Fuzzy ARTMAP and Back-Propagation Neural Networks Based

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Fuzzy ARTMAP and Back-Propagation Neural Networks Based Quantitative Structure-Property Relationships (QSPRs) for Octanol-Water Partition Coefficient of Organic Compounds Denise Yaffe,† Yoram Cohen*,† Gabriela Espinosa,‡ Alex Arenas,§ and Francesc Giralt‡ Department of Chemical Engineering, University of California, Los Angeles, Los Angeles, California 90095-1592, and Departament d’Enginyeria Quı´mica, ETSEQ, and Departament d’Enginyeria Informa`tica, ETSE, Universitat Rovira i Virgili, 43006 Tarragona, Catalunya, Spain Received May 9, 2001

Quantitative structure-property relationships (QSPRs) for estimating the logarithm octanol/water partition coefficients, logKow, at 25 °C were developed based on fuzzy ARTMAP and back-propagation neural networks using a heterogeneous set of 442 organic compounds. The set of molecular descriptors were derived from molecular connectivity indices and quantum chemical descriptors calculated from PM3 semiempirical MOtheory. Quantum chemical input descriptors include average polarizability, dipole moments, exchange energy, total electrostatic interaction energy, total two-center energy, and ionization potential. The fuzzy ARTMAP/ QSPR performed, for a logKow range of -1.6 to 7.9, with average absolute errors of 0.03 and 0.14 logKow for the overall data and test sets, respectively. The optimal 12-11-1 back-propagation/QSPR model, for the same range of logKow, exhibited larger average absolute errors of 0.23 and 0.27 logKow for the test and validation data sets, respectively, over the same range of logKow values. The present results with the fuzzy ARTMAP-based QSPR are encouraging and suggest that high performance logKow QSPR that encompasses a wider range of chemical groups could be developed, following the present approach, by training with a larger heterogeneous data set. INTRODUCTION

The octanol/water partition coefficient, Kow, which is the ratio of a chemical’s concentration in n-octanol to that in water in a two-phase system at equilibrium, is often used to quantify the lipophilic or hydrophobic nature of an organic compound. Kow is an important physicochemical property in the environmental,1-3 pharmaceutical,4-6 biochemical, and toxicological sciences.2 For example, Kow is a key parameter required for estimates of the multimedia environmental mass distribution of organic compounds1-3 including contaminant bioaccumulation in aquatic biota and plants. Kow is also an important parameter utilized to predict potential interactions of drug molecules with receptor molecules. Although experimental Kow values are available for a large data set of organic compounds, reliable experimental data are lacking for many chemical pollutants. Given the need to evaluate both present and potential future pollutants, there has been a steady increase in efforts to develop reliable Kow estimation methods. Estimation approaches include group and atom contribution methods,4-16 quantitative structure property relationships (QSPRs) derived from statistical regressions,17-24 and neural networks-based QSPRs.25-29 Kow for organic compounds spans several orders of magnitude, from less than * Corresponding author phone: (310)825-8766; fax: (310)477-3868; e-mail: [email protected]. † University of California. ‡ Departament d’Enginyeria Quı´mica, ETSEQ, Universitat Rovira i Virgili. § Departament d’Enginyeria Informa ` tica, ETSE, Universitat Rovira i Virgili.

10-4 to more than 108, and thus it is commonly reported as logKow. Group and atom contribution models have typically been based on fragments, derived either from atoms or groups of atoms, which are assigned incremental logKow contributions4,9,10 The standard deviation of predictions from group and atom contribution approaches for estimating logKow has generally been reported to vary from about 0.35-0.6 logKow units7,8 for a logKow range of -3 to 6. The commercial CLOGP model is an example of a group contribution method that has been developed based on a large data set of about 8000 compounds.5,10,11 In general, group contribution methods produce satisfactory results for simple compounds and various improvements to logKow group contribution methods have been developed to handle complex molecules through the introduction of corrections factors, refinements of fragments, and development of new fragments.7,8 One advantage of atom contribution methods, relative to group contribution methods, is that ambiguity in the choice of fragments when dividing a molecule is eliminated. Both methods require a larger number of correction factors as the complexity of the molecule increases. Also, logKow can only be predicted for compounds consisting of fragments for which logKow contribution values are available. It has been reported that logKow estimation methods using fragmental contributions are generally comparable to those using atomic contributions16 with both methods working well for simple structures. Quantitative-structure-property-relations (QSPRs) have been developed as alternate methods of estimating logKow. The premise of QSPR for logKow is that physicochemical

10.1021/ci0103267 CCC: $22.00 © 2002 American Chemical Society Published on Web 02/26/2002

OCTANOL-WATER PARTITION COEFFICIENT

properties can be correlated with molecular structural characteristics (geometric and electronic) expressed in terms of appropriate molecular descriptors.17 In general, high accuracy is obtained for QSPRs developed specifically for homologous series and data sets containing similar compound families.18 QSPRs developed for heterogeneous data sets using topological descriptors30-32 have performed with reported errors comparable to those of group contribution methods.19,20 For example, the so-called VLOGP model20 that utilizes a set of over 300 electrotopological-state32 and kappa shape indices as chemical descriptors was developed using a training set of 6675 compounds (-3.56e logKowe 7.73) and performed with an average error of 0.201 logKow units.20 In recent years, improvements in logKow QSPRs have been proposed through the use of molecular descriptors derived from semiempirical Molecular Orbital theory (quantum mechanics) calculations.21-25,33,34 For example, Bodor et al.,21 using AM1 semiempirical MO theory, reported a standard deviation of 0.306 logKow for a 18 parameter linear correlation which was developed for estimating logKow for a heterogeneous data set 302 organic compounds (-1.3 e logKow e 6.6). In later studies, Schu¨u¨rmann22,23 proposed linear correlations of logKow with a range of quantum chemical parameters based on data of 12 aromatic phosphorothionates22 and 17 substituted benzenes.23 A logKow correlation for 17 benzene derivatives over a range of approximately 4 e logKow e 8, based on the free energy of aqueous solvation and contact surface area, performed with a standard a deviation of 0.22 logKow units. In a more recent study, Eisfeld and Maurer24 proposed a logKow correlation with dipole moment, polarizability, electrostatic potential, and molar volume as chemical descriptors, based on a heterogeneous set of 202 compounds (-2 e logKow e 5.7) with a reported standard deviation and maximum absolute error of 0.287 and 1.004 logKow units, respectively. The introduction of indicator variables in the correlation, to account for the presence of nitrogen and oxygen atoms, lowered the standard deviation and maximum absolute error to 0.274 and 0.821 logKow units, respectively.24 The application of neural networks, as an alternative approach to developing QSPRs for logKow, has been introduced in recent years. For example, Duprat et al.25 developed neural network-based QSPR models of various backpropagation architectures for logKow, for a set of 323 diverse organic compounds (-1.3 e logKow e 6.5), with reported standard deviations ranging from 0.37 to 0.28 logKow. The models of Duprat et al.25 were based on a set of descriptors that included the number of carbon atoms, molecular surface, molecular weight, square root of the sum of the charges on oxygen, nitrogen, and sum of the absolute values of atomic charges on nitrogen and oxygen. More recently, Huuskonen et al.26 proposed a 39-5-1 back-propagation neural networkbased QSPR for logKow, based on a diverse set of 1870 organic compounds (-4.2 e logKow e 5.9), using atomictype electrotopological-state (E-state)32 indices as input descriptors, with a reported root-mean-square error of 0.41 logKow units.26 QSPRs for logKow based on neural networks (NN) with quantum mechanical descriptors have also been proposed in recent years.27-29 For example, Breindl et al.27 developed a NN/QSPR for logKow using two sets of 16 quantum chemical parameters that were calculated from AM133 and PM334

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semiempirical Molecular Orbital theory. The QSPRs models for the AM1 and PM3 parameter sets were based on a 1625-1 back-propagation network architecture developed with a data set of 1085 compounds (-2.06 e logKow e 7.41).27 Average absolute errors and standards deviations for the validation set (105 compounds) for AM1 and PM3 models were 0.45 (80%) and 0.30 (243.4%) logKow and 0.53 (86%) and 0.42 (227%) logKow, respectively.27 More recently, Beck et al.,29 using the same chemical data set of Breindl et al.27 and 16 quantum chemical descriptors (computed from AMI), developed a logKow QSPR based on a 16-10-1 backpropagation neural network architecture which performed with average and maximum errors for the cross-validation set of 0.56 and 2.1 logKow, respectively.29 To date, published available NN/QSPRs for octanol/water partition coefficients have been based on back-propagation neural networks.19,20,25-27,29 However, recent studies35-37 suggests that it may be possible to develop NN-based QSPRs of greater accuracy by using the cognitive classifier fuzzy ARTMAP neural network classifier. The fuzzy ARTMAP neural networks approach, which was demonstrated for estimating boiling points of aliphatic hydrocarbons,35 critical properties,36 and aqueous solubility of organics,37 has been shown to be superior to the back-propagation neural network approach as well as other regression-based statistical correlations reported in the literature. Fuzzy ARTMAP neural networks have several advantages owing to their capability to classify and analyze noisy information with fuzzy logic and to avoid the plasticity-stability dilemma of standard backpropagation architectures. In the present study, we expand recent work to demonstrate that fuzzy ARTMAP-based QSPRs for logKow can be developed using a relatively small number of quantum chemical descriptors derived from PM3 semiempirical MOtheory. The present work presents a first demonstration of using the fuzzy ARTMAP approach to arrive at adequate logKow QSPR with a modest heterogeneous data set of 442 organics with the majority of compounds being of environmental interest. The performance of the fuzzy ARTMAPbased QSPR is compared to a back-propagation QSPR developed with the same set of input descriptors and to other published multiple linear regression (MLR) and backpropagation neural network (NN) based QSPR models. II. METHODOLOGY

Data Set and Molecular Descriptors. The approach of developing the present neural network-based logKow QSPRs is summarized in Figure 1. Octanol/water partition coefficients at 25 °C for a diverse set of 442 organic compounds were compiled from the literature,4,7,10,19,38 and these are listed in Tables 1 and 3 as logKow. This heterogeneous set of compounds includes aromatic (polycyclic aromatic) and nonaromatic (normal, branched, cyclic) hydrocarbons, halogens, PCBs, mercaptans, sulfides, anilines, pyridines, alcohols, carboxylic acids, aldehydes, amines, ketones, and esters. Prior to model development, the input descriptors and octanol/water partition coefficient data were normalized from 0 to 1 as Xn ) X - Xmin/(Xmax-Xmin), where X and Xn are the actual and normalized logKow values, respectively, and Xmin and Xmax are the minimum and maximum logKow values in the data set, respectively.

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Figure 1. Process flow diagram for developing fuzzy ARTMAP and back-propagation QSPR/neural networks for predicating octanol/ water partition coefficients.

The molecular descriptors for each compound were calculated from knowledge of the chemical structure. Molecular structures were drawn using Molecular Modeling Pro 3.01 (ChemSW Software Inc.)39 and converted to threedimensional structures using the CAChe Software (Oxford Molecular Ltd.).40 The geometry of the three-dimensional structures were subsequently optimized using MOPAC34,41, a semiempirical molecular orbital modeling program with the PM3 (parametric model 3) Hamiltonian34 to arrive at the compounds’ minimum energy conformations. In conjunction with the MOPAC energy minimization, quantum chemical descriptors, derived from the PM3 MO theory, were also calculated. The calculated descriptors included average polarizability, dipole moments, moments of inertia, ionization potential, number of number of doubly occupied (filled) MO levels, molecular weight, heat of formation, total energy, electronic energy, and nuclear-nuclear (core-core), and energy components partitioned into the individual one-center and two-center terms were calculated (see Table 2). The total energy, in terms of the PM3 MO, is the sum of the total one-center and two-center terms. The one-center energy terms include electron-electron repulsion and electronnuclear attraction. The two-center energy terms include resonance energy, exchange energy, electron-electron repulsion, electron-nuclear attraction, and nuclear-nuclear repulsion. The total electrostatic (or Coulombic) interaction is equal to the sum of the following two-center energy terms: electron-electron repulsion, electron-nuclear attraction, and nuclear-nuclear repulsion energy. The resonance energy corresponds to the difference in delocalized pi electrons and pi electrons localized in a double bond.42 The exchange energy involves two electrons where the energy of attraction is between the nuclei and the overlap charge in the bond.42 Finally, molecular polarizability characterizes molecular bulk and dispersion interactions, and it has been shown to correlate with hydrophobicity as well as other biological activities.43-45 Molecular topological descriptors included the four valence molecular connectivity indices of orders 1, 2, 3, and 4 (1χv,

2χv, 3χv, 4χv)46,47

and the second Kappa shape index, 2κ.48 The above molecular indices were generated from the twodimensional molecular structure using Molecular Modeling Pro 3.01 software. Molecular connectivity indices are topological indices that encode two-dimensional structural information into numerical values or indexes. The molecular structure is expressed topologically by a hydrogen-suppressed graph. The carbons (and heteroatoms) are represented as vertices, and bonds connecting atoms are represented as edges. Briefly, the connectivity indices mχv are valenceweighted counts of connected subgraphs. The first-order term 1χv is related to the degree of branching and size of the molecule expressed as the number of non-hydrogen atoms. The second-order term 2χv represents a dissection of the molecular skeleton into “two contiguous bond” fragments. The third-order term 3χv is a weighted count of four atoms (three-bond) fragments representing the potential for rotation around the central bond and is the smallest molecular structure necessary for conformational variability. The 3χv index also reflects the degree of branching at each of the four atoms in the fragment. The fourth-order term, 4χv represents path, cluster, path/cluster, and cyclic subgraphs of four edges. Structural information from the 4χv index is useful for compounds with at least five carbon atoms in a chain. Finally, the kappa 2 shape index,19 2κ, is included to characterize the level of branching among isomers. A variable selection method, employing a nonlinear neural network-based genetic algorithm, was used to select the set of input descriptors.49 The variable selection algorithm was performed on 15 separate neural networks establishing a frequency distribution of the selected descriptors for the different generated networks. The set of 12 descriptors that was selected, for all runs, at or above the 70th percentile was chosen as the final set of input descriptors for QSPR modeling. The set of 12 input parameter included in Table 1 and listed in Table 2 include the following: the first, second, and fourth-order valence molecular connectivity indices (1χv, 2χv, 4χv), dipole moment parameters (total point



Table 1. Molecular Descriptors and Experimental Octanol/Water Partition Coefficients compound

MWa

1,1,1-trichloroethane 1,1,2,2-tetrachlorodifluoroethane 1,1,2-trichlorotrifluoroethane 1,1-dichloroethane 1,1-dichloroethene 1,1-difluoroethane 1,1-difluoroethene 1,2,3,5-tetramethylbenzene 1,2,3-trimethylbenzene 1,2,4,5-tetramethylbenzene 1,2,4-trichlorobenzene 1,2,4-trimethylbenzene 1,2-dibromoethane 1,2-dichlorobenzene 1,2-dichloroethane 1,2-dichlorotetrafluoroethane 1,2-difluorobenzene 1,3,5-heptatriene 1,3,5-trichlorobenzene 1,3,5-trimethylbenzene 1,3-butadiene 1,3-dibromopropane 1,3-dichlorobenzene 1,3-dichloropropane 1,3-difluorobenzene 1,3-dimethylnaphthalene 1,4,5-trimethylnaphthalene 1,4-cyclohexadiene 1,4-dichlorobenzene 1,4-difluorobenzene 1,4-dimethylnaphthalene 1,4-dioxane 1,4-pentadiene 1,5-dimethylnaphthalene 1,5-hexadiene 1,6-heptadiene 1-bromo-2-isoproplybenzene 1-bromobutane 1-bromoheptane 1-bromohexane 1-bromooctane 1-bromopentane 1-bromopropane 1-butanethiol 1-butene 1-chloro-1,1-difluoroethane 1-chlorobutane 1-chlorohexane 1-chloropentane 1-choropropane 1-ethylnaphthalene 1-ethylpiperidine 1-heptanol 1-heptyne 1-hexene 1-hexyne 1-methylnaphthalene 1-methylcyclohexene 1-nitropropane 1-nonene 1-octanol 1-octene 1-octyne 1-pentanol 1-pentyne 1-propanol 1-propene 2,2′,3,3′,4,6′-hexachloro-1,1′-biphenyl 2,2′,3,4,4′,5′-hexachloro-1,1′-biphenyl 2,2′,4,4′,6,6′-hexachloro-1,1′-biphenyl 2,2′,4,5,5′-pentabromo-1,1′-biphenyl 2,2′,4,5,5′-pentachloro-1,1′-biphenyl 2,2′,5,6′-tetrachloro-1,1′-biphenyl 2,2′3,3′-tetrachloro-1,1′-biphenyl 2,2′4,4′,5,5′-hexachloro-1,1′-biphenyl

133.41 203.83 187.38 98.96 96.94 66.05 64.04 134.22 120.19 134.22 181.45 120.19 187.86 147.00 98.96 170.92 114.09 92.14 181.45 120.19 54.09 201.89 147.00 112.99 114.09 156.23 170.25 80.13 147.00 114.09 156.23 88.11 68.12 156.23 82.15 96.17 199.09 137.02 179.10 165.07 193.13 151.05 122.99 89.18 56.11 100.50 92.57 120.62 106.60 78.54 156.23 113.20 116.20 96.17 84.16 82.15 142.20 96.17 89.09 126.24 130.23 112.21 110.20 88.15 68.12 60.10 42.08 360.88 360.88 360.88 548.69 326.44 291.99 291.99 360.88

