Environ. Sci. Technol. 1991, 25, 1753-1760
Linear Solvation Energy Relationships: “Rules of Thumb” for Estimation of Variable Values James P. Hickey” and Dora R. Passino-Reader
National Fisheries Research Center-Great Ann Arbor, Michigan 48105
Lakes, US. Fish and Wildlife Service, 145 1 Green Road,
For the linear solvation energy relationship (LSER),
values are listed for each of the variables (Vi/lOO,a*,P,, a,) for fundamental organic structures and functional groups. We give the guidelines to estimate LSER variable values quickly for a vast array of possible organic compounds such as those found in the environment. The difficulty in generating these variables has greatly discouraged the application of this quantitative structureactivity relationship (QSAR) method. This paper presents the first compilation of molecular functional group values together with a utilitarian set of the LSER variable estimation rules. The availability of these variable values and rules should facilitate widespread application of LSER for hazard evaluation of environmental contaminants. Introduction
Natural resource agencies, regulatory agencies, and chemical manufacturers must evaluate properties of chemicals that are either present in the environment or have the potential to be released into the environment. The everyday use of 70 000 synthetic chemicals indicates the enormity of the problem ( I ) . No toxicity data are available for about 80% of these chemicals ( I ) . The cost of testing the thousands of new chemicals either proposed for synthesis or detected in the environment is prohibitive. Consequently, researchers and managers increasingly depend on predictive models, i.e., quantitative structureactivity relationships (QSAR), for predicting chemical properties, screening chemicals for hazardous properties, and providing information to set priorities in research and development. The Kamlet-Taft linear solvation energy relationship (LSER) model is recognized as a powerful predictive QSAR model (2). Kamlet and co-workers demonstrated that many types of chemical properties (designated by XYZ) depend on solute-solvent interactions (3-8). Aqueous solubility (9,l o ) ,octanol-water partition (II-13), solubility in and partition between blood and body organs (14-17), HPLC capacity factors using a number of mobile and stationary phases (16-18), and toxicity to a variety of species (19-23) can be predicted by equations of the generalized linear solvation energy relationships. We have successfully applied the LSER model in developing predictive equations for toxicity of a wide range of environmental chemicals to Photobacterium phosphoreum (the Microtox test), Daphnia Pulex, Daphnia magna, and the fathead minnow (Pimephales promelas, ref 24 and unpublished data). These regression equations were consistently more accurate in their predictions than other widely used QSAR models such as log KO,(14-21). The equations contain three simple and conceptually explicit types of terms XYZ(property1 = cavity term + dipolar term + hydrogen-bonding terms (1) In the LSER model (3-8) chemical properties (as XYZ) are related to molecular structure through the energy re-
quired to surround a solute with solvent molecules (water or biosystem medium) and the energies gained or lost through formation of electrostatic and hydrogen bonds between the chemical and the medium to stabilize this solvent molecule cavity and keep the compound inside it. Chemical properties dependent on this solute-solvent interaction are the result of the contributions from the component groups that form the molecule. The energy terms for the component groups then make up the four energy terms for the molecule used in predictive equations: XYZ = XYZ,
+ mVi/lOO + sa* + bp, + aa,
(2)
The endoergic energy term mVi/lOO represents the free energy required to separate the solvent molecules and provide a suitably configured cavity for the contaminant molecule. Vi/lOO is the intrinsic (van der Waals) molecular volume scaled by a factor of 100 for magnitudes that are comparable to the other three variables. The dipolarpolarizability term, sa*,represents the (typically) exoergic effects of solutesolvent dipole-dipole and dipole-induced dipole interactions and P* is a measure of the molecule’s ability to stabilize a neighboring charge or dipole through nonspecific dielectric interactions. The hydrogen-bonding terms bp and aa represent the exoergic effects of hydrogen bonding involving the solvent as hydrogen bond donor acid (HBD) and the solute as hydrogen bond acceptor base P, (HBA) and the solute as hydrogen bond donor acid and the solvent as hydrogen bond acceptor base a,. In practice, all four energy terms are used without units. The absence of readily available methods to calculate the LSER variables has been noted (e.g., see ref 2), and has thwarted general application of this method to other species until now. To date, few guidelines have been published for the estimation of these variables (8-12) but many tables of values exist (3-24). The purpose of this paper is to present the first general set of rules for the estimation of LSER parameters and an extensive listing of molecular functional group values for rapid estimation of Kamlet’s four main solvatochromic parameters. Formulation Guidelines for LSER Variables ( Vi/lOO, R*,
0,01)
