.94 0.61 -0.33 tetroxoprim 53808-87-0 0.63 0.56 -2.1 thalidomide 50-35-1 0.53 0.33 -3.7 thebaine 115-37-7 1.65 -2.66 theobromine 83-67-0 -0.69 -0.72 -2.56 theophylline 58-55-9 -0.06 -0.02 272 -1.37 -1.91 -0.54 thiamphenicol 847-25-6 -0.10 -0.27 -2.15 thiamylal 77-27-0 3.03 3.23 132 -3.46 -3.60 -0.14 thioanisole 100-68-5 2.74 -15 -2.39 -2.24 0.15 thiofanox 39196-18-4 2.39 2.75 52 -1.62 -2.16 -0.54 thiopental 76-75-5 2.98 2.85 158 -3.36 -3.81 -0.45 thiophene 110-02-1 1.79 1.89 -38 -1.33 -1.29 0.04 159 thiophene-3-carboxylic acid 88-13-1 1.65 1.5 139 -1.47 -2.29 -0.82 thiophenol 108-98-5 2.53 2.52 -15 -2.12 -2.03 0.09 thiopropazate 84-06-0 5.22 -4.7 thioridazine 50-52-2 6.50 5.9 73 -5.82 -6.48 -0.66 thiourea 62-56-6 -1.02 -1.02 176 0.32 0.01 -0.31 thiram 137-26-8 1.76 1.73 155 -3.9 -2.56 1.34 threonine 72-19-5 -2.43 -2.94 270 -0.09 0.48 0.57 thymol 89-83-8 3.20 3.30 48 -2.22 -2.93 -0.71 tolazamide 1156-19-0 1.34 1.45 165 -3.68 -2.24 1.44 tolbutamide 64-77-7 2.50 2.34 128 -3.39 -3.03 0.36 tolcyclamide 664-95-9 2.94 2.9 174 -4.21 -3.93 0.28 toluene 108-88-3 2.64 2.73 -95 -2.21 -2.14 0.07 tranid 15271-41-7 0.89 159 -2.08 -1.73 0.35 trans-1,2-dimethylcyclohexane 6876-23-9 4.39 -88 -4.33 -3.89 0.44 trans-1,4-dimethylcyclohexane 2207-04-7 4.39 -37 -4.47 -3.89 0.58 trans-2-heptene 14686-13-6 3.91 -109 -3.82 -3.41 0.41 trans-2-pentene 646-04-8 2.86 -140 -2.54 -2.36 0.18 trans-crotonaldehyde 123-73-9 0.52 -77 0.32 -0.02 -0.34 triadimefon 43121-43-3 3.44 2.77 82 -3.61 -3.51 0.10 triallate 2303-17-5 4.73 4.6 29 -4.88 -4.27 0.61 triamcinolone 124-94-7 0.67 1.16 260 -3.69 -2.52 1.17 triamcinolone acetonide 76-25-5 2.17 2.53 274 -4.32 -4.16 0.16 triamcinolone diacetate 67-78-7 1.86 1.92 235 -4.13 -3.46 0.67 triazolam 28911-01-5 2.25 2.42 224 -4.08 -3.74 0.34 tribromomethane 75-25-2 2.37 2.67 8 -1.91 -1.87 0.04 tributylamine 102-82-9 4.78 -70 -3.12 -4.28 -1.16 tributylphosphorotrithioate 78-48-8 4.25 <25 -5.14 -3.75 1.39 trichlorfon 52-68-6 0.68 0.51 83 -0.22 -0.76 -0.54 trichlormethiazide 133-67-5 0.85 0.56 266 -2.68 -2.76 -0.08 trichloroacetic acid 76-03-9 1.68 1.33 57 0.60 -1.50 -2.10 trichloroehylene 79-01-6 2.63 2.61 -86 -1.96 -2.13 -0.17 triclosan 3380-34-5 5.53 58 -4.46 -5.36 -0.90 tricresyl-phosphate 1330-78-5 5.95 -33 -6.01 -5.45 0.56 tricyclazole 41814-78-2 1.83 1.70 187 -2.07 -2.95 -0.88 trietazine 1912-26-1 2.79 3.34 101 -4.06 -3.05 1.01 triethyl phosphate 78-40-0 0.28 0.80 -56 0.43 0.22 -0.21 triethylamine 121-44-8 1.40 1.45 -115 -0.14 -0.90 -0.76 trifluoperazine 117-89-5 5.21 5.03 -4.52 trifluoromethylbenzene 98-08-8 3.03 3.01 -29 -2.51 -2.53 -0.02 trifluoro-o-toluic acid 433-97-6 2.14 111 -1.6 -2.50 -0.90 triflupromazine 146-54-3 6.11 5.54 <25 -5.3 -5.61 -0.31 trifluralin 1582-09-8 5.29 5.07 48 -5.68 -5.02 0.66 triforine 26644-46-2 1.68 2.02 55 -4.19 -1.48 2.71 trimethoprim 738-70-5 0.88 0.91 201 -2.86 -2.14 0.72 trimethylamine 75-50-3 0.02 0.16 -124 1.32 0.48 -0.84 tripelennamine 91-81-6 3.31 191 -2.64 -4.47 -1.83 triphenylene 217-59-4 5.66 5.49 199 -6.74 -6.90 -0.16 tripropylamine 102-69-2 2.98 2.79 -94 -2.28 -2.48 -0.20 tropicamide 1508-75-4 1.18 -1.7 160 tubercidin 69-33-0 -1.47 247 -1.95 -0.25 1.70 tybamate 4268-36-4 3.09 -2.74 tyramine 51-67-2 0.77 162 -1.12 -1.64 -0.52 undecane 1120-21-4 6.51 6.54 -26 -7.59 -6.01 1.58 undecanoic acid 112-37-8 4.57 30 -3.55 -4.12 -0.57 undecylenic acid 112-38-9 4.08 3.86 25 -3.4 -3.58 -0.18 uracil 66-22-8 -1.06 -1.07 335 -1.49 -1.54 -0.05 urea 57-13-6 -1.66 -1.66 135 0.95 1.06 0.11 urethane 51-79-6 -0.18 -0.15 48 0.85 0.45 -0.40 uric acid 69-93-2 -1.46 -3.4 urocanic acid 104-98-3 0.07 227 -1.96 -1.59 0.37 ursodeoxycholic acid 128-13-2 4.51 203 -4.29 -5.79 -1.50 valeraldehyde 110-62-3 1.36 -92 -0.85 -0.86 -0.01 valproic acid 99-66-1 2.98 2.75 125 -1.86 -3.48 -1.62 vanillic acid 121-34-6 1.35 1.43 209 -2.05 -2.69 -0.64 veratrole 91-16-7 1.80 1.60 15 -1.31 -1.30 0.01 vernolate 1929-77-7 3.74 3.84 <25 -3.30 -3.24 0.06 vinbarbital 125-42-8 2.03 162 -2.43 -2.90 -0.47 vulvic acid 143-07-7 5.10 4.2 44 -4.62 -4.79 -0.17 warfarin 81-81-2 2.89 2.7 161 -4.26 -3.75 0.51 xanthine 69-89-6 -0.70 -0.73 -2.48 xipamide 14293-44-8 1.89 255 -3.79 -3.69 0.10 zidovudine 30516-87-1 0.04 0.05 -1.03 zileuton 111406-87-2 1.44 -3.37 161

APPENDIX B. Comparison of Predicted Solubility Using the General

Solubility Equation and the Amended Solvation Energy Relationship

