Abstract. We present a new general parameterization for aqueous solvation free energies of molecules and ions in aqueous solution. It is obtained by extending a semianalytic treatment of solvation recently proposed for use with molecular mechanics and liquid simulations by Still et al. As extended here, the solvation terms are included in a Fock operator. The model incorporates reaction field polarization effects through the generalized Born functional with charges obtained by AM1 molecular orbital calculations, and it includes cavitation, dispersion, and hydrophobic effects through an empirical function of solvent-accessible-surface area. A general parameter set, including parameters for H, C, N, O, F, S, Cl, Br, and I, has been obtained by considering a data set consisting of 141 neutral molecules, 10 cations, and 17 anions. The neutral molecules include alkanes, cycloalkanes, alkenes, arenes, alkynes, ethers, heterocycles, carboxylic acids, esters, nitriles, aldehydes, ketones, alcohols, amines, nitro compounds, sulfides, thiols, halides, and polyfunctional compounds. Then general parameterization is called Solvation Model 1, and it is particularly well suited for chemical reaction dynamics and reaction intermediates. We also discuss how the model may be refined for solvation free energies for stable neutral molecules.
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2. "Molecular Orbital Theory Calculations of Aqueous Solvation Effects on Chemical Equilibria," C. J. Cramer and D. G. Truhlar, Journal of the American Chemical Society 113, 8552-8554. Erratum: 113, 9901 (1991).
Abstract. The SM1 Model is applied to reaction equilibria, in particular, acid-base proton transfers, prototropic tautomerizations, and rotameric equilibria in a Communication to the Editor.
3. "An SCF Solvation Model for the Hydrophobic Effect and Absolute Free Energies of Aqueous Solvation," C. J. Cramer and D. G. Truhlar, Science 256, 213-217 (1992).
Abstract. A model for absolute free energies of solvation of organic, small inorganic, and biological molecules in aqueous solution is described. This model has the following features: (i) the solute charge distribution is described by distributed monopoles, and solute screening of dielectric polarization is treated with no restrictions on solute shape; (ii) the energetic effects of cavity formation, dispersion interactions, and solute-induced restructuring of water are included by a semiempirical cavity surface tension; and (iii) both of these effects are included in the solute Hamiltonian operator for self-consistent field (SCF) calculations to allow solvent-induced electronic and geometric distortion of the solute. The model is parameterized for solutes composed of H, C, N, O, F, P, S, Cl, Br, and I against experimental data for 150 neutral solutes and 28 ions, with mean absolute errors of 0.7 and 2.6 kilocalories per mole, respectively.
4. "PM3-SM3: A General Parameterization for Including Aqueous Solvation Effects in the PM3 Molecular Orbital Model," C. J. Cramer and D. G. Truhlar, Journal of Computational Chemistry 13, 1089-1097 (1992).
Abstract. Our recently proposed scheme for including aqueous solvation free energies in parameterized NDDO SCF models is extended to the Parameterized Model 3 semiempirical Hamiltonian. The solvation model takes accurate account of the hydrophobic effect for hydrocarbons, as well as electric polarization of the solvent, the free energy of cavitation, and dispersion interactions. Eight heteroatoms are included (along with H and C), and the new model is parameterized accurately for the water molecule itself, which allows meaningful treatments of specifically hydrogen bonded water molecules. The unphysical partial charges on nitrogen atoms predicted by the Parameterized Model 3 Hamiltonian limit the accuracy of the predicted solvation energies for some compounds containing nitrogen, but the model may be very useful for other systems, especially those for which PM3 is preferred of AM1 for the solute properties of the particular system under study.
5. "AM1-SM2 and PM3-SM3 Parameterized SCF Solvation Models for Free Energies in Aqueous Solution," C. J. Cramer and D. G. Truhlar, Journal of Computer-Aided Molecular Design 6, 629-666 (1992).
Abstract. Two new continuum solvation models have been presented recently, and in the paper they are explained and reviewed in detail with further examples. Solvation Model 2 (AM1-SM2) is based on the Austin Model 1 and Solvation Model 3 (PM3-SM3) on the Parameterized Model 3 semiempirical Hamiltonian. In addition to the incorporation of phosphorus parameters, both of the new models address specific deficiencies in the original Solvation Model 1 (AM1-SM1), viz., (1) more accurate account is taken of the hydrophobic effect for hydrocarbons, (2) assignment of heavy-atom surface tensions is based on the presence or absence of bonded hydrogen atoms, and (3) the treatment of specific hydration-shell water molecules is more consistent. The new models offer considerably improved performance compared to AM1-SM1 for neutral molecules and essentially equivalent performance for ions. The solute charges within the Parameterized Model 3 Hamiltonian limit the utility of PM3-SM3 for compounds containing nitrogen and possibly phosphorus. For other systems both AM1-SM2 and PM3-SM3 give realistic results, but AM1-SM2 in general outperforms PM3-SM3. Key features of the models are discussed with respect to alternative approaches.
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6. "Polarization of the Nucleic Acid Bases in Aqueous Solution," C. J. Cramer and D. G. Truhlar, Chemical Physics Letters 198, 74-80 (1992). Erratum: 202, 567 (1993).
Abstract. We present calculations of the absolute free energy of solvation of five nucleic acid bases and five methylated nucleic acid bases using a recently developed local-field SCF procedure in which the electronic structure and geometry are both optimized in the presence of solvent. The calculated solvation free energies are increased 23%-34% by the aqueous-phase relaxation.
7. "What Causes Aqueous Acceleration of the Claisen Rearrangement?" C. J. Cramer and D. G. Truhlar, Journal of the American Chemical Society 114, 8794-8799 (1992).
Abstract. We report the results of applying a new self-consistent-field solvation model to the Claisen rearrangement of allyl vinyl ether, all possible methoxy-substituted derivatives, two alkylated derivatives, and one carboxymethylated derivative in order to understand the effects of aqueous solvation on the reaction rates. We have employed the AM1-SM2 version of the model to calculate the changes in free energies of solvation in passing from the lowest-energy conformations of the starting materials to both chair and boat transition states. The hydrophobic effect is always accelerative but always small and not very structure sensitive. Other first-hydration-shell effects attributable to hydrophilic parts of the reagents are more sensitive to the substitution pattern. The polarization contributions to the activation energies are usually larger. A favorable polarization contribution is found to be associated with efficient sequestration of charges of opposite sign into separated regions of space. We conclude that aqueous acceleration of the Claisen rearrangement is caused by electric polarization and first-hydration-shell hydrophilic effects, with the relative magnitudes and even the signs of these effects being quite sensitive to substitution pattern.
8. "Quantum Chemical Conformational Analysis of Glucose in Aqueous Solution," C. J. Cramer and D. G. Truhlar, Journal of the American Chemical Society 115, 5745-5753 (1993).