D_Pb D_Hc D_Sd [debye] [debye] [debye] E2e [EV] 0.78 0.01 2.25 0.97 0.11 1.75 1.42 0.30 0.55 0.03 0.14 0.28 0.01 0.37 0.01 1.72 2.56 0.34 0.00 0.01 0.00 1.59 0.34 0.84 1.47 0.35 0.32 0.00 0.00 0.00 0.02 0.01 0.08 0.01 0.14 0.08 0.93 1.72 1.74 1.75 1.76 1.73 1.69 1.24 0.23 1.74 1.07 1.09 1.07 1.04 0.34 0.07 0.89 0.55 0.23 0.55 0.28 0.20 3.73 0.23 0.91 0.23 0.56 0.89 0.53 0.89 0.23 0.11 0.03 0.03 0.45 0.16 0.24 0.39 0.03

0.60 0.01 0.71 0.65 0.67 0.37 0.17 0.05 0.03 0.05 0.58 0.05 0.00 0.98 0.00 0.43 0.18 0.04 0.00 0.00 0.00 0.23 0.54 0.66 0.09 0.01 0.03 0.00 0.00 0.00 0.01 0.00 0.00 0.00 0.01 0.00 0.15 0.11 0.14 0.11 0.11 0.14 0.14 1.14 0.03 0.41 0.50 0.49 0.51 0.52 0.04 1.21 0.65 0.18 0.03 0.19 0.01 0.07 0.53 0.03 0.62 0.03 0.19 0.65 0.17 0.64 0.00 1.58 0.99 0.01 0.17 0.57 0.56 1.37 0.03

1.38 0.00 1.56 1.62 0.78 2.12 1.59 0.26 0.52 0.02 0.67 0.23 0.01 1.35 0.01 1.33 2.74 0.38 0.00 0.00 0.00 1.82 0.88 1.50 1.57 0.36 0.30 0.00 0.00 0.00 0.01 0.01 0.08 0.01 0.15 0.08 1.04 1.82 1.85 1.84 1.84 1.84 1.81 2.38 0.21 2.02 1.56 1.58 1.57 1.55 0.31 1.16 1.41 0.37 0.21 0.37 0.27 0.16 4.21 0.21 1.40 0.21 0.37 1.41 0.36 1.43 0.23 1.61 1.02 0.03 0.61 0.70 0.79 1.76 0.01

612.86 1392.95 1560.72 463.36 451.21 800.36 784.55 713.21 640.82 713.07 870.67 640.67 665.36 721.40 464.34 1729.34 1053.25 495.12 871.70 640.46 292.12 740.18 722.53 538.91 1055.63 837.74 911.18 430.74 722.59 1055.51 837.77 673.45 366.89 837.89 441.02 515.20 891.37 560.32 782.75 708.62 856.83 634.50 486.24 404.67 298.46 949.66 459.04 607.34 533.20 384.95 839.69 621.47 720.58 512.60 446.79 438.44 765.23 509.91 724.91 669.25 794.73 595.10 586.77 572.29 364.31 424.01 224.52 1726.06 1726.50 1728.50 2063.86 1579.62 1431.05 1429.43 1727.52

EXf [ev] -36.11 -33.16 -33.60 -37.15 -31.18 -37.89 -31.67 -147.66 -130.86 -147.68 -77.98 -130.91 -36.03 -78.84 -37.04 -34.26 -79.19 -97.25 -77.94 -130.97 -59.84 -52.71 -78.77 -53.70 -79.11 -161.81 -178.37 -87.03 -78.77 -79.12 -161.77 -76.99 -76.52 -161.76 -93.18 -109.85 -129.12 -71.17 -121.16 -104.50 -137.82 -87.83 -54.50 -71.42 -66.44 -36.66 -71.68 -105.01 -88.35 -55.02 -161.57 -126.98 -128.17 -110.08 -99.77 -93.41 -145.00 -110.35 -71.86 -149.77 -144.84 -133.10 -126.74 -94.85 -76.75 -61.51 -49.76 -150.11 -150.08 -150.02 -147.36 -150.82 -151.64 -151.72 -150.05

ELCg IPh [ev] [kcal] 29.16 38.87 43.16 28.15 25.06 36.22 32.96 110.83 98.34 110.88 65.54 98.41 25.08 64.02 27.93 48.04 71.38 73.32 65.52 98.40 42.46 37.18 63.93 40.03 71.03 124.67 137.00 64.77 63.95 71.18 124.64 69.01 54.58 124.62 66.68 78.78 97.44 50.12 86.40 74.31 98.45 62.22 38.03 50.67 46.74 36.61 51.54 75.74 63.64 39.45 124.27 97.07 97.30 79.46 70.92 67.35 112.18 81.16 61.41 107.22 109.41 95.12 91.55 73.15 55.26 48.94 34.65 129.40 129.32 129.39 118.77 127.72 126.21 126.22 129.37

10.75 11.08 11.34 10.58 9.74 12.82 10.76 9.04 9.25 8.95 9.24 9.08 11.22 9.29 10.67 11.43 9.98 8.52 9.59 9.28 9.47 11.08 9.42 10.55 10.02 8.64 8.42 9.19 9.23 9.87 8.59 10.45 10.05 8.60 10.10 10.14 9.68 10.93 10.93 10.93 10.93 10.93 10.93 11.20 10.15 11.27 10.41 10.41 10.41 10.41 8.70 8.98 10.89 10.76 10.15 10.76 8.71 9.33 12.07 10.15 10.89 10.15 10.77 10.89 10.76 10.88 10.11 9.26 9.21 9.54 9.53 9.25 9.19 9.31 9.20

POi [au] 40.13 51.21 41.28 30.76 31.89 15.34 16.88 79.44 70.68 79.74 76.04 71.24 40.17 64.47 30.35 33.23 48.42 55.96 76.51 71.01 35.26 44.30 65.47 36.98 48.32 101.82 110.09 44.66 65.99 48.48 101.17 35.15 39.50 100.98 46.40 53.70 79.44 40.18 61.58 54.47 68.70 47.36 32.94 39.08 30.32 24.57 36.47 50.68 43.60 29.32 99.72 55.58 53.45 49.93 44.67 42.78 92.33 51.61 34.44 65.97 60.52 58.88 57.03 39.32 35.61 25.23 23.25 158.75 162.76 160.83 167.20 150.83 136.64 135.97 163.88

VMC1j VMC2k VMC4l logKow 2.20 2.89 2.52 1.88 1.49 1.01 0.73 3.65 3.24 3.65 3.44 3.24 3.27 2.96 2.10 2.14 2.21 2.48 3.43 3.23 1.15 3.77 2.95 2.60 2.20 4.23 4.65 2.30 2.95 2.20 4.24 2.15 1.63 4.24 2.13 2.63 4.25 3.09 4.59 4.09 5.09 3.59 2.59 2.65 1.52 1.44 2.51 3.51 3.01 2.01 4.38 3.66 3.52 2.85 2.52 2.35 3.82 3.05 1.85 4.02 4.02 3.52 3.35 2.52 1.85 1.52 0.99 6.97 6.96 6.96 8.55 6.47 6.00 6.00 6.96

3.62 3.46 2.70 2.05 1.44 0.52 0.34 3.02 2.52 3.02 2.81 2.59 1.96 2.23 1.13 2.23 1.41 1.48 2.89 2.67 0.47 2.31 2.31 1.49 1.44 3.30 3.70 1.41 2.31 1.44 3.24 1.22 0.81 3.24 1.15 1.51 3.53 1.83 2.89 2.54 3.25 2.19 1.48 1.52 0.70 1.44 1.42 2.13 1.77 1.07 2.99 2.49 2.14 1.66 1.43 1.31 2.80 2.30 1.03 2.49 2.49 2.14 2.01 1.43 0.95 0.72 0.41 5.79 5.85 5.99 7.70 5.43 4.88 4.77 5.93

0.00 0.00 0.00 0.00 0.00 0.00 0.00 1.25 0.90 1.10 1.00 0.89 0.00 0.71 0.00 0.00 0.44 0.52 1.39 1.20 0.00 1.36 0.90 0.45 0.46 1.69 1.94 0.54 0.68 0.43 1.60 0.44 0.12 1.62 0.24 0.41 1.68 0.69 1.09 0.92 1.27 0.74 0.00 0.47 0.00 0.00 0.40 0.71 0.53 0.00 1.60 1.28 0.72 0.48 0.35 0.28 1.39 1.00 0.17 0.89 0.89 0.72 0.65 0.36 0.14 0.00 0.00 2.85 2.75 3.57 3.80 2.47 2.43 2.23 2.75

2.49 2.39 3.16 1.79 2.13 0.75 1.24 4.17 3.55 4.00 4.02 3.65 1.96 3.38 1.48 2.82 3.60 2.63 4.15 3.42 1.99 2.37 3.38 2.00 3.75 4.42 4.90 2.30 3.39 4.11 4.37 -0.27 2.48 4.38 2.45 3.51 4.20 2.75 4.36 3.80 4.89 3.37 2.10 2.28 2.40 1.08 2.55 3.54 2.73 2.04 4.39 1.75 2.03 3.01 3.99 2.73 3.87 3.51 0.65 5.15 3.15 4.57 3.50 1.40 1.98 0.34 1.77 6.24 6.69 6.70 5.96 4.12 6.63 6.67 6.72


YAFFE

ET AL.

Table 1 (Continued) compound 2,2-dimethyl-1-propanol 2,2-dimethylbutane 2,2-dimethylpentane 2,2-dimethylpropane 2,3,6-trimethylnaphthalene 2,3′-dichloro-1,1′-biphenyl 2,3-dimethyl-1-butene 2,3-dimethylbutane 2,3-dimethylnaphthalene 2,3-dimethylpentane 2,3-dimethylpyridine 2,4-dibromotetrachlorocyclohexane 2,4′-dichloro-1,1′-biphenyl 2,4-dichloro-1,1′-biphenyl 2,4-dichloro-1-chloromethylbenzene 2,4-dichlorotoluene 2,4-dimethyl-2-pentanol 2,4-dimethyl-3-pentanone 2,4-dimethylpentane 2,4-dimethylphenol 2,5′-dichloro-1,1′-biphenyl 2,5-dimethylphenol 2,6,dimethylnaphthalene 2,6-dichloro-1,1′-biphenyl 2,6-dichlorotoluene 2,6-dimethyl-phenol 2-aminotoluene 2-bromobutane 2-bromophenol 2-bromopropane 2-bromotoluene 2-butanone 2-butene 2-butyne 2-chloro-1,1′-biphenyl 2-chloro-1-ethylbenzene 2-chloro-2-methyl-butane 2-chlorophenol 2-chloropropane 2-ethyl pyridine 2-ethylnaphthalene 2-ethylphenol 2-ethylthiophene 2-fluoro-3-bromotetrachlorocyclohexane 2-fluorochlorobenzene 2-fluorophenol 2-heptanone 2-heptene 2-hexanol 2-hexanone 2-iodophenol 2-methoxynitrobenzene (2-nitroanisole) 2-methyl-1,3-butadiene 2-methyl-1-pentene 2-methyl-2-butene 2-methyl-2-nitropropane 2-methylbutane (isopentane) 2-methyl-hexane 2-methylnaphthalene 2-methyl-pentane 2-methylpyridine 2-nitropropane 2-nitrotoluene 2-nonanone 2-octanone 2-pentanol 2-pentanone 2-pentene 2-phenyl-1-ethanol 2-phenylthiophene 2-propanol 2-propanone 2-pyrimidone 3,3,3-trifluoropropylbenzene 3,3′,4,4′-tetrachloro-1,1′-biphenyl

D_Pb D_Hc D_Sd MWa [debye] [debye] [debye] E2e [EV] 88.15 86.18 100.20 72.15 170.25 223.10 84.16 86.18 156.23 100.20 107.16 379.73 223.10 223.10 195.48 161.03 116.20 114.19 100.20 122.17 223.10 122.17 156.23 223.10 161.03 122.17 107.16 137.02 173.01 122.99 171.04 72.11 56.11 54.09 188.66 140.61 106.60 128.56 78.54 107.16 156.23 122.17 112.19 318.83 130.55 112.10 114.19 98.19 102.18 100.16 220.01 153.14 68.12 84.16 70.13 103.12 72.15 100.20 142.20 86.18 93.13 89.09 137.14 142.24 128.21 88.15 86.13 70.13 122.17 160.23 60.10 58.08 96.09 174.17 291.99

0.76 0.09 0.11 0.00 0.34 0.71 0.37 0.00 0.52 0.04 0.76 0.69 0.56 0.21 0.34 0.61 1.07 2.07 0.11 0.39 0.27 0.63 0.01 0.74 0.05 0.49 0.76 1.94 0.74 1.93 0.89 2.24 0.00 0.00 0.24 0.46 1.15 0.44 1.16 0.38 0.40 0.99 1.10 0.98 1.56 1.28 2.16 0.02 0.98 2.20 0.47 5.03 0.20 0.33 0.19 3.73 0.06 0.05 0.30 0.06 0.48 3.64 4.37 2.15 2.19 1.02 2.19 0.04 0.72 1.10 0.98 2.33 3.73 2.28 0.01

0.65 0.03 0.05 0.00 0.05 0.43 0.02 0.00 0.06 0.02 1.33 0.49 0.94 0.69 0.07 0.53 0.65 0.37 0.08 0.71 0.11 0.66 0.00 0.29 0.56 0.70 1.19 0.10 0.59 0.11 0.10 0.47 0.01 0.00 0.62 0.53 0.52 0.26 0.51 1.39 0.04 0.65 1.67 0.57 0.63 0.58 0.51 0.02 0.68 0.48 0.69 0.80 0.02 0.06 0.05 0.53 0.03 0.03 0.02 0.05 1.34 0.53 0.63 0.48 0.46 0.66 0.50 0.02 0.59 1.70 0.66 0.46 1.70 0.19 0.01

1.35 0.07 0.06 0.00 0.32 1.07 0.36 0.00 0.47 0.04 1.91 0.22 1.49 0.83 0.39 1.09 1.55 2.44 0.03 0.93 0.28 1.19 0.01 1.03 0.51 1.18 1.33 2.04 0.61 2.04 0.98 2.70 0.00 0.00 0.81 0.84 1.66 0.67 1.66 1.67 0.39 1.64 0.76 0.49 2.04 0.94 2.66 0.04 1.52 2.66 0.68 5.83 0.19 0.37 0.22 4.25 0.04 0.04 0.31 0.02 1.75 4.16 5.00 2.62 2.63 1.53 2.68 0.04 1.26 0.63 1.52 2.78 5.28 2.46 0.00

EXf [ev]

ELCg IPh [ev] [kcal]

POi [au]

571.04 -94.91 73.26 10.91 38.52 452.46 -106.32 75.26 11.48 42.24 526.54 -122.97 87.34 11.19 49.41 377.56 -89.78 63.20 12.06 35.06 910.72 -178.50 137.11 8.55 110.16 1134.18 -153.06 122.99 9.06 121.30 445.48 -99.84 71.31 9.83 44.27 452.94 -106.27 75.17 11.30 42.63 838.09 -161.74 124.68 8.64 101.55 527.44 -122.87 87.26 11.25 49.71 595.49 -107.69 86.27 9.60 60.56 1559.01 -91.53 73.41 10.84 100.15 1133.42 -153.31 123.10 9.15 119.08 1133.59 -153.11 123.06 8.92 124.28 948.45 -94.27 77.07 9.44 82.00 795.15 -95.58 76.49 9.26 74.02 722.96 -127.95 96.74 11.19 53.04 709.35 -121.77 93.06 10.35 52.44 526.84 -122.94 87.24 11.49 49.70 758.15 -119.72 96.91 8.85 68.05 1133.62 -153.11 122.93 9.01 122.12 758.88 -119.63 96.77 8.96 67.78 837.89 -161.76 124.62 8.60 100.98 1133.94 -152.96 122.96 9.00 120.66 795.23 -95.58 76.46 9.38 73.10 758.30 -119.64 96.83 8.96 67.47 594.97 -108.35 87.33 8.54 63.94 562.05 -71.16 50.28 10.87 41.01 860.36 -84.60 71.71 9.37 62.42 488.11 -54.51 38.22 10.86 33.96 743.31 -95.84 73.36 9.64 65.59 488.50 -71.78 56.63 10.66 31.69 297.76 -66.51 46.96 9.64 30.98 286.03 -60.33 44.18 10.34 30.95 984.14 -153.98 121.47 8.95 110.88 719.69 -1144.93 87.02 9.28 70.55 533.91 -88.36 63.70 10.36 43.58 763.24 -85.19 73.37 9.21 59.63 385.68 -55.01 39.41 10.42 29.82 596.77 -107.58 85.86 9.76 59.75 839.26 -161.68 124.34 8.75 100.87 761.88 -119.35 96.38 8.99 66.91 531.79 -91.22 65.85 9.44 58.30 1627.22 -92.39 79.01 10.71 86.02 887.61 -79.00 67.63 9.51 56.66 929.44 -85.39 77.16 9.40 52.17 711.13 -121.77 92.90 10.68 52.80 520.03 -116.48 83.27 9.70 53.55 648.03 -111.40 84.96 11.00 46.34 636.93 -105.10 80.80 10.68 45.76 818.82 -84.35 71.50 9.04 67.68 1172.17 -118.45 105.82 9.94 74.08 365.16 -76.61 54.90 9.36 39.36 445.54 -99.86 71.29 9.79 44.55 370.23 -83.27 59.47 9.40 39.03 797.27 -88.59 73.69 11.81 40.96 378.59 -89.66 63.09 11.43 35.73 526.85 -122.99 87.29 11.18 49.86 765.12 -145.03 112.23 8.76 93.38 452.44 -106.36 75.22 11.31 42.70 523.14 -90.90 73.71 9.80 52.34 723.98 -71.92 61.60 11.92 34.20 989.28 -112.70 94.66 10.24 68.72 859.44 -155.09 117.09 10.68 66.94 785.24 -138.43 104.98 10.68 59.90 573.86 -94.74 72.87 11.00 39.28 562.84 -88.44 68.69 10.67 38.71 371.86 -83.18 59.05 9.60 38.37 763.51 -119.15 95.54 9.46 65.10 796.00 -132.25 100.39 8.95 99.84 425.16 -61.48 48.72 11.04 25.03 415.03 -55.10 44.46 10.77 24.53 670.24 -74.30 73.06 9.41 49.93 1606.76 -128.21 112.03 9.74 69.47 1430.61 -151.52 126.15 8.96 149.44