Name CLOGP MLOGP MP log S„ log Sw log S„ Expt ASER GSE methane 1.10 1.09 25 -0.90 -0.48 -0.60 ethane 1.75 1.81 25 -1.36 -1.04 -1.25 propane 2.28 2.36 25 -1.94 -1.60 -1.78 butane 2.81 2.89 25 -2.57 -2.16 -2.31 2-methylpropane 2.68 2.76 25 -2.55 -2.16 -2.18 pentane 3.34 3.39 25 -3.18 -2.72 -2.84 2-methylbutane 3.21 25 -3.18 -2.72 -2.71 hexane 3.87 3.90 25 -3.84 -3.29 -3.37 2-methylpentane 3.74 25 -3.74 -3.29 -3.24 3-methylpentane 3.74 25 -3.68 -3.29 -3.24 2,2-dimethylbutane 3.61 3.82 25 -3.55 -3.29 -3.11 2,3-dimethylbutane 3.61 3.42 25 -3.65 -3.29 -3.11 heptane 4.40 4.66 25 -4.53 -3.85 -3.90 2,2-dimethylpentane 4.14 25 -4.36 -3.85 -3.64 2,3-dimethylpentane 4.14 25 -4.28 -3.85 -3.64 2,4-dimethylpentane 4.14 25 -4.26 -3.85 -3.64 3,3-dimethylpentane 4.14 25 -4.23 -3.85 -3.64 2,2,3-trimethylbutane 4.01 25 -4.36 -3.85 -3.51 octane 4.93 5.18 25 -5.24 -4.41 -4.43 2-methylheptane 4.80 25 -5.08 -4.41 -4.30 3-methylheptane 4.80 25 -5.16 -4.41 -4.30 4-methyloctane 5.32 4.69 25 -6.05 -4.41 -4.82 2,2,4-triniethylpentane 4.54 25 -4.74 -4.41 -4.04 2,3,4-trimethylpentane 4.54 25 -4.80 -4.41 -4.04 nonane 5.65 5.45 25 -5.88 -4.97 -5.15 2,2,5-trimethylhexane 5.06 25 -5.05 -4.97 -4.56 decane 5.98 5.01 25 -6.98 -5.53 -5.48 undecane 6.51 6.50 25 -7.59 -6.09 -6.01 dodecane 7.04 6.10 25 -7.67 -6.66 -6.54 tetradecane 8.10 8.00 25 -7.96 -7.78 -7.60 hexadecane 9.16 25 -8.40 -8.90 -8.66 cyclopentane 2.79 3.00 25 -2.64 -2.48 -2.29 methylcyclopentane 3.31 3.37 25 -3.30 -3.00 -2.81 propylcyclopentane 4.37 25 -4.74 -4.12 -3.87 pentylcyclopentane 5.43 25 -6.08 -5.24 -4.93 cyclohexane 3.35 3.44 25 -3.10 -3.08 -2.85 methylcyclohexane 3.87 3.61 25 -3.85 -3.61 -3.37 cis-1,2-diniethylcyclohexane 4.39 25 -4.30 -4.18 -3.89 trans-1,4-diniethylcyclohexane 4.39 25 -4.47 -4.10 -3.89 ethylcyclohexane 4.40 25 -4.25 -4.16 -3.90 cycloheptane 3.91 4.00 25 -3.51 -3.69 -3.41 cyclooctane 4.47 4.45 25 -4.15 -4.31 -3.97 decalin 4.79 25 -5.19 -4.98 -4.29 ethylene 1.27 1.13 25 -0.40 -0.60 -0.77 propylene 1.80 1.77 25 -1.08 -1.17 -1.30 1-butene 2.33 2.40 25 -1.94 -1.73 -1.83 2-methylpropene 2.20 2.34 25 -2.33 -1.73 -1.70 1-pentene 2.86 2.80 25 -2.68 -2.29 -2.36 cis-2-pentene 2.86 25 -2.54 -2.34 -2.36 trans-2-pentene 2.86 25 -2.54 -2.32 -2.36 2-methyl-1-butene 2.73 25 -2.73 -2.31 -2.23 3-methyl-1-butene 2.73 25 -2.73 -2.26 -2.23 2-methyl-2-butene 2.73 2.67 25 -2.56 -2.35 -2.23 1-hexene 3.38 3.39 25 -3.23 -2.83 -2.88 2-niethyl-1-pentene 3.25 25 -3.03 -2.85 -2.75 1-heptene 3.91 3.99 25 -3.73 -3.41 -3.41 trans-2-heptene 3.91 25 -3.82 -3.44 -3.41 1-octene 4.44 4.57 25 -4.44 -3.97 -3.94 1-nonene 4.97 5.15 25 -5.05 -4.53 -4.47 1-decene 5.50 25 -5.51 -5.10 -5.00 1,3-butadiene 1.90 1.99 25 -1.87 -1.54 -1.40 2-methyl-1,3-butadiene 2.30 25 -2.03 -2.09 -1.80 2,3-diniethyl-1,3-butadiene 2.70 25 -2.40 -2.53 -2.20 1,4-pentadiene 2.37 2.47 25 -2.09 -1.99 -1.87 1,5-hexadiene 2.90 2.87 25 -2.68 -2.56 -2.40 cyclopentene 2.31 25 -2.10 -1.87 -1.81 cyclohexene 2.87 2.86 25 -2.59 -2.50 -2.37 1 -methylcyclohexene 3.39 25 -3.27 -3.07 -2.89 cycloheptene 3.43 25 -3.18 -3.07 -2.93 1,4-cyclohexadiene 2.39 2.30 25 -2.06 -2.02 -1.89 ethyne 0.39 0.37 25 0.29 -0.13 0.11 propyne 0.92 0.94 25 -0.41 -0.45 -0.42 1-butyne 1.45 1.46 25 -1.24 -1.16 -0.95 1-pentyne 1.98 1.98 25 -1.64 -1.66 -1.48 1-hexyne 2.51 2.73 25 -2.36 -2.25 -2.01 3-hexyne 2.51 25 -1.99 -2.30 -2.01 1-heptyne 3.04 3.32 25 -3.01 -2.91 -2.54 1-octyne 3.57 3.92 25 -3.66 -3.46 -3.07 1-nonyne 4.10 4.51 25 -4.24 -4.02 -3.60 dichloromethane 1.25 1.25 25 -0.63 -0.99 -0.75 trichloromethane 1.95 1.97 25 -1.17 -1.59 -1.45 tetrachloromethane 2.88 2.83 25 -2.31 -2.60 -2.38 chloroethane 1.47 1.43 25 -1.06 -1.02 -0.97 1,1-dichloroethane 1.78 1.79 25 -1.29 -1.35 -1.28 1,2-dichloroethane 1.46 1.47 25 -1.06 -1.29 -0.96 1,1,1-trichloroethane 2.48 2.49 25 -2.00 -2.18 -1.98 1,1,2-trichloroethane 2.05 2.07 25 -1.48 -1.70 -1.55 1,1,2,2-tetrachloroethane 2.64 2.62 25 -1.74 -2.21 -2.14 1,1,1,2-tetrachloroethane 3.03 2.62 25 -2.18 -2.52 -2.53 pentachloroethane 3.63 3.22 25 -2.60 -3.03 -3.13 hexachloroethane 4.61 4.14 25 -3.67 -4.23 -4.11 1-chloropropane 1.99 2.04 25 -1.47 -1.57 -1.49 2-chloropropane 1.99 1.90 25 -1.41 -1.49 -1.49 1,2-dichloropropane 1.99 1.99 25 -1.60 -1.81 -1.49 1,3-dichloropropane 1.71 2.00 25 -1.62 -1.84 -1.21 1-chlorobutane 2.52 2.64 25 -2.03 -2.13 -2.02 1-chloro-2-methy Ipropane 2.39 25 -2.00 -2.05 -1.89 2-chlorobutane 2.52 2.33 25 -1.96 -2.06 -2.02 1-chloropentane 3.05 3.11 25 -2.73 -2.69 -2.55 2-chloro-2-methylbutane 2.92 2.52 25 -2.51 -2.85 -2.42 1-chlorohexane 3.58 3.66 25 -3.12 -3.24 -3.08 1-chloroheptane 4.11 4.15 25 -4.00 -3.80 -3.61 chloroethylene 1.52 25 -1.75 -1.11 -1.02 1,1-dichloroethylene 2.37 2.13 25 -1.64 -1.73 -1.87 cis-1,2-dichloroethylene 1.77 1.86 25 -1.30 -1.38 -1.27 trichloroethylene 2.63 2.61 25 -1.96 -2.28 -2.13 tetrachloroethylene 3.48 3.40 25 -2.54 -3.12 -2.98 hexachloro-1,3-butadiene 4.90 4.78 25 -4.92 -5.12 -4.40 bromomethane 1.08 1.19 25 -0.79 -0.82 -0.58 dibromomethane 1.53 1.88 25 -1.17 -1.56 -1.03 tribromomethane 2.37 2.67 25 -1.91 -2.47 -1.87 tetrabromomethane 3.43 3.42 90 -3.14 -3.74 -3.58 bromoethane 1.60 1.61 25 -1.09 -1.29 -1.10 1,2-dibromoethane 1.74 1.96 25 -1.68 -1.72 -1.24 l-bromopropane 2.13 2.10 25 -1.73 -1.85 -1.63 2-bromopropane 2.13 2.14 25 -1.59 -1.77 -1.63 1-bromobutane 2.66 2.75 25 -2.37 -2.40 -2.16 1-bromo-2-methylpropane 2.53 25 -2.43 -2.40 -2.03 1-bromopentane 3.19 3.37 25 -3.08 -2.96 -2.69 1-bromohexane 3.72 3.80 25 -3.81 -3.52 -3.22 1 -bromoheptane 4.25 4.36 25 -4.43 -4.07 -3.75 1-bromooctane 4.78 4.89 25 -5.06 -4.63 -4.28 iodomethane 1.47 1.51 25 -1.00 -1.30 -0.97 diiodomethane 2.31 2.30 25 -2.34 -2.42 -1.81 iodoethane 2.00 2.00 25 -1.60 -1.77 -1.50 1-iodopropane 2.52 2.54 25 -2.29 -2.32 -2.02 2-iodopropane 2.52 2.89 25 -2.09 -2.26 -2.02 1-iodobutane 3.05 3.08 25 -2.96 -2.88 -2.55 1 -iodoheptane 4.64 4.70 25 -4.81 -4.54 -4.14 bromochloromethane 1.39 1.41 25 -0.89 -1.32 -0.89 bromodichloromethane 2.09 2.10 25 -1.54 -1.84 -1.59 chlorodibromethane 2.23 2.24 25 -1.90 -2.12 -1.73 1-chloro-2-bromoethane 1.60 25 -1.32 -1.69 -1.10 1,1,2-trichlorotrifluoroethane 3.29 3.16 25 -3.04 -2.62 -2.79 1,2-dichlorotetrafluoroethane 2.85 2.82 25 -2.74 -2.41 -2.35 diethyl ether 0.87 0.89 25 -0.09 -0.34 -0.37 164