Abstract. We have calculated the aqueous solvation effects on the anomeric and conformational equilibria of D-glucopyranose using a quantum solvation model based on a continuum treatment of dielectric polarization and solvent accessible surface area. The solvation model puts the relative ordering of the hydroxymethyl conformers in line with the experimentally determined ordering of populations. Our calculations indicate that the anomeric equilibrium is controlled primarily by effects that are also present in the gas-phase potential energy function, that the gauche/trans O-C(6)-C(5)-O hydroxymethyl conformational equilibrium is dominated by favorable solute-solvent hydrogen bonding interactions, and that other rotameric equilibria are controlled mainly by dielectric polarization of the solvent. The description of the aqueous free energy changes of the latter require at least a distributed monopole representation since they do not correlate with overall dipole moment.
9. General Discussion (on the solvent effect in phosphate ester hydrolysis), C. J. Cramer, G. D. Hawkins, and D. G. Truhlar, Journal of the Chemical Society Faraday Transactions 90, 1802-1804 (1994). Erratum: 90, 3203 (1994).
Abstract. Using PM3-SM3 calculations, the differential free energy of solvation between cyclic and acyclic phosphate esters is shown to result from solute screening of solute charges from the dielectric of the solvent.
10. "Correlation and Solvation Effects on Heterocyclic Equilibria in Aqueous Solution," C. J. Cramer and D. G. Truhlar, Journal of the American Chemical Society 115, 8810-8817 (1993).
Abstract. We report extended-basis-set electronic structure calculations with high levels of electron correlation for heterocyclic tautomerizations, augmented by a detailed analysis of the aqueous solvation free energy differences which includes both electronic and geometric relaxation in aqueous solution, according to the Austin Model 1-Solvation Model 2 (AM1-SM2). The equilibria used as test cases are the competition between the hydroxy and oxo forms of 5-hydroxyisoxazoles; these involve two oxo (keto) and two hydroxy (enol) forms. For the unsubstituted parent system, it is found that the energy differences between the two oxo forms and between oxo and hydroxy forms are both very sensitive not only to extending the basis sets and including electron correlation but also to including electron correlation at levels higher than second order, indicating the difficulty of treating sp2 and sp3 centers on an equal footing in ring systems. We also find that treatments of electrostatic components of solvation free energies based on the popular Onsager model underestimate the solvation energy of the syn-hydroxy form because local bond moments have significant effects on the bulk electric polarization even when they largely cancel in the net dipole moment. Finally, we note that there is a significant difference in first-hydration-shell effects for the oxo and hydroxy forms over and above that accounted for by electrostatic polarization. The effects of methyl substitution on the isoxazole ring are explored, and the calculated equilibrium shifts are consistent with available experimental data, which are thereby explained in terms of a combination of changes in both the gas-phase and solvation free energies.
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11. "Entropic Contributions to Free Energies of Solvation," D. J. Giesen, C. J. Cramer, and D. G. Truhlar, Journal of Physical Chemistry 98, 4141-4147 (1994).
Abstract. Two alternative ways to treat the entropy of solution in the molecular thermodynamics of liquid-phase solutions have proved useful under various circumstances. The first is the ideal solution theory in which the entropic effects are the same as for mixing ideal gases. The second is the theory of Flory and Huggins which is most appropriate for nondilute solutions of chain molecules in small solvents. The two theories are compared for their ability to describe solutions of alkanes, both straight-chain and branched, in aqueous solution. The alkanes provide an especially appropriate testing field because electrostatic effects are minimal, and it is reasonable to assume that the solvation free energy consists almost entirely of entropic contributions and first-hydration-shell effects. The tests show that the experimental data are better correlated by the ideal solution theory than by adding an explicit volume-dependent contribution from Flory-Huggins theory, as suggested by Sharp, Nicholls, Friedman, and Honig. We disagree with a recent recommendation that one should use Flory-Huggins theory to change the definition of the experimental free energy of transfer of a solute from the gas phase into solution and also with the suggestions that there is a general volume contribution to the free energy of solvation that is well modeled by the Flory-Huggins term.
12. "Quantum Chemical Conformational Analysis of 1,2-Ethanediol: Correlation and Solvation Effects on the Tendency to Form Internal Hydrogen Bonds in the Gas Phase and Aqueous Solution," C. J. Cramer and D. G. Truhlar, Journal of the American Chemical Society 116, 3892-3900 (1994).
Abstract.Correlated ab initio calculations with very large (correlation-consistent polarized valence triple-zeta) basis sets predict that 1,2-ethanediol adopts a gas-phase population of conformers at 298 K comprised of rotamers 98% gauche and 2% trans about the C-C bond. Gauche conformers that have internal hydrogen bonds make up 83% of the total population. Changes in relative energy of up to 0.6 kcal/mol are observed upon decreasing the size of the basis set to correlation-consistent polarized double-zeta (which is still larger than commonly used polarized double-zeta basis sets), illustrating the difficulty of even gas-phase conformational analysis in the seemingly simple molecule; the extra variational freedom and more complete polarization space in the larger basis stabilizes trans hydroxyl conformations and increases by a factor of 2 both the predicted fractional population of trans C-C rotamers and the predicted population of conformers with no internal hydrogen bond. Solvation effects were studied using the SMx series of quantum statistical aqueous solvation models. By adding calculated free energies of solvation to gas-phase free energies, it is found that the trans population increases from 2 to 12%, and the portion of conformers having no internal hydrogen bond increases from 17 to 25%. The calculated results are in reasonable agreement with experimental results both in the gas phase and in aqueous solution. The results provide a consistent picture of the competition between the various effects (electronic energies, zero point effects, thermal vibrational-rotational free energy components, and electric polarization and first hydration shell contributions to solvation free energies) that, when combined with the proper statistics, contribute to determining the populations of all possible isomers in aqueous solution. Calculated relative solvation free energies for gauche vs trans C-C torsion are also in good agreement with classical Monte Carlo and molecular dynamics simulation results.
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13. "Solvation Modeling in Aqueous and Nonaqueous Solvents: New Techniques and a Re-examination of the Claisen Rearrangement," J. W. Storer, D. J. Giesen, G. D. Hawkins, G. C. Lynch, C. J. Cramer, D. G. Truhlar, and D. A. Liotard, in Structure and Reactivity in Aqueous Solution: Characterization of Chemical and Biological Systems, edited by C. J. Cramer and D. G. Truhlar (American Chemical Society, Washington, DC, 1994), pp. 24-49.
Abstract. This chapter presents an overview of recent improvements and extensions of the quantum mechanical generalized-Born-plus-surface-tensions (GB/ST) approach to calculating free energies of solvation, followed by a new treatment of solvation effects on the Claisen rearrangement. The general improvements include more efficient algorithms in the AMSOL computer code and the use of class IV charge models. These improvements are used with specific reaction parameters to calculate the solvation effect on the Claisen rearrangement both in alkane and in water, and the results are compared to other recent work on this reaction.
