Solvation commonly used models

The most common approach to solvation studies using an implicit solvent is to add a self-consistent reaction field (SCRF) term to an ab initio (or semi-empirical) calculation. One of the problems with SCRF methods is the number of different possible approaches. Orozco and Luque28 and Colominas et al27 found that 6-31G ab initio calculations with the polarizable continuum model (PCM) method of Miertius, Scrocco, and Tomasi (referred to in these papers as the MST method)45 gave results in reasonable agreement with the MD-FEP results, but the AM1-AMSOL method differed by a number of kJ/mol, and sometimes gave qualitatively wrong results. 

If a solvent is to be considered as explicitly present in a simulation, obviously there must be some atomistic manner in which it is represented in the energy expression - this being the fundamental distinction from a continuum solvation model. However, since the solvent molecules greatly outnumber the solute molecule(s), there are advantages of efficiency that accrue from adopting as simple a representation as possible, and that is reflected in many of the solvent models in common use. 

Generalized Bom (GB) approach. The most common implicit models used for small molecules are the Conductor-Like Screening Model (COSMO) [77,78], the DPCM [79], the Conductor-Like Modification to the Polarized Continuum Model (CPCM) [80,81], the Integral Equation Formalism Implementation of PCM (IEF-PCM) [82] PB models, and the GB SMx models of Cramer and Truhlar [23,83-86]. The newest Minnesota solvation models are the SMD universal Solvation Model based on solute electron density [26] and the SMLVE method, which combines the surface and volume polarization for electrostatic interactions model (SVPE) [87-89] with semiempirical terms that account for local electrostatics [90]. Further details on these methods can be found in Chapter 11 of Reference [23]. 

Solvent Characteristics. In an attempt to rationalize the effect of solvent characteristics on solvation, we make use of the three-component Hansen solubility parameter model.3043 These solubility parameters are commonly used in polymer chemistry to predict the solubility of a polymer in a solvent. The Hansen solubility parameters are defined in terms of the cohesive energy density that relates to the amount of energy required to vaporize 1 mol of the solvent. 

However, %Vbur does have some limitations as a metric. Values are typically calculated from X-ray diffraction data or DFT-derived structures, which represent the solid state and gas phase, respectively. It can therefore be difficult to infer the structure in the solution phase the vast majority of the most commonly used computational solvation models do not take into account specific solvation effects, and instead apply an electric field to simulate the effect of solvent. In addition, %Vbur a static measure, and only takes into account the steric impact of the specific conformation examined. In solution, many ligands will adopt a number of conformations. Although it is possible to conduct very elegant and detailed studies assessing the dynamic behavior of ligands in specific environments [39], these studies are time-consuming and computationally expensive. 

The principle of transferability is commonly used in the construction of the intramolecular potential function of a macromolecule. It has been recently used to construct intermolecu-lar interactions or solute-solvent interaction. The main idea is to transfer the parameters describing the interaction between small molecules, e.g., methane and water, on to larger molecules, say methane-ethanol, or ethane-water. In this book we used a similar idea to extract information from small model compounds and apply it to biopolymers. The information we are interested in is the conditional solvation Gibbs energies of various groups, e.g., methyl, ethyl, hydroxyl, and so on, and intramolecular solvent-induced interactions between such groups. In this appendix we describe the methodology of this transferability principle and examine its adequacy and extent of its reliability. 

Complementing the results obtained for the study of ground electronic states in solution, many computational studies indicate that approaches exploiting continuum solvation models are very effective tools for evaluating the solvent effect on the excited-state properties. Among continuum models, the polarizable continuum model (PCM) is probably the one most commonly used. In the following, we thus focus mainly on this method [78, 82]. 

Additional factors, including the role of specific solvation and of some commonly used additives, have been included in the computational modeling of... 

The method universally employed to get round this problem is to use modd compounds to mimic the quaUtative, for example, UV, or quantitative, for example, pf, properties of the species concerned. Such models must he as dose as possible to their originals in electronic terms for example, to replace -OH by -OMe or -NH by -NMe would generally be considered acceptable, whereas replacement by -OPh or -NPh would not One of two assumptions is commonly made either substitution of H by alkyl does not affect either pK, or it affects both values equally. Equation (12.2) and Eq. (12.3) represent these two options, respectively, as they apply to amides and are chosen for illustration K, is K, for the tautomeric mixture. Almost all reported quantitative estimations involving model compounds have employed one assumption or the other [2b]. Unfortunately, both are wrong. The problem Hes in cation solvation, (Figure 12.2) the NH and OH originals are generally much better solvated than the models for them. 

From the results described above it is clear that a different QSPR model can be obtained depending on what data is used to train the model and on the method used to derive the model. This state of affairs is not so much a problem if, when using the model to predict the solubility of a compound, it is clear which model is appropriate to use. The large disparity between models also highlights the difficulty in extrapolating any physical significance from the models. Common to all models described above is the influence of H-bonding, a feature that does at least have a physical interpretation in the process of aqueous solvation. 

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