Solvation modeling

In a few cases, where solvent effects are primarily due to the coordination of solute molecules with the solute, the lowest-energy solvent configuration is sufficient to predict the solvation effects. In general, this is a poor way to model solvation effects. 

The SM1-SM3 methods model solvation in water with various degrees of sophistication. The SM4 method models solvation in alkane solvents. The SM5 method is generalized to model any solvent. The SM5.42R method is designed to work with HF, DFT or hybrid HF/DFT calculations, as well as with AMI or PM3. SM5.42R is implemented using a SCRF algorithm as described below. A description of the differences between these methods can be found in the manual accompanying the AMSOL program and in the reviews listed at the end of this chapter. Available Hamiltonians and solvents are summarized in Table 24.1. 

This chapter focuses on the simulation of bulk liquids. This is a dilferent task from modeling solvation effects, which are discussed in Chapter 24. Solvation effects are changes in the properties of the solute due to the presence of a solvent. They are defined for an individual molecule or pair of molecules. This chapter discusses the modeling of bulk liquids, which implies properties that are not defined for an individual molecule, such as viscosity. 

In the presence of a severalfold excess of (i )-TFAE, an (5)-enriched sample of lactone 38a shows lowfield nonequivalence for the benzyl methylene hydrogens and highfield nonequivalence for the methyl group, in accord with the model. However (5)-enriched samples of the nitrated lactones afford different results not predicted by the usual model (solvates 39). The senses of methyl nonequivalence for... 

Of course, concerns about periodicity only relate to systems that are not periodic. The discussion above pertains primarily to the simulations of liquids, or solutes in liquid solutions, where PBCs are a useful approximation that helps to model solvation phenomena more realistically than would be the case for a small cluster. If the system truly is periodic, e.g., a zeolite crystal, tlien PBCs are integral to the model. Moreover, imposing PBCs can provide certain advantages in a simulation. For instance, Ewald summation, which accounts for electrostatic interactions to infinite length as discussed in Chapter 2, can only be carried out within the context of PBCs. 

One variation on this theme that should be borne in mind when analyzing actual chemical situations is tliat certain species in the real system may be buffered . That is, their concentrations may be held constant by external means. A good example of this occurs in condensed phases, where solvent molecules may play explicit roles in chemical equilibria but tlie concentration of the free solvent is so much larger than that for any other species that it may be considered to be effectively constant. Modeling solvation phenomena in general is covered in detail in the next two chapters, but it is instructive to consider here a particular case as it relates to computing equilibria. Consider such a reaction as... 

As a second example, we have determined the influence of solvation on the steric retardation of SN2 reactions of chloride with ethyl and neopentyl chlorides in water, which has recently been studied by Vayner and coworkers [91]. In their study solvent effects were examined by means of QM-MM Monte Carlo simulations as well as with the CPCM model. Solvation causes a large increase in the activation energies of these reactions, but has a very small differential effect on the ethyl and neopentyl substrates. Nevertheless, a quantitative difference was found between the stability of the transition states determined using discrete and continuum treatments of solvation, since the activation free energies for ethyl chloride and neopentyl chloride amount to 23.9 and 30.4kcalmoF1 according to MC-FEP simulations, but to 38.4 and 47.6 kcal moF1 from CPCM computations. 

B. Mennucci J.M. Martinez, How to model solvation of peptides Insights from a quantum mechanical and molecular dynamics study of N-methylacetamide. 2. 15N and 170 nuclear shielding in water and in acetone. J. Phys. Chem. B, 109, 9818, 9830 (2005)... 

The formaldehyde disproportionation has been examined by semi-empirical MO methods (Rzepa and Miller, 1985). With the MNDO procedure, transfer of hydride from hydrate mono-anion to formaldehyde is exothermic by 109 kJ mol-1, and the transition structure [29], corresponding to near symmetrical transfer of hydride, lies 72 kJ mol -1 above the separated reactants. Inclusion of two water molecules, to model solvation effects, stabilizes reactants and transition structures equally. Hydride transfer from the hydrate dianion was found to have a less symmetrical transition structure [30] not unexpected for a more exothermic reaction, but the calculated activation energy, 213 kJ mol-1, is unexpectedly high. Semi-classical primary kinetic isotope effects, kH/kD = 2.864 and 3.941 respectively, have been calculated. Pathways involving electron or atom transfers have also been examined, and these are predicted to be competitive with concerted hydride transfers in reactions of aromatic aldehydes. Experimental evidence for these alternatives is discussed later. 

Solvation plays a crucial role for the structure, dynamics and function of small molecules as well as for proteins and nucleic acids. When modeling solvation effects, especially for biomolecules, one often has to deal with large molecular systems and long timescales. Indeed, a proper account for solvation generally requires the inclusion of many solvent molecules, which leads to expanded system size and long simulation timescales required for capturing collective solvent response. 

Keywords Excited state properties, Polarizable Continuum Model, Solvation dynamics, Time-... 

Generahzed Bom model, solvation, 395 Generalized Bom/Surface Area (GB/SA)... 

Kinetic balance, of basis sets, 214 Kirkwood model, solvation, 395 Kirkwood-Westheimer model, solvation, 395... 

Molecular descriptors defined in order to model solvation entropy and describe dispersion interactions in solution. Taking into account the characteristic dimension of the molecules by atomic parameters, they are defined as ... 

Electric polarization, dipole moments and other related physical quantities, such as multipole moments and polarizabilities, constitute another group of both local and molecular descriptors, which can be defined either in terms of classical physics or quantum mechanics. They encode information about the charge distribution in molecules [Bbttcher et al, 1973]. They are particularly important in modelling solvation properties of compounds which depend on solute/solvent interactions and in fact are frequently used to represent the -> dipolarity/polarizability term in - linear solvation energy relationships. Moreover, they can be used to model the polar interactions which contribute to the determination of the -> lipophilicity of compounds. 

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