14. "Improved Methods for Semiempirical Solvation Models," D. A. Liotard, G. D. Hawkins, G. C. Lynch, C. J. Cramer, and D. G. Truhlar, Journal of Computational Chemistry, 16, 422-440 (1995).
Abstract. We present improved algorithms for the SMx (x = 1, 1a, 2, 3) solvation models presented previously [see the overview in C. J. Cramer and D. G. Truhlar, J. Comput.-Aided Mol. Design, 6, 629 (1992)]. These models estimate the free energy of solvation by augmenting a semiempirical Hartree-Fock calculation on the solute with the generalized Born (GB) model for electric polarization of the solvent and a surface tension term based on solvent-accessible surface area. This paper presents three improvements in the algorithms used to carry out such calculations, namely (i) an analytical accessible surface area algorithm, (ii) a more efficient radial integration scheme for the dielectric screening computation in the GB model, and (iii) a damping algorithm for updating the GB contribution to the Fock update during the iterations to achieve a self-consistent field. Improvements (i) and (ii) decrease the computer time, and improvement (iii) leads to more stable convergence. Improvement (ii) removes a small systematic numerical error that was explicitly absorbed into the parameterization in the SMx models. Therefore we have adjusted the parameters for one of the previous models to yield essentially identical performance as was obtained originally while simultaneously taking advantage of improvement (ii). The resulting model is called SM2.1. The fact that we obtain similar results after removing the systematic quadrature bias attests to the robustness of the original parameterization.
15. "A General Semiempirical Quantum Mechanical Solvation Model for Nonpolar Solvation Energies. n-Hexadecane," D. J. Giesen, J. W. Storer, C. J. Cramer, and D. G. Truhlar, Journal of the American Chemical Society, 117, 1057-1068 (1995).
Abstract. A new solvation model has been developed that accurately predicts solvation free energies in the nonpolar solvent n-hexadecane. The model is based on AM1-CM1A and PM3-CM1P partial charges, and it is based on a single set of parameters that is applicable to both the AM1 and PM3 Hamiltonians. To take account of both short-range and long-range solvation-shell interactions, each atom has two surface tensions associated with different effective solvent radii. For hydrogen, one of these surface tensions depends on the bond orders to carbon, nitrogen, oxygen, and sulfur, although only weakly. In addition to presenting the general parameterization, the article provides an analysis of the surface tension parameterization based on data for three rare gases. The model yields an RMS error of 0.41 kcal/mol over a set of 306 data points (153 molecules, 2 Hamiltonians) that includes alkanes, alkenes, alkynes, aromatics, alcohols, ethers, aldehydes, ketones, esters, amines, nitriles, pyridines, thiols, sulfides, fluorides, chlorides, bromides, iodides, water, and ammonia.
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16. "Continuum Solvation Models: Classical and Quantum Mechanical Implementations," C. J. Cramer and D. G. Truhlar, in Reviews in Computational Chemistry, Vol. 6, edited by K. B. Lipkowitz and D. B. Boyd (VCH Publishers, New York, 1995), 1-72.
Abstract. A comprehensive review, this book chapter covers theory and applications of many continuum solvation models and includes comparative results for a number of systems.
17. "Development and Biological Applications of Quantum Mechanical Continuum Solvation Models," C. J. Cramer and D. G. Truhlar, in Solute/Solvent Interactions (Theoretical and Computational Chemistry, Vol. 1), edited by P. Politzer and J. S. Murray (Elsevier, Amsterdam, 1994), pp. 9-54.
Abstract. This book chapter examines the various methods that include solvent effects using a dielectric continuum and discusses how the models can be applied to systems of biological interest. Dielectric continuum models can be used to gain further insight into the electronic structure and molecular conformation of compounds such a dopamine and glucose. The role of dielectric continuum models in the calculation of predictors in QSAR and LSER relationships is explored.
18. "A Semiempirical Quantum Mechanical Solvation Model for Solvation Free Energies in All Alkane Solvents," D. J. Giesen, C. J. Cramer, and D. G. Truhlar, Journal of Physical Chemistry, 99, 7137-7146 (1995).
Abstract. Using a linear fit of the solvent-ordering part of the microscopic surface tension to experimental macroscopic surface tensions, the Generalized Born/Surface Tension solvation model presented previously for n-hexadecane (called Solvation Model 4 or SM4), is extended to include all alkanes as solvents, including normal, branched, and cyclic alkanes. The general SM4 alkane model is applicable to any alkane solvent for which the macroscopic dielectric constant and surface tension are either known or estimable. It treats electrostatic effects, including polarization of the solute by a reaction field, in terms of a continuum dielectric model of the solvent, uses element-based surface tension terms to account for first-solvation-shell effects, and uses an element-independent surface tension to account for solvent-ordering effects that extend further into solution. The electrostatic terms are based on the recently developed Charge Model 1 (CM1) for computing atomic partial charges. This charge model allows the development of a single set of parameters which is applicable to both the AM1 and PM3 Hamiltonians and also to any other electronic structure method that provides reasonably accurate geometries and partial charges.
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19. "Relative Stability of Alternative Chair Forms and Hydroxymethyl Conformations of D-Glucopyranose," S. E. Barrows, F. J. Dulles, C. J. Cramer, D. G. Truhlar, and A. D. French, Carbohydrate Research, 276, 219-251 (1995).
Abstract. The relative energies of two hydroxymethyl conformers for each of the two chair forms (4C1 and 1C4) of beta-D-glucose were calculated atmuch more complete levels of quantum mechanical (QM) electronic structure theory than previously available, and relative free energies in solution were calculated by adding vibrational, rotational, and solvent effects. The gas-phase results are based on very large basis sets (up to 624 contracted basis functions), and the coupled cluster method for electron correlation. Solvation Model 4 was used to calculate the effects of hydration or nonpolar solvation. Molecular mechanics (MM) and quantum mechanical (QM) electronic structure theory have been applied to analyze the factors contributing to the relative energies of these conformers. Relative energies varied widely (up to 35 kcal/mol) depending on theoretical level, and several levels of theory predict the experimentally unobserved 1C4 ring conformation to be the lower in energy. The highest-level calculations predict the 4C1 chair to be lower in free energy by about 8 kcal/mol, and we also find that the gauche+, i.e., gt, conformer of 4C1 is lower than the trans, i.e., tg. Low-energy structures optimized by either quantum mechanical or molecular mechanical methods were commonly characterized by multiple intramolecular hydrogen bonds. Superior hydrogen bonding geometries are available in the 1C4 chair, but are counteracted by increased steric repulsions between axial substituents; MM calculations also indicate increased torsional strain in the 1C4 chair. Manifestations of greater steric strain in the calculated 1C4 structures compared to the 4C1 structures include longer ring bonds, a larger bond angle at the ring oxygen atom, and smaller puckering amplitudes. The MM and QM 4C1 structures compare well with each other and with available X-ray diffraction data. The largest discrepancies between the two kinds of models occur for geometric parameters associated with the anomeric center-the QM structure agrees better with experiment. Greater differences between QM and MM structures are observed for 1C4 structures, especially in the relative orientations of hydroxyl groups serving as hydrogen bond acceptors. In water, the 4C1 chairs are better solvated than the 1C4 chairs by about 5 to 9 kcal/mol because of both larger polarization free energies and improved hydrogen bonding interactions with the first solvation shell. In (a hypothetical) n-hexadecane solution, the 4C1 chairs are better solvated by about 2 to 4 kcal/mol both because of larger polarization free energies and because the larger solvent accessible surface areas of the 4C1 conformers allow increased favorable dispersion interactions. The differential polarization free energies are associated primarily with the hydroxyl groups; the greater steric congestion in the 1C4 chairs reduces opportunities for favorable dielectric screening.
