CCL: PCM vs. explicit water with PCM - effect on reaction profile

"One thing to consider is that PCM type models are parameterized models, and the values of the parameters have been derived to fit experiments, _without_ an explicit first solvation shell. A large fraction of solvation is the first shell, and that has been absorbed by the parameters. Introducing an explicit solvation shell and then put a PCM on top of that may therefore give you a kind of double counting. Of course the cavity changes, and there are the usual problems of electron density outside the cavity, etc.... In short, there is a risk that the results will _deteriorate_ when putting in an explicit first solvation shell.
I am not aware of any study where the performance of PCM type models where the first solvation shell is considered explicitly, but if you find any, I would appreciate the reference(s). In principle such an approach should be able to provide more accurate results than a pure continuum model, but the PCM parameters may have to be returned. This, of course, is not trivial, and the optimal set of parameters may depend on which method you use for the solvent molecules (HF, DFT, MP2, etc). Sorting this out should keep you busy for a while ;-)"

Rare for me to disagree with Frank, but I would say that, if you "materialize" a solvent molecule out of the continuum, your results should not change if you are using a decent continuum model. The exception to this rule is simple -- when the solvent molecule being materialized is in fact not behaving at all like a solvent molecule, but instead is part of a supersolute because it enjoys some uniquely strong interaction with the solute. There are many examples of this, e.g., the first coordination shell of highly charged monatomic ions (where, indeed, we do not refer to the ion as an isolated species, but as an aquo complex, if the solvent is water, for example). Or, again using water because it is simple, an organic molecule with a hydrogen bond donor and an acceptor separated by exactly one water molecule's width (i.e., that water snuggles right in there and becomes an intimate part of the molecule, not a typical solvent).

It is true that good continuum models are parameterized to account for the deviation of the first shell from bulk electrostatic behavior. But, of course, if they ARE good then the materialization of the solvent molecule (or the "explicitization", if you will) covers the surface area being excluded with exactly the effects that the model is losing, and exposes new first-shell area (the area about the new piece of the supersolute) that itself will now have first solvation shell effects. Way, way back in 1992 we considered this to be an important test for a solvation model, and we showed, for instance, that the aqueous solvation free energy for piperidine using the SM2 and SM3 solvation models remained unaffected by materializing first one and then a second water molecule, hydrogen bonding to the two secondary amine groups. (Of course, one must use the proper thermodynamic cycle to evaluate this, where the sum of the gas-phase free energy of complexation plus the free energy of continuum solvation for the cluster must equal the sum of the solvation free energies of the isolated solute and isolated water molecules.) See Cramer, C. J.; Truhlar, D. G. "Comparative Analysis of the AM1-SM2 and PM3-SM3 Parametrized SCF Solvation Models for Free Energies in Aqueous Solution" J. Comput.-Aid. Mol. Des. 1992, 6, 629.

More recently, we have evaluated this in the context of our latest solvation model, SM6, where we showed that it is indeed important to materialize at leat one water in order to compute accurate solvation free energies for ions having concentrated charge, and that adding more waters did not have much effect when the charge was only +/- 1. See Kelly, C. P.; Cramer, C. J.; Truhlar, D. G. "Aqueous Solvation Free Energies of Ions and Ion-Water Clusters Based on An Accurate Value for the Absolute Aqueous Solvation Free Energy of the Proton" J. Phys. Chem. B 2006, 110, 16066. and its precursor Kelly, C. P.; Cramer, C. J.; Truhlar, D. G. "SM6: A Density Functional Theory Continuum Solvation Model for Calculating Aqueous Solvation Free Energies of Neutrals, Ions, and Solute-Water Clusters" J. Chem. Theory Comput. 2005, 1, 1133.

And, finally, if I may plagiarize myself (assuming Wiley will be reluctant to sue me), Section 12.5.4 of Essentials of Computational Chemistry, entitled Mixed Explicit/Implicit Models opines:

Having identified the strongest points of the explicit and implicit solvent models, it seems an obvious step to try to combine them in a way that takes advantage of the strengths of each. For instance, to the extent first-solvation-shell effects are qualitatively different from those deriving from the bulk, one might choose to include the first solvation shell explicitly and model the remainder of the system with a continuum (see, for instance, Chalmet, Rinaldi, and Ruiz-Lopez, 2001).
There are certain instances where this approach may be regarded as an attractive option. For example, Cossi and Crescenzi (2003) found that accurate computation of 17O NMR chemical shifts for alcohols, ethers, and carbonyls in aqueous solution required at least one explicit solvent shell, but that beyond that shell a continuum could be used to replace what would otherwise be a need for a much larger cluster. However, just as the strengths of the two models are combined, so are the weaknesses. A typical first shell of solvent for a small molecule may be expected to be composed of a dozen or so solvent molecules. The resulting supermolecular cluster will inevitably be characterized by a large number of accessible structures that are local minima on the cluster PES, so that statistical sampling will have to be undertaken to obtain a proper equilibrium distribution. Thus, QM methods require a substantial investment of computational resources. In addition, certain technical points require attention, e.g., how does one keep the first solvent shell from ‘exchanging’ with the continuum since both, in principle, foster identical solvation interactions?
So, while there is growing interest in hybrid models of all sorts (as discussed in more detail in the next chapter), the choice of a mixed solvent model is not necessarily intrinsically better than a pure explicit or pure implicit model. In general, unless there is a strong suspicion that first-solvation-shell effects are drastically different > from those more typically encountered, there is no particularly compelling reason to pursue a mixed modeling strategy. An example of such a situation might be the aqueous coordination sphere surrounding a highly charged metal cation. In that case, the electrostriction of the first shell makes the water molecules more ligand-like than solvent-like, and their explicit inclusion in the solute complex is entirely warranted.

where the references are:  Chalmet, S., Rinaldi, D., and Ruiz-L«opez, M. F. 2001. Int. J. Quantum Chem., 84, 559 and Cossi, M. and Crescenzi, O. 2003. J. Chem. Phys., 118, 8863.

Returning to the original post, I would say that the energy changes that were reported upon inclusion of a specific solvent molecule are not unusual for a case where one (or more) solvent molecules are indeed playing a role as part of a supersolute. Sadly, the only way to determine this is to do the experiment, but one's intuition can often be good after a bit of experience.



Christopher J. Cramer

University of Minnesota

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    of Computational Chemistry:  Theories and Models, 2nd Edition")