2.72 2.91 3.31 3.00 3.68 3.83 2.00 2.49 3.28 2.63 1.91 6.79 3.83 3.83 2.98 2.74 3.41 2.71 3.02 2.29 3.83 2.29 3.24 3.78 2.66 2.24 1.86 2.75 2.30 2.84 2.60 1.06 0.67 0.50 3.25 2.35 3.09 1.86 1.88 1.67 3.04 1.98 2.46 5.73 1.82 1.45 2.16 1.71 1.99 1.81 2.59 1.90 1.05 1.71 1.37 2.28 1.80 2.54 2.85 2.18 1.47 1.32 2.01 2.87 2.51 1.64 1.45 0.98 1.96 3.29 1.09 0.91 1.09 2.60 4.88

0.00 0.00 0.75 0.00 1.77 1.79 0.00 0.00 1.47 0.47 0.56 4.60 1.69 1.86 1.40 0.97 1.00 0.67 0.94 0.81 1.73 0.72 1.62 1.99 0.98 0.81 0.59 0.00 0.74 0.00 0.84 0.00 0.00 0.00 1.56 1.05 0.00 0.59 0.00 0.61 1.46 0.81 1.17 3.42 0.57 0.45 0.62 0.49 0.50 0.43 0.83 0.76 0.00 0.43 0.00 0.00 0.00 0.61 1.31 0.58 0.45 0.00 0.75 0.98 0.80 0.42 0.35 0.24 0.77 1.78 0.00 0.00 0.31 0.93 1.95

1.36 3.88 3.11 3.11 4.73 5.02 3.13 3.85 4.40 3.63 1.22 3.98 5.10 5.15 3.82 4.24 2.13 1.86 3.63 2.30 5.18 2.33 4.31 5.30 4.29 2.36 1.32 2.58 2.35 2.14 2.92 0.29 2.31 1.46 4.54 2.95 2.52 2.15 1.90 1.69 4.38 2.47 2.87 3.28 2.77 1.71 1.98 3.56 1.76 1.38 2.65 1.73 2.42 3.21 2.67 1.01 2.72 3.71 3.86 2.34 1.11 0.93 2.30 3.18 2.76 1.19 0.91 2.58 1.36 3.74 0.05 -0.24 -1.62 3.31 6.04



Table 1 (Continued) compound 3,3′,5,5′-tetrachloro-1,1′-biphenyl 3,3-dimethyl-2-butanol 3,4-dichloro-1,1-biphenyl 3,4-dimethylchlorobenzene 3,4-dimethylphenol 3,5-dichloro-1,1′-biphenyl 3,5-dimethylphenol 3-bromophenol 3-chlorophenol 3-ethylpentane 3-ethylthiophene 3-fluorophenol 3-hexanol 3-iodophenol 3-methyl-1-butanol 3-methyl-1-butene 3-methyl-2-butanol 3-methyl-2-butanone 3-methylpentane 3-methylpyridine 3-methylthiophene 3-nitrotoluene 3-pentanol 3-phenyl-1-chloropropane 4,4′-dichloro-1,1′-biphenyl 4-bromophenol 4-bromotoluene 4-chloro-1,1′-biphenyl 4-chlorophenol 4-cyclopropyl-2-butanone 4-ethenylcyclohexene 4-ethylphenyl acetate 4-fluorophenol 4-iodophenol 4-methylpyridine 4-methyl-1-pentene 4-methyl-2-pentanone 4-methylphenol 4-n-propylphenol 4-phenylbutyric acid 4-phenylphenol 4-pyrimidone 5-methyl-2-hexanone 5-methyl-furfural(5-methylfuraldehyde) 5-nonanone 5-phenyl-2-pentanone 9-fluorenone 9-methylanthracene a,a,a-trichlorotoluene a,a,a-trifluorotoluene a-bromotoluene acenaphthene acenaphthylene acetic acid acetonitrile acetophenone a-chlorotoluene acrylophenone allyl alcohol (2-propen-1-ol) allyl bromide (3-bromo-1-propene) allylbenzene (2-propenyl) amylamine (pentyl) aniline anthracene benz[a]anthracene benzaldehyde benzene benzoic acid benzoic acid methyl ester benzonitrile benzothiophene benzyl acetate benzylamine benzylphenyl ether beta-phenylethyl chloride (2-)

D_Pb D_Hc D_Sd MWa [debye] [debye] [debye] E2e [EV] 291.99 102.18 223.10 140.61 122.17 223.10 122.17 173.01 128.56 100.20 112.19 112.10 102.18 220.01 88.15 70.13 88.15 86.13 86.18 93.13 98.16 137.14 88.15 154.64 223.10 173.01 171.04 188.66 128.56 112.17 108.18 164.20 112.10 220.01 93.13 84.16 100.16 108.14 136.19 164.20 170.21 96.09 114.19 110.11 142.24 162.23 180.21 192.26 195.48 146.11 171.04 154.21 152.20 60.05 41.05 120.15 126.59 132.16 58.08 120.98 118.18 87.16 93.13 178.23 228.29 106.12 78.11 122.12 136.15 103.12 134.20 150.18 107.16 184.24 140.61

0.02 0.87 0.62 0.93 0.99 0.70 0.73 0.58 0.78 0.05 0.68 0.98 1.02 0.29 0.95 0.18 0.91 2.18 0.07 0.81 0.71 4.97 1.04 0.87 0.01 0.95 1.41 0.54 0.49 2.16 0.19 1.46 1.33 0.70 0.97 0.27 2.11 0.68 0.78 2.04 0.46 2.62 2.21 2.70 2.05 2.18 2.39 0.36 1.27 2.87 1.33 0.59 0.22 2.16 2.29 2.36 0.75 2.07 0.88 1.52 0.09 0.19 0.62 0.00 0.04 2.27 0.00 2.62 2.12 2.75 0.57 1.88 0.24 0.50 0.87

0.02 0.68 0.96 0.54 0.68 0.51 0.70 0.62 1.20 0.01 1.65 0.62 0.67 0.71 0.60 0.04 0.68 0.43 0.01 1.29 1.66 0.49 0.68 0.55 0.00 0.71 0.09 0.52 0.93 0.49 0.06 0.18 0.71 0.68 1.31 0.05 0.52 0.68 0.64 0.43 0.69 1.00 0.47 0.42 0.49 0.54 0.46 0.04 0.57 0.24 0.22 0.03 0.07 0.41 0.91 0.44 0.59 0.43 0.64 0.18 0.06 1.44 1.17 0.00 0.02 0.42 0.00 0.40 0.06 0.86 1.63 0.08 1.44 0.41 0.49

0.00 1.46 1.57 1.45 1.47 1.21 1.24 0.47 1.94 0.05 1.00 0.71 1.60 0.52 1.44 0.16 1.48 2.60 0.07 2.07 0.95 5.46 1.61 1.41 0.01 1.52 1.49 1.06 1.39 2.64 0.14 1.63 1.84 1.28 2.27 0.25 2.62 1.18 1.23 1.77 1.11 1.97 2.67 3.08 2.54 2.72 2.85 0.32 1.84 3.11 1.54 0.56 0.30 1.83 3.21 2.79 1.33 2.50 1.48 1.69 0.15 1.32 1.30 0.00 0.02 2.69 0.00 2.25 2.08 3.61 1.09 1.85 1.39 0.92 1.35

1432.88 647.12 1132.63 718.15 759.17 1133.85 759.30 861.49 763.79 527.31 532.25 930.66 647.94 819.73 572.44 372.15 573.38 561.98 453.03 522.89 458.10 987.54 573.66 798.40 1133.99 861.29 743.31 984.18 763.66 706.29 579.49 1090.27 930.15 819.60 523.35 446.89 636.88 686.14 834.43 1100.35 1025.01 672.26 711.10 793.52 858.82 976.45 1076.76 1035.21 949.79 1456.81 749.71 828.99 821.33 538.69 239.64 753.10 649.27 819.89 418.24 479.66 638.20 480.21 522.68 962.20 1232.08 677.51 422.94 876.60 943.00 577.42 653.98 1018.71 596.80 1094.99 724.10

EXf [ev] -151.40 -111.41 -153.21 -113.22 -119.63 -153.14 -119.68 -84.59 -85.22 -122.85 -91.29 -85.36 -111.39 -84.35 -94.80 -83.15 -94.76 -88.49 -106.28 -90.89 -74.63 -112.86 -94.73 -129.32 -153.14 -84.57 -95.83 -154.03 -85.19 -115.16 -120.33 -151.66 -85.37 -84.34 -90.87 -99.77 -105.09 -102.90 -136.20 -151.46 -160.47 -74.15 -121.75 -91.62 -155.11 -162.72 -164.53 -192.53 -93.79 -94.96 -95.52 -155.50 -148.85 -43.86 -37.08 -112.72 -96.02 -122.77 -54.92 -47.92 -124.02 -100.21 -91.57 -175.83 -223.51 -96.02 -80.55 -101.54 -118.24 -94.87 -105.37 -134.85 -107.94 -177.04 -112.65

ELCg IPh [ev] [kcal] 126.02 85.09 123.04 87.41 96.79 122.95 96.75 71.75 73.40 87.19 65.79 76.81 84.94 71.49 73.17 58.87 72.89 68.79 75.21 73.87 53.67 94.82 72.87 98.21 123.02 71.68 73.28 121.48 73.36 90.49 88.72 126.80 77.02 71.41 73.87 70.91 80.77 84.36 108.53 125.86 130.89 72.92 92.89 81.66 117.14 127.39 135.51 150.89 75.66 87.53 72.56 122.02 117.78 42.98 31.24 90.68 73.97 98.28 44.63 33.68 93.28 76.22 74.83 138.45 177.31 78.71 60.89 89.18 101.73 77.76 80.38 113.80 86.63 142.60 86.03

9.36 10.94 8.92 9.13 8.87 9.16 9.04 9.41 9.28 11.00 9.27 9.43 10.92 9.05 10.78 10.27 11.01 10.56 11.44 9.80 9.31 10.28 10.92 9.54 8.85 9.31 9.55 8.87 9.01 10.67 9.59 9.08 9.27 8.84 10.06 10.02 10.65 8.95 8.93 9.52 8.64 9.56 10.66 9.46 10.58 9.45 9.22 8.14 10.07 10.34 9.73 8.59 9.06 11.44 12.33 10.00 9.66 9.96 10.07 10.49 9.39 9.38 8.61 8.25 8.33 10.05 9.75 10.13 10.08 10.09 8.80 9.58 9.29 9.13 9.62

POi [au] 145.45 45.54 124.94 72.53 67.93 123.54 67.63 63.16 60.70 50.12 57.91 52.14 46.26 68.89 39.14 37.08 39.03 38.25 42.74 52.21 50.77 68.60 39.19 76.75 128.40 63.15 66.60 114.81 60.76 52.21 59.27 87.24 52.46 68.86 51.97 44.26 45.28 59.63 74.57 81.94 109.40 49.49 52.52 55.79 67.15 85.90 113.17 140.21 81.14 54.18 64.88 98.45 101.78 20.52 18.63 65.37 61.49 75.98 26.12 34.19 71.47 41.65 55.86 131.41 173.21 58.35 45.60 61.38 70.27 61.85 78.83 77.08 60.22 110.20 70.24


5.06 3.04 3.81 2.66 2.27 3.90 2.35 2.39 1.92 2.09 2.26 1.48 1.85 2.71 1.91 1.48 1.98 1.77 1.92 1.53 2.08 2.07 1.47 2.66 3.88 2.39 2.71 3.31 1.91 2.68 2.28 2.59 1.48 2.70 1.52 1.92 2.30 1.84 2.42 2.73 2.91 1.10 2.63 1.57 2.75 3.04 3.42 3.94 4.14 1.86 2.18 3.43 3.13 0.52 0.22 1.92 1.89 1.93 0.47 1.09 1.98 1.97 1.41 3.55 4.71 1.53 1.15 1.67 1.86 1.48 2.90 2.27 1.69 3.09 2.30

2.49 0.00 1.60 0.93 0.73 1.88 0.95 0.86 0.66 0.87 1.24 0.48 0.54 0.99 0.26 0.00 0.00 0.00 0.29 0.45 1.00 0.72 0.29 1.05 1.54 0.70 0.80 1.40 0.57 1.31 1.03 0.96 0.44 0.79 0.43 0.33 0.57 0.54 0.95 1.09 1.28 0.30 0.49 0.52 0.87 1.19 1.98 2.24 1.00 0.63 0.94 2.19 1.86 0.00 0.00 0.67 0.74 0.72 0.00 0.00 0.78 0.33 0.45 1.88 2.70 0.53 0.38 0.58 0.69 0.51 1.69 0.76 0.61 1.26 0.97

6.85 1.48 5.51 3.82 2.23 5.37 2.35 2.63 2.52 2.40 2.82 1.93 1.65 2.93 1.16 2.59 1.28 0.84 3.60 1.20 2.34 2.45 1.21 3.55 5.58 2.43 3.33 4.61 2.35 1.50 3.34 2.56 1.79 2.91 1.20 3.08 1.31 1.94 3.23 2.42 3.20 -1.38 1.88 1.85 2.88 2.42 3.58 5.07 2.92 2.79 2.92 3.92 4.03 -0.17 -0.34 1.58 2.30 1.88 -0.31 1.79 3.27 1.45 0.90 4.54 5.61 1.48 2.13 1.81 2.12 1.56 3.12 1.96 1.09 3.79 2.95


YAFFE

ET AL.

Table 1 (Continued) compound

MWa

biphenyl bromobenzene bromochloromethane bromocyclohexane bromoethane bromomethane bromotrifluoromethane butanol butylamine butyl benzene butyl ethyl ether butyldimethylamine butylmethylamine butyraldehyde butyric acid butyronitrile chlorobenzene chlorodifluoromethane chloroethane chloromethane chlorotrifluoromethane cis-1-2-dimethylcyclohexane crotonic acid (2-butenoic acid) cycloheptane cycloheptene cyclohexane cyclohexanol cyclohexanone cyclohexene cyclooctane cyclopentane cyclopentanone cyclopentene cyclopropane decachlorobiphenyl decanoic acid di(n-propyl) ether diallylamine dibromomethane dichlorodifluoromethane dichlorofluoromethane dichloromomethane diethyl sulfide diethylamine diethyl ether difluoromethane dimethyl ether dimethyl sulfide dimethyl sulfoxide di-n-butylamine di-n-propyl-amine di-n-propyl-amine diphenylacetic acid diphenylmethane diphenylsulfide ethane ethanol ethene ethoxybenzene ethyl acetate ethyl benzene ethyl benzoate ethyl mercaptan ethyl propionate (C5H10O2) ethylallylamine ethyldiisopropylamine ethyldimethylamine ethylene oxide (oxirane) ethylvinyl ether ethynylbenzene fluorene fluorobenzene fluoromethane fluoropentachlorocyclohexane formaldehyde

154.21 157.01 129.38 163.06 108.97 94.94 148.91 74.12 73.14 134.22 102.18 101.19 87.16 72.11 88.11 69.11 112.56 86.47 64.51 50.49 104.46 112.21 86.09 98.19 96.17 84.16 100.16 98.14 82.15 112.21 70.13 84.12 68.12 42.08 498.66 172.27 102.18 97.16 173.84 120.91 102.92 84.93 90.18 73.14 74.12 52.02 46.07 62.13 78.13 129.25 101.19 101.19 212.25 168.24 186.27 30.07 46.07 28.05 122.17 88.11 106.17 150.18 61.12 102.13 85.15 129.25 73.14 44.05 72.11 102.14 166.22 96.10 34.03 274.38 30.03


0.00 0.09 0.62 0.06 0.14 0.19 0.03 0.62 1.45 0.04 0.37 1.20 1.32 0.35 0.46 0.87 0.54 0.43 0.53 0.57 0.27 0.01 0.40 0.05 0.05 0.00 0.67 0.37 0.01 0.01 0.02 0.32 0.01 0.00 0.00 0.48 0.41 1.31 0.32 0.39 0.56 0.68 1.57 1.31 0.37 0.36 0.40 1.60 2.11 1.34 1.35 1.35 0.58 0.02 1.76 0.00 0.62 0.00 0.36 0.05 0.03 0.04 1.16 0.11 1.29 1.19 1.20 0.10 0.36 0.17 0.01 0.11 0.30 0.31 0.34

0.00 1.18 1.51 2.05 1.85 1.55 0.90 1.42 1.34 0.34 1.12 1.10 1.21 2.54 1.81 3.30 0.93 1.52 1.55 1.38 1.04 0.01 2.16 0.02 0.21 0.00 1.50 2.81 0.17 0.00 0.01 2.71 0.15 0.00 0.05 1.79 1.11 1.10 1.45 0.80 1.25 1.36 1.94 1.18 1.15 1.81 1.26 1.96 4.49 1.15 1.16 1.16 1.67 0.17 0.75 0.00 1.45 0.00 1.12 1.92 0.33 2.09 2.33 1.83 1.22 1.04 1.12 1.78 1.60 0.17 0.37 1.60 1.44 0.55 2.16