This section contains the general computation rules for the estimation of the LSER variables, which are used with the current LSER variable contributions for typical molecular structures and functional groups in Tables I and 11. Some of the estimation rules have been reported in recent papers (8-12), and a few of the functional group contributions are scattered throughout the LSER literature (3-24). Most computation guidelines presented here were deduced and most functional group values were either extrapolated or surmised from values for analogous compounds in the literature (3-24). The variables a*,p, and a in eq 2 are solvatochromic parameters, so named because these parameters were originally determined from UV/ visible spectral solvatochromic shifts. Some values for /3 and a have been adjusted to reflect experimental values
Not subject to U.S. Copyright. Published 1991 by the American Chemical Society
Environ. Sci. Technoi., Vol. 25, No. 10, 1991
1753
McGowan (32),is easily calculated with atomic volumes and accounting for the number of bonds. The characteristic atomic volumes V, in cm3/mol are
Table I. Basic Compound Values for LSER Variables (%/loo, r*, 8, a) variables compound n-butane n-pentane 2-methylbutane n-hexane 2-methylpentane n-heptane 2-methylhexane n-octane 2-methylheptane 2,2,4-trimethylpentane
VJ100
P
(Y
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
0.310 0.450 0.500 0.598 0.690 0.815 0.884 0.982 0.249 0.455 0.553 0.508 0.460 0.431 0.556 0.509
4.02 4.01 0.00 0.00 0.00 0.00 0.02 0.02 0.56 0.58 0.51 0.55 0.14 0.27 0.17 0.44
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.50 0.51 0.50 0.41 0.70 0.54 0.70 0.27
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
Aromatic 0.491 0.784 0.883 0.920 0.753 0.753 0.960 1.015 1.015 0.370 1.581 1.616 0.428 0.401 0.472 0.440 0.487 0.445
0.59 0.52 0.50 1.20 0.70 0.90 1.18 0.81 0.81 0.40 0.60 0.45 0.74 0.87 0.87 0.87 0.35 0.70
0.14 0.14 0.14 0.28 0.20 0.35 0.25 0.20 0.20 0.35 0.30 0.60 0.69 0.64 0.43 0.64 0.54 0.25
0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.41 0.41 0.00 0.00 0.00
Aliphatic 0.455 0.553 0.543 0.648 0.638 0.745 0.735 0.842 0.832 0.812
cyclopropane cyclobutane cyclopentane cyclohexane cycloheptane cyclooctane trans-octahydro- lH-indene decahydronaphthalene ethylene oxide tetrahydrofuran tetrahydropyran 1,4-dioxane pyrrolidine imidazolidine piperidine tetrahydrothiophene benzene indan tetrahydronaphthalene biphenyl naphthalene azulene 9H-fluorene anthracene phenanthrene furan dibenzofuran dibenzo-p-dioxin pyrrole imidazole pyridine pyrimidine diazine thiophene
T*
0.00
measured by Abraham and co-workers (25-28). The values for substituents reflect their use in an aliphatic, aromatic, or nonspecific system. Throughout this section, elements in upper case refer to aliphatic systems and elements in lower case refer to aromatic systems (e.g., “C” vs “c”, and “N” vs “n”). LSER Parameters. (1) Volume ( V , or V,)/lOO. The volume term--, Vi,or V , (29--32)-has several available conventions. The solute intrinsic (van der Waals) molar volume, which is Viin eq 2, can be computer generated by the methods of Leahy (29) or Pearlman (30) or estimated by simple additivity methods like those of Bondi (31) or Abraham and McGowan (32). We use the convention Vibased on Leahy’s computer-calculated intrinsic volume (29). Contributions to Vi/lOO offered in this guidelines section and Tables I and I1 for all fundamental structures are based on extrapolations from the many data tables in the literature (3-24). The volume contributions are strictly additive for the volume of the whole molecule. The rules for computation of V , are also included here and also must be scaled by 1/100. An acceptable alternative, the characteristic volume V , of Abraham and 1754
Environ. Scl. Technol., Vol. 25,No. 10, 1991
C si Ge Sn
16.35 26.83 31.02 39.35
N P
14.39 24.87 As 29.42 S b 37.74
0
12.43 22.91 Se 27.81 Te 36.14
S
F C1 Br I
10.48 20.95 26.21 34.53
H 8.71 B 18.32
The total atomic volume is calculated, and 6.56 cm3/mol is subtracted for both single and multiple bonds between atoms. A multiple bond (olefin or alkyne) is treated as one bond; the unsaturation is accounted for by subtracting the number of bonds from the total volume. The two volumes are entirely equivalent and related through the equation (32)
V i= 0.597 + 0.6823 V ,
(r2 = 0.998)
By way of example, for benzoic acid for V, C
C
0 H
6X 1X 2X 6X
16.35 = 16.35 = 12.43 = 8.71 =
-bonds 15 x 6.56 =
98.10 16.35 24.86 52.26 191.57 -98.40 93.17
for Vi/lOO phenyl CGH, 0.491 aromatic C(=O)OH 90.640 Vi = 0.640 X 100 = 64.00
and
