Computing reaction mechanisms using solvation effects

Question

I am about to compute reaction steps for a series of compounds using DFT. A key point in our discussion is the dependency of the experimental rate of reaction w.r.t. solvent used, so it is very important that we incorporate solvation effects in our computational models.

I am aware of the best practices in choosing functionals, dispersion corrections, basis sets, etc.. By reading a little I decided on using the SMD model for implicit solvation. I may use either ORCA or NWChem.

My questions are:

1. a. Should geometries be optimised in solvent, in the gas phase or both? b. In case I use only gas phase geometries, should I calculate frequencies using implicit solvation (I doubt) or can I use the calculated free energy of solvation (done in a single point calculation) to correct the gas phase free energy?
2. a. In case I decide on using (one or two) explicit solvent molecules to better model the system, are there best practices on using them together with an implicit solvation model (in terms of calculating free energy of solvation and in deciding when it has converged/is adequate)? b. What about the points addressed in 1. (gas phase versus condensed optimisation and frequency calculations) for this case?

References from literature are greatly appreciated. I am looking forward to hear from you!

Answer 1

1) Yes, geometries must be calculated both in the gas phase and in the solvent. To analize your results in the solvent you need something to compare that's why the gas phase calculation is always needed and often is considered "the only source of truth".

Frequencies must be calculated both in the solvent and in the gas phase as well, on the respective converged geometries.

2) I never worked with explicit solvent but I feel that the use cases of two methods are not overlapping. When performing calculations on a multi step reaction usually you don't have enough computational resources to calculate all the solvent molecules needed. This is why people use implicit solvent calculations. If you want to benchmark your solvent calculations, compare it with the gas phase ones and evaluate wether there is some improvement in the replication of experimental data.

Answer 2

For explicit solvent interactions I would recommend for example FDE (Frozen-Density-Embedding) or embedding techniques in general.

In FDE the subsystems (solvent/solute molecules) "see" only the electron density of the other subsystems.

One problem you should consider when calculation with explicit solvent interactions is that molecules move all the time.

So to really get accurate measurements for that case you should consider doing an MD simulation to get a couple of snapshots for your QM-Level energy calculations.

Since this will get extremely expensive for your case, I wouldn't recommend using explicit interactions.

If you omit explicit interactions, consider using a Continuum Solvation model like COSMO/PCM or force field methods.

Optimize your geometries in gas phase (so you have a converged geometry already), but for calculations, optimize them again with solvent environments.

The change might not be big, but can be significant nonetheless.