834.28 670.63 487.57 701.50 412.50 336.32 1285.01 498.13 405.93 717.90 640.19 554.27 480.41 488.07 686.86 387.92 572.87 874.14 310.94 235.97 1189.55 591.74 679.73 517.72 511.25 444.05 639.06 628.36 436.51 592.36 369.99 554.83 364.25 226.29 2314.97 1131.74 640.17 543.23 584.96 1020.93 705.44 388.12 408.85 406.28 491.95 724.24 343.01 261.81 468.70 702.87 554.58 554.58 1363.07 908.69 935.91 155.85 349.87 150.98 756.42 680.12 569.59 1017.96 256.26 753.89 474.85 703.67 405.97 338.59 485.82 554.38 896.37 739.66 402.89 1527.97 262.53

EXf [ev]

ELCg [ev]

IPh [kcal]

POi [au]

-154.92 -79.03 -20.12 -98.24 -37.82 -21.19 -19.25 -78.18 -83.60 -147.33 -111.48 -116.65 -100.17 -71.68 -77.16 -70.40 -79.66 -20.02 -38.34 -21.72 -19.49 -133.40 -70.66 -116.69 -110.20 -100.10 -105.19 -98.83 -93.60 -133.26 -83.45 -82.18 -76.79 -49.72 -146.63 -177.16 -111.48 -103.67 -19.60 -18.89 -19.60 -20.50 -76.44 -83.49 -78.15 -21.30 -44.89 -43.13 -48.47 -150.15 -116.81 -116.81 -192.52 -171.66 -158.63 -39.70 -44.85 -33.05 -119.36 -77.18 -114.00 -134.86 -38.10 -93.83 -93.57 -149.72 -83.32 -37.99 -71.77 -101.18 -165.66 -79.81 -22.13 -92.82 -21.73

119.94 60.77 14.93 71.94 25.94 13.72 29.58 61.03 64.18 109.69 85.25 87.75 76.12 56.55 67.11 55.34 62.43 25.07 27.35 15.34 30.28 96.93 62.79 84.78 80.77 72.66 82.44 78.24 68.95 96.75 60.35 66.03 56.15 36.35 134.64 139.71 85.27 79.62 13.17 25.59 20.78 16.11 52.60 63.88 61.09 24.80 37.52 28.15 28.10 112.27 88.03 88.03 160.33 132.00 121.52 26.79 36.86 22.31 96.02 67.27 85.50 113.44 26.51 79.35 71.70 111.07 63.58 33.65 57.27 77.67 130.28 65.97 19.84 80.37 20.53

8.92 9.80 10.56 10.86 10.91 11.01 12.23 10.89 9.38 9.41 10.48 9.06 9.19 10.62 11.36 11.89 9.38 11.36 10.41 10.48 11.88 10.96 10.61 11.03 9.76 11.29 10.89 10.48 9.52 11.06 11.09 10.60 9.52 11.77 8.89 11.35 10.48 9.28 10.59 11.33 10.99 10.58 8.86 9.15 10.48 12.86 10.69 8.88 9.35 9.19 9.18 9.18 9.55 9.42 7.91 11.98 10.90 10.64 9.07 11.25 9.40 10.06 11.21 11.15 9.18 8.96 9.05 11.34 9.46 9.39 8.84 9.80 12.92 10.37 10.63

102.00 57.59 26.20 54.27 25.99 17.07 20.17 32.28 34.76 76.07 47.83 50.01 42.51 31.72 34.78 33.12 55.14 17.11 22.24 14.02 17.01 55.26 37.99 48.56 49.67 41.86 45.08 44.80 43.64 55.09 33.86 37.02 35.87 20.85 220.38 77.18 47.83 53.48 27.97 26.94 25.13 22.36 43.08 35.68 33.58 8.19 18.64 26.75 35.55 64.01 49.82 49.82 124.17 102.60 129.00 14.95 18.20 15.01 67.95 36.43 61.53 78.21 24.64 43.77 44.22 64.18 35.79 17.18 36.12 66.19 108.81 46.96 7.92 78.31 9.92


2.73 2.21 1.57 3.53 1.39 0.00 1.33 1.08 1.14 2.59 1.55 2.16 1.46 0.96 1.14 0.91 1.73 0.58 0.80 0.00 0.86 3.24 0.84 2.47 2.11 2.12 2.29 2.10 1.76 2.83 1.77 1.75 1.40 1.06 7.66 3.27 1.61 1.24 2.72 1.57 1.23 0.91 2.34 0.96 0.78 0.10 0.41 1.22 1.58 2.46 1.75 1.75 3.59 3.54 3.87 0.00 0.32 0.00 1.75 0.92 1.84 2.09 0.95 1.16 1.10 3.02 1.40 0.61 0.62 1.51 3.49 1.30 0.00 5.18 0.00

1.26 0.72 0.00 1.70 0.00 0.00 0.00 0.16 0.20 1.03 0.39 0.47 0.35 0.12 0.21 0.11 0.56 0.00 0.00 0.00 0.00 1.50 0.14 1.24 0.94 1.06 1.08 0.95 0.76 1.41 0.88 0.77 0.59 0.53 4.30 1.23 0.39 0.29 0.00 0.00 0.00 0.00 0.61 0.25 0.20 0.00 0.00 0.00 0.00 0.73 0.48 0.48 1.77 1.68 1.97 0.00 0.00 0.00 0.68 0.20 0.71 0.79 0.00 0.26 0.25 1.33 0.00 0.22 0.12 0.53 2.08 0.41 0.00 2.88 0.00

4.09 2.99 1.41 3.20 1.61 1.19 1.86 0.88 0.81 4.26 2.03 1.70 1.33 0.88 0.79 0.53 2.84 1.08 1.43 0.91 1.65 4.01 0.72 4.00 3.45 3.44 1.23 0.81 2.86 4.45 3.00 0.63 2.47 1.72 7.92 4.09 2.03 1.11 1.57 2.16 1.55 1.25 1.95 0.57 0.89 0.20 0.10 0.92 -1.35 2.68 1.73 1.67 3.05 4.14 4.41 1.87 0.10 1.13 2.51 0.73 3.15 2.63 1.21 1.21 0.81 2.68 0.70 -0.30 1.04 2.53 4.18 2.27 0.51 3.19 0.35




MWa

formic acid furan hexachlorobenzene hexachlorocyclopentadiene hexafluorobenzene hexafluroethane hexamethylbenzene hexanal hexane hexanenitrile hexanoic acid hydroquinone indane indene iodobenzene iodoethane iodomethane isobutane isobutanol isobutyl acetate isobutylamine isobutyronitrile isopentanol isopropylamine isopropylbenzene m-chlorotoluene m-cresol (3-hydroxytoluene) methanol methoxybenzene(anisole) methycyclopentane methyl acetate methylamine methyl butyl ether methyl mercaptan methyl propanoate methyl propyl ether methylbenzylamine methylcyclohexane methylethylamine methylthiobenzene m-methyl styrene m-methylbenzyl alcohol m-phenylphenol m-xylene naphthalene n-benzylaniline n-butane n-ethylaniline n-heptylamine n-hexylamine nitrobenzene nitroethane nitromethane N-methylaniline N-methy-N-benzylaniline N,N-dimethyl acetamide N,N-dimethylaniline n-propylamine n-propylaniline n-propylbenzene n-propylpropionate o-cresol (2-hydroxytoluene) octafluorocyclobutane octane o-ethyltoluene o-isobutylphenol o-methylbenzaldehyde o-methylbenzyl alcohol o-phenylphenol o-sec-butylphenol o-xylene pentachlorobenzene pentafluoroethylbenzene pentanal pentane

46.03 68.08 284.78 272.77 186.06 138.01 162.27 100.16 86.18 97.16 116.16 110.11 118.18 116.16 204.01 155.97 141.94 58.12 74.12 116.16 73.14 69.11 88.15 59.11 120.19 126.59 108.14 32.04 108.14 84.16 74.08 31.06 88.15 47.10 88.11 60.10 107.16 98.19 59.11 124.20 118.18 122.17 170.21 106.17 128.17 183.25 58.12 121.18 115.22 101.19 123.11 75.07 61.04 107.16 183.25 87.12 121.18 59.11 135.21 120.19 116.16 108.14 200.03 114.23 120.19 150.22 120.15 122.17 170.21 150.22 106.17 250.34 196.12 86.13 72.15


0.91 0.15 0.00 0.05 0.00 0.00 0.00 0.34 0.00 0.85 0.47 1.36 0.02 0.02 0.03 0.06 0.12 0.04 0.65 0.06 1.53 0.86 0.60 1.43 0.04 0.52 0.69 0.62 0.37 0.02 0.07 1.45 0.39 1.24 0.12 0.39 1.07 0.02 1.32 1.62 0.03 0.66 0.68 0.02 0.00 1.04 0.00 1.08 1.47 1.45 0.48 0.55 0.59 1.06 0.85 0.81 0.94 1.46 1.09 0.06 0.10 0.67 0.00 0.00 0.03 0.73 0.42 0.59 0.65 0.72 0.01 0.61 0.07 0.36 0.03

3.94 0.22 0.00 0.78 0.00 0.01 0.01 2.58 0.00 3.35 1.80 2.22 0.45 0.52 0.79 1.83 1.44 0.01 1.39 1.94 1.36 3.29 1.44 1.32 0.21 1.12 0.96 1.49 1.08 0.04 1.83 1.40 1.18 2.23 1.76 1.21 1.27 0.02 1.23 1.63 0.25 1.18 1.05 0.26 0.00 1.23 0.00 1.27 1.33 1.33 5.24 4.06 3.99 1.28 0.83 3.18 1.21 1.34 1.26 0.34 1.83 1.40 0.01 0.00 0.45 0.87 2.79 1.39 1.38 0.88 0.46 0.43 2.25 2.56 0.00

460.17 468.69 1312.02 1248.22 2298.86 2064.12 859.01 636.30 452.51 536.18 835.15 804.33 633.52 627.56 628.92 369.10 293.26 304.03 497.82 828.00 406.50 387.78 572.39 331.70 643.18 645.62 686.62 275.22 681.78 443.91 605.17 183.41 565.72 182.06 678.96 417.48 597.34 517.80 332.12 598.71 635.87 761.28 1025.37 567.94 692.59 1010.58 304.20 671.75 628.33 554.23 914.88 650.39 577.26 597.38 1010.53 591.97 671.61 331.79 745.87 643.75 827.88 686.28 2826.00 600.81 642.30 908.51 750.49 761.65 1025.18 908.51 567.95 1165.34 2137.11 561.88 378.35

EXf [ev]

ELCg [ev]

IPh [kcal]

POi [au]

-27.35 -59.25 -75.76 -65.12 -77.08 -35.43 -181.00 -105.01 -106.37 -103.72 -110.50 -91.63 -124.56 -117.85 -78.79 -37.65 -21.02 -73.06 -78.19 -110.52 -83.58 -70.43 -94.80 -66.94 -130.70 -96.45 -102.88 -28.21 -102.73 -100.13 -60.55 -33.62 -94.85 -21.46 -77.22 -61.52 -108.09 -116.77 --66.85 -100.95 -124.19 -119.32 -160.44 -114.16 -128.23 -182.35 -73.04 -124.70 -133.58 -116.92 -96.06 -55.25 -38.57 -108.11 -182.34 -82.51 -124.53 -66.94 -141.37 -130.66 -110.51 -102.83 -60.60 -139.69 -130.73 -152.81 -112.78 -119.20 -160.37 -152.83 -114.13 -76.48 -110.90 -88.36 -89.70

31.55 51.36 70.32 60.78 93.50 57.55 135.63 80.74 75.19 79.51 91.35 82.88 95.34 91.09 60.51 25.98 13.66 51.03 61.06 91.46 64.06 55.31 73.15 51.97 97.60 74.92 84.31 25.06 84.25 72.50 55.49 28.06 73.49 14.37 67.61 49.30 86.71 84.84 51.98 74.88 93.67 95.92 130.76 85.90 99.73 145.36 50.99 98.64 100.38 88.31 82.30 49.48 37.24 86.79 144.83 69.79 98.32 52.09 110.73 97.59 91.45 84.31 88.72 99.35 97.96 120.61 91.14 96.10 130.97 120.66 85.89 68.74 112.19 68.69 63.08

11.29 9.38 9.31 9.04 10.85 14.47 8.87 10.63 11.28 11.70 11.36 8.76 9.22 8.97 9.04 9.44 9.47 11.59 10.92 11.24 9.43 12.07 10.80 9.38 9.53 9.32 9.11 11.14 9.11 11.11 11.27 9.40 10.58 11.26 11.17 10.57 8.55 11.06 9.18 8.56 9.07 9.29 8.91 9.31 8.84 8.55 11.35 8.54 9.40 9.39 10.60 12.08 12.17 8.55 8.34 9.50 8.44 9.39 8.53 9.40 11.16 9.06 13.19 11.27 9.32 9.03 9.76 9.23 8.69 9.03 9.30 9.25 10.43 10.63 11.30

13.66 32.09 108.70 97.73 54.96 16.67 96.21 45.94 43.01 47.36 48.86 56.33 67.86 71.47 63.21 29.61 19.95 28.61 31.98 50.42 34.54 32.70 39.14 27.54 67.96 63.78 59.21 10.94 59.74 40.70 28.71 13.55 40.32 18.55 36.00 26.13 64.05 48.58 28.38 69.94 74.90 66.21 107.38 62.57 83.80 115.05 28.95 72.04 55.97 48.88 59.94 27.19 19.98 64.04 117.68 39.89 72.30 27.71 79.45 68.88 50.96 58.99 33.49 57.13 69.38 80.81 66.76 66.60 107.90 80.79 62.31 97.46 69.62 38.88 35.97


0.11 0.79 4.15 4.66 1.88 1.00 3.75 1.66 1.71 1.62 1.85 1.52 2.62 2.31 2.52 1.77 0.00 1.73 1.58 2.20 1.39 1.28 1.91 1.24 2.57 2.23 1.84 0.00 1.52 2.39 0.70 0.00 1.35 0.00 0.93 0.58 1.62 2.74 0.71 2.39 2.12 2.15 2.92 2.16 2.35 3.21 1.00 1.90 2.20 1.85 1.56 0.61 0.42 1.62 3.23 1.41 2.23 0.79 2.29 2.24 1.57 1.79 2.30 2.41 2.28 3.23 1.97 2.08 2.88 3.23 2.08 3.73 2.40 1.31 1.35

0.00 0.23 2.00 2.13 0.58 0.00 1.69 0.48 0.50 0.45 0.53 0.45 1.51 1.20 0.82 0.00 0.00 0.00 0.00 0.28 0.00 0.00 0.26 0.00 0.84 0.85 0.63 0.00 0.56 1.13 0.00 0.00 0.29 0.00 0.14 0.00 0.60 1.31 0.00 0.98 0.80 0.81 1.32 0.81 1.13 1.36 0.00 0.76 0.75 0.57 0.54 0.00 0.00 0.60 1.45 0.00 0.73 0.00 0.83 0.93 0.32 0.56 0.66 0.85 1.01 1.12 0.72 0.79 1.34 1.12 0.66 1.65 0.96 0.29 0.35

-0.54 1.34 5.23 5.04 2.22 2.00 4.31 1.78 4.11 1.66 1.88 0.59 3.23 2.92 3.25 2.00 1.51 2.76 0.65 1.78 0.88 0.46 1.42 -0.03 3.66 3.42 1.96 -0.66 2.11 3.37 0.18 -0.57 1.66 0.78 1.96 1.21 1.52 3.61 0.15 2.74 3.44 1.60 3.23 3.13 3.35 3.13 2.89 2.16 2.57 2.06 1.85 0.18 0.08 1.82 4.22 -0.77 2.31 0.48 2.45 3.68 1.85 1.95 2.29 5.18 3.53 3.31 2.26 1.58 3.09 3.27 3.12 5.17 3.36 1.31 3.62


YAFFE

ET AL.