Vi = 0.597 + 0.6823 V, = 0.597 + 0.6823 (93.17) = 64-17 (2) Dipolarity-Polarization ( T * ) . The a* parameter represents solute dipolarity or polarizability. For select compounds, viz., compounds with a single dominant bond dipole moment, a* values are very nearly equivalent to molecular dipole moments (8,21). For compounds with a known dipole moment ( P ) , a* can be estimated by (10, 21) the following: a* = 0.03 + 0 . 2 3 ~for nonpolyhalogenated aliphatics, a* = 0.27 + 0 . 3 5 ~for polyhalogenated aliphatics, and a* = 0.56 + 0 . 1 1 for ~ aromatic compounds. A correction factor occasionally used with a* is the Hildebrand solubility parameter 6 in the expression (sa* + d6). Certain classes of compounds have specific values for 6 (refs 4,8, and 13 and references therein). For aromatic systems, 6 = 1.00 for a phenyl ring (e.g., benzene, biphenyl, fluorene) and 1.00 for a PAH system (naphthalene, phenanthrene, etc.). In aliphatic systems, 6 = 0.00 for nonpolyhalogenated aliphatics, otherwise 6 = 0.5O/Cl, Br, or I and 0.25/F. The value for the coefficient d is determined during the multiple linear regression analysis. The value for d is generally a t or near 0.00 for systems with a* near maximum (highly polar), and around -0.40 for systems having a* near minimum net polarizability (nonpolar). (3) Hydrogen Bond Acceptor Basicity (0). The p, parameter represents HBA basicity, i.e., the ability to accept a proton in a solute-solvent hydrogen bond. The subscript m indicates that, for compounds that are capable of self-association (amphiprotic hydrogen-bonding compounds), the parameter applies to the monomeric solute, rather than the self-associated oligomeric solvent. For compounds that are not capable of self-association, p, = p (subject to some conditions set forth in the parameter estimation rules; see refs 8-12). Contributions from each component are added for the whole molecule.
+
The correction factor {is infrequently used in (bo e{) as a coordinate covalency functional group parameter and is dependent on electronegativity and other factors that act on HBA base electron lone pair(s). The parameter has specific values for certain functional groups (adapted from refs 4, 8, 12, 33): 5
Vi/100 2 cyclopentane rings
0.20 0.00
P-0
0.00 0.00 0.20 1.00 0.60 0.10
S=O N=O 0
C=O
phosphine oxides aldehydes, ketones, acids, acid halides and anhydrides, amides, carbamates, ureas sulfoxide, sulfone, sulfate amine N-oxide, nitroso, nitro water, alcohol, ether sp3 amines sp2 amines, pyridines sp amines
The value for the coefficient e is set during the multiple linear regression analysis. (4) Hydrogen Bond Donor Acidity (a).The a, parameter represents HBD acidity, the ability to donate a proton in a solute-solvent hydrogen bond. As with p, (vide supra), the subscript m indicates that the parameter applies to the monomeric solute, and generally, a , = a. Contributions from each component are added for the whole molecule. Structural Considerations
Acyclic (Nonring) Systems. For straight or branched chains and units attached to aliphatic rings, sum the values for each segment, including substituents, with the values in Tables I and I1 (adapted from ref 12). For groups directly attached to an aromatic ring, see Substituent Addition below. Rings. Ring structures are divided into aliphatic, aromatic, and multiple and condensed ring systems, and substituent addition is treated as described below. (1) Aliphatic. To form an aliphatic ring from a chain, determine Vi/lOO for the chain and then add Vi/lOO = -0.050 and a* = 0.06. To expand (or contract) an aliphatic ring, add (or subtract) Vi/lOO = 0.095/CH2 group. Aliphatic ring systems with simple double or triple bonds are treated as saturated systems, and each multiple bond unit is treated as a separate substituent (see Table 11). Contributions for all substituent groups are summed with the values for the aliphatic rings. (2) Aromatic. An aromatic ring is treated as a complete unit, and benzene is the basic structure (see Table I). To form an aromatic ring from an aliphatic ring (where possible), add Vi/lOO = -0.107, a* = 0.59, and p = 0.10. When necessary, adjust substituent contributions to reflect the new environment (see Table 11). (3) Multiple and Condensed Ring Systems. To form multiple ring systems such as bicyclohexyl or biphenyl, add contributions from both ring systems for all parameters unless otherwise dictated by the specific system and subtract VJ100 = 0.128 for each aliphatic ring-ring junction, and VJ100 = 0.062 for each aromatic ring-ring junction. No provision is made to account for extended delocalization in aromatic systems. For each aromatiealiphatic ring junction, subtract Vi/100 = 0.095. To extend an aliphatic fused-ring system, add contributions for each ring system and subtract Vi/lOO = 0.107 and ?r* = 0.01 for each shared carbon atom. For shared carbon atoms in an aromatic-aliphatic ring fusion, subtract V,/lOO = 0.103 for each shared carbon. As an example, for octahydropentalene
0.00
0.00 0.00 0.00 0.00
0.00 0.00 0.00 0.00
0.00
0.00 -0.01 -0.01
-0.107 -0.107 0.786
functional group
a 0.00
0.00
1.000
-2 “shared” C
P 0.00 0.00
x*
0.500 0.500
-0.02
To increase a polynuclear aromatic ring system, add the variable contributions VJ100 = 0.262, a* = 0.11, and p = 0.05 for each additional ring to the values for phenanthrene or anthracene in Table I. Sum any substituent contributions from Table I1 for each ring system. Alternatively, sum the parameter values for each ring system and account for duplicated volume contributions by subtracting Vi/ 100 = 0.1145/redundant carbon and add for a* = 0.59 (first ring) and then O.ll/ring, and for p = 0.14 (first ring), 0.06 (second ring), 0.00 (third ring), and 0.05/all subsequent rings. For example, for benz[a]anthracene anthracene next ring
Vi/lOO
7r*
P
a
1.015 0.262 1.277
0.81 0.11 0.92
0.20 0.05 0.25
0.00 0.00 0.00
Alternatively 4 benzene rings
-8 shared carbons
Vi/10O
x*
P
0.491 0.491 0.491 0.491 1.964 -0.687 1.277
0.59 0.11 0.11 0.11 0.92 0.00 0.92
0.14 0.06 0.00 0.05 0.25 0.00 0.25
CY
0.00 0.00 0.00 0.00
0.00 0.00 0.00