20. "Pairwise Solute Screening of Solute Charges from a Dielectric Medium," G. D. Hawkins, C. J. Cramer, and D. G. Truhlar, Chemical Physics Letters, 246, 122-129 (1995).
Abstract. We present an algorithm for incorporating a pairwise descreening approximation into the calculation of the electrostatic component of the polarization free energy of solvation within the generalized Born approximation. The method was tested on a set of 139 molecules containing H, C, O, and N. The complexity of the descreening calculation is greatly simplified by the pairwise approximation; nevertheless, using the pairwise descreening method to parameterize a new version of a previous generalized Born solvation model, we found that the RMS error relative to experiment increased by only 0.2 kcal/mol.
21. "Continuum Solvation Models" C. J. Cramer and D. G. Truhlar, in Solvent Effects and Chemical Reactivity, edited by O. Tapia and J. Bertran (Kluwer, Dordrecht, 1996), pp. 1-80.
Abstract. This chapter reviews the theoretical background for continuum models of solvation, recent advances in their implementation, and illustrative examples of their use. Continuum models are the most efficient way to include condensed-phase effects into quantum mechanical calculations, and this is typically accomplished by the using self-consistent reaction field (SCRF) approach for the electrostatic component. This approach does not automatically include the non-electrostatic component of solvation, and we review various approaches for including that aspect. The performance of various models is compared for a number of applications, with emphasis on heterocyclic tautomeric equilibria because they have been the subject of the widest variety of studies. For nonequilibrium applications, e.g., dynamics and spectroscopy, one must consider the various time scales of the solvation process and the dynamical process under consideration, and the final section of the review discusses these issues.
22. "Quantum Chemical Conformational Analysis and X-Ray Structure of 4-Methyl-3-Thiosemicarbazide," C. C. Chambers, E. Archibong, S. M. Mazhari, A. Jabalameli, J. D. Zubkowski, R. H. Sullivan, E. J. Valente, C. J. Cramer, and D. G. Truhlar, Journal of Molecular Structure: Theochem 388, 161-167 (1996).
Abstract. We present X-ray crystallographic results and gas-phase electronic structure calculations of the geometry of 4-methyl-3-thiosemicarbazide. Using Hartree- Fock theory with a 6-31G* basis set, we calculated relative energies for eight different conformations. For the lowest-energy conformations of each of the four possible combinations of rotamers about the two C-N bonds, we also included electron correlation by Møller-Plesset second-order (MP2) perturbation theory with the same basis set. From these calculations, we selected the lowest-energy structure and calculated structural parameters at the MP2 level of theory with the larger correlation-consistent cc-pVDZ basis set. The geometry of the minimum- energy gas-phase structure is in good agreement with the structure observed experimentally in the crystal.
23. "Factors Controlling Regioselectivity in the Reduction of Polynitroaromatics in Aqueous Solution," S. E. Barrows, C. J. Cramer, D. G. Truhlar, M. S. Elovitz, and E. J. Weber, Environmental Science and Technology 30, 3028-3038 (1996).
Abstract. Regioselectivities in the bisulfide reduction of ten polynitroaromatics to monoamine products have been determined; four of these compounds have also been reduced by anoxic sediments in heterogeneous aqueous solution, and the same regioselectivities are observed. This suggests that reduction takes place in the liquid phase and is mediated by an organic electron shuttle reagent. Analyses of Austin Model 1-Solvation Model 2 electrostatic potential surfaces for the radical anions of these polynitroaromatic compounds provides a reliable method of predicting the regioselectivity of their reduction. In particular, at their minimum-energy geometries in aqueous solution, it is the more negative nitro group that is selectively reduced. This is consistent with a mechanism where regioselection occurs upon kinetic protonation at the site of maximum negative charge in the radical anion formed after the first electron transfer to the neutral PNA . Inclusion of solvation effects is critical in order to confidently predict the electrostatic preference for the reduction of one nitro group over the others. Sterically uncongested nitroaromatic radical anions have gas-phase geometries in which the nitro group is coplanar with the aromatic ring. However, ortho substituents and solvation effects both oppose this tendency, and can lead to nitro groups that are rotated out of the ring plane and pyramidalized.
24. "Model for Aqueous Solvation Based on Class IV Atomic Charges and First-Solvation Shell Effects," C. C. Chambers, G. D. Hawkins, C. J. Cramer, and D. G. Truhlar, Journal of Physical Chemistry 100, 16385-16398 (1996).
Abstract. We present a new set of geometry-based functional forms for parameterizing effective coulomb radii and atomic surface tensions of organic solutes in water. In particular, the radii and surface tensions depend in some cases on distances to nearby atoms. Combining the surface tensions with electrostatic effects included in a Fock operator by the generalized Born model enables one to calculate free energies of solvation, and experimental free energies of solvation are used to parameterize the theory for water. Atomic charges are obtained by both the AM1-CM1A and PM3-CM1P class IV charge models, which yield similar results, and hence the same radii and surface tensions are used with both charge models. We considered 215 neutral solutes containing H, C, N, O, F, S, Cl, Br, and I and encompassing a very wide variety of organic functional groups, and we obtained a mean unsigned error in the free energy of hydration of 0.50 kcal/mol using CM1A charges and 0.48 kcal/mol using CM1P charges. The predicted solvation energies for 12 cationic and 22 anionic solutes have mean unsigned deviations from experiment of 4.6 and 4.8 kcal/mol for models based on AM1 and PM3, respectively.
25. "Exo-anomeric Effects on Energies and Geometries of Different Conformations of Glucose and Related Systems in the Gas Phase and Aqueous Solution," C. J. Cramer, D. G. Truhlar, and A. D. French, Carbohydrate Research 298, 1-14 (1997).