MWa

pentanenitrile pentanoic acid p-ethyltoluene phenanthrene phenol phenyl benzoate phenyl formate phenylacetaldehyde phenylacetic acid phenylacetic acid ethyl ester phenylacetic acid methyl ester phenylacetonitrile phenylacetylene phenylethyl sulfide phenylpropyl ether p-isobutylphenol p-methyl styrene p-methylacetophenone p-methylbenzyl alcohol propane propanenitrile propionaldehyde propionicacid propiophenone propyl formate propylallylamine propylbutylamine propylisobutylamine propyl-sec-butylamine propyne p-xylene pyrazine pyrazine-2-one pyridine pyrrole pyrrolidine sec-butyl alcohol sec-butylamine sec-butylbenzene styrene tert-butylbenzene tert-butyl alcohol tert-butyl amine tetrachlorocyclohexane tetrachloroethene tetrachloromethane tetrafluoromethane tetrahydrofuran tetrahydropyran thiophene thiophenol toluene trans-1,2-diphenylethene tribromomethane trichloroethene trichlorofluoromethane trichloromethane triethylamine trifluorobenzene trifluoromethane trifluoromethylbenzene triiodomethane trimethylamine tripropylamine vinyl bromide

83.13 102.13 120.19 178.23 94.11 198.22 122.12 120.15 136.15 164.20 150.18 117.15 102.14 138.23 136.19 150.22 118.18 134.18 122.17 44.10 55.08 58.08 74.08 134.18 88.11 99.18 115.22 115.22 115.22 40.07 106.17 80.09 96.09 79.10 67.09 71.12 74.12 73.14 134.22 104.15 134.22 74.12 73.14 221.94 165.83 153.82 88.01 72.11 86.13 84.14 100.14 92.14 180.25 252.73 131.39 137.37 119.38 101.19 132.09 70.01 146.11 393.73 59.11 143.27 106.95

D_Pb D_Hc D_Sd [debye] [debye] [debye] E2e [EV] 2.49 2.17 0.07 0.05 0.53 2.16 3.11 2.13 1.69 1.61 1.49 2.32 0.34 0.59 0.80 0.76 0.30 2.60 0.69 0.03 2.38 2.15 2.16 2.23 3.33 0.32 0.22 0.24 0.33 0.51 0.02 0.00 2.89 0.62 1.89 0.22 0.91 0.23 0.30 0.02 0.30 0.98 0.28 0.02 0.00 0.01 0.00 1.29 0.98 1.01 0.60 0.25 0.00 0.60 0.14 0.98 0.41 0.14 0.00 1.56 2.87 0.43 0.05 0.26 1.18

0.84 0.48 0.03 0.02 0.69 0.13 0.47 0.35 0.32 0.16 0.13 0.90 0.17 1.61 0.37 0.62 0.02 0.43 0.66 0.03 0.87 0.36 0.46 0.46 0.61 1.31 1.35 1.38 1.35 0.15 0.03 0.00 1.44 1.31 0.29 1.37 0.69 1.52 0.04 0.01 0.02 0.70 1.52 0.01 0.00 0.00 0.00 0.38 0.40 1.68 2.28 0.02 0.00 0.35 0.63 0.42 0.60 1.16 0.00 0.33 0.24 0.18 1.20 1.24 0.15

3.33 1.80 0.04 0.03 1.14 2.27 3.53 2.45 1.54 1.76 1.63 3.20 0.17 1.64 1.12 1.25 0.30 3.02 1.29 0.00 3.25 2.51 1.80 2.69 3.90 1.18 1.16 1.14 1.12 0.36 0.05 0.00 3.47 1.93 2.18 1.46 1.48 1.37 0.27 0.02 0.30 1.54 1.36 0.03 0.00 0.01 0.00 1.67 1.38 0.67 1.69 0.26 0.00 0.95 0.49 0.56 1.02 1.06 0.00 1.89 3.11 0.61 1.15 1.00 1.33

462.04 760.96 642.11 962.48 613.91 1281.58 866.28 753.21 952.51 1093.92 1018.96 652.51 554.39 672.31 830.47 908.55 635.79 825.86 761.20 230.04 313.72 413.93 612.56 826.59 676.96 549.01 628.72 628.81 629.23 216.17 567.85 477.16 670.20 450.57 387.11 399.05 498.97 406.50 717.97 563.31 717.41 499.47 406.10 1059.93 746.46 685.86 1357.35 485.09 559.13 386.08 573.99 495.45 975.15 828.40 600.09 852.90 538.25 554.45 1370.93 1044.43 1456.81 704.29 331.52 777.06 402.44

EXf [ev]

ELCg [ev]

IPh [kcal]

POi [au]

-87.06 -93.84 -130.77 -175.88 -86.08 -175.87 -101.70 -112.62 -118.02 -151.33 -134.72 -111.40 -101.18 -117.61 -136.02 -152.81 -124.19 -129.52 -119.32 -56.37 -53.74 -55.01 -60.52 -129.40 -77.27 -110.23 -133.48 -133.47 -133.36 -43.40 -114.17 -67.65 -74.37 -74.07 -65.44 -77.19 -78.14 -83.57 -147.27 -107.39 -147.28 -78.18 -83.62 -94.83 -29.58 -18.39 -20.33 -71.84 -88.54 -57.80 -63.29 -97.35 -181.73 -18.26 -30.32 -18.53 -19.39 -116.52 -78.46 -20.61 -94.96 -17.72 -66.75 -166.50 -31.31

67.44 79.24 97.98 138.56 71.81 148.37 90.44 91.16 101.60 125.85 114.16 89.85 77.66 87.12 108.07 120.59 93.69 103.19 95.94 38.89 43.26 44.45 55.08 102.88 67.65 83.79 100.16 100.19 99.94 31.12 85.92 61.85 73.11 61.32 53.72 61.07 60.82 64.05 109.68 81.22 109.67 60.69 63.95 74.99 27.77 17.85 35.55 58.31 70.76 41.05 52.39 73.38 140.11 13.15 26.40 21.45 16.95 87.36 76.08 29.75 87.53 12.93 51.72 123.62 21.76

11.80 40.24 11.36 41.82 9.18 70.30 8.74 123.59 9.18 50.76 9.31 114.95 9.61 64.58 9.73 64.84 9.60 67.36 9.54 84.47 9.56 76.36 9.85 65.84 9.40 66.17 8.55 78.69 9.08 75.28 8.94 81.43 8.94 75.94 9.72 74.73 9.18 66.61 11.51 21.93 12.01 25.81 10.62 24.59 11.35 27.69 10.00 72.87 11.16 36.95 9.20 51.42 9.18 56.90 9.13 56.57 9.17 56.81 10.89 20.97 9.18 62.95 10.16 41.91 9.27 50.29 10.10 43.62 8.93 35.76 9.27 32.80 11.04 32.14 9.43 34.55 9.52 75.50 9.13 66.26 9.50 74.90 11.28 31.58 9.47 34.08 10.17 70.95 9.22 52.79 10.99 42.79 16.79 8.02 10.26 30.42 10.57 38.59 9.54 42.24 9.27 47.46 9.44 45.60 8.63 131.69 10.84 39.97 9.38 42.05 11.16 35.44 10.84 32.20 9.04 50.43 10.37 49.65 14.36 8.27 10.34 54.18 8.98 64.07 9.07 28.46 9.07 71.93 10.44 25.86

VMC1j VMC2k VMC4l logKow 2.28 2.49 3.38 4.82 2.13 4.68 2.59 2.91 3.05 4.02 3.43 2.84 2.45 4.09 3.61 3.96 3.02 3.28 2.99 1.41 1.28 1.35 1.49 3.43 1.97 2.73 3.62 3.48 3.54 0.79 2.82 1.70 1.88 1.85 1.58 2.21 1.95 2.03 3.89 2.61 3.66 1.72 1.79 4.91 2.51 2.26 0.76 2.08 2.58 2.41 2.50 2.41 4.73 3.40 2.07 1.89 1.96 3.07 2.30 0.65 2.73 4.33 1.34 4.57 1.54

1.26 1.50 2.34 3.51 1.34 3.07 1.53 1.86 2.06 2.47 2.24 1.82 1.51 3.08 2.16 3.26 2.11 2.42 2.14 0.71 0.51 0.57 0.75 2.14 0.97 1.49 2.10 2.60 2.26 0.29 2.15 0.89 1.10 1.02 0.88 1.46 1.26 1.39 2.72 1.61 3.62 2.17 2.37 4.77 2.41 3.85 0.43 1.32 1.67 1.61 1.87 1.65 3.15 6.66 1.62 2.57 2.22 1.62 1.59 0.25 1.86 10.83 1.34 2.84 0.80

0.26 0.33 0.82 1.95 0.43 1.23 0.55 0.71 0.77 0.97 0.83 0.69 0.53 1.36 0.74 1.10 0.70 0.79 0.69 0.00 0.00 0.00 0.00 0.83 0.17 0.38 0.60 0.57 0.54 0.00 0.64 0.25 0.31 0.31 0.28 0.63 0.00 0.00 1.02 0.59 0.94 0.00 0.00 2.38 0.00 0.00 0.00 0.51 0.69 0.68 0.72 0.53 1.32 0.00 0.00 0.00 0.00 0.67 0.52 0.00 0.63 0.00 0.00 1.28 0.00

1.12 3.00 3.63 4.57 1.46 3.59 1.26 1.78 1.41 2.42 1.96 1.56 2.40 3.20 3.18 2.94 3.35 2.28 1.59 2.36 0.16 0.59 0.33 2.19 0.82 1.33 2.12 2.07 1.91 0.94 3.20 -0.22 -1.49 0.64 0.75 0.46 0.61 0.74 4.57 3.16 4.11 0.37 0.40 3.72 3.40 2.83 1.18 0.46 0.95 1.81 2.52 2.69 4.81 3.20 2.42 2.53 1.97 1.44 2.52 0.64 3.01 2.00 0.27 2.79 1.57

a MW ) molecular weight. b D•P ) dipole moment•total point-charge [debye]. c D•H ) dipole moment•total hybrid [debye]. d D•S ) dipole moment•total sum [debye]. e E2 ) total two-center energy [ev]. f EX ) exchange energy (two-center term) [ev]. g ELC ) total electrostatic interaction (two-center term) [ev]. h IP ) ionization potential [kcal]. i PO ) average polarizability [au]. j VMC1 ) first-order valence molecular connectivity index. k VMC2 ) second-order valence molecular connectivity index. l VMC4 ) fourth-order valence molecular connectivity index.

charge component, total hybridization component, and total sum ) point charge + hybrid), molecular weight, first-order average polarizability, ionization potential, exchange energy,

total two-center energy, and total electrostatic interaction energy (two-center). We note that, in all 15 runs, the following descriptors were selected: dipole moment-total



Table 2. Molecular Descriptors Generated for NN/QSPRs

type of molecular descriptors generated

units

molecular weight Quantum Chemical Descriptors number of filled molecular orbital levels ionization potential average molecular polarizability dipole moments total dipole (point charge) total dipole (hybridization) total dipole (sum ) point charge + hybridization) principal moments of inertia moment of inertia, A direction moment of inertia, B direction moment of inertia, C direction heat of formation total energya total one-center energyb electron-electron repulsion (one-center term) electron-nuclear attraction (one-center term) total two-center energyc resonance energy (two-center term) exchange energy (two-center term) resonance energy + exchange energy (two-center term) total electrostatic inaction energy (two-center term)d electron-electron repulsion (two-center term) electron-nuclear attraction (two-center term) nuclear-nuclear repulsion (two-center term) Topological Indices first-order valence molecular connectivity index second-order valence molecular connectivity index third-order valence molecular connectivity index fourth-order valence molecular connectivity index second-order kappa shape index

variables selected for NN/QSPR X

kcal au

X X

debye debye debye

X X X

cm-1 cm-1 cm-1 ev ev ev ev ev ev ev ev ev ev

X X X

ev ev ev X X X

a Total energy ) total one-center energy + total two-center energy. Total one-center energy ) electron-electron repulsion + electronnuclear attraction. c Total two-center energy ) resonance energy + exchange energy + total electrostatic inaction energy. d Total electrostatic inaction energy ) electron-electron repulsion (two-center term) + electron-nuclear attraction (two-center term) + nuclear-nuclear repulsion (two-center term).

b

Figure 2. Block diagram of the fuzzy ARTMAP neural network.

hybridization component, dipole moment-total sum, and total electrostatic interaction energy. The average polarizability and first-order valence molecular connectivity index were ranked at the 93rd and 86th percentile range, respectively. The remaining descriptors listed in Tables 1 and 2 were ranked at or above the 73rd percentile range.

Fuzzy ARTMAP Neural Network Systems. The present study focused on the development of logKow QSPRS derived based on a fuzzy ARTMAP and back-propagation neural networks. The fuzzy ARTMAP neural network system used in the present study was recently introduced for developing QSPRs for boiling temperatures,35 critical properties,36 and aqueous solubilities.37 The current fuzzy ARTMAP system is the modification introduced by Giralt et al.50,51 to the original model of Carpenter et al.52-56 Briefly, the basic learning mechanism of the fuzzy ARTMAP neural system consists of creating new categories (equivalent to hidden units in back-propagation) when dissimilar molecular descriptors and different values of the physical property are encountered. The modified network consists of two fuzzy ART modules, artA and artB, that are linked together via an inter-ART module (Figure 2). Each ART system includes a field, Fo, of nodes that represent a current input vector and a field F1 that receives both bottom-up input from Fo and top-down input from a field F2 that represents the active code or category. The artA module categorizes the input patterns (molecular descriptors), while artB module develops categories of the target patterns (physical property) during supervised learning (training). During supervised learning, the artA module receives the molecular descriptors, and the artB module receives the correct physical property prediction of the input pattern presented to Foa. The artA module attempts the prediction through the map field of the category to which the current target belongs. The inter-ART module, called a map field, is an associative learning network that forms an internal controller designed to create a minimal number of artA recognition categories, or “hidden units”, by following the match tracking rule. The fuzzy ARTMAP dynamics are determined by vigilance Fa, Fb, Fab ∈[0,1], learning rates βa, βb ∈[0,1], and choice R > 0, parameters. The vigilance parameters calibrate how well an input pattern must match the learned prototype or cluster of input features that the category deems to be relevant, for a category to be accepted. The learning rate parameter determines how the map field weights change through the learning process. Finally, the choice parameter controls the fuzzy subsethood of the category choice function and accounts for the noise in the activation of the F1 layer. Additional information about fuzzy ART and fuzzy ARTMAP systems can be found elsewhere.57-61 The fuzzy ARTMAP-based QSPR for logKow was developed following the methodology described in Figure 1. About 85% (371) of compounds in the complete data set were selected for training by the fuzzy ART classifier to ensure that adequate information was provided to the system. Training of the fuzzy ARTMAP consisted of presenting the molecular descriptors and target properties of the training set to modules artA and artB (see Figure 2), respectively, to establish input and output categories and relate them through the map field (F1ab). After training with a data set of 371 compounds, the hypothesis components of the artB module (Fob and F1b) were disconnected and an output in its category layer F2b was implemented.35 Therefore, through the map field module F1ab, a prediction for the target physical property is obtained for any input of descriptors presented to module artA. The model was then evaluated with a test a set containing 71 compounds.


YAFFE

ET AL.

Table 3. Experimental and Predicted Octanol/Water Partition Coefficients Using Fuzzy ARTMAP and Back-Propagation QSPRs data seta

absolute error, logKow

logKow

absolute percent error, %b

compounds

fuzzy ARTMAP

backpropagation

reported logKow

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

1,1,1-trichloroethane 1,1,2,2,-tetrachlorodifluoroethane 1,1,2-trichlorotrifluoroethane 1,1-dichloroethane 1,1-dichloroethene 1,1-difluoroethane 1,1-difluoroethene 1,2,3,5-tetramethylbenzene 1,2,3-trimethylbenzene 1,2,4,5-tetramethylbenzene 1,2,4-trichlorobenzene 1,2,4-trimethylbenzene 1,2-dibromoethane 1,2-dichlorobenzene 1,2-dichloroethane 1,2-dichlorotetrafluoroethane 1,2-difluorobenzene 1,3,5-heptatriene 1,3,5-trichlorobenzene 1,3,5-trimethylbenzene 1,3-butadiene 1,3-dibromopropane 1,3-dichlorobenzene 1,3-dichloropropane 1,3-difluorobenzene 1,3-dimethylnaphthalene 1,4,5-trimethylnaphthalene 1,4-cyclohexadiene 1,4-dichlorobenzene 1,4-difluorobenzene 1,4-dimethylnaphthalene 1,4-dioxane 1,4-pentadiene 1,5-dimethylnaphthalene 1,5-hexadiene 1,6-heptadiene 1-bromo-2-isoproplybenzene 1-bromobutane 1-bromoheptane 1-bromohexane 1-bromooctane 1-bromopentane 1-bromopropane 1-butanethiol 1-butene 1-chloro-1,1-difluoroethane 1-chlorobutane 1-chlorohexane 1-chloropentane 1-choropropane 1-ethylnaphthalene 1-ethylpiperidine 1-heptanol 1-heptyne 1-hexene 1-hexyne 1-methylnaphthalene 1-methylcyclohexene 1-nitropropane 1-nonene 1-octanol 1-octene 1-octyne 1-pentanol 1-pentyne 1-propanol 1-propene 2,2′,3,3′,4,6′-hexachloro-1,1′-biphenyl 2,2′,3,4,4′,5′-hexachloro-1,1′-biphenyl 2,2′,4,4′,6,6′-hexachloro-1,1′-biphenyl

tr tr tr tr tr tr tr ts tr tr tr tr tr tr tr tr tr tr tr ts tr tr ts tr tr ts tr tr ts tr tr tr tr ts tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr ts tr tr tr tr tr ts tr tr tr tr tr tr tr tr tr tr tr ts ts

tr/v tr/v tr/v tr/v tr/v tr/v v ts tr/v tr/v tr/v tr/v tr/v tr/v tr/v tr/v tr/v tr/v tr/v ts v v ts v v ts tr/v v ts tr/v tr/v v tr/v ts tr/v tr/v tr/v tr/v v tr/v tr/v tr/v tr/v tr/v tr/v tr/v v v tr/v v ts tr/v tr/v tr/v v v ts tr/v tr/v v v tr/v v v tr/v tr/v tr/v v ts ts

2.49 2.39 3.16 1.79 2.13 0.75 1.24 4.17 3.55 4 4.02 3.65 1.96 3.38 1.48 2.82 3.6 2.63 4.15 3.42 1.99 2.37 3.38 2 3.75 4.42 4.9 2.3 3.39 4.11 4.37 -0.27 2.48 4.38 2.45 3.51 4.2 2.75 4.36 3.8 4.89 3.37 2.1 2.28 2.4 1.08 2.55 3.54 2.73 2.04 4.39 1.75 2.03 3.01 3.99 2.73 3.87 3.51 0.65 5.15 3.15 4.57 3.5 1.4 1.98 0.34 1.77 6.24 6.69 6.7

2.47 2.39 3.15 1.76 2.10 0.72 1.22 3.98 3.55 3.98 4.01 3.63 1.94 3.36 1.48 2.82 3.59 2.63 4.15 3.63 1.98 2.35 3.42 1.98 3.72 4.36 4.89 2.29 3.15 4.09 4.36 -0.30 2.47 4.36 2.43 3.51 4.18 2.72 4.36 3.79 4.89 3.36 2.10 2.26 2.39 1.08 2.55 3.51 2.72 2.03 4.36 1.75 2.03 2.99 3.98 2.72 3.86 3.51 0.65 5.15 3.15 4.54 3.50 1.38 1.98 0.33 1.76 6.24 6.24 6.85

2.52 2.84 2.90 1.91 1.76 0.43 1.56 3.68 3.26 3.95 3.86 3.49 1.94 3.44 2.23 2.60 3.15 2.58 3.98 3.75 1.61 2.07 3.32 2.14 3.34 4.11 4.29 2.65 3.68 2.80 4.38 1.96 2.25 4.39 2.85 3.50 4.14 2.45 4.11 3.64 4.51 3.04 1.96 2.04 1.83 1.56 2.05 3.12 2.60 1.60 4.14 2.20 2.43 3.24 3.10 2.63 3.94 3.24 0.93 4.43 2.86 4.08 3.70 1.49 2.00 0.51 1.15 5.80 6.92 6.87