Substituent Addition. The methods for substituent addition are adapted from ref 12. For alkyl and aryl groups on aromatic ring systems, calculate the values for the LSER variables for the ring system (Table I) and the substituents/side chains (Table 11) separately. For multiple ring and polynuclear aromatic derivatives, determine the substituent variable values for each ring separately and then sum the results. The hydrocarbon skeletal values are in Table I (expanded from ref 12). A convention exists for computation of halogen contributions to a* and /3 for polyhalogenated aromatic compounds. Values for Vi/lOO and a are determined by summation. For Vi/lOO add 0.030/F, 0.09O/Cl,O.l31/Br, and 0.181/1. The convention for a* and p depends on the aromatic system. The halide contributions are summed over successive substitutions and depend on the position on the ring. For substituted benzenes, biphenyls, and PAHs 7r*
substitution pattern first X / r h g next X/ring third X/ring fourth X/ring fifth X/ring sixth X/ring
(any position) 2,3 or 4,5 2,(4 or 6) or 3,5 2,5 2,3,4 or 3,4,5 2,(3 or 4),5 2,485 2,3,4,5 or 2,3,5,6 2,3,4,5,6 (1,2,3,4,5,6)
P
F,Cl/Br,I
F,Cl/Br,I
0.10/0.15 0.10/0.15 0.05/0.10 -0.05/-0.10 0.05/0.10 -0.05/-0.15 0.00/0.10 -0).05/-0.15 -0.05/-0.15 -0.05/-0.15
-0.03/-0.04 -0.04/-0.05 -0.03/-0.04 0.00 0.00 0.00
The numbering scheme assumes substitution by some other group in the 1-position (e.g., the other ring in biphenyl). In addition, to calculate a* and p for biphenyl Envlron. Sci. Technol., Voi. 25, No. 10, 1991
1755
Table 11. Functional Group Values for LSER Variables (V,/lOO,
T*,
j3, a),*
variables functional group ion pair (+,-) unsaturation
VJ100
Y*
0.50
p
variables a
aliph/arom
0.000
0.50 0.00
olefin alkyne -C=CCH, CH3, CHp, CH, and
aliph/arom aliph/arom aliph/arom C substituents
-0.026 -0.036 0.315
prim, sec tert, quat 1-3 CH3 4-6 CH3 1-3 CHp 4-6 CHZ subsequent carbons
aliph 0.098 0.00 0.00 0.00 aliph 0.088 0.00 0.00 0.00 arom 0.098 -0.04 0.01 0.00 arom 0.098 -0.04 0.02 0.00 arom 0.098 -0.02 0.01 0.00 arom 0.098 -0.02 0.02 0.00 in a chain use aliphatic values (vide supra)
0.10 0.10 0.05 0.20 0.20 0.13 0.20 0.17 0.13
substituent groups aliph/arom aliph/arom aliph arom on pyr aliph/arom CF, (trifluoromethyl) on pyr C1 (chloride) aliph arom b on pyr CHPCl aliph (chloromethyl) arom CC13 aliph (trichloromethyl) arom on pyr Br (bromide) aliph arom b on pyr CHzBr aliph (bromomethyl) arom aliph CBr3 (tribromome thyl) arom on pyr I (iodide) aliph arom b on pyr OH (hydroxy) aliph b, on a ring arom phenol OH ortho to NO2 OH meta to NOp OH para to NOz aliph CHzOH (hydroxymethyl) arom 0 (ether) aliph b, as ROMe b, in a ring arom b, as PhO C(=O) (ketone) aliph b b, as MeC(=O) b, in a ring arom b, as MeC(=O) b, as PhC(=O) HC(=O)H aliph C(=O)H (aldehyde) b arom HC(=O)OH aliphjarom OC(=O)H (formate) CBHF, (phenyl) CPh3 (trityl) F (fluoride)
1756
0.491 1.485 0.030 0.030 0.030 0.188 0.188 0.090 0.090 0.090 0.090 0.188 0.188 0.368 0.368 0.368 0.131 0.131 0.131 0.131 0.257 0.257 0.491 0.491 0.491 0.181 0.181 0.181 0.181 0.045 0.045 0.045 0.536 0.676 0.676 0.676 0.143 0.143 0.045 0.143 0.045 0.045 0.443 0.098 0.098 0.200 0.098 0.098 0.138 0.589 0.140 0.115 0.115 0.115 0.224 0.225
0.59 1.45 0.08 0.03 0.04 0.25 0.25 0.35 0.12 0.05 0.04 0.35 0.35 0.35 0.35 0.35 0.43 0.20 0.04 0.04 0.38 0.05 0.40 0.40 0.40 0.45 0.22 0.04 0.04 0.40 0.45 0.13 0.72 1.11 1.16 1.21 0.40 0.25 0.27 0.13 0.54 0.10 0.66 0.67 0.30 0.35 0.76 0.39 0.13 0.59 0.69 0.65 0.33 0.33 0.65 0.62
Environ. Sci. Technol., Vol. 25, No. 10, 1991
0.14 0.40 0.19 -0.05 0.09 -0.25 -0.25 0.15 -0.04 -0.05 0.09 -0.05 -0.04 -0.15 -0.10 -0.10 0.17 -0.08 -0.04 0.07 0.05 -0.05 -0.10 -0.10 -0.10 0.18 0.02 -0.04 0.05 0.47 0.51 0.23 0.33 0.50 0.50 0.53 0.47 0.30 0.45 0.22 0.51 0.22 0.23 0.48 0.35 0.48 0.52 0.39 0.12 0.20 0.43 0.41 0.33 0.42 0.38 0.37
0.00 0.00 0.06 0.08 0.00 0.15 0.15 0.06 0.00 0.00 0.00 0.03 0.05 0.15 0.15 0.10 0.05 0.10 0.00 0.07 0.00 0.00 0.12 0.15 0.10 0.04 0.10 0.00 0.05 0.33 0.31 0.60 0.60 0.12 0.80 0.90 0.33 0.45 0.00 0.00 0.00 0.06 0.06 0.00 0.00 0.00 0.00 0.06 0.12 0.12 0.00 0.00 0.00 0.00 0.65 0.00
functional group C(=O)OH (acid) C (=O)O-Na' C(=O)O(ester) (lactone)
oc(=O) 0-
OC(=O)OH HOC(=O)OH SH (mercapto)
S (sulfide) SS (disulfide) S(=O) (sulfoxide) S(=O), (sulfone)
s(=o)zoS03H (sulfate) S(=O)zO-Na+ HC(=O)SH C(=O)SH (thioacid) OC(=O)SH OC(=O)SHSC(=O)SH SC(=O)SH sc(=O) sSC (=O) H (thioformate) -C(=O)S(thioester) SC(=O)OH HSC(=O)OH NHp (primary amine) NH (secondary amine) N (tertiary amine) C(=O)NH, (amide) C(=O)NH(lactam)
C(=S)NHC(=O) N < (lactam)
HC(=O)NHp (formamide) HNC(=O)H >NC(=O)H HzNC(=O)OH (carbamic acid) H,NC(=O)SH (thiocarbamic acid) OC(=O)NHp SC(=O)NHz HNC(=O)OH HNC(=O)SH OC(=O)NHOC(=S)NHHNC(=O)SSC(=S)NH>NC(=O)OH
aliph arom aliph/arom aliph b, on a ring b, in a ring or add to cyclic ether arom as an o-phthalate aliph/arom aliph/arom aliph arom aliph/ arom aliph/ arom aliph arom aliph arom aliph/arom aliph/arom aliph/arom aliph/arom aliph/ arom aliph/arom aliph/arom aliph/arom aliph/arom aliph/ arom aliph/arom aliph arom aliph arom aliph arom aliph arom aliph b, in a ring or add to cyclic amine arom aliph arom aliph b , in a ring or add to cyclic amine arom aliph/arom aliph/arom
V,/lOO
TT*
p
1y
0.139 0.149 0.189 0.139 0.139 0.139 0.019
0.60 0.15 0.65 0.55 0.55 0.68 0.14
0.45 0.30 0.80 0.45 0.49 0.51 0.00
0.55 0.59 0.00 0.12 0.12 0.12 0.12