Abstract. Ab initio calculations predict that in 2-hydroxy- and 2-methoxy-tetrahydropyran, hyperconjugative delocalization of lone pair density on the exocyclic oxygen atom at C(1) into the sigma* orbital of the C(1)O(5) bond is maximized when the OR group at C(1) is oriented gauche to C(1)O(5). This exo-anomeric effect lengthens the C(1)O(5) bond, shortens the exocyclic C(1)O bond, and stabilizes the gauche conformers by about 4 kcal/mol over the anti. In the anti orientation, hyperconjugative interaction of the OR group at C(1) with other appropriately oriented sigma* orbitals increases, but the geometric and energetic consequences are less marked. Solvation effects reduce the energetic stabilization associated with the exo-anomeric effect in the tetrahydropyrans. This derives from a combination of changes in the overall electrostatics and also from decreased accessibility of the hydrophilic groups in the gauche conformers. For glucose or glucosides, instead of the simple tetrahydropyran model systems, the interactions of the exocyclic OR group at C(1) with the hydroxy group at C(2) can significantly affect these hyperconjugative delocalizations. In the glucose and glucoside systems, solvation effects oppose the formation of intramolecular hydrogen bonds. MM3(94) force field calculations show systematic deviations in the relative energies and structures of the various model systems with respect to the more reliable HF/cc-pVDZ predictions.
26. "Parameterized Models of Aqueous Free Energies of Solvation Based on Pairwise Descreening of solute Atomic charges from a Dielectric Medium," G. D. Hawkins, C. J. Cramer, and D. G. Truhlar, Journal of Physical Chemistry 100, 19824-19839 (1996).
Abstract. The pairwise descreening approximation provides a rapid computational algorithm for the evaluation of solute shape effects on electrostatic contributions to solvation energies. In this article we show that solvation models based on this algorithm are useful for predicting free energies of solvation across a wide range of solute functionalities, and we present six new general parameterizations of aqueous free energies of solvation based on this approach. The first new model is based on SM2-type atomic surface tensions, the AM1 model for the solute, and Mulliken charges. The next two new models are based on SM5-type surface tensions, either the AM1 or the PM3 model for the solute, and Mulliken charges. The final three models are based on SM5-type atomic surface tensions and are parameterized using the AM1 or the PM3 model for the solute and CM1 charges. The parameterizations are based on experimental data for a set of 219 neutral solute molecules containing a wide range of organic functional groups and the atom types H, C, N, O, F, P, S, Cl, Br, and I and on data for 42 ions containing the same elements. The average errors relative to experiment are slightly better than previous methods, but--more significantly--the computational cost is reduced for large molecules, and the methods are well suited to using analytic derivatives.
27. "A Universal Organic Solvation Model," D. J. Giesen, M. Z. Gu, C. J. Cramer, and D. G. Truhlar, Journal of Organic Chemistry 61, 8720-8721 (1996).
Abstract. A solvation model is presented for the quantum mechanical calculation of gas-to-liquid and liquid-to-liquid transfer free energies; for a data set spanning 90 organic solvents and 205 organic solutes, the mean unsigned error in 1784 molar transfer free energies is 0.5 kcal (0.35 log10 units at 298 K).
28. "A Solvation Model for Chloroform Based on Class IV Atomic Charges," D. J. Giesen, C. C. Chambers, C. J. Cramer, and D. G. Truhlar, Journal of Physical Chemistry 101, 2061-2069 (1997).
Abstract. We present a parameterization of the SM5.4 solvation model, previously applied to aqueous solutions and general organic solvents, for predicting free energies of solvation in chloroform. As in all SM5 models, the calculations are based on a set of geometry-based functional forms for parameterizing atomic surface tensions of organic solutes. In particular, the atomic surface tensions depend in some cases on distances to nearby atoms. Combining the atomic surface tensions with electrostatic effects included in a Fock operator by the generalized Born model enables one to calculate free energies of solvation. Atomic charges are obtained by both the AM1-CM1A and PM3-CM1P class IV charge models, which yield similar results, and hence the same atomic radii and similar surface tensions are used with both charge models. Experimental free energies of solvation and free energies of transfer from aqueous solution are used to parameterize the theory for chloroform. The parameterization is based on a set of 205 neutral solutes containing H, C, N, O, F, S, Cl, Br, and I that we used previously to parameterize a model for general organic solvents plus 32 additional solutes added for this study. For the present parameterization, we used free energies of solvation in chloroform for 88 solutes, free energies of solvation in other solvents for 123 solutes, and free energies of transfer from water to chloroform for 26 other solutes. We obtained a mean unsigned error in the free energies of solvation in chloroform of 0.43 kcal/mol using CM1A atomic charges and 0.34 kcal/mol using CM1P atomic charges.
29. "New Methods for Potential Functions for Simulating Biological Molecules," G. D. Hawkins, C. J. Cramer, and D. G. Truhlar, Journal de Chimie Physique 94, 1448-1481 (1997).
Abstract. We calculate atomic charges and solvation energies for 9-methyladenine, thymine, alamine dipeptide, and N-acetylserine-N'-methanylamide using the CM1A class IV charge model and the SM5.4/A and SM5.4PD/A solvation models. The CM1A charge model provides atomic charges as accurate as or more accurate than those used in popular molecular dynamics force fields but is very economical in both computer time and the effort required to generate charges; thus it is very promising for examining effects of conformational changes, substituents, solvation, binding, and even reaction. The solvation models have been parameterized over broad functionalities and are well suited to rapid calculations on large systems.
30. "Quantum Mechanical and 13C Dynamic NMR Study of 1,3-Dimethylthiourea Conformational Isomerizations," C. C. Chambers, E. F. Archibong, A. Jabalameli, R. H. Sullivan, D. J. Giesen, C. J. Cramer, and D. G. Truhlar, Journal of Molecular Structure: Theochem 425, 61-68 (1998).
Abstract. We present 13C dynamic NMR results for relative free energies of equilibrium structures and free energies of activation for conformational transformations of 1,3-dimethylthiourea in aqueous solution, and we compare the results to theoretical predictions. The latter are based on ab initio gas-phase electronic structure calculations of the geometries, dipole moments, and energies combined with semiempirical molecular orbital calculations of the free energies of solvation in three different solvents. The gas-phase electronic structure calculations were performed using Moller-Plesset second-order (MP2) perturbation theory with a correlation-consistent polarized valence-double-zeta basis set; we calculated relative energies for the three minima Z,Z, E,Z, and E,E and for three transition states on the potential energy surface. The solvation energy calculations were carried out using the SM5.4/A-aqueous, -chloroform, and -organic solvation models; these solvation models are based on semiempirical molecular orbital theory with class IV charges and geometry-based first-solvation-shell effects. The relative energies of the conformers and transition states are compared to experiment in water and five organic solvents.
