From owner-chemistry $#at#$ ccl.net Wed Oct 11 09:14:01 2006 From: "Christopher Cramer cramer~!~chem.umn.edu" To: CCL Subject: CCL: PCM vs. explicit water with PCM - effect on reaction profile Message-Id: <-32763-061010190121-946-8uvwtQyoolytcVgiM9JNvQ:_:server.ccl.net> X-Original-From: Christopher Cramer Content-Type: multipart/alternative; boundary=Apple-Mail-34--324735766 Date: Tue, 10 Oct 2006 17:16:14 -0500 Mime-Version: 1.0 (Apple Message framework v752.2) Sent to CCL by: Christopher Cramer [cramer**chem.umn.edu] --Apple-Mail-34--324735766 Content-Transfer-Encoding: quoted-printable Content-Type: text/plain; charset=WINDOWS-1252; delsp=yes; format=flowed > > "One thing to consider is that PCM type models are parameterized =20 > models, and the values of the parameters have been derived to fit =20 > experiments, _without_ an explicit first solvation shell. A large =20 > fraction of solvation is the first shell, and that has been =20 > absorbed by the parameters. Introducing an explicit solvation shell =20= > and then put a PCM on top of that may therefore give you a kind of =20 > double counting. Of course the cavity changes, and there are the =20 > usual problems of electron density outside the cavity, etc.... In =20 > short, there is a risk that the results will _deteriorate_ when =20 > putting in an explicit first solvation shell. > I am not aware of any study where the performance of PCM type =20 > models where the first solvation shell is considered explicitly, =20 > but if you find any, I would appreciate the reference(s). In =20 > principle such an approach should be able to provide more accurate =20 > results than a pure continuum model, but the PCM parameters may =20 > have to be returned. This, of course, is not trivial, and the =20 > optimal set of parameters may depend on which method you use for =20 > the solvent molecules (HF, DFT, MP2, etc). Sorting this out should =20 > keep you busy for a while ;-)" > Rare for me to disagree with Frank, but I would say that, if you =20 "materialize" a solvent molecule out of the continuum, your results =20 should not change if you are using a decent continuum model. The =20 exception to this rule is simple -- when the solvent molecule being =20 materialized is in fact not behaving at all like a solvent molecule, =20 but instead is part of a supersolute because it enjoys some uniquely =20 strong interaction with the solute. There are many examples of this, =20 e.g., the first coordination shell of highly charged monatomic ions =20 (where, indeed, we do not refer to the ion as an isolated species, =20 but as an aquo complex, if the solvent is water, for example). Or, =20 again using water because it is simple, an organic molecule with a =20 hydrogen bond donor and an acceptor separated by exactly one water =20 molecule's width (i.e., that water snuggles right in there and =20 becomes an intimate part of the molecule, not a typical solvent). It is true that good continuum models are parameterized to account =20 for the deviation of the first shell from bulk electrostatic =20 behavior. But, of course, if they ARE good then the materialization =20 of the solvent molecule (or the "explicitization", if you will) =20 covers the surface area being excluded with exactly the effects that =20 the model is losing, and exposes new first-shell area (the area about =20= the new piece of the supersolute) that itself will now have first =20 solvation shell effects. Way, way back in 1992 we considered this to =20 be an important test for a solvation model, and we showed, for =20 instance, that the aqueous solvation free energy for piperidine using =20= the SM2 and SM3 solvation models remained unaffected by materializing =20= first one and then a second water molecule, hydrogen bonding to the =20 two secondary amine groups. (Of course, one must use the proper =20 thermodynamic cycle to evaluate this, where the sum of the gas-phase =20 free energy of complexation plus the free energy of continuum =20 solvation for the cluster must equal the sum of the solvation free =20 energies of the isolated solute and isolated water molecules.) See =20 Cramer, C. J.; Truhlar, D. G. "Comparative Analysis of the AM1-SM2 =20 and PM3-SM3 Parametrized SCF Solvation Models for Free Energies in =20 Aqueous Solution" J. Comput.-Aid. Mol. Des. 1992, 6, 629. More recently, we have evaluated this in the context of our latest =20 solvation model, SM6, where we showed that it is indeed important to =20 materialize at leat one water in order to compute accurate solvation =20 free energies for ions having concentrated charge, and that adding =20 more waters did not have much effect when the charge was only +/- 1. =20 See Kelly, C. P.; Cramer, C. J.; Truhlar, D. G. "Aqueous Solvation =20 Free Energies of Ions and Ion-Water Clusters Based on An Accurate =20 Value for the Absolute Aqueous Solvation Free Energy of the Proton" =20 J. Phys. Chem. B 2006, 110, 16066. and its precursor Kelly, C. P.; =20 Cramer, C. J.; Truhlar, D. G. "SM6: A Density Functional Theory =20 Continuum Solvation Model for Calculating Aqueous Solvation Free =20 Energies of Neutrals, Ions, and Solute-Water Clusters" J. Chem. =20 Theory Comput. 