0.139 0.683 0.185 0.185 0.185 0.117 0.117 0.117 0.234 0.150 0.154 0.170 0.174 0.221 0.266 0.306 0.294 0.294 0.339 0.339 0.374 0.374 0.374 0.294 0.294 0.339 0.339 0.080 0.080 0.080 0.080 0.080 0.080 0.185 0.185 0.183 0.183 0.022
0.17 0.68 0.45 0.55 0.45 0.35 0.35 0.36 0.58 1.00 1.00 1.00 1.00 0.85 1.00 1.50 0.55 0.55 0.45 0.42 0.35 0.45 0.35 0.55 0.50 0.35 0.40 0.32 0.13 0.25 0.13 0.15 0.13 0.95 0.35 0.85 0.72 0.55
0.29 0.76 0.38 0.48 0.60 0.16 0.02 0.28 0.10 0.78 0.62 0.48 0.42 0.60 0.76 1.26 0.25 0.25 0.35 0.30 0.45 0.38 0.33 0.30 0.30 0.38 0.52 0.69 0.38 0.70 0.30 0.65 0.73 0.74 0.65 0.74 0.70 0.00
0.12 0.12 0.12 0.55 0.65 0.03 0.23 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.75 0.00 0.05 0.05 0.15 0.14 0.10 0.05 0.00 0.00 0.00 0.50 0.65 0.00 0.26 0.00 0.17 0.00 0.00 0.56 0.49 0.25 0.28 0.28
0.183 0.225 0.225 0.183 0.183 0.022
0.30 0.65 0.65 0.76 0.74 0.55
0.65 0.52 0.48 0.66 0.80 0.00
0.30 0.31 0.44 0.00 0.00 0.00
0.185 0.35 0.65 0.00 0.185 0.95 0.65 0.49 0.185 0.91 0.67 0.25 0.185 0.80 0.66 0.00 0.202 0.80 0.80 0.85 0.312 0.53 0.65 0.53
aliph/arom aliph/arom aliph/arom aliph/arom aliph arom aliph/ arom aliph/ arom aliph/arom aliph/ arom
0.202 0.312 0.202 0.312 0.202 0.202 0.270 0.312 0.312 0.202
0.48 0.52 0.78 0.50 0.76 0.76 0.56 0.50 0.53 0.76
0.78 0.65 0.82 0.63 0.62 0.57 0.42 0.63 0.40 0.84
0.55 0.38 0.70 0.23 0.36 0.36 0.36 0.19 0.39 0.60
Table I1 (Continued) variables
variables functional group
>NC (=O)SH >NC(=O)O>NC(=O)SH2NC(=O)NH2 (urea) HNC(=O)NH, >NC(=O)NH, HNC(=O)NH-HNC (=S)NH->NC(=O)NH->NC(=O)N< N=C< (imine) >C=NOH (oxime) N=C=S (thiocyanate) NHNHz NHNH>NNHz >NNH>NN< N=N (azo) NHOH NHO>NO>NOH N=O (nitroso) NOp (nitro)
aliph/arom aliph/arom aliph/ arom aliph/arom aliph/ arom aliph/arom aliph/arom aliph/arom aliph/arom aliph/arom aliph/arom aliph/arom aliph arom aliph arom aliph arom aliph arom aliph arom aliph/arom aliph arom aliph arom aliph arom aliph arom aliph arom aliph b arom
VJ100
a*
p
a
0.312 0.228 0.312 0.265 0.265 0.265 0.265 0.307 0.265 0.265 0.152 0.197 0.278 0.150 0.138 0.150 0.138 0.150 0.138 0.150 0.138 0.150 0.138 0.125 0.130 0.130 0.130 0.120 0.128 0.116 0.130 0.116 0.100 0.100 0.140 0.140 0.140
0.48 0.75 0.48 0.90 0.89 0.88 0.87 0.67 0.85 0.83 0.30 0.55 0.63 0.75 0.55 0.60 0.45 0.65 0.65 0.50 0.33 0.30 0.30 0.15 0.56 0.26 0.52 0.35 0.35 0.35 0.35 0.35 0.50 0.45 0.79 0.35 0.42
0.62 0.65 0.60 0.74 0.75 0.77 0.77 0.55 0.78 0.74 0.75 0.45 0.22 0.90 0.90 0.85 0.85 0.90 0.90 0.85 0.85 0.80 0.75 0.15 0.93 0.83 0.90 0.80 0.90 0.70 0.90 0.70 0.15 0.10 0.25 0.20 0.20
0.05 0.00 0.00 0.76 0.65 0.38 0.38 0.38 0.19 0.00 0.00 0.32 0.00 0.15 0.45 0.05 0.35 0.15 0.20 0.00 0.17 0.00 0.00 0.00 0.26 0.46 0.05 0.22 0.05 0.05 0.14 0.14 0.00 0.00 0.12 0.00 0.16
V,/lOO
A*
p
a
aliph arom aliph arom aliph arom aliph arom aliph arom on Pyr
0.140 0.200 0.188 0.200 0.188 0.198 0.178 0.198 0.178 0.100 0.099 0.099
0.10 0.65 0.55 0.60 0.45 0.45 0.40 0.45 0.45 0.65 0.20 0.20
0.25 0.80 0.60 0.75 0.55 0.85 0.45 0.70 0.50 0.44 0.37 0.37
0.16 0.10 0.25 0.00 0.17 0.00 0.00 0.05 0.05 0.22 0.22 0.20
aliph arom aliph arom aliph/arom
0.160 0.160 0.195 0.195 0.237
0.30 0.30 0.90 0.90 0.75
0.65 0.75 1.05 0.92 0.47
0.00 0.00 0.00 0.00 0.00
aliph arom aliph arom aliph/arom
0.295 0.295 0.270 0.270 0.459
0.45 0.45 0.75 0.75 0.55
0.72 0.50 0.75 0.55 1.02
0.00 0.00 0.00 0.00 0.00
aliph
0.315
0.65 0.77 0.00
arom aliph arom
0.315 0.387 0.387
0.65 0.62 0.00 0.60 0.38 0.00 0.60 0.92 0.00
aliph arom aliph arom
0.208 0.00 0.00 0.00 0.188 0.00 0.00 0.00 0.240 0.10 0.05 0.00 0.220 0.10 0.05 0.00
functional group
b NHSH NHS-
>NS>NSH C=N (nitrile)
phoshorus R3P (phosphine) R3P=0 (phosphine oxide) R,P=S (phosphine sulfide) P(0-), (phosphite) P(=O)R(O-)Z (phosphonate) P(=S)R(O-)2 (thiophosphonate) P(=O)(O-), (phosphate)
P(=S)(O-)3 (thiophosphate) miscellaneous inorganics organosilane organotin
Aliphatic (aliph), aromatic (arm), and aliphatic/aromatic (aliph/arom) indicate when values apply. *With other groups. pyr, pyridine.
and fluorene, sum both ring totals and subtract 0.8 from the result for T * , For naphthalene, biphenylene, and higher PAHs, use analogous benzene positions and substitution guidelines and sum contribution totals for each ring. A good rule of thumb is to add 0.05 to T* if the next substitution increases the dipole moment and to subtract 0.05 if the dipole would decrease. For example, for pentachlorophenol Vj/lOO A* P a phenol chlorines
2 3 4 5 6
0.72 0.10 0.10 0.05 -0.05 -0.05 0.87
0.33 -0.03 -0.04 -0.03 0.00 0.00 0.23
0.60 0.00 0.00 0.00 0.00 0.00 0.60
Vi/lOO
a*
B
a
0.920 0.090 0.090 0.090 0.090 0.090
1.20 0.10 0.10 0.05 0.10 0.10 -0.80 0.85
0.28 -0.03 -0.04 -0.03 -0.03 -0.04
0.00 0.00 0.00 0.00 0.00 0.00
0.11
0.00
0.536 0.090 0.090 0.090 0.090 0.090 0.986
and for 3,4,5,3’,4’-biphenyl biphenyl chlorines
from
3 4 5 3’ 4’
A*
1.370
For polyhalogenated dibenzofurans, the substitution hierarchy on each ring proceeds from the most reactive to
Table 111. Replacement Values for LSER Variables (vJ100,r*, 8, a ) a variables
desired change C to N c to n N ton c to 0 c to s C to Si OH to NH2 NH2 to OH
aliph arom aliph to airom aliph aliph aliph arom arom
Vi/lOO
A*
p
(Y
-0.019 -0.021 0.00 -0.045 0.190 0.110 0.035 -0.035
0.00 0.28 0.14 0.00 0.44 0.00 0.00 0.00
0.00 0.34 0.00 0.00 0.27 0.00 0.15 -0.15
0.00 0.00 0.00 0.00 0.00 0.00 -0.34 0.34
Aliphatic (aliph), aromatic (arom), and aliphatic/aromatic (aliph/arom) indicate when values apply.