31. "What Controls the Partitioning of Nucleic Acid Bases Between Chloroform and Water?," D. J. Giesen, C. C. Chambers, C. J. Cramer, and D. G. Truhlar, Journal of Physical Chemistry, Journal of Physical Chemistry B 101, 5084-5088 (1997)
Abstract. The free energies of partitioning between water and chloroform are predicted for six nucleic acid bases using the SM5.4/A water and chloroform solvation models. We obtain a mean unsigned accuracy of 0.2 log10 units compared to experiment. Predictions are made for an additional six unnatural nucleic acid bases. Functional group contributions to the solvent-solvent partitioning phenomenon are examined and the validity of fragment-based partitioning models is assessed
32. "Parameterized Model for Aqueous Free Energies of Solvation Using Geometry-Dependent Atomic Surface Tensions with Implicit Electrostatics," G. D. Hawkins, C. J. Cramer, and D. G. Truhlar, Journal of Physical Chemistry B 101, 7147-7157 (1997).
Abstract. We present a new model for predicting aqueous solvation energies based entirely on geometry-dependent atomic surface tensions. The model is especially suited for rapid estimations on large molecules or large sets of molecules. This method is designed to be employed with gas-phase geometries to obtain solvation free energies of organic molecules containing H, C, N, O, F, S, Cl, and Br. We parameterized the model by using a training set containing 235 neutral solutes with a variety of functional groups, and we achieve a mean unsigned error of 0.55 kcal/mol when the model is applied using gas-phase geometries calculated at the Hartree-Fock level with a heteroatom-polarized valence-double-zeta basis set (HF/MIDI!) and a mean unsigned error of 0.57 kcal/mol when it is applied using gas-phase geometries from Austin Model 1 (AM1). For a smaller set of 99 solutes, we compared the new model to two previously published models based on atomic solvation parameters and we achieve a mean unsigned error of 0.56 kcal/mol as compared to 1.87 and 2.13 kcal/mol for the previous models. A simple extension is provided to allow treatment of certain kinds of charged groups. The model is expected to be especially useful for problems requiring high efficiency because of the size of the system, e. g., protein folding, or problems requiring rapid estimations because of the large number of calculations required, e. g., scoring of combinatorial libraries.
33. "Modeling Free Energies of Solvation and Transfer," D. J. Giesen, C. C. Chambers, G. D. Hawkins, C. J. Cramer, and D. G. Truhlar, in Computational Thermochemistry, edited by K. Irikura and D. J. Frurip (American Chemical Society Symposium Series, Washington, DC, 1997), in press.
Abstract. The free energy of transfer of a solute from one medium to another, which is the free energy of solvation if the first medium is the gas phase and the second is a liquid-phase solution, controls all solvation and partitioning phenomena. The SM5.4 quantum mechanical solvation model allows for the calculation of (i) partitioning free energies between the gas phase and a solvent (i.e., free energies of solvation) or (ii) partitioning free energies between two solvents. The model provides a framework for interpreting the factors responsible for differential solvation effects and can be used to predict solvation effects on chemical equilibria and kinetics--examples in this chapter include partitioning of the nucleic acid bases between water and chloroform, solvation effects on anomeric conformational equilibria, and solvation effects on the rate of the Claisen rearrangement.
34. "A Universal Solvation Model for the Quanutm Mechanical Calculation of Free Energies of Solvation in Non-Aqueous Solvents," D. J. Giesen, G. D. Hawkins, D. A. Liotard, C. J. Cramer, and D. G. Truhlar, Theoretical Chemistry Accounts 98, 85-109 (1997); erratum: 101, 309 (1999).
Abstract.The SM5.4 quantum mechanical solvation model has been extended to calculate free energies of solvation in virtually any organic solvent. Electrostatics and solute-solvent polarization are included self-consistently by the generalized Born equation with class IV charges, and first-solvation-shell effects are modeled in terms of solvent-accessible surface areas that depend on solute geometries and four solvent descriptors. The inclusion of solvent properties into the first-solvation-shell term provides a model that predicts accurate solvation free energies in any solvent for which those properties are known. The model was developed using 1786 experimentally measured solvation free energies for 206 solutes in one or more of 90 solvents. Parameters have been obtained for solutes containing H, C, N, O, F, S, Cl, Br, and I, and the solutes used for parameterization span a wide range of organic functional groups. Solvents used in the parameterization contain H, C, N, O, F, P, S, Cl, Br, and I and include the most common organic solvents. Two general parameterizations are presented here, one for use with the AM1 Hamiltonian (SM5.4/A) and one for use with the PM3 Hamiltonian (SM5.4/P). In each case, one parameter is specially re-optimized for benzene and toluene to reduce systematic errors for these solvents. Chloroform is also treated with special parameters. The final mean unsigned error for both the SM5.4/A and SM5.4/P parameterizations is less than 0.5 kcal mol-1 over the entire data set of 1786 free energies of solvation in 90 organic solvents.
35. "Modeling the effect of Solvation of Sturcture, Reactivity, and Partitioning of Organic solutes: Utility in Drug Design," C. C. Chambers, D. J. Giesen, G. D. Hawkins, W. H. J. Vaes, C. J. Cramer, and D. G. Truhlar, in Rational Drug Design, edited by D. G. Truhlar, W. J. Howe, J. M. Blaney, A. J. Hopfinger, and R. A. Dammkoehler (Springer, New York), in press.
Abstract.
36. "Singlet-Triplet Splittings and 1,2-Hydrogen Shift Barriers for Methylphenylborenide, Methylphenylcarbene, and Methylphenylnitrenium in the Gas Phase and Solution. What a Difference a Charge Makes," C. J. Cramer, D. G. Truhlar, and D. E. Falvey, Journal of the American Chemical Society 119, 12338-12342 (1997).
Abstract.
37. "Universal Quantum Mechanical Model for Solvation Free Energies Based on Gas-Phase Geometries," G. D. Hawkins, C. J. Cramer, and D. G. Truhlar, Journal of Physical Chemistry B 102, 3257-3271 (1998).
Abstract. We present a new solvation model for predicting free energies of transfer of organic solutes from the gas phase to aqueous and organic solvents. The model is based on class II charges, gas-phase geometries, a generalized Born approximation to the polarization free energy, and SM5-type atomic surface tensions. The initial parameterization of the new model was developed to utilize the MNDO/d Hamiltonian, and we also present parameters for the MNDO, AM1, and PM3 Hamiltonians. These parameterizations are based on reasonably accurate gas-phase geometries for 43 ions and 260 neutral solute molecules composed of H, C, N, O, F, S, Cl, Br, and I and containing a wide variety of functional groups. For aqueous solutions, the parameterization is based on data for 248 of the neutrals and all of the ions. For organic solvents, it is based on 1836 experimental data points for 227 of the neutral solutes in 90 organic solvents. The parameterization based on the MNDO/d Hamiltonian is called SM5.2R/MNDO/d, and it yields a mean unsigned error of 3.8 kcal/mol for the free energy of hydration of ions, and a mean unsigned error of 0.38 kcal/mol for the free energy of solvation of neutral solutes. Gas-phase geometries for all solute molecules were calculated at the Hartree-Fock level with a heteroatom-polarized valence-double-zeta basis set (HF/MIDI!), and we confirmed that the average errors increase only about 0.1 kcal/mol if we use the MNDO/d geometries.