0.02 0.00 0.01 0.03 0.03 0.03 0.02 0.19 0.00 0.02 0.01 0.02 0.02 0.02 0.00 0.00 0.01 0.00 0.00 0.21 0.01 0.02 0.04 0.02 0.03 0.06 0.01 0.01 0.24 0.02 0.01 0.03 0.01 0.02 0.02 0.00 0.02 0.03 0.00 0.01 0.00 0.01 0.00 0.02 0.01 0.00 0.00 0.03 0.01 0.01 0.03 0.00 0.00 0.02 0.01 0.01 0.01 0.00 0.00 0.00 0.00 0.03 0.00 0.02 0.00 0.01 0.01 0.00 0.45 0.15

0.03 0.45 0.26 0.12 0.37 0.32 0.32 0.49 0.29 0.05 0.16 0.16 0.02 0.06 0.75 0.22 0.45 0.05 0.17 0.33 0.38 0.30 0.06 0.14 0.41 0.31 0.61 0.35 0.29 1.31 0.01 2.23 0.23 0.01 0.40 0.01 0.06 0.30 0.25 0.16 0.38 0.33 0.14 0.24 0.57 0.48 0.50 0.42 0.13 0.44 0.25 0.45 0.40 0.23 0.89 0.10 0.07 0.27 0.28 0.72 0.29 0.49 0.20 0.09 0.02 0.17 0.62 0.44 0.23 0.17

0.80 0.00 0.32 1.68 1.41 4.00 1.61 4.56 0.00 0.50 0.25 0.55 1.02 0.59 0.00 0.00 0.28 0.00 0.00 6.14 0.50 0.84 1.18 1.00 0.80 1.36 0.20 0.43 7.08 0.49 0.23 11.11 0.40 0.46 0.82 0.00 0.48 1.09 0.00 0.26 0.00 0.30 0.00 0.88 0.42 0.00 0.00 0.85 0.37 0.49 0.68 0.00 0.00 0.66 0.25 0.37 0.26 0.00 0.00 0.00 0.00 0.66 0.00 1.43 0.00 2.94 0.56 0.00 6.73 2.24

1.40 18.69 8.28 6.90 17.14 42.87 25.51 11.86 8.14 1.30 3.87 4.49 0.78 1.91 50.73 7.83 12.38 2.07 4.21 9.74 19.24 12.81 1.74 6.99 10.81 6.95 12.44 15.21 8.64 31.92 0.22 827.10 9.34 0.12 16.33 0.20 1.49 10.75 5.78 4.17 7.71 9.90 6.43 10.59 23.78 44.80 19.66 11.92 4.66 21.45 5.68 25.46 19.87 7.53 22.34 3.70 1.81 7.78 42.62 14.04 9.28 10.78 5.82 6.74 1.21 49.89 34.83 7.13 3.47 2.61



Table 3 (Continued) data seta


logKow


compounds

fuzzy ARTMAP

backpropagation

reported logKow

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

2,2′,4,5,5′-pentabromo-1,1′-biphenyl 2,2′,4,5,5′-pentachloro-1,1′-biphenyl 2,2′,5,6′-tetrachloro-1,1′-biphenyl 2,2′3,3′-tetrachloro-1,1′-biphenyl 2,2′4,4′,5,5′-hexachloro-1,1′-biphenyl 2,2-dimethyl-1-propanol 2,2-dimethylbutane 2,2-dimethylpentane 2,2-dimethylpropane 2,3,6-trimethylnaphthalene 2,3′-dichloro-1,1′-biphenyl 2,3-dimethyl-1-butene 2,3-dimethylbutane 2,3-dimethylnaphthalene 2,3-dimethylpentane 2,3-dimethylpyridine 2,4-dibromotetrachlorocyclohexane 2,4′-dichloro-1,1′-biphenyl 2,4-dichloro-1,1′-biphenyl 2,4-dichloro-1-chloromethylbenzene 2,4-dichlorotoluene 2,4-dimethyl-2-pentanol 2,4-dimethyl-3-pentanone 2,4-dimethylpentane 2,4-dimethyl-phenol 2,5′-dichloro-1,1′-biphenyl 2,5-dimethylphenol 2,6,dimethylnaphthalene 2,6-dichloro-1,1′-biphenyl 2,6-dichlorotoluene 2,6-dimethyl-phenol 2-aminotoluene 2-bromobutane 2-bromophenol 2-bromopropane 2-bromotoluene 2-butanone 2-butene 2-butyne 2-chloro-1,1′-biphenyl 2-chloro-1-ethylbenzene 2-chloro-2-methylbutane 2-chlorophenol 2-chloropropane 2-ethyl pyridine 2-ethylnaphthalene 2-ethylphenol 2-ethylthiophene 2-fluoro-3-bromotetrachlorocyclohexane 2-fluorochlorobenzene 2-fluorophenol 2-heptanone 2-heptene 2-hexanol 2-hexanone 2-iodophenol 2-methoxynitrobenzene (2-nitroanisole) 2-methyl-1,3-butadiene 2-methyl-1-pentene 2-methyl-2-butene 2-methyl-2-nitropropane 2-methylbutane (isopentane) 2-methylhexane 2-methylnaphthalene 2-methylpentane 2-methylpyridine 2-nitropropane 2-nitrotoluene 2-nonanone 2-octanone 2-pentanol 2-pentanone 2-pentene 2-phenyl-1-ethanol

tr tr tr tr ts tr tr tr tr tr ts tr tr ts tr tr tr ts ts tr tr ts tr tr tr tr tr ts tr ts tr tr ts tr ts ts tr tr tr tr tr ts tr tr tr tr tr tr tr tr tr tr ts ts tr ts tr ts ts ts tr tr tr tr tr tr tr tr tr ts tr ts tr tr

tr/v tr/v tr/v tr/v ts tr/v tr/v v tr/v tr/v ts tr/v tr/v ts tr/v tr/v tr/v ts ts tr/v v ts tr/v tr/v tr/v v tr/v ts tr/v ts tr/v tr/v ts tr/v ts ts tr/v tr/v tr/v tr/v tr/v ts tr/v v v tr/v tr/v tr/v v tr/v tr/v tr/v ts ts tr/v ts tr/v ts ts ts tr/v tr/v tr/v v tr/v tr/v tr/v tr/v tr/v ts tr/v ts tr/v v

5.96 4.12 6.63 6.67 6.72 1.36 3.88 3.11 3.11 4.73 5.02 3.13 3.85 4.4 3.63 1.22 3.98 5.1 5.15 3.82 4.24 2.13 1.86 3.63 2.3 5.18 2.33 4.31 5.3 4.29 2.36 1.32 2.58 2.35 2.14 2.92 0.29 2.31 1.46 4.54 2.95 2.52 2.15 1.9 1.69 4.38 2.47 2.87 3.28 2.77 1.71 1.98 3.56 1.76 1.38 2.65 1.73 2.42 3.21 2.67 1.01 2.72 3.71 3.86 2.34 1.11 0.93 2.3 3.18 2.76 1.19 0.91 2.58 1.36

5.96 4.09 6.63 6.67 6.85 1.33 3.86 3.11 3.11 4.73 5.30 3.11 3.82 4.36 3.63 1.22 3.98 5.30 5.30 3.82 4.24 2.03 1.85 3.63 2.29 5.15 2.31 4.36 5.30 4.24 2.35 1.31 2.72 2.35 2.10 3.33 0.27 2.31 1.43 4.54 2.95 2.72 2.15 1.90 1.69 4.36 2.47 2.86 3.28 2.76 1.70 1.98 3.51 1.76 1.38 2.91 1.70 2.47 3.05 2.58 1.01 2.72 3.71 3.86 2.31 1.11 0.92 2.29 3.18 3.18 1.18 0.81 2.58 1.33

6.30 3.77 6.55 6.60 6.93 1.26 3.34 3.79 3.05 4.32 4.99 2.69 3.52 3.98 4.10 1.44 3.96 4.91 5.07 4.49 3.85 2.12 1.86 3.88 2.18 5.34 2.16 4.39 4.95 3.70 2.12 1.33 2.26 2.85 1.88 3.46 0.27 1.80 1.72 4.28 3.69 2.28 2.73 1.47 1.65 4.20 2.08 2.74 3.58 2.73 1.78 1.91 3.69 1.91 1.54 2.68 1.68 2.16 2.65 2.08 1.25 2.98 4.15 4.00 3.51 1.17 0.91 2.04 2.65 2.28 1.37 1.07 2.42 2.12

0.00 0.03 0.00 0.00 0.13 0.03 0.02 0.00 0.00 0.00 0.28 0.02 0.03 0.04 0.00 0.00 0.00 0.20 0.15 0.00 0.00 0.10 0.01 0.00 0.01 0.03 0.02 0.05 0.00 0.05 0.01 0.01 0.14 0.00 0.04 0.41 0.02 0.00 0.03 0.00 0.00 0.20 0.00 0.00 0.00 0.02 0.00 0.01 0.00 0.01 0.01 0.00 0.05 0.00 0.00 0.26 0.03 0.05 0.16 0.09 0.00 0.00 0.00 0.00 0.03 0.00 0.01 0.01 0.00 0.42 0.01 0.10 0.00 0.03

0.34 0.35 0.08 0.07 0.21 0.10 0.54 0.68 0.06 0.41 0.03 0.44 0.33 0.42 0.47 0.22 0.02 0.19 0.08 0.67 0.39 0.01 0.00 0.25 0.12 0.16 0.17 0.08 0.35 0.59 0.24 0.01 0.32 0.50 0.26 0.54 0.02 0.51 0.26 0.26 0.74 0.24 0.58 0.43 0.04 0.18 0.39 0.13 0.30 0.04 0.07 0.07 0.13 0.15 0.16 0.03 0.05 0.26 0.56 0.59 0.24 0.26 0.44 0.14 1.17 0.06 0.02 0.26 0.53 0.48 0.18 0.16 0.16 0.76

0.00 0.73 0.00 0.00 1.93 2.21 0.52 0.00 0.00 0.00 5.58 0.64 0.78 0.91 0.00 0.00 0.00 3.92 2.91 0.00 0.00 4.69 0.54 0.00 0.43 0.58 0.86 1.16 0.00 1.17 0.42 0.76 5.43 0.00 1.87 14.04 6.90 0.00 2.05 0.00 0.00 7.94 0.00 0.00 0.00 0.46 0.00 0.35 0.00 0.36 0.59 0.00 1.40 0.00 0.00 9.81 1.73 2.07 4.98 3.37 0.00 0.00 0.00 0.00 1.28 0.00 1.08 0.43 0.00 15.22 0.84 10.99 0.00 2.21

5.64 8.44 1.26 1.12 3.17 7.52 13.97 21.77 1.94 8.60 0.54 13.99 8.55 9.46 13.01 17.86 0.60 3.70 1.50 17.51 9.15 0.66 0.01 7.00 5.28 3.15 7.34 1.75 6.69 13.79 10.24 1.03 12.47 21.45 11.97 18.42 6.18 21.98 17.53 5.70 24.97 9.65 27.03 22.56 2.20 4.18 15.67 4.55 9.28 1.54 4.29 3.76 3.73 8.39 11.33 1.24 2.95 10.82 17.58 21.94 23.80 9.47 11.92 3.67 49.98 5.19 2.16 11.50 16.76 17.44 15.20 17.56 6.12 55.60


YAFFE

ET AL.



logKow


compounds

fuzzy ARTMAP

backpropagation

reported logKow

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

2-phenylthiophene 2-propanol 2-propanone 2-pyrimidone 3,3,3-trifluoropropylbenzene 3,3′,4,4′-tetrachloro-1,1′-biphenyl 3,3′,5,5′-tetrachloro-1,1′-biphenyl 3,3-dimethyl-2-butanol 3,4-dichloro-1,1-biphenyl 3,4-dimethylchlorobenzene 3,4-dimethylphenol 3,5-dichloro-1,1′-biphenyl 3,5-dimethylphenol 3-bromophenol 3-chlorophenol 3-ethylpentane 3-ethylthiophene 3-fluorophenol 3-hexanol 3-iodophenol 3-methyl-1-butanol 3-methyl-1-butene 3-methyl-2-butanol 3-methyl-2-butanone 3-methylpentane 3-methylpyridine 3-methylthiophene 3-nitrotoluene 3-pentanol 3-phenyl-1-chloropropane 4,4′-dichloro-1,1′-biphenyl 4-bromophenol 4-bromotoluene 4-chloro-1,1′-biphenyl 4-chlorophenol 4-cyclopropyl-2-butanone 4-ethenylcyclohexene 4-ethylphenyl acetate 4-fluorophenol 4-iodophenol 4-methyl pyridine 4-methyl-1-pentene 4-methyl-2-pentanone 4-methylphenol 4-n-propylphenol 4-phenylbutyric acid 4-phenylphenol 4-pyrimidone 5-methyl-2-hexanone 5-methyl-furfural(5-methylfuraldehyde) 5-nonanone 5-phenyl-2-pentanone 9-fluorenone 9-methylanthracene a,a,a-trichlorotoluene a,a,a-trifluorotoluene a-bromotoluene acenaphthene acenaphthylene acetic acid acetonitrile acetophenone a-chlorotoluene acrylophenone allyl alcohol (2-propen-1-ol) allyl bromide (3-bromo-1-propene) allylbenzene (2-propenyl) amylamine (pentyl) aniline anthracene benz[a]anthracene benzaldehyde benzene benzoic acid

tr tr tr tr tr tr tr tr ts tr tr ts tr ts tr tr tr tr tr ts ts tr tr tr tr ts tr tr tr tr tr tr tr tr tr tr tr ts tr tr tr tr tr tr tr tr ts tr ts tr tr tr tr tr tr tr ts tr tr tr tr tr tr tr tr tr tr ts tr ts tr tr tr tr

tr/v tr/v tr/v tr/v tr/v tr/v v tr/v ts v tr/v ts tr/v ts v tr/v v tr/v v ts ts tr/v tr/v v tr/v ts v tr/v tr/v tr/v v v tr/v tr/v v v tr/v ts tr/v tr/v tr/v tr/v v tr/v tr/tv tr/v ts tr/v ts v v tr/v v tr/v tr/v tr/v ts tr/v tr/v v v tr/v tr/v tr/v tr/v v tr/v ts tr/v ts tr/v v v tr/v

3.74 0.05 -0.24 -1.62 3.31 6.04 6.85 1.48 5.51 3.82 2.23 5.37 2.35 2.63 2.52 2.4 2.82 1.93 1.65 2.93 1.16 2.59 1.28 0.84 3.6 1.2 2.34 2.45 1.21 3.55 5.58 2.43 3.33 4.61 2.35 1.5 3.34 2.56 1.79 2.91 1.2 3.08 1.31 1.94 3.23 2.42 3.2 -1.38 1.88 1.85 2.88 2.42 3.58 5.07 2.92 2.79 2.92 3.92 4.03 -0.17 -0.34 1.58 2.3 1.88 -0.31 1.79 3.27 1.45 0.9 4.54 5.61 1.48 2.13 1.81

3.72 0.05 -0.24 -1.62 3.28 6.04 6.85 1.48 5.30 3.82 2.22 5.30 2.35 2.35 2.51 2.39 2.82 1.90 1.65 2.91 1.38 2.58 1.26 0.81 3.59 1.18 2.31 2.43 1.18 3.55 5.58 2.43 3.33 4.61 2.35 1.48 3.33 2.39 1.76 2.91 1.18 3.05 1.31 1.94 3.23 2.39 3.23 -1.38 1.98 1.85 2.86 2.39 3.55 5.07 2.91 2.76 3.33 3.92 4.01 -0.17 -0.34 1.58 2.29 1.85 -0.34 1.76 3.25 1.33 0.88 4.54 5.58 1.48 2.10 1.81

3.94 0.14 -0.14 -1.05 3.67 5.92 6.81 1.78 5.05 3.09 2.05 4.99 1.98 2.78 2.02 2.19 2.88 1.86 1.88 2.63 1.40 2.38 1.42 1.16 3.67 1.07 2.28 2.18 1.41 3.70 5.60 3.15 3.49 4.36 2.59 1.78 3.60 2.73 1.80 3.05 1.06 2.81 1.39 1.86 2.49 2.43 3.33 -1.19 1.96 1.45 2.74 2.87 3.41 4.81 4.01 2.86 3.18 4.03 4.31 -0.22 -0.45 1.87 2.99 2.09 -0.21 1.90 3.61 1.11 1.06 4.97 5.98 1.58 2.59 1.46

0.02 0.00 0.00 0.00 0.03 0.00 0.00 0.00 0.21 0.00 0.01 0.07 0.00 0.28 0.01 0.01 0.00 0.03 0.00 0.02 0.22 0.01 0.02 0.03 0.01 0.02 0.03 0.02 0.03 0.00 0.00 0.00 0.00 0.00 0.00 0.02 0.01 0.17 0.03 0.00 0.02 0.03 0.00 0.00 0.00 0.03 0.03 0.00 0.10 0.00 0.02 0.03 0.03 0.00 0.01 0.03 0.41 0.00 0.02 0.00 0.00 0.00 0.01 0.03 0.03 0.03 0.02 0.12 0.02 0.00 0.03 0.00 0.03 0.00