-1.43 -1.43 dipropyl ether 1.93 2.03 25 -1.10 -1.64 -0.99 diisopropyl ether 1.49 1.52 25 -1.10 -2.54 -2.41 dibutyl ether 2.91 3.22 25 -1.85 -0.44 -0.37 methyl propyl ether 0.87 1.21 25 -0.39 -0.95 -0.90 methyl butyl ether 1.40 1.66 25 -0.99 -0.23 -0.55 methyl tert-butyl ether 1.05 0.94 25 -0.24 -0.86 -0.90 ethyl propyl ether 1.40 25 -0.66 -1.44 -1.21 propyl isopropyl ether 1.71 25 -1.34 -0.39 -0.51 ethyl vinyl ether 1.01 1.04 25 -0.85 0.79 0.93 dimethoxymethane -0.43 0.18 25 0.48 0.59 -0.43 1.1-diethoxyethane 0.93 0.84 25 -0.43 0.15 -0.43 1.2-diethoxyethane 0.93 0.66 25 -0.77 0.25 1.2-propylene oxide 0.25 0.13 25 -0.59 0.70 0.18 -0.03 tetrahydrofuran 0.53 0.47 25 0.49 -0.15 -0.54 2-methyltetrahydrofuran 1.04 25 0.11 -0.37 -0.45 tetrahydropyran 0.95 0.95 25 -0.03 0.58 0.55 0.20 propionaldehyde 0.30 0.59 25 -0.01 0.00 -0.33 butyraldehyde 0.83 0.88 25 -0.54 -0.86 valeraldehyde 1.36 25 -0.85 -1.39 caproaldehyde 1.89 1.78 25 -1.30 -1.09 -1.10 -1.25 2-ethylbutanol 1.75 25 -1.52 -2.24 -2.31 2-ethylhexanol 2.81 25 -2.13 0.32 0.29 -0.02 trans-crotonaldehyde 0.52 25 -2.46 -2.04 -2.09 2-ethyl-2-hexanol 2.59 25 0.52 0.31 0.18 2-butanone 0.32 0.29 25 -0.24 -0.35 2-pentanone 0.85 0.91 25 -0.19 -0.27 -0.35 3-pentanone 0.85 0.82 25 -0.28 -0.35 3-methyl-2-butanone 0.85 0.84 25 -0.12 -0.26 -0.80 -0.88 2-hexanone 1.38 1.38 25 -0.80 -0.81 -0.88 3-hexanone 1.38 25 -0.83 -0.80 -0.88 3-methyl-2-pentanone 1.38 25 -0.67 -0.80 -0.75 4-methyl-2-pentanone 1.25 1.31 25 -0.74 -0.75 3.3-dimethyl-2-butanone 1.25 1.20 25 -0.72 -0.82 -1.35 -1.41 2-heptanone 1.91 1.98 25 -1.45 -1.35 -1.41 4-heptanone 1.91 2.04 25 -1.30 -1.36 -1.41 2.4-dimethyl-3-pentanone 1.91 1.86 25 -1.30 -1.89 -1.94 2-octanone 2.44 2.37 25 -2.05 -2.47 -2.47 2-nonanone 2.97 3.14 25 -2.58 -2.47 5-nonanone 2.97 2,88 25 -2.58 -2.47 -3.02 -2.99 2-decanone 3.49 3,73 25 -3.30 -0.60 -0.28 -0.36 cyclohexanone 0.86 0.81 25 -2.70 -1.51 carvone 2.01 25 -2.06 -2.15 -3.20 camphor 2.18 2,38 177 -1.96 -2.35 -2.63 -2.33 menthone 2.83 25 0.61 0.76 methyl formate -0.26 0.03 25 0.58 0.08 0.24 ethyl formate 0.26 25 0.15 -0.50 -0.29 propyl formate 0.79 0.83 25 -0.49 -0.39 -0.07 isopropyl formate 0.57 25 -0.63 165 butyl acetate 1.77 1.78 25 -1.37 -1.05 -1.27 isobutyl formate 1.19 25 -1.01 -0.96 -0.69 isopentyl formate 1.72 25 -1.52 -1.52 -1.22 methyl acetate 0.18 0.18 25 0.46 0.36 0.32 ethyl acetate 0.71 0.73 25 -0.04 -0.18 -0.21 propyl acetate 1.24 1.24 25 -0.72 -0.74 -0.74 isopropyl acetate 1.24 1.22 25 -0.55 -0.64 -0.74 isobutyl acetate 1.64 1.76 25 -1.21 -1.20 -1.14 pentyl acetate 2.30 2.29 25 -1.89 -1.84 -1.80 isopentyl acetate 2.17 2.25 25 -1.92 -1.76 -1.67 methyl propionate 0.71 0.82 25 -0.14 -0.22 -0.21 ethyl propionate 1.24 1.21 25 -0.66 -0.75 -0.74 methyl butyrate 1.24 1.29 25 -0.82 -0.76 -0.74 ethyl butyrate 1.77 1.71 25 -1.28 -1.30 -1.27 propyl butyrate 2.30 2.15 25 -1.92 -1.86 -1.80 methyl pentanoate 1.77 1.96 25 -1.36 -1.32 -1.27 ethyl pentanoate 2.30 25 -1.75 -1.84 -1.80 propyl propanoate 1.77 25 -1.34 -1.30 -1.27 pentyl propanoate 2.83 2.67 25 -2.25 -2.42 -2.33 methyl hexanoate 2.30 2.42 25 -1.87 -1.85 -1.80 ethyl hexanoate 2.83 25 -2.35 -2.39 -2.33 ethyl heptanoate 3.36 25 -2.74 -2.94 -2.86 methyl octanoate 3.36 25 -3.17 -2.96 -2.86 ethyl octanoate 3.88 25 -3.39 -3.50 -3.38 methyl nonanoate 3.88 3.87 25 -3.38 -3.52 -3.38 ethyl nonanoate 4.41 25 -3.80 -4.06 -3.91 methyl decanoate 4.41 4.41 25 -4.69 -4.07 -3.91 ethyl decanoate 4.94 25 -4.10 -4.61 -4.44 methyl acrylate 0.80 0.80 25 -0.22 -0.25 -0.30 glyceryl triacetate 0.67 0.25 25 -0.60 0.73 -0.17 malonic acid diethyl ester 1.13 0.96 25 -0.82 -0.53 -0.63 acetonitrile -0.39 -0.34 25 0,26 0.80 0.89 propionitrile 0.13 0.16 25 0.28 0.42 0.37 acrylonitrile 0.29 0.25 25 0,15 0.35 0.21 ethylamine -0.13 -0.13 25 2,06 1.20 0.63 propylamine 0.39 0.47 25 1,52 0.65 0.11 butylamine 0.92 0.97 25 0,96 0.09 -0.42 pentylamine 1.45 1.49 25 0.27 -0.46 -0.95 hexylamine 1.98 2.06 25 -0,25 -1.01 -1.48 heptylamine 2.51 2.57 25 -0,90 -1.57 -2.01 octylamine 3.04 3.09 25 -1.46 -2.12 -2.54 diethylamine 0.54 0.58 25 1.03 0.43 -0.04 dipropylamine 1.60 1.67 25 -0.46 -0.67 -1.10 dibutylamine 2.66 2.83 25 -1,44 -1.77 -2.16 trimethylamine 0.02 0.16 25 1.32 0.86 0.48 triethylamine 1.40 1.45 25 -0.14 -0.32 -0.90 tripropylamine 2.98 2.79 25 -2.28 -1.85 -2.48 nitromethane -0.28 -0.35 25 0.26 0.63 0.78 166 nitroethane 0.25 0.18 25 -0.22 0.15 0.25 1-nitropropane 0.77 0.87 25 -0.80 -0.49 -0.27 2-nitropropane 0.55 0.80 25 -0.62 -0.40 -0.05 chloropicrin 1.60 2.09 25 -2.00 -2.07 -1.10 acetamide -1.11 -1.09 81 