2005, 1, 1133. And, finally, if I may plagiarize myself (assuming Wiley will be =20 reluctant to sue me), Section 12.5.4 of Essentials of Computational =20 Chemistry, entitled Mixed Explicit/Implicit Models opines: Having identified the strongest points of the explicit and implicit =20 solvent models, it seems an obvious step to try to combine them in a =20 way that takes advantage of the strengths of each. For instance, to =20 the extent first-solvation-shell effects are qualitatively different =20 > from those deriving from the bulk, one might choose to include the =20 first solvation shell explicitly and model the remainder of the =20 system with a continuum (see, for instance, Chalmet, Rinaldi, and =20 Ruiz-Lopez, 2001). There are certain instances where this approach may be regarded as an =20= attractive option. For example, Cossi and Crescenzi (2003) found that =20= accurate computation of 17O NMR chemical shifts for alcohols, ethers, =20= and carbonyls in aqueous solution required at least one explicit =20 solvent shell, but that beyond that shell a continuum could be used =20 to replace what would otherwise be a need for a much larger cluster. =20 However, just as the strengths of the two models are combined, so are =20= the weaknesses. A typical first shell of solvent for a small molecule =20= may be expected to be composed of a dozen or so solvent molecules. =20 The resulting supermolecular cluster will inevitably be characterized =20= by a large number of accessible structures that are local minima on =20 the cluster PES, so that statistical sampling will have to be =20 undertaken to obtain a proper equilibrium distribution. Thus, QM =20 methods require a substantial investment of computational resources. =20 In addition, certain technical points require attention, e.g., how =20 does one keep the first solvent shell from =91exchanging=92 with the =20 continuum since both, in principle, foster identical solvation =20 interactions? So, while there is growing interest in hybrid models of all sorts (as =20= discussed in more detail in the next chapter), the choice of a mixed =20 solvent model is not necessarily intrinsically better than a pure =20 explicit or pure implicit model. In general, unless there is a strong =20= suspicion that first-solvation-shell effects are drastically =20 different from those more typically encountered, there is no =20 particularly compelling reason to pursue a mixed modeling strategy. =20 An example of such a situation might be the aqueous coordination =20 sphere surrounding a highly charged metal cation. In that case, the =20 electrostriction of the first shell makes the water molecules more =20 ligand-like than solvent-like, and their explicit inclusion in the =20 solute complex is entirely warranted. where the references are: Chalmet, S., Rinaldi, D., and Ruiz-L=ABopez, =20= M. F. 2001. Int. J. Quantum Chem., 84, 559 and Cossi, M. and =20 Crescenzi, O. 2003. J. Chem. Phys., 118, 8863. Returning to the original post, I would say that the energy changes =20 that were reported upon inclusion of a specific solvent molecule are =20 not unusual for a case where one (or more) solvent molecules are =20 indeed playing a role as part of a supersolute. Sadly, the only way =20 to determine this is to do the experiment, but one's intuition can =20 often be good after a bit of experience. Chris -- Christopher J. Cramer University of Minnesota Department of Chemistry 207 Pleasant St. SE Minneapolis, MN 55455-0431 -------------------------- Phone: (612) 624-0859 || FAX: (612) 626-2006 Mobile: (952) 297-2575 cramer*pollux.chem.umn.edu http://pollux.chem.umn.edu/~cramer (website includes information about the textbook "Essentials of Computational Chemistry: Theories and Models, 2nd Edition") --Apple-Mail-34--324735766 Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset=WINDOWS-1252

"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=A0Cramer, 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=A0Kelly, 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=A0Kelly, 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 =91exchanging=92 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:=A0=A0Chalmet, S., Rinaldi, D., and Ruiz-L=ABopez, M. = F. 2001. Int. J. Quantum Chem., 84, 559 and=A0Cossi, 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.

Chris


--


Christopher J. Cramer

University of Minnesota

Department of Chemistry

207 Pleasant St. = SE

Minneapolis, MN 55455-0431

--------------------------

=

Phone:=A0 (612) 624-0859 || FAX:=A0 (612) 626-2006

Mobile: (952) = 297-2575

cramer*pollux.chem.umn.edu<= /FONT>

http://pollux.chem.umn.edu/~cr= amer

(website = includes information about the textbook "Essentials

=A0 =A0 of Computational = Chemistry:=A0 Theories and = Models, 2nd Edition")


= --Apple-Mail-34--324735766--