the least reactive position (3, 7 2 2, 8 > 4,6 I1,9). The variable contributions are determined by ring A* P first X/ring
next X/ring third X/ring fourth X/ring
positions
F,Cl/Br,I
F,Cl/Br,I
3 or 7 2 or 8 4 or 6 1 or 9 2 or 8 4 or 6 1 or 9 4 or 6 1 or 9 1 or 9
0.15/0.20 0.10/0.20 0.05/0.10 -0.05/-0.10 0.10/0.20 0.05/0.10 -0.05/-0.15 0.05/0.10 -0.05/-0.15 0.00/-0.15
-0.03/-0.04
-0.03/-0.04 -0.03/-0.04 0.00
For example, for 1,3-difluoro-6,8-dibromodibenzofuran Environ. Sci. Technol., Vol. 25, No. IO, 1991 1757
dibenzofuran fluorines bromines
1 3 6 8
V,/lOO
7r*
P
a
1.581 0.030 0.030 0.131 0.131
0.60 -0.05 0.15 0.10 0.20 1.00
0.30 -0.03 -0.03 -0.04 -0.04 0.16
0.00 0.00 0.00 0.00 0.00
1.903
0.00
For polyhalogenated dibenzo-p-dioxins, the substitution hierarchy on each ring proceeds from the most reactive to the least reactive position (2, 3, 7, 8 1 4,6 2 1, 9). The values arise from
first X/ring next X/ring third X/ring fourth X/ring
T*
P
ring position
F,Cl/Br,I
F,Cl/Br,I
2, 3, 7, or 8 4 or 6 1 or 9 2, 3, 7, or 8 4 or 6 1 or 9 4 or 6 1 or 9 1 or 9
0.15/0.20 0.05/0.10 -0.05/-0.10 0.15/0.20 0.05/0.10 -0.10/-0.15 0.05/0.10 -0.10/-0.15 -0.10/-0.15
-0.03/-0.04 -0.03/-0.04
bution from CC1, could be considered redundant and a becomes 0.97 - 0.10 = 0.87. In an alternate method, when a dominant substituent (e.g., nitro, nitroso, cyano, etc.) is on an aromatic ring, for each subsequent substituent add (instead of full contribution) T* = (ortho) 0.01, (meta) 0.05, or (para) 0.00. Also, for fl values for the following groups, use the following: NMexH,,, 0.10; OH or OR, 0.10; C1, Br, or I, -0.04 or -0.lQ and F, -0.02 or -0.05. The halide contributions to fl depend on the presence of other electron-withdrawing groups (halogens, alkyls, etc.) or electron-donating groups (amines, sulfides, etc.). The values for a remain unchanged (see Table 11). For example, for 3-ethoxy-4-iodo-1-nitrobenzene benzene ring nitro ethoxy iodide
-0.03/-0.04 0.00
from Tables I and I1
VJ100
7r*
0.491 0.140 0.241 0.181 1.053 1.053
0.59 0.10 0.05 0.00 0.74 0.83
P
u
0.14 0.25 0.10 -0.04
0.00 0.16 0.06 0.00
0.45 0.58
0.22 0.22
The parameter values for aromatic systems can be For example, for 2-nitro-1,3,6,9-tetrachlorodibenzo-p-di- modified to account for induction and resonance a t an oxin aromatic ring position. Tables of Hammet u+ constants (34) for the various functional groups have proven very Vi/lOO lr* P a useful, a n d the modifications are usually minor dibenzo-p-dioxin 1.616 0.60 0.00 0.45 (hO.10-0.15). Also, accounting for hydrogen bonding be1 0.090 chlorines 4.10 -0.03 0.00 tween two neighboring groups is presently highly subjec-0.03 0.00 3 0.090 0.15 tive. Presently, /3 and cy contributions for the participating -0.03 0.00 6 0.090 0.05 groups are multiplied by 0.1-0.3, inversely proportional -0.03 0.00 9 0.090 -0.10 to the suspected strength of the hydrogen bond, For exnitro group 0.140 0.25 0.16 0.10 ample, for the nitrophenol congeners 2.116 0.55 0.73 0.16
v,/ 100 lr* P cy The same contributions to T* and p apply to analogous systems where oxygen was replaced by other heteroatom(s) phenol 0.536 0.72 0.33 0.60 nitro -0.140 0.42 0.20 0.16 in the ring system. The values for the ring systems have to be derived or determined by some means if not found 0.676 1.14 0.53 0.76 in Table I. Values for substituents other than halides are Hammet constants (34) indicate that the nitro group (urn determined as outlined elsewhere in this guidelines section. = 0.71; up = 0.78) is a very strong electron-withdrawing Corrections to ?r*, 8, and a. The presented guidelines unit in both meta and para positions. A nitro substituent provide a method for consistent variable value calculations. increases the phenolic acidity in the meta and para posiIn some instances, such as for aromatic systems with tions but is a very strong hydrogen bond acceptor in the multiple substituents and for the T* variable in aliphatic ortho position. p is largely unaffected, and the polarizasystems, the investigator may feel that the sum of conbility increases from minimum with ortho substitution to tributions may yield an intuitively unrealistic value. The maximum with para substitution. The result of nitro investigator has the option of adjusting these parameter substitutions on phenol could be values using several approximations, and each variable can be considered separately. For example, discounting a VJ100 7r* P u minor component group contribution from the sum or 0.50 0.12 0.676 1.11 ortho multiplying the total parameter value(s) by 0.8-0.9 can 0.50 0.80 0.676 1.16 meta simulate a vector sum or reflect diminishing contributions 0.53 0.90 0.676 1.21 para from multiple similar substituents. The different modifications outlined above are not exFor example, for 3-trichloromethyl-5-cyano-1-hydroxypected to give the same results for a given compound since benzene they can reflect adjustments for different factors. Their v,/100 7r* P a use is optional. The primary consideration is that the investigator be consistent with his/her derivation of values 0.14 0.00 0.59 0.491 benzene ring for a particular chemical data set. 0.23 0.60 0.13 0.045 hydroxyl 0.37 0.22 Miscellany. The replacement values in Table I1 can 0.20 0.099 cyano -0.10 0.15 0.35 0.368 trichloromethyl provide a shortcut in calculations and can be used judiciously when the only difference between molecules is a 1.003 1.27 0.64 0.97 particular atom. For example, for quinoline but neither the dipolarity nor the acidity is very likely to V,/lOO 7r* P u be as pronounced as the sums indicate. A leveling effect naphthalene 0.753 0.70 0.20 0.00 for both parameters is more likely. The approximation change c to n 1-0.021 0.28 0.34 0.00 for T* could be 1.27 x 0.8 = 1.02. The effect could be less 0.732 0.98 0.54 0.00 for acidity, such as 0.97 X 0.9 = 0.87. Or, the a contri1758
Environ. Sci. Technol., Vol. 25, No. 10, 1991