1.58 1.86 1.05 N,N-dimethylacetamide -0.80 -0.77 25 1.11 1.34 1.30 urea -1.66 -1.66 132 0.96 2.32 1.09 o-ethyl carbamate -0.18 -0.15 25 0.85 0.79 0.68 acetic acid -0.19 -0.17 25 2.00 1.18 0.69 hexanoic acid 1.92 1.92 25 -1.06 -0.99 -1.42 decanoic acid 4.04 4.09 31 -3.44 -3.19 -3.60 methacrylic acid 0.66 0.93 25 0.00 0.05 -0.16 chloroacetic acid -0.08 0.22 61 1.81 0.87 0.22 trichloroacetic acid 1.68 1.33 57 0.60 -0.01 -1.50 methanol -0.76 -0.77 25 1.56 1.59 1.26 ethanol -0.24 -0.31 25 1.10 1.04 0.74 1-propane] 0.29 0.25 25 0.62 0.49 0.21 2-propanol 0.07 0.05 25 0.43 0.70 0.43 1-butanol 0.82 0.88 25 0.00 -0.06 -0.32 2-methylpropan-1-ol 0.69 0.76 25 0.10 -0.07 -0.19 butan-2-ol 0.60 0.61 25 0.47 -0.07 -0.10 1-pentanol 1.35 1.56 25 -0.60 -0.62 -0.85 2-pentanol 1.13 1.19 25 -0.29 -0.41 -0.63 3-pentanol 1.13 1.21 25 -0.24 -0.43 -0.63 2-methylbutanol 1.22 1.29 25 -0.47 -0.64 -0.72 3-methylbutan-l-ol 1.22 1.16 25 -0.51 -0.61 -0.72 2-methylbutan-2-ol 1.00 0.89 25 0.15 -0.33 -0.50 3-methyl-2-butanol 1.00 1.28 25 -0.18 -0.43 -0.50 2,2-dimethylpropanol 1.09 1.31 53 -0.40 -0.51 -0.87 1-hexanol 1.88 2.03 25 -1.24 -1.17 -1.38 2-hexanol 1.66 1.76 25 -0.89 -0.96 -1.16 3-hexanol 1.66 1.65 25 -0.80 -0.98 -1.16 2-methylpentanol 1.75 25 -1.11 -1.19 -1.25 3-methyl-2-pentanol 1.53 25 -0.72 -1.19 -1.03 4-methylpentanol 1.75 25 -1.14 -1.18 -1.25 2-methyl-2-pentanol 1.53 25 -0.49 -0.87 -1.03 3-methyl-2-pentanol 1.53 25 -0.71 -0.97 -1.03 4-methyl-2-pentanol 1.53 25 -0.80 -0.97 -1.03 2-methyl-3-pentanol 1.53 25 -0.70 -1.01 -1.03 3-methyl-3-pentanol 1.53 25 -0.36 -0.91 -1.03 2-ethyl-1-butanol 1.75 25 -1.17 -1.21 -1.25 2,2-dimethyl-1-butanol 1.62 25 -1.04 -1.23 -1.12 3,3-dimethyl-1-butanol 1.62 25 -0.50 -1.19 -1.12 3,3-dimethy 1-2-butanol 1.40 1.47 25 -0.62 -1.02 -0.90 1 -heptanol 2.41 2.72 25 -1.81 -1.73 -1.91 2-heptanol 2.19 2.31 25 -1.55 -1.53 -1.69 3-heptanol 2.19 2.24 25 -1.47 -1.52 -1.69 4-heptanol 2.19 2.22 25 -1.40 -1.52 -1.69 2-methyl-2-hexanol 2.06 25 -1.08 1.42 -1.56 3-methyl-3-hexanol 2.06 25 -0.98 1.46 -1.56 3-ethyl-3-pentanol 2.06 25 -0.85 -1.50 -1.56 2,2-dimethylpentanol 2.15 25 -1.52 -1.79 -1.65 2,4-dimethyl-2-pentanol 1.93 25 -0.92 -1.45 -1.43 2,4-dimethyl-3-pentanol 1.93 25 -1.22 -1.59 -1.43 1-octanol 2.94 3.00 25 -2.39 -2.28 -2.44 2-octanol 2.72 2.90 25 -2.09 -2.06 -2.22 3-octanol 2.72 25 -1.98 -2.08 -2.22 2-methyl-2-heptanol 2.59 25 -1.72 -1.99 -2.09 3-methyl-3-heptanol 2.59 25 -1.60 -2.01 -2.09 2-ethyl-l-hexanol 2.81 25 -2.11 -2.32 -2.31 1-nonanol 3.47 3.67 25 -3.01 -2.84 -2.97 2-nonanol 3.25 25 -2.74 -2.63 -2.75 1-decanol 4.00 4.57 25 -3.63 -3.40 -3.50 2-undecanol 4.31 25 -2.94 -3.75 -3.81 1-dodecanol 5.06 5.13 25 -4.80 -4.50 -4.56 1-tetradecanol 6.11 6.36 40 -5.84 -5.61 -5.76 1-pentadecanol 6.64 46 -6.35 -6.17 -6.35 1-hexadecanol 7.17 56 -7.00 -6.73 -6.98 1-octadecanol 7.70 61 -8.40 -7.84 -7.56 cyclohexanol 1.27 1.23 25 -0.44 -0.64 -0,77

cycloheptanol 1.83 25 -0.88 -1.22 -1.330 0 0 0 cyclooctanol 2.38 25 -1.29 -1.83 1 4-pentene-l-ol 0.87 25 -0.15 -0.28 -0.37 1 -hexene-3-ol 1.38 25 -0.59 -0.88 -0.88 2-butoxyethanol 0,84 0.83 25 -0.42 -0.24 -0.34 ethanethiol 1.17 25 -0.60 -0.80 -0.67 butanethiol 2.23 2.28 25 -2.18 -1.91 -1.73 dimethyl sulfide 0.84 1.05 25 -0.45 -0.57 -0.34 diethyl sulfide 1.90 1.95 25 -1.34 -1.54 -1.40 di-n-propyl sulfide 2.96 25 -2.58 -2.65 -2.46 diisopropl sulfide 2.52 2.84 25 -2.24 -2.45 -2.02 dimethyl disulfide 1.74 1.77 25 -1.44 -1.51 -1.24 diethyl disulfide 2.80 25 -2.42 -2.58 -2.30 thiourea -1.02 -1.02 176 0.32 1.14 0.01 triethyl phosphate 0.28 0.80 25 0.43 0.23 0.22 benzene 2.14 2.13 25 -1.64 -1.96 -1.64 toluene 2.64 2.73 25 -2.21 -2.51 -2.14 ethylbenzene 3.17 3.15 25 -2.77 -3.05 -2.67 o-xylene 3.09 3.12 25 -2.80 -3.02 -2.59 m-xylene 3.14 3.20 25 -2.82 -3.01 -2.64 p-xylene 3.14 3.15 25 -2.77 -3.00 -2.64 propylbenzene 3.70 3.72 25 -3.37 -3.61 -3.20 isopropylbenzene 3.57 3.66 25 -3.27 -3.57 -3.07 1.2.3-trimethylbenzene 3.54 3.59 25 -3.20 -3.48 -3.04 1.2.4-trimethylbenzene 3.59 3.63 25 -3.31 -3.47 -3.09 1.3.5-trimethylbenzene 3.64 3.58 25 -3.40 -3.47 -3.14 168

2-ethyltoluene 3.62 3.53 25 -3.21 -3.52 -3.12 4-ethyltoluene 3.67 25 -3.11 -3.50 -3.17 butyltoluene 4.68 25 -4.06 -4.16 -4.18 isobutyltoluene 4.55 25 -4.12 -4.17 -4.05 tert-butylbenzene 3.97 4.11 25 -3.66 -4.07 -3.47 1,2-diethylbenzene 4.15 3.72 25 -3.28 -4.10 -3.65 1,4-diethylbenzene 4.20 25 -3.75 -4.08 -3.70 1,2,4,5-tetramethylbenzene 4.04 4.00 80 -4.59 -4.06 -4.09 2-isopropyltoluene 4.02 25 -3.76 -4.04 -3.52 4-isopropyltoluene 4.07 4.10 25 -3.77 -4.01 -3.57 pentylbenzene 4.76 4.90 25 -4.64 -4.71 -4.26 tert-pentylbenzene 4.50 25 -4.15 -4.71 -4.00 pentamethylbenzene 4.49 4.56 50 -4.00 -4.60 -4.24 hexylbenzene 5.29 5.52 25 -5.21 -5.28 -4.79 hexamethylbenzene 4.99 4.61 164 -5.23 -4.92 -5.88 styrene 2.87 2.95 25 -2.82 -2.96 -2.37 diphenylmethane 4.21 4.14 26 -4.08 -4.35 -3.72 bibenzyl 4.59 4.79 52 -4.62 -4.91 -4.36 biphenyl 4.03 4.01 70 -4.35 -4.26 -3.98 4-methylbiphenyl 4.53 4.63 45 -4.62 -4.83 -4.23 naphthalene 3.32 3.30 80 -3.60 -3.60 -3.37 1 -methylnaphthalene 3.81 3.87 25 -3.70 -4.16 -3.31 2-niethylnaphthalene 3.81 3.86 35 -3.77 -4.12 -3.41 1,3-dimethylnaphthalene 4.31 4.42 25 -4.29 -4.77 -3.81 1,4-dimethylnaphthalene 4.31 4.37 25 -4.14 -4.79 -3.81 1,5-dimethylnaphthalene 4.31 4.38 82 -4.68 -4.79 -4.38 2,3-dimethylnaphthalene 4.26 4.40 103 -4.72 -4.79 -4.54 2,6-dimethylnaphthalene 4.31 4.31 109 -4.89 -4.72 -4.65 1-ethylnaphthalene 4.34 4.39 25 -4.17 -4.78 -3.84 2-ethylnaphthalene 4.34 4.38 25 -4.29 -4.73 -3.84 1,2,3,4-tetrahydronaphthaiene 3.71 3.49 25 -4.37 -3.83 -3.21 indan 3.15 3.18 25 -3.04 -3.31 -2.65 acenaphthene 3.77 3.92 95 -4.63 -4.37 -3.97 acenaphthylene 3.62 90 -3.96 -4.11 -3.77 fluorene 4.07 4.18 116 -5.00 -4.61 -4.48 1-methylfluorene 4.57 4.97 87 -5.22 -5.17 -4.69 anthracene 4.49 4.45 216 -6.35 -5.36 -5.90 2-methylanthracene 4.99 205 -6.96 -5.83 -6.29 9-methylanthracene 4.99 5.07 79 -5.89 -5.87 -5.03 9,10-dimethylanthracene 5.49 5.69 183 -6.57 -6.35 -6.57 phenanthrene 4.49 4.47 100 -5.26 -5.12 -4.74 1-methylphenanthrene 4.99 5.08 123 -5.85 -5.71 -5.47 2-methylphenanthrene 4.99 4.86 57 -5.84 -5.71 -4.81 fluoranthene 4.95 5.16 110 -6.00 -5.98 -5.30 benzo [a] fluorene 5.25 5.68 187 -6.68 -6.79 -6.37 benzo[b]fluorene 5.25 5.77 212 -8.04 -6.77 -6.62 pyrene 4.95 4.88 150 -6.18 -6.12 -5.70 7,12-dimethylbenz [a] anthracene 6.66 5.80 122 -7.02 -8.13 -7.13 naphthacene 5.66 5.90 357 -8.60 -7.07 -8.48 chrysene 5.66 5.81 255 -8.06 -6.93 -7.46 5 -methylchrysene 6.16 117 -6.59 -7.49 -6.58 6-methylchrysene 6.16 160 -6.57 -7.49 -7.01 5,6-diniethyIchry sene 6.61 128 -7.01 -8.06 -7.14 triphenylene 5.66 5.49 199 -6.73 -6.67 -6.90 perylene 6.12 5.82 278 -8.80 -7.40 -8.15 benzo [b] fluoranthene 6.12 167 -8.23 -7.38 -7.04 benzo [jlfluoranthene 6.12 165 -8.00 -7.52 -7.02 benzo [k]fluoranthene 6.12 6.11 216 -8.49 -7.60 -7.53 cholanthrene 6.12 173 -7.85 -7.45 -7.10 3-methylcholanthrene 6.62 6.42 179 -7.92 -8.04 -7.66 benzo[a]pyrene 6.12 6.13 179 -8.70 -7.83 -7.16 benzo[e]pyrene 6.12 6.44 178 -7.80 -7.92 -7.15 benzo[ghi]perylene 6.58 6.63 278 -9.02 -8.51 -8.61 picene 6.84 7.11 366 -7.87 -8.80 -9.75 fluorobenzene 2.28 2.27 25 -1.80 -2.02 -1.78 1,3-difluorobenzene 2.43 25 -2.00 -2.15 -1.93 1,4-difluorobenzene 2.43 25 -1.97 -1.98 -1.93 benzyl trifluoride 3.03 3.01 25 -2.51 -2.50 -2.53 chlorobenzene 2.86 2.89 25 -2.38 -2.75 -2.36 1,2-dichlorobenzene 3.45 3.43 25 -3.05 -3.42 -2.95 1,3-dichlorobenzene 3.57 3.53 25 -3.04 -3.52 -3.07 1,4-dichlorobenzene 3.57 3.44 54 -3.27 -3.48 -3.36 1,2,3-trichlorobenzene 4.04 4.14 25 -4.00 -4.17 -3.54 1,2,4-trichlorobenzene 4.16 4.05 25 -3.59 -4.16 -3.66 1,3,5-trichlorobenzene 4.28 4.19 63 -4.48 -4.22 -4.16 1,2,3,4-tetrachlorobenzene 4.63 4.64 46 -4.57 -4.77 -4.34 1,2,3,5-tetrachlorobenzene 4.75 4.66 54 -4.63 -4.80 -4.54 1,2,4,5-tetrachlorobenzene 4.75 4.60 139 -5.56 -4.79 -5.39 pentachlorobenzene 5.35 5.18 50 -5.65 -5.37 -5.10 hexachlorobenzene 6.06 5.73 227 -7.68 -6.00 -7.58 2-chlorotoluene 3.35 3.42 25 -3.52 -3.36 -2.85 4-chlorotoluene 3.35 3.33 25 -3.08 -3.31 -2.85 benzyl chloride 2.70 25 -2.39 -2.18 -2.20 1-chloronaphthalene 4.03 4.10 25 -3.93 -4.36 -3.53 2-chloronaphthalene 4.03 4.14 60 -4.14 -4.36 -3.88 2-chlorobiphenyl 4.49 4.53 32 -4.54 -4.99 -4.06 3-chlorobiphenyl 4.49 25 -4.88 -4.96 -3.99 bromobenzene 3.01 2.99 25 -2.55 -2.98 -2.51 1,2-dibromobenzene 3.67 3.64 25 -3.50 -4.02 -3.17 1,3-dibromobenzene 3.87 3.75 25 -3.54 -4.06 -3.37 1,4-dibromobenzene 3.87 3.79 87 -4.07 -4.06 -3.99 1,3,5-tribromobenzene 4.73 4.51 121 -5.60 -5.13 -5.19 1,2,4,5-tetrabromobenzene 5.19 5.13 182 -6.98 -5.88 -6.26 2-broniotoluene 3.50 25 -2.23 -3.59 -3.00 4-broniotoluene 3.50 29 -3.19 -3.53 -3.04 1-bromonaphthalene 4.18 25 -4.35 -4.69 -3.68 2-bromonaphthalene 4.18 54 -4.40 -4.62 -3.97 iodobenzene 3.27 3.25 25 -3.01 -3.42 -2.77 1-iodonaphthalene 4.44 25 -4.55 -5.16 -3.94 o-fluorobromobenzene 3.15 25 -2.70 -3.29 -2.65 m-fluorobromobenzene 3.15 25 -2.67 -3.25 -2.65 o-chlorobromobenzene 3.44 25 -3.19 -3.90 -2.94 m-chlorobromobenzene 3.72 25 -3.21 -3.92 -3.22 p-chlorobromobenzene 3.72 67 -3.63 -3.88 -3.64 o-chloroiodobenzene 3.98 25 -3.54 -4.43 -3.48 m-chloroiodobenzene 3.98 55 -3.55 -4.42 -3.78 p-chloroiodobenzene 3.98 53 -4.03 -4.42 -3.76 p-bromoiodobenzene 4.13 90 -4.56 -4.64 -4.28 anisole 2.06 2.11 37 -1.85 -2.04 -1.68 2-chloroanisole 2.75 2.68 25 -2.46 -2.92 -2.25 3-chloroanisole 2.91 2.98 25 -2.78 -2.90 -2.41 4-chloroanisole 2.91 2.78 25 -2.78 -2.78 -2.41 diphenyl ether 4.24 4.21 28 -3.96 -4.58 -3.77 benzaldehyde 1.50 1.47 25 -1.19 -1.36 -1.00 p-methoxybenzaldehyde 1.78 1.76 25 -1.49 -1.53 -1.28 acetophenone 1.58 1.58 25 -1.28 -1.53 -1.08 benzophenone 3.18 3.18 49 -3.12 -3.56 -2.92 anthraquinone 2.62 3.39 284 -5.19 -3.73 -4.71 methyl benzoate 2.11 2.12 25 -1.85 -1.89 -1.61 ethyl benzoate 2.64 2.64 25 -2.32 -2.41 -2.14 dimethyl phthalate 1.56 1.56 25 -1.66 -1.32 -1.06 diethyl phthalate 2.62 2.47 25 -2.35 -2.31 -2.12 di(2-ethylhexyl)phthalate 8.71 7.45 25 -6.96 -8.94 -8.21 benzonitrile 1.57 1.56 25 -1.00 -1.45 -1.07 phthalonitrile 1.01 0.99 140 -2.38 -1.10 -1.66 aniline 0.91 0.90 25 -0.41 -1.01 -0.41 o-toluidine 1.36 