Solvation models for molecular properties

SOLVATION MODELS FOR MOLECULAR PROPERTIES CONTINUUM VERSUS DISCRETE APPROACHES... 

Solvent continuum models are now routinely used in quantum mechanical (QM) studies to calculate solvation effects on molecular properties and reactivity. In these models, the solvent is represented by a dielectric continuum that in the presence of electronic and nuclear charges of the solute polarizes, creating an electrostatic potential, the so-called reaction field . The concept goes back to classical electrostatic schemes by Martin [1], Bell [2] and Onsager [3] who made fundamental contributions to the theory of solutions. Scholte [4] and Kirkwood [5] introduced the use of multipole moment distributions. The first implementation in QM calculations was reported in a pioneer work by Rivail and Rinaldi [6,7], Other fundamental investigations were carried out by Tapia and Goscinski [8], Hilton-McCreery et al. [9] and Miertus et al. [10], Many improvements have been made since then (for a review,... 

Given the diversity of different SCRF models, and the fact that solvation energies in water may range from a few kcal/mol for say ethane to perhaps 100 kcal/mol for an ion, it is difficult to evaluate just how accurately continuum methods may in principle be able to represent solvation. It seems clear, however, that molecular shaped cavities must be employed, the electiostatic polarization needs a description either in terms of atomic charges or quite high-order multipoles, and cavity and dispersion terms must be included. Properly parameterized, such models appear to be able to give absolute values with an accuracy of a few kcal/mol." Molecular properties are in many cases also sensitive to the environment, but a detailed discussion of this is outside the scope of this book. ... 

In common with similar approaches that relate solvent accessible surface to cavity free energy90-93, the simple SMI model required careful parameterization, and assumed that atoms interacted with solvent in a manner independent of their immediate molecular environment and their hybridization76. In more recent implementations of the SMx approach, ak parameters are selected for particular atoms based on properties determined from the SCF wavefunction that is evaluated during calculation of the solute and solvent polarization energies27. On the other hand, the inclusion of more parameters in the solvation model requires access to substantial amounts of experimental data for the solvation free energies of molecules in the training set94 95. 

How well can continuum solvation models distinguish changes in one or another of these solvent properties This is illustrated in Table 2, which compares solvation energies for three representative solutes in eight test solvents. Three of the test solvents are those shown in Table 1, one is water, and the other four were selected to provide useful comparisons on the basis of their solvent descriptors, which are shown in Table 3. Notice that all four solvents in Table 3 have no acidity, which makes them more suitable, in this respect, than 1-octanol or chloroform for modeling biomembranes. Table 2 shows that the SM5.2R model, with gas-phase geometries and semiempirical molecular orbital theory for the wave function, does very well indeed in reproducing all the trends in the data. 

Most continuum models are properly referred to as equilibrium solvation models. This appellation emphasizes that the design of the model is predicated on equilibrium properties of the solvent, such as the bulk dielectric constant, for instance. The amount of time required for a solvent to equilibrate to the sudden introduction of a solute (i.e., the solvent relaxation time) varies from one solvent to another, but typically is in the range of molecular vibrational and rotational timescales, which is to say on the order of picoseconds. 

Effects of solvation on zwitterion formation between methylamine and fom-aldehydewere studied by various solvation methods. The SM2/AM1 model predicted the expected zwitterionc minimum while SM3/PM3 failed to do so [127]. Calculations were performed with the use of AMSOL to account for solvation effects in the study of molecular properties and pharmacokinetic behavior of ce-tirizine, a zwitterionic third-generation antihistaminic. Results indicated that the folded conformation remains of low energy not only in vacuo but also in water solution [128]. 

T. Vreven, B. Mennucci, C. O. da Silva, K. Morokuma and J. Tomasi, The ONIOM-PCM method Combining the hybrid molecular orbital method and the polarizable continuum model for solvation. Application to the geometry and properties of a merocyanine in solution, J. Chem. Phys., 115 (2001) 62-72. 

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