Supplementary Material:
38. "OMNISOL: Fast Prediction of Free Energies of Solvation and Partition Coefficients," G. D. Hawkins, D. A. Liotard, C. J. Cramer, and D. G. Truhlar, Journal of Organic Chemistry 63, 4305-4313 (1998).
Abstract. The SM5.0R model for predicting solvation energies using only geometry-dependent atomic surface tensions was developed previously for aqueous solution. Here we extend it to organic solvents. The method is based on gas-phase geometries and exposed atomic surface areas; electrostatics are treated only implicitly so a wavefunction or charge model is not required (which speeds up the calculations by about two orders of magnitude). The SM5.0R model has been parameterized for solvation free energies of solutes containing H, C, N, O, F, S, Cl, Br, and I. The training set for organic solvents consists of 227 neutral solutes in 90 organic solvents for a total of 1836 data points. The method achieves a mean unsigned error of 0.38 kcal/mol when applied using gas-phase geometries calculated at the Hartree-Fock level with a heteroatom-polarized valence-double-zeta basis set (HF/MIDI!) and a mean unsigned error of 0.39 kcal/mol when applied using semiempirical molecular orbital gas-phase geometries. In related work reported here, the parameterization for predicting aqueous solvation free energies is also extended to include organic solutes containing iodine. This extension is based on 8 solutes and yields a mean unsigned error of 0.25 kcal/mol. The resulting SM5.0R model for solvation energies in aqueous and organic solvents can therefore be used to predict partition coefficients for any solute containing H, C, N, O, F, S, Cl, Br, and/or I.
Supplementary Material:
39. "Density Functional Solvation Model Based on CM2 Atomic Charges," T. Zhu, J. Li, G. D. Hawkins, C. J. Cramer, and D. G. Truhlar, Journal of Chemical Physics 109, 9117-9133 (1998).
Abstract. We extend the SM5 solvation model for calculating solvation free energies of a variety of organic solutes in both aqueous and organic solvents so that it can be employed in conjunction with high-level electronic structure calculations. The extension is illustrated by presenting three implementations based on density-functional theory (DFT). The three implementations are called SM5.42R/BPW91/MIDI!6D, SM5.42R/BPW91/DZVP, and SM5.42R/BPW91/6-31G*. They have the following features: (1) They utilize gradient-corrected DFT with polarized double zeta basis sets to describe the electronic structure of a solute. The particular exchange-correlation functional adopted is Becke’s exchange with Perdew-Wang 1991 correlation functional, usually called BPW91. The MIDI!6D, DZVP, and 6-31G* basis sets are used. (2) They employ fixed solute geometries in solvation calculations. The model is designed to predict solvation free energies based on any reasonably accurate gas-phase solute geometry. (3) The electric polarization in the solute-solvent system is described by the generalized Born approximation with self-consistent reaction-field solute partial atomic charges obtained from the CM2 charge model. (4) The solvation effects within the first solvation shell are included in the form of SM5-type atomic surface tensions. Both DFT parameterizations are developed using 275 neutral solutes and 49 ions with gas-phase Hartree-Fock/MIDI! geometries. These solutes contain a wide variety of organic functional groups which include H, C, N, O, F, P, S, Cl, Br, and I atoms. For 2135 free energies of solvation of the neutral molecules in water and 90 organic solvents, SM5.42R/BPW91/MIDI!6D, SM5.42R/BPW91/DZVP, and SM5.42R/BPW91/6-31G* yield mean unsigned errors in solvation free energies of 0.45 kcal/mol, 0.44 kcal/mol, and 0.43 kcal/mol, respectively. For 49 ions in water, SM5.42R/BPW91/MIDI!6D produces a mean unsigned error of 3.9 kcal/mol, while SM5.42R/BPW91/DZVP and SM5.42R/BPW91/6-31G* give 3.6 kcal/mol and 3.9 kcal/mol respectively.
Supplementary Material:
40. "Universal Reaction Field Model Based on Ab Initio Hartree-Fock Theory," J. Li, G. D. Hawkins, C. J. Cramer, and D. G. Truhlar, Chemical Physics Letters 288, 293-298 (1998).
Abstract. We present a model for free energies of solvation based on Hartree-Fock self-consistent-reaction-field (SCRF) calculations for electrostatics combined with atomic surface tensions (AST) for deviations from bulk electrostatics in the first solvation shell, including cavity, dispersion, and solvent-structure contributions. The SCRF part combines an ab initio treatment of the solute with solute-solvent interactions modeled using class IV charges. The AST part is parameterized for both water and general organic solvents. Mean unsigned errors are 3.9 kcal/mol for 49 ions in water and 0.46 kcal/mol for 275 neutrals in 91 solvents.
41. "Factors Controlling the Relative Stability of Anomers and Hydroxymethyl Conformers of Glucopyranose," S. E. Barrows, J. W. Storer, C. J. Cramer, A. D. French, and D. G. Truhlar, Journal of Computational Chemistry 19, 1111-1129 (1998). (special issue in honor of N. L. Allinger)
Abstract.
42. "Interface of Electronic Structure and Dynamics for Reactions in Solution," Y.-Y. Chuang, C. J. Cramer, and D. G. Truhlar, International Journal of Quantum Chemistry 70, 887-896 (1998). (Sanibel issue)
Abstract. We compare two systematic approaches to the calculation
of reaction rates in liquid solutions: the separable equilibrium solvation
(SES) approximation and the equilibrium solvation path (ESP) approximation.
These approaches are tested for two
reactions,
ClCH3 + NH3 -> Cl-? + H3CNH3+ (R1)
and
NH4+…N´H3 -> NH3 …N´H4+ (R2)
both in aqueous solution. The first reaction illustrates the
importance of variational optimization of the transition state, and the
second illustrates the importance of tunneling. Free energies of
solvation are calculated by Solvation Model 5. All calculations are
carried out by the new AMSOLRATE program, which is an interface of the
AMSOL and POLYRATE programs.
43. General Discussion (on solvent effects on 1,3-dipolar addition reactions), D. G. Truhlar and C. J. Cramer, Faraday Discussions Chemical Society 110, 477-479 (1998).
Abstract. In these discussion remarks we compare the predictions of SM5.42R/AM1 calculations of solvent effects on 1,3-dipolar addition reactions to the prediction of explicit-solvent Monte Carlo calcuations by Repaskey and Jorgensen, and we extend the calculations to larger systems. The new calculations allow us to improve and understand better the comparison of theory with experiment.