1.32 25 -2.21 -1.50 -0.86 m-methylaniline 1.36 1.32 25 -0.85 -1.46 -0.86 p-methylaniline 1.41 1.39 43 -1.21 -1.44 -1.09 o-chloroaniline 1.96 1.90 25 -1.52 -1.96 -1.46 m-chloroaniline 1.96 1.88 25 -1.37 -1.82 -1.46 p-choroaniline 1.96 1.88 73 -1.66 -1.77 -1.94 o-nitroaniline 1.92 1.85 72 -1.96 -1.75 -1.89 m-nitroaniline 1.38 1.37 114 -2.19 -1.44 -1.77 p-nitroaniline 1.38 1.39 146 -2.37 -1.23 -2.09 ethyl-p-aminobenzoate 2.03 1.86 89 -2.10 -2.03 -2.17 risocaine 2.55 2.43 75 -2.45 -2.60 -2.55 butamben 3.08 2.87 58 -3.08 -3.17 -2.91 N-methylaniline 1.64 1.66 25 -1.28 -1.61 -1.14 N-ethylaniline 2.17 2.16 25 -1.70 -2.21 -1.67 N,N-dimethylaniline 2.34 2.31 25 -1.92 -2.46 -1.84 N,N-diethylaniline 3.23 3.31 25 -3.03 -3.59 -2.73 1-naphthylamine 2.09 2.25 49 -1.92 -2.45 -1.83 p,p'-biphenyldiamine 1.58 1.34 128 -2.70 -2.74 -2.11 171 benzylamine 1.09 1.09 25 -1.54 -0.43 -0.59 procaine 2.54 2.14 61 -1.78 -2.23 -2.40 diphenylamine 3.62 3.50 52 -3.50 -3.63 -3.39 azobenzene 3.85 3.82 69 -2.75 -4.28 -3.79 nitrobenzene 1.88 1.85 25 -1.80 -1.87 -1.38 o-nitrotoluene 2.30 2.30 25 -2.33 -2.42 -1.80 m-nitrotoluene 2.38 2.42 25 -2.44 -2.57 -1.88 p-nitrotoluene 2.38 2.37 55 -2.49 -2.43 -2.18 o-chloronitrobenzene 2.40 2.52 34 -2.55 -2.61 -1.99 m-chloronitrobenzene 2.60 2.47 43 -2.77 -2.59 -2.28 p-chloronitrobenzene 2.60 2.39 84 -2.92 -2.75 -2.69 o-nitroanisole 1.82 1.73 25 -1.96 -2.16 -1.32 p-nitroanisole 2.10 2.03 54 -2.41 -2.11 -1.89 1,2-dinitrobenzene 1.63 1.69 118 -3.10 -1.98 -2.06 1,3-dinitrobenzene 1.63 1.49 90 -2.29 -1.66 -1.78 1,4-dinitrobenzene 1.63 1.47 173 -3.39 -1.66 -2.61 2,4-dinitrotoluene 2.05 1.98 69 -2.82 -2.22 -1.99 2,6-dinitrotoIuene 2.05 2.10 65 -3.00 -2.30 -1.95 2,4,6-trinitrotoluene 1.71 1.60 81 -3.22 -2.12 -1.77 1,3,5-trinitrobenzene 1.37 1.18 123 -2.89 -1.55 -1.85 1-nitronaphthalene 3.06 3.19 59 -3.54 -3.72 -2.90 2,3-dichloronitrobenzene 3.11 3.05 61 -3.48 -3.37 -2.97 3,4-dichIoronitrobenzene 3.19 3.12 41 -3.20 -3.44 -2.85 benzamide 0.65 0.64 128 -0.96 -0.40 -1.18 acetanilide 1.16 1.16 114 -1.33 -0.89 -1.55 p-fluoroacetanilide 1.56 1.47 153 -1.78 -1.11 -2.34 p-chloroacetanilide 2.13 2.12 178 -2.84 -1.81 -3.16 p-bromoacetanilide 2.28 2.29 165 -3.08 -2.09 -3.18 4-nitroacetanilide 1.46 1.66 215 -2.69 -1.83 -2.86 phenacetin 1.77 1.58 135 -2.35 -1.74 -2.37 lidocain 1.95 2.26 68 -1.71 -2.41 -1.88 benzoic acid 1.88 1.87 122 -1.55 -1.06 -2.35 o-toluic acid 2.38 2.40 105 -2.06 -1.74 -2.68 m-toluic acid 2.38 2.37 112 -2.14 -1.66 -2.75 p-toluic acid 2.38 2.27 182 -2.60 -1.61 -3.45 o-ch!orobenzoic acid 2.10 2.05 142 -1.89 -1.52 -2.77 m-chlorobenzoic acid 2.70 2.68 158 -2.59 -1.77 -3.53 p-chlorobenzoic acid 2.70 2.65 243 -3.31 -1.85 -4.38 2-bromobenzoic acid 2.20 2.20 149 -2.28 -1.74 -2.94 4-bromobenzoic acid 2.85 2.86 246 -3.54 -2.16 -4.56 m-nitrobenzoic acid 1.84 1.83 142 -1.68 -1.53 -2.51 p-nitrobenzoic acid 1.84 1.89 242 -2.80 -1.55 -3.51 o-aminobenzoic acid 1.21 1.21 145 -1.52 -1.02 -1.91 aspirin 1.02 1.19 135 -1.72 -1.13 -1.62 phenylacetic acid 1.41 1.41 77 -0.89 -1.09 -1.43 ibuprofen 3.68 3.50 76 -3.76 -3.93 -3.69 naproxen 2.82 3.34 153 -4.20 -3.89 -3.60 phenol 1.47 1.47 41 0.00 -0.73 -1.13 2-methylphenol 1.97 1.95 31 -0.62 -1.44 -1.53 3-methylphenol 1.97 1.96 25 -0.68 -1.26 -1.47 p-cresol 1.97 1.94 33 -0.73 -1.33 -1.55 2,4-dimethylphenol 2.47 2.30 28 -1.19 -1.82 -2.00 2,6-dimethylphenol 2.47 2.36 49 -1.29 -1.96 -2.21 3,4-dimethyIphenol 2.42 2.23 63 -1.38 -1.73 -2.30 3,5-diinethylphenol 2.47 2.35 64 -1.40 -1.80 -2.36 2,4,6-trimethylphenol 2.97 71 -2.05 -2.39 -2.93 p-tert-butylphenol 3.30 3.31 98 -2.41 -2.77 -3.53 thymol 3.20 3.30 48 -2.22 -2.81 -2.93 p-phenylphenol 3.36 3.20 167 -3.48 -3.18 -4.28 2-chlorophenol 2.15 2.15 25 -1.06 -1.56 -1.65 3-chlorophenol 2.48 2.50 34 -0.70 -1.37 -2.07 4-chlorophenol 2.48 2.39 43 -0.70 -1.30 -2.16 4-bromophenol 2.63 2.59 66 -1.09 -1.60 -2.54 2,3-dichlorophenol 2.84 2.84 59 -1.30 -2.22 -2.68 2,4-dichlorophenol 2.96 3.06 45 -1.55 -2.25 -2.66 2,6-dichlorophenol 2.63 2.75 67 -1.79 -2.22 -2.55 3,4-dichlorophenol 3.17 3.33 67 -1.25 -1.81 -3.09 3,5-dichlorophenol 3.29 3.52 68 -1.34 -1.83 -3.22 2,3,4-trichlorophenol 3.58 79 -2.67 -2.57 -3.62 2,3,5-trichlorophenol 3.58 57 -2.67 -2.60 -3.40 2,3,6-trichlorophenol 3.37 3.77 56 -2.64 -2.71 -3.18 2,4,5-trichlorophenol 3.58 3.72 68 -2.21 -2.64 -3.51 2,4,6-trichlorophenol 3.37 3.69 70 -2.34 -2.67 -3.32 2,3,4,5-tetrachlorophenol 4.30 4.21 116 -3.15 -3.26 -4.71 2,3,4,6-tetrachlorophenol 4.09 4.12 70 -3.10 -3.49 -4.04 2,3,5,6-tetrachlorophenol 4.09 3.88 114 -3.37 -3.39 -4.48 pentachlorophenol 4.68 5.12 174 -4.28 -3.48 -5.67 o-methoxyphenol 1.32 1.32 28 -1.96 -1.21 -0.85 p-hydroxybenzaldehyde 1.44 1.35 25 -0.96 -0.67 -0.94 o-aminophenol 0.62 0.62 175 -0.72 -0.47 -1.62 p-aminophenol 0.25 0.04 189 -0.80 -0.13 -1.39 o-nitrophenol 1.85 1.79 44 -1.74 -1.86 -1.54 m-nitrophenol 1.85 2.00 97 -1.01 -1.04 -2.07 p-nitrophenol 1.85 1.91 113 -0.74 -0.85 -2.23 salicylic acid 2.19 2.26 159 -1.82 -1.48 -3.03 p-hydroxybenzoic acid 1.56 1.58 217 -1.41 -1.07 -2.98 1,2-benzenediol 0.88 0.88 104 0.62 -0.42 -1.17 1,3-benzenediol 0.81 0.80 110 0.81 -0.27 -1.16 1,4-benzenediol 0.81 0.59 170 -0.17 -0.32 -1.76 methylparaben 1.98 1.96 128 -1.83 -1.48 -2.51 ethyl-p-hydroxybenzoate 2.51 2.47 117 -2.35 -2.02 -2.93 o-hydroxybenzamide 1.28 1.28 140 -1.82 -1.11 -1.93 p-hydroxyacetanilide 0.49 0.51 169 -1.03 -1.02 -1.43 1-naphthol 2.65 2.84 96 -2.22 -2.64 -2.86 2-naphthol 2.65 2.70 121 -2.28 -2.54 -3.11 phenylmethanol 1.10 1.10 25 -0.40 -0.79 -0.60 173