Results and Discussion The present system allows quick determination of numerical values for the four primary solvatochromic LSER variables, Vi/lOO, T*,0, and a,for a desired compound by summing the contributions from its components. The guidelines section contains the computation guidelines, and the solvatochromic parameter contributions are tabulated for most of the common organic structures (Table I) and substituents (Table 11). These structure (Table I) and functional group (Table 11) listings also greatly expand the types of organic moieties and heteroatom groups for which LSER variable contributions are available. The lisitings include values for typical nitrogen-, sulfur-, and phosphorus-containing moieties and general organosilicon and organotin parameters. The contributions by an ion-pair situation to the LSER values are also offered in Table 11, making estimations of parameters for salts and zwitterions possible for the first time. The guidelines section and Tables I and I1 significantly simplify computation of values for the LSER variables for complex organic molecules, especially the larger compounds of environmental and biological interest. While computations of a*,p , and a values are presently designed to be simple sums of component group contributions, some users may feel that a vector sum or a sum with a component group hierarchy of importance (use/not use, and to what degree) would give a better value. At present, that must be left to the discretion of the user. Also, the values given for aromatic substituents in Table I1 do not reflect the effects of ring position or hydrogen bonding, and the investigator may want to weigh contributions for resonance and induction effects with tables of Hammet u constants (34). The values used by the investigator are valid for comparison, providing the method of computation is consistent throughout. We found that these corrections are minor in most cases and well within the experimental error of most measured data sets. The examples in the guidelines section should clarify the computation process and guide the user in these subjective adjustments. The replacement values listed in Table I11 provide a shortcut in calculations but should be used judiciously when the only difference between molecules is a particular atom. There is currently no provision to differentiate between possible geometric (cis/ trans) or optical isomers of compounds. The different forms have different properties, but no applicable weighting scheme has been developed as yet for the present system. The availability of the rules in the guidelines and structural and functional group values in Tables I and I1 should encourage extensive application of this accurate QSAR model by investigators with widely varying objectives. The model will only be appropriate where solubility processes dominate the system being modeled. Blum and Speece (21,who collaborated with Kamlet and co-workers, compared the accuracy of three QSAR methods for prediction of toxicity of varied types of chemicals t o heterotrophic bacteria. Using the same data set, they found the correlation coefficient (r2)to be 0.82 with log P, the most widely used QSAR. T h e correlation coefficient was 0.78 for molecular connectivity, a QSAR parameter for which the parameters may be readily calculated with little knowledge of chemical properties. For the LSER method, their correlation coefficient was 0.92 and demonstrated the greater accuracy of LSER. They recommended extensive use of LSER contingent upon the further development of methods for calculating the LSER variables. They also
pointed out the need for an expert system for calculating LSER variable values. On the basis of these rules and component group values, we recently developed expert system software (24) to evaluate a compound’s structure and then assign the LSER parameter values. The LSER methodology in this expert system is presently used to predict acute toxicities of contaminants prior to laboratory bioassays, thus saving both time and expense in range-finding tests. The LSER methods outlined in this paper and our expert system are also used in hazard assessment research to evaluate sites of concern in the Great Lakes by screening contaminants for toxicity. Concluding Remarks This is the first inventory of the LSER variable values for molecular functional groups and variable estimation rules. Except for certain cases, the values for the whole molecule are simply the sums of the contributions for each component group. We expect this set of computation guidelines and list of functional group values to facilitate widespread application of the LSER model of QSAR by a broad spectrum of investigators, including environmental toxicologists, analytical chemists, and hazard assessment personnel. Acknowledgments We dedicate this work to the memory of the late Dr. Mortimer J. Kamlet, whose inspiration and drive with the LSER concept helped make this work necessary and possible. We also thank Dr. Michael H. Abraham (University College London) for tutelage, consultation, and encouragement in LSER theory and practice. Glossary VJ100 characteristic molar volume (+ 100) Vi/100 intrinsic molecular volume (+ 100) a* dipolar-polarizability factor Pm hydrogen bond acceptor base ffm hydrogen bond donor acid I.L dipole moment 6 Hildebrand solubility parameter 5 coordinate covalency functional group parameter um, u Hammet u substituent constants QSAk quantitative structure-activity relationships LSER linear solvation energy relationships Registry No. n-Butane, 106-97-8; n-pentane, 109-66-0; 2methylbutane, 78-78-4; n-hexane, 110-54-3; 2-methylpentane, 107-83-5;n-heptane, 142-82-5;2-methylhexane, 591-76-4;n-octane, 111-65-9; 2-methylheptane, 592-27-8; 2,2,4-trimethylpentane, 540-84-1; cyclopropane, 75-19-4; cyclobutane, 287-23-0; cyclopentane, 287-92-3; cyclohexane, 110-82-7;cycloheptane, 291-64-5; cyclooctane, 292-64-8; trans-octahydro-1H-indene,3296-50-2; decahydronaphthalene, 91-17-8; ethylene oxide, 75-21-8; tetrahydrofuran, 109-99-9; tetrahydropyran, 142-68-7; 1,4-dioxane, 123-91-1;pyrrolidine, 123-75-1;imidazolidine, 504-74-5;piperidine, 110-89-4;tetrahydrothiophene, 110-01-0;benzene, 71-43-2;indan, 496-11-7; tetrahydronaphthalene, 119-64-2; biphenyl, 92-52-4; naphthalene, 91-20-3; azulene, 275-51-4; 9H-fluorene, 86-73-7; anthracene, 120-12-7; phenanthrene, 85-01-8; furan, 110-00-9; dibenzofuran, 132-64-9; dibenzo-p-dioxin, 262-12-4; pyrrole, 109-97-7; imidazole, 288-32-4; pyridine, 110-86-1; pyrimidine, 289-95-2; diazene, 3618-05-1; thiophene, 110-02-1. Literature Cited (1) Postel, S. In State of the World, 1987;Worldwatch Institute Report; W. W. Norton: New York, 1987; pp 157-176. (2) Blum, D. J. W.; Speece, R. E. Enuiron. Sci. Technol. 1990, 24, 284-293. (3) Taft, R. W.; Abboud, J.-L. M.; Kamlet, M. J.; Abraham, M. H. J. Solution Chem. 1985, 14, 153-175. Environ. Sci. Technol., Vol. 25, No. 10, 1991
1759
Environ. Sci. Technol. I W l , 25, 1760-1766
Kamlet, M. J.; Doherty, R. M.; Abboud, J.-L. M.; Taft, R. W.CHEMTECH 1986, 16, 566-576. ( 5 ) Kamlet, M. J.; Taft, R. W. Acta Chem. Scand. 1985, B39,
Quantitative Structure-Activity Relationships (QSAR) in Environmental Technology;Turner, J. E., Williams, M. W., Schultz, T. W., Kwaak, N. J., Eds.; CONF-880520-
(4)
611-628.