44. "Quantum Chemical Analysis of Para-Substitution Effects on the Electronic Structure of Phenylnitrenium Ions in the Gas Phase and Aqueous Solution," M. B. Sullivan, K. Brown, C. J. Cramer, and D. G. Truhlar, Journal of the American Chemical Society 120, 11778-11783 (1998).
Abstract.
45. "Universal Solvation Models," G. D. Hawkins, T. Zhu, J. Li, C. C. Chambers, D. J. Giesen, D. A. Liotard, C. J. Cramer, and D. G. Truhlar, in Combined Quantum Mechanical and Molecular Mechanical Methods, edited by J. Gao and M. A. Thompson (American Chemical Society Symposium Series volume 712, Washington, DC, 1998), pp. 201-219.
Abstract. This chapter presents an overview of the SM5 suite of universal solvation models for computing free energies of solvation in water and nonaqueous solvents. After a general review of the theoretical components of all the SM5 solvation models, we specifically compare the performance of those that have been parameterized for both aqueous and organic solvents. These are called the universal solvation models, and they include models based on semiempirical neglect of diatomic differential overlap molecular orbital theory, density functional theory, and ab initio Hartree-Fock theory, and also a model with implicit electrostatics.
46. "Analytical Energy Gradients of a Self-Consistent Reaction-Field Solvation Model Based on CM2 Charges," T. Zhu, J. Li, D. A. Liotard, C. J. Cramer, and D. G. Truhlar, Journal of Chemical Physics 110, 5503-5513 (1999).
Abstract. Analytical energy gradients have been derived for an SM5-type solvation model based on Hartree-Fock self-consistent-reaction-field theory and CM2 atomic charges. The method is combined with an analytic treatment of the first derivatives of non-electrostatic first-solvation-shell contributions to the free energy and implemented in the General Atomic and Molecular Electronic Structure package (GAMESS). The resulting equations allow one to use accurate class IV charges to calculate equilibrium geometries of solutes in liquid-phase solutions. The algorithm is illustrated by calculations of optimized geometries and solvation free energies for water, methanol, dimethyl disulfide, and 9-methyladenine in water and 1-octanol.
47. "Ethylene Polymerization by Zirconocene Catalysis," P. K. Das, D. W. Dockter, D. R. Fahey, D. E. Lauffer, G. D. Hawkins, J. Li, T. Zhu, C. J. Cramer, D. G. Truhlar, S. Dapprich, R. D. J. Froese, M. C. Holthausen, Z. Liu, K. Mogi, S. Vyboishchikov, D. G. Musaev, and K. Morokuma, in Transition State Modeling for Catalysis, edited by D. G. Truhlar and K. Morokuma (American Chemical Society Symposium Series Volume 721, Washington, DC, 1999), pp. 208-224.
Abstract.
48. "Application of a Universal Solvation Model to Nucleic Acid Bases. Comparison of Semiempirical Molecular Orbital Theory, Ab Initio Hartree-Fock Theory, and Density Functional theory," J. Li, C. J. Cramer, and D. G. Truhlar, Biophysical Chemistry 103, 3802-3803 (1999). (Special issue on Implicit Solvent Representation in Biomolecular Chemistry)
Abstract. The free energies of solvation of six nucleic acid bases (adenine, cytosine, hypoxanthine, guanine, thymine, and uracil) in water and chloroform are calculated using CM2 class IV charges and SM5.42R atomic surface tensions. Using any of three approximations to the electronic wave function, (AM1, Hartree-Fock, or DFT), we obtain good agreement with experiment for five cases where the experimental results are known for the partition coefficients between the two solvents. Decomposition of the solvation effects into bulk electrostatic contributions and first-solvation-shell effects shows that the partitioning is dominated by the former, and this illustrates the importance of using accurate partial atomic charges for modeling these molecules in aqueous solution.
49. "Extension of the Platform of Applicability of the SM5.42R Universal Solvation Model," J. Li, T. Zhu, G. D. Hawkins, P. Winget, D. A. Liotard, C. J. Cramer, and D. G. Truhlar, Theoretical Chemistry Accounts, in press.
Abstract. We present eight new parameterizations of the SM5.42R solvation model, in particular we present parameterizations for HF/MIDI!, HF/6-31G*, HF/6-31+G*, HF/cc-pVDZ, AM1, PM3, BPW91/MIDI!, and B3LYP/MIDI!. Two of the new cases are parameterized using the reaction field operator presented previously, and six of the new cases are parameterized with a simplified reaction field operator; results obtained by the two methods are compared for selected examples. For a training set of 2135 data for 275 neutral solutes containing H, C, N, O, F, S, P, Cl, Br, and I in 91 solvents (water and 90 nonaqueous solvents), seven of the eight new parameterizations give mean unsigned errors in the range 0.43?0.46 kcal/mol, and the eighth—for a basis set containing diffuse functions—gives a main unsigned error of 0.53 kcal/mol. The mean unsigned error for 49 ionic solutes (containing the same elements) in water is 3.5?3.9 kcal/mol for the HF (Hartree-Fock), BPW91 (Becke-Perdew-Wang 1991), and B3LYP (Becke three-parameter Lee-Yang-Parr) cases and 4.1 and 4.0 kcal/mol for PM3 (Parameterized Model 3) and AM1 (Austin Model 1), respectively. The methods are tested for sensitivity of solvation free energies to geometry and for predicting partition coefficients of carbonates, which were not included in the training set.
50. "Direct Dynamics for Free Radical Kinetics in Solution: Solvent Effect on the Rate Constant for the Reaction of Methanol with Atomic Hydrogen," Y.-Y. Chuang, M. L. Radhakrishnan, P. L. Fast, C. J. Cramer, and D. G. Truhlar, Journal of Physical Chemistry, in press.
Abstract.
51. "New Tools for Rational Drug Design," G. D. Hawkins, J. Li, T. Zhu, C. C. Chambers, D. J. Giesen, D. A. Liotard, C. J. Cramer, and D. G. Truhlar, in Rational Drug Design: Novel Methodology and Practical Applications, edited by A. L. Parrill and M. R. Reddy, ACS Symposium Series volume 719, Chapter 8, to be published.
Abstract. We have developed two new tools for molecular modeling that can be very useful for computer-aided drug design, namely class IV charges and the SMx series of solvation models. This contribution overviews the current status of our efforts in these areas, including the CM2 charge model and the SM5 series of solvation models. The solvation models may be used to estimate partition coefficients for phase transfer equilibria of organic solutes between water and 1-octanol, the most widely used mimic of cellular biophases, and also between water and other solvents that have been used for this purpose, e.g., hexadecane and chloroform.
52. "Implicit Solvation Models: Equilibria, Structure, Spectra, and Dynamics," C. J. Cramer and D. G. Truhlar, Chemical Reviews, to be published.
Abstract. A review.