1-phenylethanol 1.41 1.42 25 -0.92 -1.06 -0.91 2-phenoxyethanol 1.19 1.16 25 -0.70 -0.88 -0.69 ephedrine 0.89 0.93 38 -0.47 -0.78 -0.52 thiophenol 2.53 2.52 25 -2.12 -2.55 -2.03 phenylthiourea 0.75 0.73 154 -1.77 -1.02 -1.54 p-toluenesulfonamide 0.80 0.82 139 -1.74 -1.06 -1.44 furane 1.32 1.34 25 -0.82 -1.03 -0.82 furfural 0.67 0.41 25 -0.10 -0.15 -0.17 dibenzofurane 4.09 4.12 83 -4.60 -4.47 -4.17 pyridine 0.64 0.65 25 0.76 0.04 -0.14 2,3-dimethylpyridine 1.59 25 0.38 -0.74 -1.09 2,4-dimethylpyridine 1.64 25 0.38 -0.68 -1.14 2,6-dimethylpyridine 1.64 1.68 25 0.45 -0.70 -1.14 3,4-dimethyIpyridine 1.59 25 0.36 -0.69 -1.09 3,5-dimethylpyridine 1.64 1.78 25 0.38 -0.81 -1.14 2-ethyl pyridine 1.67 1.69 25 0.51 -0.87 -1.17 4-ethyl pyridine 1.67 1.65 25 0.83 -0.90 -1.17 cocaine 2.57 2.30 98 -2.25 -2.17 -2.80 atropine 1.32 1.83 116 -2.12 -2.53 -1.73 quinoline 2.03 2.03 25 -1.30 -1.88 -1.53 isoquinoline 1.82 2.08 26 -1.45 -1.80 -1.33 carbazole 3.52 3.48 247 -5.27 -3.87 -5.24 antipyrene 0.20 0.23 109 0.72 0.44 -0.54 morpholine -0.41 -0.86 25 1.97 1.62 0.91 theophylline -0.06 -0.02 272 -1.39 -0.21 -1.91 caffeine -0.06 -0.07 235 -0.88 0.45 -1.54 morphine 0.59 0.76 254 -3.28 -2.38 -2.38 codeine 0.98 1.14 155 -1.52 -2.28 -1.78 thiophene 1.79 1.89 25 -1.33 -1.65 -1.29 imipramine 5.04 4.44 174 -4.19 -4.15 -6.03 progesterone 3.77 3.87 131 -4.42 -4.02 -4.33 testosterone 3.22 3.32 155 -4.02 -4.08 -4.02 deoxycorticosterone 3.25 2.88 136 -3.45 -3.98 -3.86 hydroxyprogesterone-17a 3.15 3.17 276 -3.82 -4.24 -5.16 corticosterone 2.32 1.94 181 -3.24 -4.04 -3.38 cortisone 1.30 1.47 222 -3.11 -3.29 -2.77 hydrocortisone 1.70 1.61 213 -3.09 -4.93 -3.08 17a-methyltestosterone 3.74 3.36 162 -4.00 -4.34 -4.61 prednisolone 1.38 1.62 240 -3.18 -5.20 -3.03 hydrocortisone 21-acetate 2.23 2.19 223 -4.88 -4.69 -3.71 estrone 3.38 3.13 255 -3.96 -4.07 -5.18 estradiol 3.78 3.86 173 -5.03 -4.39 -4.76 dexamethasone 1.75 2.01 262 -3.59 -5.35 -3.62 5,5-dimethylbarbituric acid -0.40 -0.44 278 -1.74 0.20 -1.63 5-methyl-5-ethylbarbituric acid 0.13 0.08 212 -1.23 -0.36 -1.50 barbital 0.66 0.65 190 -2.40 -0.96 -1.81 5-ethyl-5-isopropylbarbituric acid 1.05 1.10 203 -2.15 -1.49 -2.33 butabarbital 1.58 1.65 166 -2.39 -1.97 -2.49 174 pentobarbital 2.11 2.10 129 -2.39 -2.54 -2.65 5-ethyl-5-(3-methylbutyI)barbitaI 2.11 2.07 156 -2.66 -2.54 -2.92 5,5-diisopropylbarbital 1.45 1.56 228 -2.77 -2.00 -2.98 5-allyl-5-methylbarbital 0.17 0.36 166 -1.16 -0.68 -1.08 5-allyl-5-ethylbarbital 0.70 0.87 160 -1.61 -1.24 -1.55 5-allyl-5-isopropylbarbitaI 1.37 1.37 143 -1.71 -1.70 -2.05 secobarbital 2.16 1.97 132 -2.36 -2.82 -2.73 5,5-diallylbarbital 0.75 1.15 174 -2.08 -1.73 -1.74 5-(3-methyl-2-butenyl)-5-ethylbarbital 1.63 1.73 155 -2.25 -2.34 -2.43 5-(3-methyl-2-butenyl)-5-isoprbarbital 2.23 2.23 131 -2.59 -2.87 -2.80 5-ethyl-5-phenylbarbital 1.37 1.47 174 -2.32 -2.88 -2.36 5-allyl-5-phenylbarbital 1.41 1.69 133 -2.37 -3.28 -1.99 cyclobutyl-5-spirobarbituric acid -0.57 -0.27 256 -1.66 -0.12 -1.24 cyclopentyl-5-spirobarbituric acid -0.01 0.24 270 -2.35 -0.73 -1.94 cyclohexyl-5-spirobarbituric acid 0.55 0.91 289 -3.06 -1.33 -2.69 cycloheptyl-5-spirobarbituric acid 1.11 1.36 266 -3.17 -1.94 -3.02 cyclooctyl-5-spirobarbituric acid 1.67 1.79 228 -2.98 -2.56 -3.20 amitrole -0.53 -0.87 159 0.52 0.86 -0.31 carbaryl 2.38 2.36 142 -3.22 -2.74 -3.05 carbofuran 2.47 1.63 152 -2.80 -1.77 -3.24 chlorfenac 3.43 3.20 161 -3.08 -3.10 -4.29 coumatetralyl 4.83 180 -2.84 -4.77 -5.88 2,4-DB 3.42 3.53 117 -3.73 -3.60 -3.84 DDT 6.76 6.91 109 -7.15 -7.46 -7.10 desmedipham 3.40 3.39 120 -4.63 -5.10 -3.85 dichlorophen 4.89 178 -3.95 -4.58 -5.92 dichlorprop 3.26 3.43 118 -2.83 -3.35 -3.69 diuron 2.68 2.68 159 -3.05 -2.98 -3.52 DNOC 2.29 2.13 86 -1.46 -2.40 -2.40 etofenprox 7.36 7.05 37 -8.60 -7.84 -6.98 fenoxycarb 4.46 4.30 54 -4.70 -4.82 -4.25 fenuron 0.98 0.98 133 -1.60 -1.64 -1.56 fluometuron 2.39 2.42 163 -3.43 -2.11 -3.27 isoprocarb 2.29 2.31 93 -2.86 -2.21 -2.47 isoproturon 2.40 2.50 158 -3.54 -3.00 -3.23 linuron 3.00 3.20 93 -3.59 -3.39 -3.18 methyldymron 3.24 3.01 60 -3.35 -3.74 -3.09 metolcarb 1.71 1.70 76 -1.80 -1.57 -1.72 metoxuron 1.78 1.64 125 -2.56 -2.18 -2.28 monolinuron 2.31 2.30 80 -2.57 -2.36 -2.36 propoxur 1.65 1.52 91 -2.05 -1.62 -1.81 warfarin 2.89 2.70 161 -4.26 -4.07 -3.75 XMC 2.21 2.23 99 -2.58 -2.08 -2.45 cyclopropyl-5-spirobarbituric acid -1.13 -0.53 325 -1.89 0.36 -1.37 uracil -1.06 -1.07 335 -1.49 1.19 -1.54 chlorpheniramine 3.15 3.17 25 -0.24 -3.06 -2.65 fentanyl 3.62 3.89 83 -1.13 -4.22 -3.70 adenine -0.29 -0.09 363 -2.43 0.19 -2.59 175

APPENDIX C. Predicted Solubility for Test Set 1.