0.20 0.09 0.10 0.57 0.36 0.12 0.04 0.30 0.46 0.73 0.18 0.38 0.37 0.15 0.50 0.21 0.06 0.07 0.23 0.30 0.24 0.21 0.14 0.32 0.07 0.13 0.06 0.27 0.20 0.15 0.02 0.72 0.16 0.25 0.24 0.28 0.26 0.17 0.01 0.14 0.14 0.27 0.08 0.08 0.74 0.01 0.13 0.19 0.08 0.40 0.14 0.45 0.17 0.26 1.09 0.07 0.26 0.11 0.28 0.05 0.11 0.29 0.69 0.21 0.10 0.11 0.34 0.34 0.16 0.43 0.37 0.10 0.46 0.35

0.53 0.01 0.00 0.00 0.91 0.00 0.00 0.00 3.81 0.00 0.45 1.30 0.00 10.65 0.40 0.42 0.00 1.55 0.00 0.68 18.97 0.39 1.56 3.57 0.28 1.67 1.28 0.82 2.48 0.00 0.00 0.00 0.00 0.00 0.00 1.33 0.30 6.64 1.68 0.00 1.67 0.97 0.00 0.00 0.00 1.24 0.94 0.00 5.32 0.00 0.69 1.24 0.84 0.00 0.34 1.08 14.04 0.00 0.50 0.00 0.00 0.00 0.43 1.60 9.68 1.68 0.61 8.28 2.22 0.00 0.53 0.00 1.41 0.00

5.46 179.44 40.93 35.08 11.01 1.93 0.57 20.18 8.40 19.00 8.04 6.99 15.82 5.86 19.75 8.62 2.18 3.86 13.91 10.13 20.80 8.16 10.88 37.71 1.98 10.95 2.56 11.08 16.92 4.31 0.32 29.52 4.88 5.47 10.15 18.52 7.77 6.58 0.33 4.81 11.86 8.62 5.89 4.34 22.91 0.60 3.97 13.56 3.99 21.83 4.95 18.55 4.69 5.05 37.36 2.65 8.85 2.75 7.05 27.40 32.27 18.17 30.05 10.92 30.97 6.30 10.32 23.65 17.77 9.39 6.64 6.49 21.79 19.57





logKow


compounds

fuzzy ARTMAP

backpropagation

reported logKow

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

benzoic acid methyl ester benzonitrile benzothiophene benzyl acetate benzylamine benzylphenyl ether beta-phenylethyl chloride (2-) biphenyl bromobenzene bromochloromethane bromocyclohexane bromoethane bromomethane bromotrifluoromethane butanol butylamine butyl benzene butyl ethyl ether butyldimethylamine butylmethylamine butyraldehyde butyric acid butyronitrile chlorobenzene chlorodifluoromethane chloroethane chloromethane chlorotrifluoromethane cis-1-2-dimethylcyclohexane crotonic acid (2-butenoic acid) cycloheptane cycloheptene cyclohexane cyclohexanol cyclohexanone cyclohexene cyclooctane cyclopentane cyclopentanone cyclopentene cyclopropane decachlorobiphenyl decanoic acid di(n-propyl) ether diallylamine dibromomethane dichlorodifluoromethane dichlorofluoromethane dichloromomethane diethyl sulfide diethylamine diethyl ether difluoromethane dimethyl ether dimethyl sulfide dimethyl sulfoxide di-n-butylamine di-n-propylamine di-n-propylamine diphenylacetic acid diphenylmethane diphenylsulfide ethane ethanol ethene ethoxybenzene ethyl acetate ethyl benzene ethyl benzoate ethyl mercaptan ethyl propionate (C5H10O2) ethylallylamine ethyldiisopropylamine ethyldimethylamine

tr tr ts ts tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr ts tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr ts tr tr tr ts tr tr tr tr tr tr tr tr tr tr tr tr tr tr ts tr ts tr tr ts tr tr tr tr tr tr tr tr v tr

v v ts ts tr/v tr/v v tr/v tr/v tr/v v tr/v tr/v tr/v tr/v tr/v tr/v tr/v tr/v v tr/v ts tr/v v v tr/v tr/v tr/v v tr/v tr/v tr/v tr/v tr/v tr/v tr/v v tr/v tr/v ts v tr/v v ts v tr/v tr/v tr/v tr/v v tr/v v tr/v v v tr/v tr/v tr/v ts tr/v ts tr/v v ts tr/v v v tr/v v v tr/v v v tr/v

2.12 1.56 3.12 1.96 1.09 3.79 2.95 4.09 2.99 1.41 3.2 1.61 1.19 1.86 0.88 0.81 4.26 2.03 1.7 1.33 0.88 0.79 0.53 2.84 1.08 1.43 0.91 1.65 4.01 0.72 4 3.45 3.44 1.23 0.81 2.86 4.45 3 0.63 2.47 1.72 7.92 4.09 2.03 1.11 1.57 2.16 1.55 1.25 1.95 0.57 0.89 0.2 0.1 0.92 -1.35 2.68 1.73 1.67 3.05 4.14 4.41 1.87 0.1 1.13 2.51 0.73 3.15 2.63 1.21 1.21 0.81 2.68 0.7

2.10 1.55 3.18 1.94 1.08 3.79 2.95 4.09 2.99 1.38 3.18 1.58 1.18 1.85 0.88 0.81 4.24 2.03 1.70 1.33 0.88 0.78 0.51 2.82 1.08 1.43 0.88 1.65 4.01 0.72 3.98 3.42 3.42 1.22 0.81 2.86 4.45 2.99 0.61 2.58 1.70 7.92 4.09 2.03 1.11 1.55 2.15 1.55 1.22 1.94 0.57 0.88 0.18 0.08 0.92 -1.38 2.68 1.70 1.70 3.05 4.36 4.41 1.85 0.08 1.11 2.51 0.72 3.15 2.63 1.18 1.18 0.81 2.68 0.70

1.87 1.31 3.44 2.29 1.34 3.57 3.42 4.46 2.94 1.93 3.25 1.61 1.29 1.30 1.01 0.67 4.04 2.33 1.68 1.19 0.76 0.67 0.52 2.56 1.20 1.12 0.72 1.31 4.45 0.50 4.07 3.45 3.62 1.88 1.55 2.92 4.66 2.89 1.10 2.30 2.04 6.92 3.19 2.32 1.12 2.08 1.83 1.71 1.56 2.06 0.76 1.18 0.17 0.10 1.07 -1.55 2.50 1.70 1.70 3.84 4.55 4.47 1.68 0.20 0.93 2.26 0.97 3.28 2.34 1.08 1.55 0.96 2.17 0.82

0.02 0.01 0.06 0.02 0.01 0.00 0.00 0.00 0.00 0.03 0.02 0.03 0.01 0.01 0.00 0.00 0.02 0.00 0.00 0.00 0.00 0.01 0.02 0.02 0.00 0.00 0.03 0.00 0.00 0.00 0.02 0.03 0.02 0.01 0.00 0.00 0.00 0.01 0.02 0.11 0.02 0.00 0.00 0.00 0.00 0.02 0.01 0.00 0.03 0.01 0.00 0.01 0.02 0.02 0.00 0.03 0.00 0.03 0.03 0.00 0.22 0.00 0.02 0.02 0.02 0.00 0.01 0.00 0.00 0.03 0.03 0.00 0.00 0.00

0.25 0.25 0.32 0.33 0.25 0.22 0.47 0.37 0.05 0.52 0.05 0.00 0.10 0.56 0.13 0.14 0.22 0.30 0.02 0.14 0.12 0.12 0.01 0.28 0.12 0.31 0.19 0.34 0.44 0.22 0.07 0.00 0.18 0.65 0.74 0.06 0.21 0.11 0.47 0.17 0.32 1.00 0.90 0.29 0.01 0.51 0.33 0.16 0.31 0.11 0.19 0.29 0.03 0.00 0.15 0.20 0.18 0.03 0.03 0.79 0.41 0.06 0.19 0.10 0.20 0.25 0.24 0.13 0.29 0.13 0.34 0.15 0.51 0.12

0.94 0.64 1.92 1.02 0.92 0.00 0.00 0.00 0.00 2.13 0.62 1.86 0.84 0.54 0.00 0.00 0.47 0.00 0.00 0.00 0.00 1.27 3.77 0.70 0.00 0.00 3.30 0.00 0.00 0.00 0.50 0.87 0.58 0.81 0.00 0.00 0.00 0.33 3.17 4.45 1.16 0.00 0.00 0.00 0.00 1.27 0.46 0.00 2.40 0.51 0.00 1.12 10.00 20.00 0.00 2.22 0.00 1.73 1.80 0.00 5.31 0.00 1.07 20.00 1.77 0.00 1.37 0.00 0.00 2.48 2.48 0.00 0.00 0.00

11.92 16.23 10.11 16.61 22.73 5.81 15.87 8.94 1.61 37.15 1.59 0.26 8.62 30.02 14.42 17.25 5.25 14.81 0.96 10.18 13.31 15.01 1.56 9.78 11.11 21.43 21.39 20.89 11.02 30.17 1.87 0.13 5.31 52.87 90.79 1.97 4.65 3.51 74.50 6.89 18.41 12.67 22.08 14.37 1.29 32.71 15.45 10.56 24.85 5.60 33.66 32.38 13.33 0.71 15.84 15.04 6.58 1.81 1.72 25.83 9.86 1.34 10.37 96.40 17.48 9.83 33.29 4.05 10.95 10.81 28.45 18.11 19.11 17.02


YAFFE

ET AL.



logKow


compounds

fuzzy ARTMAP

backpropagation

reported logKow

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

ethylene oxide (oxirane) ethylvinyl ether ethynylbenzene fluorene fluorobenzene fluoromethane fluoropentachlorocyclohexane formaldehyde formic acid furan hexachlorobenzene hexachlorocyclopentadiene hexafluorobenzene hexafluroethane hexamethylbenzene hexanal hexane hexanenitrile hexanoic acid hydroquinone indane indene iodobenzene iodoethane iodomethane isobutane isobutanol isobutyl acetate isobutylamine isobutyronitrile isopentanol isopropylamine isopropylbenzene m-chlorotoluene m-cresol (3-hydroxytoluene) methanol methoxybenzene (anisole) methycyclopentane methyl acetate methylamine methyl butyl ether methyl mercaptan methyl propanoate methyl propyl ether methylbenzylamine methylcyclohexane methylethylamine methylthiobenzene m-methyl styrene m-methylbenzyl alcohol m-phenylphenol m-xylene naphthalene n-benzylaniline n-butane n-ethylaniline n-heptylamine n-hexylamine nitrobenzene nitroethane nitromethane N-methylaniline N-methyl-N-benzylaniline N,N-dimethyl acetamide N,N-dimethylaniline n-propylamine n-propylaniline n-propylbenzene n-propylpropionate o-cresol (2-hydroxytoluene) octafluorocyclobutane octane o-ethyl-toluene o-isobutylphenol o-methylbenzaldehyde o-methylbenzyl alcohol

tr tr tr tr tr tr tr tr tr tr tr ts tr tr tr tr tr tr tr tr tr tr tr ts tr tr tr tr tr ts ts tr tr tr tr tr ts tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr ts ts tr tr tr ts ts tr tr

tr/v tr/v tr/v v v v v v tr/v tr/v tr/v ts tr/v tr/v tr/v v tr/v tr/v tr/v v tr/v v tr/v ts tr/v v v tr/v tr/v ts ts tr/v v v tr/v tr/v ts v v tr/v tr/v v tr/v v tr/v v tr/v tr/v tr/v tr/v v v v tr/v tr/v v tr/v tr/v tr/v tr/v tr/v tr/v tr/v v v tr/v v ts ts tr/v v tr/v ts ts tr/v tr/v

-0.3 1.04 2.53 4.18 2.27 0.51 3.19 0.35 -0.54 1.34 5.23 5.04 2.22 2 4.31 1.78 4.11 1.66 1.88 0.59 3.23 2.92 3.25 2 1.51 2.76 0.65 1.78 0.88 0.46 1.42 -0.03 3.66 3.42 1.96 -0.66 2.11 3.37 0.18 -0.57 1.66 0.78 1.96 1.21 1.52 3.61 0.15 2.74 3.44 1.6 3.23 3.13 3.35 3.13 2.89 2.16 2.57 2.06 1.85 0.18 0.08 1.82 4.22 -0.77 2.31 0.48 2.45 3.68 1.85 1.95 2.29 5.18 3.53 3.31 2.26 1.58

-0.30 1.01 2.51 4.18 2.26 0.51 3.18 0.33 -0.57 1.33 5.23 5.23 2.22 1.98 4.31 1.76 4.09 1.65 1.85 0.57 3.23 2.91 3.25 1.58 1.48 2.76 0.65 1.76 0.88 0.51 1.38 -0.03 3.63 3.42 1.94 -0.66 1.94 3.36 0.18 -0.57 1.65 0.78 1.94 1.18 1.52 3.59 0.15 2.72 3.42 1.58 3.23 3.11 3.33 3.11 2.86 2.15 2.55 2.03 1.85 0.18 0.08 1.81 4.22 -0.77 2.31 0.46 2.43 3.63 1.76 1.94 2.29 5.15 3.55 2.91 2.26 1.58

-0.15 0.82 2.91 4.45 1.85 0.71 3.83 0.63 -0.81 1.10 5.09 4.89 2.68 2.00 4.40 1.59 3.81 1.39 1.62 0.63 3.54 3.30 2.84 1.86 1.62 2.41 0.92 1.99 0.61 0.45 1.41 -0.12 3.81 2.86 1.83 -0.45 1.82 3.35 0.36 -0.79 1.62 0.75 0.90 0.52 1.46 4.01 0.20 3.36 3.46 2.11 3.24 3.21 4.01 3.27 2.59 1.84 1.98 1.59 1.83 0.31 0.14 1.45 3.33 -0.45 1.92 0.18 2.27 3.65 2.11 1.80 1.31 4.85 3.39 3.01 1.89 2.03

0.00 0.03 0.02 0.00 0.01 0.00 0.01 0.02 0.03 0.01 0.00 0.19 0.00 0.02 0.00 0.02 0.02 0.01 0.03 0.02 0.00 0.01 0.00 0.42 0.03 0.00 0.00 0.02 0.00 0.05 0.04 0.00 0.03 0.00 0.02 0.00 0.17 0.01 0.00 0.00 0.01 0.00 0.02 0.03 0.00 0.02 0.00 0.02 0.02 0.02 0.00 0.02 0.02 0.02 0.03 0.01 0.02 0.03 0.00 0.00 0.00 0.01 0.00 0.00 0.00 0.02 0.02 0.05 0.09 0.01 0.00 0.03 0.02 0.40 0.00 0.00

0.15 0.22 0.38 0.27 0.42 0.20 0.64 0.28 0.27 0.24 0.14 0.15 0.46 0.00 0.09 0.19 0.30 0.27 0.26 0.04 0.31 0.38 0.41 0.14 0.11 0.35 0.27 0.21 0.27 0.01 0.01 0.09 0.15 0.56 0.13 0.21 0.29 0.02 0.18 0.22 0.04 0.03 1.06 0.69 0.06 0.40 0.05 0.62 0.02 0.51 0.01 0.08 0.66 0.14 0.30 0.32 0.59 0.47 0.02 0.13 0.06 0.37 0.89 0.32 0.39 0.30 0.18 0.03 0.26 0.15 0.98 0.33 0.14 0.30 0.37 0.45

0.00 2.88 0.79 0.00 0.44 0.00 0.31 5.72 5.56 0.75 0.00 3.77 0.00 1.00 0.00 1.12 0.49 0.60 1.60 3.39 0.00 0.34 0.00 21.00 1.99 0.00 0.00 1.12 0.00 10.87 2.82 0.01 0.82 0.00 1.02 0.00 8.06 0.30 0.00 0.00 0.60 0.00 1.02 2.48 0.00 0.55 0.00 0.73 0.58 1.25 0.00 0.64 0.60 0.64 1.04 0.46 0.78 1.46 0.00 0.00 0.00 0.55 0.00 0.00 0.00 4.17 0.82 1.36 4.86 0.51 0.00 0.58 0.57 12.08 0.00 0.00

49.77 20.99 14.99 6.44 18.53 40.03 20.14 80.50 49.95 18.28 2.68 3.00 20.66 0.04 2.04 10.70 7.23 16.34 13.96 7.45 9.48 13.17 12.62 6.93 7.51 12.77 42.08 11.59 30.27 1.29 1.03 290.82 4.18 16.31 6.65 31.26 13.87 0.52 99.33 38.33 2.33 4.04 54.29 57.21 4.01 11.10 36.60 22.59 0.52 31.85 0.29 2.55 19.83 4.62 10.49 14.82 22.78 22.85 0.92 74.85 76.13 20.08 21.03 41.00 17.01 62.99 7.40 0.86 13.92 7.86 42.59 6.38 3.89 9.08 16.51 28.69





logKow


compounds

fuzzy ARTMAP

backpropagation

reported logKow

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

o-phenylphenol o-sec-butylphenol o-xylene pentachlorobenzene pentafluoroethylbenzene pentanal pentane pentanenitrile pentanoic acid p-ethyltoluene phenanthrene phenol phenyl benzoate phenyl formate phenylacetaldehyde phenylacetic acid phenylacetic acid ethyl ester phenylacetic acid methyl ester phenylacetonitrile phenylacetylene phenylethyl sulfide phenylpropyl ether p-isobutylphenol p-methyl styrene p-methylacetophenone p-methylbenzyl alcohol propane propanenitrile propionaldehyde propionicacid propiophenone propyl formate propylallylamine propylbutylamine propylisobutylamine propyl-sec-butylamine propyne p-xylene pyrazine pyrazine-2-one pyridine pyrrole pyrrolidine sec-butyl alcohol sec-butylamine sec-butylbenzene styrene tert-butylbenzene tert-butyl alcohol tert-butyl amine tetrachlorocyclohexane tetrachloroethene tetrachloromethane tetrafluoromethane tetrahydrofuran tetrahydropyran thiophene thiophenol toluene trans-1,2-diphenylethene tribromomethane trichloroethene trichlorofluoromethane trichloromethane triethylamine trifluorobenzene trifluoromethane trifluoromethylbenzene triiodomethane trimethylamine tripropylamine vinyl bromide

ts ts ts tr tr tr tr tr tr tr tr tr tr tr tr tr ts tr tr tr tr ts tr ts tr tr tr tr tr tr ts tr tr tr tr tr tr ts tr tr tr tr tr tr tr ts tr tr tr tr tr tr tr tr tr tr tr tr tr tr tr ts tr tr tr tr tr ts tr tr tr tr

ts ts ts tr/v tr/v tr/v tr/v tr/v v v v tr/v tr/v tr/v tr/v tr/v ts v tr/v v tr/v ts tr/v ts tr/v v tr/v tr/v tr/v tr/v ts tr/v tr/v tr/v tr/v tr/v tr/v ts tr/v v tr/v tr/v v tr/v tr/v ts tr/v v tr/v tr/v tr/v tr/v tr/v v tr/v v v tr/v v v tr/v ts tr/v tr/v v tr/v v ts tr/v v tr/v v