Kamlet, M. J.; Abboud, J.-L. M.; Taft, R. W. Prog. Phys. Org. Chem. 1981, 13, 485-630. (7) Abraham, M. H.; Doherty, R. M.; Kamlet, M. J.; Taft, R. W. Chem. Br. 1986,22, 551-554. ( 8 ) Kamlet, M. J.;Abboud, J.-L.; Abraham, M. H.; Taft, R. W. J . Org. Chem. 1983,48, 2877-2887. (9) Kamlet, M. J.; Doherty, R. M.; Abraham, M. H.; Carr, P. W.; Doherty, R. F.; Taft, R. W. J. Phys. Chem. 1987,91, (6)
1996-2004. (10) Kamlet, M. J.;Doherty, R. M.; Abboud, J.-L. M.; Abraham, M. H.; Taft, R. W. J. Pharm. Sci. 1986, 75, 338-349. (11) Kamlet, M. J.; Doherty, R. M.; Carr, P. W.; Mackay, D.; Abraham, M. H.; Taft, R. W. Enuiron. Sci. Technol. 1988, 22, 503-509. (12) Kamlet, M. J.; Doherty, R. M.; Abraham, M. H.; Taft, R. W. J . Phys. Chem. 1988, 92, 5244-5255. (13) Taft, R. W.; Abraham, M. H.; Famini, G. R.; Doherty, R. M.; Kamlet, M. J. J . Pharm. Sci. 1985, 74, 807-814. (14) Kamlet, M. J.; Doherty, R. M.; Abraham, D. J.; Taft, R. W.; Abraham, M. H. J . Pharm. Sci. 1986, 75, 350-355. (15) Kamlet, M. J.; Doherty, R. M.; Fiserova-Bergerova,V.; Carr, P. W.; Abraham, M. H.; Taft, R. W. J . Pharm. Sci. 1987, 76, 14-17. (16) Leahy, D. E.; Carr, P. W.; Pearlman, R. S.; Taft, R. W.; Kamlet, M. J. Chromatographia 1986,21, 473-478. (17) Sadek, P. C.; Carr, P. W.; Doherty, R. M.; Kamlet, M. J.; Taft, R. W.; Abraham, M. H. Anal. Chem. 1985, 57, 2971-2978.
(18) Carr, P. W.; Doherty, R. M.; Kamlet, M. J.; Taft, R. W.;
Melander, M.; Horvath, C. Anal. Chem. 1986,58,2674-2680. (19) Kamlet, M. J.; Doherty, R. M.; Taft, R. W.; Abraham, M. H. Enuiron. Sci. Technol. 1986, 20, 690-695. (20) Kamlet, M. J.; Doherty, R. M.; Taft, R. W.; Abraham, M. H.; Veith, G.; Abraham, D. J. Environ. Sci. Technol. 1987,
(DE88013180); U.S.Department of Energy: Oak Ridge, TN; 1988; pp 131-146. (23) Passino, D. R. M. In Proceedings of the Technology Transfer Conference;Ontario Ministry of the Environment: Toronto, ON, Canada, 1986; Part B, pp 1-26. (24) Hickey, J. P.; Aldridge, A. J.; Passino, D. R. M.; Frank, A. M. In Enuironmental Expert Systems; Hushon, J., Ed.; ACS Symposium Series 431; American Chemical Society: Washington, DC, 1990; pp 90-107. (25) Abraham, M. H.; Grellier, P. L.; Prior, D. V.; Morris, J. J.; Taylor, P. J.; Laurence, C.; Berthelot, M. Tetrahedron Lett. 1989,30, 2571-2574. (26)
Abraham, M. H.; Grellier, P. L.; Prior, D. V.; Duce, P. P.; Morris, J. J.; Taylor, P. J. J. Chem. Soc., Perkin Trans. 2 1989, 699-711.
Abraham, M. H.; Buist, G. J.; Grellier, P. L.; McGill, R. A.; Prior, P. V.; Oliver, S.; Turner, E.; Morris, J. J.; Taylor, P. J.; Nicolet, P.; Maria, P.-C.; Gal, J.-F.; Abboud, J.-L. M.; Doherty, R. M.; Kamlet, M. J.; Shuely, W. J.; Taft, R. W. J . Phys. Org. Chem. 1989,2, 540-552. (28) Abraham, M. H.; Duce, P. P.; Prior, D. V.; Barratt, D. G.; Morris, J. J.; Taylor, P. J. J. Chem. SOC.,Perkin Trans. 2 (27)
1989, 1355-1375.
Leahy, D. E. J. Pharm. Sci. 1986, 75, 629-636. Pearlman, R. S. In Partition CoefficientDetermination and Estimation;Dunn, W. J.,Block, J. H., Pearlman, R. S., Eds.; Pergamon Press: New York, 1986; pp 3-20. (31) Bondi, A. J . Phys. Chem. 1964,68,441-449. (32) Abraham, M. H.; McGowan, J. C. Chromatographia 1987, (29) (30)
23, 243-246.
Kamlet, M. J.;Gal, J.-F.;Maria, P.-C.; Taft, R. W. J. Chem. SOC.,Perkin Trans. 2 1985, 1583-1589. (34) Hansch, C.; Leo, A. Substituent Constants for Correlation Analysis in Chemistry and Biology;J. Wiley & Sons: New York, 1979; pp 49-54.
(33)
21, 149-155.
Kamlet, M. J.; Doherty, R. M.; Abraham, D. J.; Taft, R. W. Quant. Strut.-Act. Relat. 1988, 7, 71-78. (22) Passino, D. R. M.; Hickey, J. P.; Frank, A. M. In QSAR 8 8 Proceedings of the Third International Workshop on
(21)
Received for review March 4,1991. Revised manuscript received May 27,1991. Accepted May 28,1991. Contribution 780 of the National Fisheries Research Center-Great Lakes, Ann Arbor, MI.
Determining the Fates of Contaminated Wastes Dumped in the New York Bight Apex by Use of Metal Enrichment Factors Vincent S. Zdanowicz National Oceanic and Atmospheric Administration, National Marine Fisheries Service, Sandy Hook Laboratory, Highlands, New Jersey 07732
The major sources of contaminants to the New York Bight apex in 1983 were sewage sludge and dredged spoils dumping and the outflow of the Hudson-Raritan estuary. Metal distributions were determined in sediments collected during a 1983 survey and metal enrichment factors, based on ratios of trace metals to iron, were used to distinguish fates of sewage sludge and dredged spoils dumped in the Bight apex. Lead enrichment factors indicated that the portion of the apex that was directly affected by dredged spoils dumping was in the immediate vicinity of that site, even though this activity constituted the largest source of solid materials to the apex. Sewage sludge dumping, in contrast, while contributing much less total mass than dredged spoils dumping, appeared to directly affect -8 times as much area.
Introduction The New York Bight (Figure 1)is bordered by an industrialized, metropolitan region inhabited by approxi1760 Environ. Sci. Technol., Vol. 25, No. 10, 1991
mately 18 million people and consequently receives a variety of wastes from numerous sources. In addition to relatively minor inputs of metal contaminants from the atmosphere and coastal runoff, more substantial inputs have been derived from the Hudson-Raritan outflow and from ocean dumping of dredged materials and sewage sludge (1). The northwest corner, or apex, of the Bight covers approximately 2000 km2,or -5% of the total area. It is the most intensively utilized portion of the Bight for both commerce and recreation and has been the locus of disposal sites for acid wastes, construction rubble, dredged spoils, and sewage sludge. Contaminant monitoring has been conducted in the Bight, and more extensively in the apex (Figure 2), since the late 1960s as a part of numerous studies by the National Oceanic and Atmospheric Administration (NOAA), the Army Corps of Engineers, and others (2-5). Such studies have documented distributions of contaminants in surface sediment throughout the Bight; high concen-
Not subject to US. Copyright. Published 1991 by the American Chemical Society