Name MPCO CLOGP MIogP lOgSvv logSw logS„ logS„ Expt GSE AOUAFAC GClogP 2,2',4,5,5'-PCB 77 6.97 6.85 -6.77 -6.99 -7.21 -7.51 benzocaine 89 1.92 1.86 -2.32 -2.06 -2.16 -2.56 acetylsalicylicacid 135 1.02 1.19 -1.61 -1.62 -1.36 -1.07 theophylline 272 -0.06 -0.02 -1.37 -1.91 -2.77 -1.13 antipyrine 111 0.20 0.23 0.39 -0.56 -1.34 -0.11 atrazine 175 2.50 2.61 -3.55 -3.50 -2.86 -3.49 phenobarbital 176 1.37 1.47 -2.34 -2.38 -2.24 -2.67 diuron 159 2.68 2.68 -3.76 -3.52 -3.55 -3.57 nitrofurantoin 272 -0.47 -0.47 -3.38 -1.50 -2.98 -2.58 phenytoin 295 2.08 2.26 -3.99 -4.28 -4.72 -3.13 diazepam 125 3.16 2.99 -3.76 -3.66 -3.97 -4.00 testosterone 155 3.22 3.32 -4.07 -4.02 -4.84 -4.07 lindane 113 3.75 3.72 -4.60 -4.13 -5.57 -3.85 parathion <25 3.47 3.83 -4.29 -2.97 -4.08 -3.88 diazinon 120 3.50 3.30 -3.76 -3.95 -4.77 -4.05 phenolphthalein 264 2.63 -2.90 -4.52 -4.95 -2.54 malathion <25 2.70 2.38 -3.36 -2.20 -2.41 -2.87 chlorpyriphos 43 4.49 4.82 -5.67 -4.17 -5.10 -5.07 prostaglandin e2 67 2.01 2.82 -2.47 -1.93 -3.38 -3.39 p,p'-DDT 109 6.76 6.91 -8.08 -7.10 -6.77 -6.77 chlordane <25 5.80 6.00 -5.35 -5.30 -6.40 -7.05 176

APPENDIX D. Predicted Solubility for Test Set 2.

Name MPCO CLOGP MlogP logS« logS„ logS„ logS«, Expt GSE AQUAFAC GClogP aminopyrine 108 0.57 1.00 -0.36 -0.90 -1.77 -0.65 ephedrine 38 0.89 0.93 -0.47 -0.52 -0.55 -0.66 caffeine 235 -0.06 -0.07 -0.88 -1.54 -1.88 -0.85 paracetamol 169 0.49 0.51 -0.99 -1.43 -1.48 -0.37 metronidazole 160 -0.46 -0.02 -1.22 -0.39 -1.53 -0.10 dl-coniine -18 2.51 -1.50 -2.01 -1.17 -2.02 procaine 61 2.54 2.14 -1.78 -2.40 -1.99 -2.61 methylparaben 128 1.98 1.96 -1.83 -2.51 -1.80 -1.85 cyclobarbital 171 1.87 1.77 -2.02 -2.83 -2.92 -3.58 atropine 116 1.32 1.83 -2.20 -1.73 -2.45 -1.24 cocaine 98 2.57 2.30 -2.25 -2.80 -2.26 -2.69 phenacetin 135 1.77 1.58 -2.35 -2.37 -2.66 -1.76 barbital 190 0.66 0.65 -2.40 -1.81 -1.72 -1.89 tripelennamine 191 3.31 -2.64 -4.47 -3.52 -2.68 pipemedic acid 253 -2.73 -2.98 0.95 -1.43 -0.04 chlorfenac 161 3.43 3.20 -3.08 -4.29 -3.84 -4.17 prednisolone 240 1.38 1.62 -3.18 -3.03 -3.68 -3.42 nalidixic acid 227 1.32 1.59 -3.37 -2.84 -3.30 -3.07 doxepin 120 4.09 -3.40 -4.54 -4.62 -3.57 lorazepam 167 2.36 2.39 -3.60 -3.28 -4.24 -3.84 dibucaine 64 5.34 4.40 -3.70 -5.23 -4.47 -5.98 ibuprofen 76 3.68 3.50 -3.76 -3.69 -3.12 -3.68 nitrazipam 224 2.31 2.13 -3.80 -3.80 -4.51 -3.85 mebandazole 289 3.06 2.83 -3.88 -5.20 -4.55 -5.16 oxazepam 205 2.29 2.24 -3.95 -3.59 -3.98 -3.65 prasterone 150 3.07 3.23 -4.06 -3.82 -4.66 -4.00 triazolam 224 2.25 2.42 -4.08 -3.74 -6.03 -3.88 hydrastine 132 2.08 -4.11 -2.65 -2.96 -3.32 imipramine 174 5.04 4.44 -4.19 -6.03 -4.77 -4.65 naproxen 153 2.82 3.34 -4.20 -3.60 -3.85 -3.66 warfarin 161 2.89 2.70 -4.26 -3.75 -3.62 -3.36 indomethacine 159 4.18 4.27 -4.62 -5.02 -4.94 -6.10 norethindrone 203 2.78 2.97 -4.63 -4.06 -4.96 -4.16 sulindac 184 3.16 3.05 -5.00 -4.25 -6.21 -4.79 estradiol 220 3.78 3.86 -5.03 -5.23 -4.73 -4.00 chlorpromazine 57 5.80 5.35 -5.10 -5.62 -4.23 -4.88 thioridazine 73 6.50 5.90 -5.82 -6.48 -6.07 -5.75 fluotrimazole 164 5.15 -8.40 -6.04 -6.64 -4.88 177

APPENDIX E. Predicted Solubility for Test Set 3.

Name CLOGP MlogP lOgSvv logS„ Error Expt GClogP Pred-Obs 1,3,5-trichlorobenzene 4.28 4.19 -4.44 -4.00 0.44 4-aminobenzoic acid 0.98 0.83 -1.37 -1.60 -0.23 4-hydroxypteridine -0.20 -1.47 -0.89 0.58 5 -methyl-5 -ethylbarbiturate 0.13 0.08 -1.16 -1.41 -0.25 6-aminopteridine -0.83 -2.34 -1.08 1.26 6-methoxypteridine 0.09 -1.14 -1.34 -0.20 7-butyltheophylline 1.53 -1.81 -2.29 -0.48 7-chlorpteridine -0.14 -0.88 -1.14 -0.26 7-dimethylaminopteridine 0.07 -0.02 -1.55 -1.53 7-methyIpteridine -0.36 -0.85 -0.76 0.09 acetazolamide -1.25 -0.26 -2.49 -1.08 1.41 adenosine -2.27 -1.05 -1.73 -0.84 0.89 atrazine 2.50 2.61 -3.49 -3.49 0.00 baclofen -0.62 -0.96 -1.70 -0.73 0.97 benzanthr acene (benzo [a] anthracene) 5.66 5.54 -7.21 -6.69 0.52 busulfan -0.59 -0.52 -2.27 0.25 2.52 clofazimine 6.69 7.48 -5.80 -9.22 -3.42 cortisone 1.30 1.47 -3.27 -3.56 -0.29 cyclohexane-spirobarbiturate 1.11 1.36 -3.17 -2.61 0.56 diatrizoic acid 0.65 -2.79 -2.26 0.53 disopyramide 2.58 2.71 -1.70 -2.18 -0.48 ethyl-4-aminobenzoate (benzocaine) 1.92 1.86 -2.62 -2.56 0.06 fenchlorphos 4.96 5.07 -4.10 -5.33 -1.23 flurbiprofen 3.75 4.16 -3.74 -4.64 -0.90 glafenine 3.04 -4.57 -5.59 -1.02 glutethimide 1.99 1.90 -2.34 -2.50 -0.16 guanine -1.28 -0.96 -3.58 -1.29 2.29 heptabarbital 2.43 2.03 -3.00 -4.09 -1.09 hydrochlorothiazide -0.40 -0.07 -2.69 -2.15 0.54 indapamide 2.94 -3.79 -5.44 -1.65 indoprofen 2.74 2.77 -4.82 -3.42 1.40 isocarboxazid 0.97 1.49 -2.46 -2.18 0.28 i-dopa -2.82 -2.74 -1.82 1.67 3.49 lidocaine 1.95 2.26 -1.77 -1.30 0.47 linuron 3.00 3.20 -3.52 -4.01 -0.49 mefenamic acid 4.94 5.12 -3.77 -5.78 -2.01 meprobamate 0.91 0.70 -1.81 -1.70 0.11 methyprylon 1.78 0.78 -0.38 -2.16 -1.78 minocycline 0.19 -0.94 -3.41 -2.47 mitomycin c -2.55 -0.40 -2.56 -1.55 1.01 nalidixic acid 1.32 1.59 -3.37 -3.07 0.30 nicotinic acid 0.80 -0.85 -0.98 -0.13 nitrofurantoin -0.47 -0.47 -3.48 -2.58 0.90 propylparaben 3.04 3.04 -2.56 -2.81 -0.25 propylthiouracil -0.33 -2.19 -1.85 0.34 178 salicylic acid 2.19 2.26 -1.80 -1.99 -0.19 strychnine 1.66 1.93 -3.33 -2.76 0.57 sulfamethoxazole 0.55 0.89 -2.71 -2.35 0.36 talbutal 1.63 1.47 -2.02 -2.72 -0.70 tenoxicam 1.61 0.81 -3.88 -3.99 -0.11 terfenadine 6.09 5.69 -4.67 -5.34 -0.67 tetroxoprim 0.63 0.56 -2.10 -2.71 -0.61 theobromine -0.69 -0.72 -2.56 -1.29 1.27 179

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