3.09 3.27 3.12 5.17 3.36 1.31 3.62 1.12 3 3.63 4.57 1.46 3.59 1.26 1.78 1.41 2.42 1.96 1.56 2.4 3.2 3.18 2.94 3.35 2.28 1.59 2.36 0.16 0.59 0.33 2.19 0.82 1.33 2.12 2.07 1.91 0.94 3.2 -0.22 -1.49 0.64 0.75 0.46 0.61 0.74 4.57 3.16 4.11 0.37 0.4 3.72 3.4 2.83 1.18 0.46 0.95 1.81 2.52 2.69 4.81 3.2 2.42 2.53 1.97 1.44 2.52 0.64 3.01 2 0.27 2.79 1.57

3.23 2.91 3.11 5.15 3.36 1.31 3.59 1.11 2.99 3.63 4.54 1.43 3.59 1.26 1.76 1.38 2.39 1.94 1.55 2.39 3.18 3.23 2.91 3.25 2.26 1.58 2.35 0.15 0.57 0.33 1.85 0.81 1.33 2.10 2.07 1.90 0.92 3.11 -0.24 -1.49 0.61 0.72 0.46 0.61 0.72 4.24 3.15 4.09 0.37 0.37 3.72 3.40 2.82 1.18 0.46 0.92 1.81 2.51 2.68 4.81 3.18 2.10 2.51 1.94 1.43 2.51 0.61 2.76 1.98 0.27 2.76 1.55

3.19 3.01 3.06 4.64 4.07 1.20 3.12 0.98 3.15 3.85 4.86 1.50 3.34 1.61 1.84 1.92 2.63 2.25 1.54 2.91 3.51 2.66 2.89 3.44 2.28 2.01 2.00 0.05 0.49 0.23 2.21 0.81 1.38 2.11 2.11 2.07 0.79 3.41 -0.70 -1.59 0.73 0.70 0.69 0.70 0.62 4.08 3.37 4.15 0.72 0.45 3.89 2.98 2.62 1.46 0.59 1.62 1.76 1.47 2.41 4.96 2.74 2.49 2.17 2.04 1.64 2.87 0.41 2.86 2.15 0.21 2.63 1.26

0.14 0.36 0.01 0.02 0.00 0.00 0.03 0.01 0.01 0.00 0.03 0.03 0.00 0.00 0.02 0.03 0.03 0.02 0.01 0.01 0.02 0.05 0.03 0.10 0.02 0.01 0.01 0.01 0.02 0.00 0.34 0.01 0.00 0.02 0.00 0.01 0.02 0.09 0.02 0.00 0.03 0.03 0.00 0.00 0.02 0.33 0.01 0.02 0.00 0.03 0.00 0.00 0.01 0.00 0.00 0.03 0.00 0.01 0.01 0.00 0.02 0.32 0.02 0.03 0.01 0.01 0.03 0.25 0.02 0.00 0.03 0.02

0.10 0.26 0.06 0.53 0.71 0.11 0.50 0.14 0.15 0.22 0.29 0.04 0.25 0.35 0.06 0.51 0.21 0.29 0.02 0.51 0.31 0.52 0.05 0.09 0.00 0.42 0.36 0.11 0.10 0.10 0.02 0.01 0.05 0.01 0.04 0.16 0.15 0.21 0.48 0.10 0.09 0.05 0.23 0.09 0.12 0.49 0.21 0.04 0.35 0.05 0.17 0.42 0.21 0.28 0.13 0.67 0.05 1.05 0.28 0.15 0.46 0.07 0.36 0.07 0.20 0.35 0.23 0.15 0.15 0.06 0.16 0.31

4.53 11.01 0.32 0.39 0.00 0.00 0.83 0.89 0.33 0.00 0.66 2.05 0.00 0.00 1.12 2.13 1.24 1.02 0.64 0.42 0.62 1.57 1.02 2.99 0.88 0.63 0.42 6.25 3.39 0.00 15.52 1.22 0.00 0.94 0.00 0.52 2.13 2.81 9.09 0.00 4.69 4.00 0.00 0.00 2.70 7.22 0.32 0.49 0.00 7.50 0.00 0.00 0.35 0.00 0.00 3.16 0.00 0.40 0.37 0.00 0.62 13.22 0.79 1.52 0.69 0.40 4.69 8.31 1.00 0.00 1.08 1.27

3.25 8.08 1.89 10.21 21.21 8.67 13.86 12.52 5.14 6.14 6.44 2.56 6.91 27.55 3.51 35.83 8.68 14.79 1.38 21.21 9.82 16.20 1.83 2.72 0.07 26.65 15.26 69.13 16.31 31.49 0.94 1.62 3.79 0.28 1.78 8.63 16.45 6.67 220.17 6.83 14.43 6.47 49.38 14.22 15.98 10.65 6.57 0.98 93.32 13.00 4.56 12.42 7.38 23.83 28.70 70.44 2.55 41.61 10.24 3.20 14.33 2.84 14.34 3.47 13.58 14.08 36.48 4.84 7.71 23.31 5.70 19.48

a ts ) test set, tr ) training set, v ) validation set; tr/v designate the training compounds added to the validation set to form a cross-validation set. b Absolute percent error % ) (|(logKow)EXP - (logKow)PRE|*100)/(|(logKow)EXP|) where subsripts EXP and PRE designate the experimental and predicted values, respectively.


YAFFE

ET AL.

Figure 3. Octanol/water partition coefficient results for the fuzzy ARTMAP QSPR.

Back-Propagation Neural Network System. The normalized logKow data and molecular descriptors, normalized from 0 to 1, were divided into training, validation, and test data sets. The test data set of 71 compounds (about15% of the complete data set) was identical to the fuzzy ARTMAP test set to enable direct comparison of the QSPRs derived from two different networks. A random selection of 259 compounds of the remaining 371 compounds (about 58% of the total data set) made up the training set. However, to maintain an adequate validation set, the training (259 compounds) and nontraining data sets (112 compounds) were combined. Model building with the back-propagation neural network proceeded with the same 12 input descriptors and logKow data set used for the fuzzy ARTMAP model. The architecture of the neural network was developed using a cascade method of network construction, together with a Kalman filtering learning rule.62 In the above approach, hidden nodes are added one or two at a time with new hidden units having connections from both the input buffer and previously established hidden nodes. Construction is stopped when the validation set shows no further performance improvement. The optimal back-propagation neural network/QSPR for logKow had a 12-11-1 architecture in which the hyperbolic tangent transfer functions were chosen to correlate weighted inputs and outputs of the hidden layer. The optimal neural network architecture was then validated and tested using two separate data subsets as described above. III. RESULTS AND DISCUSSION

The optimal fuzzy ARTMAP/QSPR for logKow was obtained (i.e. training phase) for vigilance parameters Fa ) 0, Fb ) 0.996, Fab ) 0.996, learning rate parameters βa )1, βb ) 1, and choice parameter R ) 0.0001. Τhe performances of the above model and the logKow QSPR resulting from

the 12-11-1 back-propagation neural network are described in Table 3 and Figures 3 and 4, with a summary of the error analysis provided in Tables 4 and 5. The performance of the fuzzy ARTMAP logKow QSPR for the complete data set of 442 compounds was with average absolute and maximum errors of 0.03 and 0.45 logKow units, respectively, and a corresponding standard deviation of 0.07 logKow units (see Table 4). The fuzzy ARTMAP/QSPR performance for the test data set was evaluated with a relaxed vigilance parameter setting of Fa ) 0.9, resulting in average and maximum absolute errors and standard deviation of 0.14, 0.45, and 0.13 logKow units, respectively. Although the performance of the logKow fuzzy ARTMAP/QSPR was excellent for the relatively heterogeneous compound data set, there were several compounds which were misclassified, thereby resulting in elevated logKow errors. It appears that while chemical input descriptors parameters can be similar for some chemicals (e.g., structural isomers), there may be a relatively large difference in their logKow values. For example, 2,2′,3,4,4′,5-hexachloro-1,1′-biphenyl (2,2′3,4,4′5PCB) with a logKow ) 6.69 was matched to the recognition category represented by 2,2′3,3′4,6-PCB with a logKow ) 6.24, resulting in an absolute error of 0.45 logKow units. Another example of misclassification is the placing of 3-methyl-1-butanol into a recognition category generated for 1-pentanol; both compounds are primary alcohols with molecular formula of C5H12O but with logKow values of 1.16 and 1.4, respectively. There were two cases for iodoethane and 2-octanone where high errors were observed since a suitable recognition category was not available. Iodoethane (logKow ) 2) was classified with bromoethane (logKow ) 1.6), and 2-octanone (logKow ) 2.76) was matched with 2-nonanone (logKow) 3.18), resulting in absolute errors of 0.4 and 0.42 logKow units, respectively. The above examples clearly suggest that further improvements of the accuracy of the logKow QSPR would require a data set that contains



Figure 4. Octanol/water partition coefficient results for back-propagation QSPR. Table 4. QSPR Performance for Octanol/Water Partition Coefficients (logKow): Fuzzy ARTMAP and Back-Propagation Neural Networks based Modelsa

data set

av absolute error no. of data points logKow %

max. absolute error SD logKow % logKow %

all data training test

442 371 71

Fuzzy ARTMAP 0.03 1.55 0.45 0.01 0.84 0.03 0.14 5.24 0.45

21 20 21

0.07 0.01 0.13

3.1 1.7 5.2

all data training validation test

442 259 371 71

Back-Propagation 0.27 18.0 2.2 0.26 17.6 1.3 0.27 19.5 2.2 0.23 9.4 0.59

827 291 827 96.4

0.23 0.22 0.24 0.16

45 28 49.1 12.0

a

Errors are expressed as logKow estimation errors.

a larger number of compounds per class and a refined set of molecular descriptors to allow greater ability to differentiate among complex or apparently very similar structures. The performance of the optimal 11-12-1 back-propagation/QSPR was inferior, relative to the fuzzy ARTMAP based model, with average and maximum errors and standard deviation for the training set of 0.26 logKow units (17.6%), 1.3 logKow units (290.9%), and 0.22 logKow units (28%), respectively. Performance of the back-propagation/QSPR for the validation set was with with average and maximum errors and standard deviation of 0.27 logKow units (19.5%), 2.2 logKow units (827%), and 0.24 logKow units (49%), respectively. Performance of the back-propagation/QSPR was also lower relative to the fuzzy ARTMAP, for the same test set, with average and maximum absolute errors and standard deviation of 0.23 logKow units (9.4%), 0.59 logKow units (96.4%), and 0.16 logKow units (12.0%), respectively. We note, however, that the average absolute error and standard deviation for both the present fuzzy ARTMAP and backpropagation QSPRs are lower than those reported for

Figure 5. Octanol/water partition coefficient estimates for PCBs at 298 K.

experimental octanol/water partition data, which are generally of the order of about 0.4 logKow units.4,5 The highest error was encounter for 1,4-dioxan (2.2 logKow or 827%), which was classified as an outlier for the backpropagation/QSPR model. Three other outliers for the above model include isopropylamine, pyrazine, and 2-propanol (logKow of -0.03, -0.22, and 0.05, respectively) with corresponding logKow errors of 0.08 (or 291%), 0.48 (or 220%), and 0.08 (or 179%), respectively. The above four outliers were among the 15 compounds in the data set (representing 3% of the total data set) with |logKow| values ranging from 0.03 to 0.27. It should also be noted that absolute percent errors were generally higher for compounds with |logKow| < 0.3. The logKow estimation performance of the present QSPR models for a broad spectrum of compounds was further evaluated by inspecting chemical group-specific errors as given in Table 5 and Figures 5-8. Although absolute logKow errors are commonly reported in the literature, such errors can be misleading since the actual percent error can be


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ET AL.

Table 5. Error Analysis Based on Chemical Class and Functional Groupa av absolute error

percent absolute error

chemical class and functional group

no. of compds

fuzzy ARTMAP

backpropagation

fuzzy ARTMAP

backpropagation

alkanes alkenes alkynes aromatics carboxcyclic acids aldehydes ketones alcohols ethers amines PCBs, PBrBsb halogenated nonaromatic halogenated aromatics nitriles nitro esters PAHsc phenols heterocyclic ring-nitrogen (e.g. pyridines) mercaptans (sulfure containing) furan (heterocyclic ring - oxygen)d halogenate phenols aromatic amines

27 24 6 23 12 8 22 23 9 29 21 59 41 8 9 15 25 25 11 16 3 12 11

0.01 0.03 0.01 0.05 0.01 0.01 0.06 0.02 0.01 0.01 0.08 0.03 0.04 0.01 0.01 0.03 0.03 0.05 0.01 0.02 0.00 0.05 0.01

0.35 0.33 0.16 0.23 0.31 0.17 0.25 0.20 0.24 0.16 0.25 0.27 0.38 0.12 0.15 0.30 0.27 0.27 0.24 0.23 0.26 0.28 0.26

0.42 1.04 0.87 1.26 1.01 1.42 3.23 2.98 3.01 1.09 1.42 1.82 1.38 2.96 0.45 1.53 0.67 2.10 1.92 0.75 0.25 2.11 0.58

11.23 12.45 8.71 7.29 23.09 19.50 21.55 32.88 22.04 25.77 4.31 15.36 11.59 18.84 27.34 23.10 6.63 12.93 37.46 10.29 22.93 11.53 12.06

a Errors are reported as logK b c ow estimation errors averaged for each listed chemical group. PBrBs are polybromobiphenyls. Group contains some halogenated PAHs. d 1,4-Dioxan was declared an outliner and therefore was not included in this analysis.

Figure 6. Octanol/water partition coefficient estimates for thiols at 298 K.

Figure 7. Octanol/water partition coefficient estimates for amines at 298 K.

significant even for a seemingly low absolute logKow error if, for example, the logKow values for such compounds are small. Conversely, a reported high absolute logKow error can

Figure 8. Octanol/water partition coefficient estimates for halogens at 298 K.

also be misleading if it pertains to a range of high logKow values. Therefore, to present a more balanced evaluation of the model performance for the 24 chemical groups in the complete data set, both the average |logKow| error along with the absolute percent logKow error are presented in Table 5. For the present QSPR models, the absolute average and percent logKow errors for the different chemical groups varied by factors ranging from about 3.1-5 and 8.7-12%, respectively. The ranges for the average absolute and percent logKow errors for the fuzzy ARTMAP/QSPR were 0.0-0.8 logKow units and 0.25-3.23%, respectively. The average absolute and percent logKow errors for the back-propagation QSPR, for the different chemical groups, ranged from 0.12 to 0.38 logKow units and 4.31 to 37.46%, respectively. Inspection of Table 5 confirms that errors for the different chemical groups are of similar order for each respective model. Superior performance (in terms of absolute percent logKow error) of the back-propagation model was obtained for PCBs, PAHs, aromatics, and alkynes, relative to the other



Table 6. Comparison of the Present QSPRS with Other Published QSPRs comparison with present study fuzzy ARTMAP

study

approach

no. of compds in study

no. of common data pointsa

av absolute errorb

1663

274

219

205

6675

111

202

91

0.18 (14.05) 0.31 (18.71) 0.29 (31.53) 0.18 (25.54) 0.19 (3.52) 0.17 (3.21) 0.37 (23.9)

Klopmann et al. (1994)

group contribution

Basak et al. (1996)

linear regression QSPR

Gombar and Enslein (1996) Eisfeld and Maurer (1999)

multiple linear regression QSPR linear regression QSPR

Sblijic et al. (1993)


31

15

Kamlet et al. (1988)


102

22

Huuskonen et al. (2000)

neural network QSPR

1870

12

back-propagation

absolute SDb

av absolute errorb

absolute SD

av absolute errorb

absolute SD

0.21 (34.58) 0.39 (66.35) 0.53 (66.3) 0.13 (58.28) 0.21 (3.19) 0.23 (3.18) 0.29 (22.3)

0.027 (1.52) 0.03 (1.23) 0.03 (1.31) 0.02 (1.7) 0.04 (1.05) 0.021 (0.41) 0.019 (1.01)

0.03 (1.23) 0.06 (2.35) 0.06 (2.58) 0.04 (3.65) 0.07 (1.82) 0.03 (0.58) 0.024 (1.26)

0.25 (17.86) 0.25 (15.67) 0.25 (19.85) 0.25 (22.25) 0.30 (6.97) 0.28 (5.86) 0.29 (20.9)

0.2 (28) 0.19 (28.33) 0.19 (37.08) 0.19 (27.4) 0.23 (5.35) 0.22 (4.44) 0.22 (19.9)

a Number of compounds common with the present study. b Absolute errors and standard deviation are given in terms of logK ow units. The corresponding percent absolute logKow error and standard deviation are enclosed in parentheses.

groups (

Fuzzy ARTMAP and Back-Propagation Neural Networks Based

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