Did you do geometry optimization with each functional? Any large differences between the two structure? Any transition metals in the system? Did you use solvation models? Better provide more information of your system and the calculations for identifying the sources of the differences.

Hi Peng,

I have done a geometry optimisation with every functional on the same structure and the structure has a metal (Os) using the same solvation model.

Why there is a big difference in the free energy of reaction. Although M06-2X is not recommended for transition metals but it works very well kinetically.

Does the optimized structures from two methods exhibit large differences? If so, it may be one source for the big differences.

Metal ions could also be one source. You can try different ECP potentials/basis sets for the metal ion. You are right, M06-2X is not recommended for transition metals. I suggest you try M06 or M05 instead, if you want to keep the Minnesota functionals.

Large polarizable atoms such as S, Br, I etc. could be a major source of the free energy differences. For non-metal systems, M06-2X works better.

The solvation model is critical for calculating the reaction free energies. If you are using SMD solvation model, you can consider to try the sSAS approach, which introduces a scaling factor and the solvent accessible surface of the default SMD model. When coupled with M06-2X, it works well for non-metal systems, even with polarizable atoms such as S. But you probably have to optimize the scaling factor for your system. Here is the reference:

Article Quantum Chemical Calculation of pKas of Environmentally Rele...

Hi,

I think that the reason behined this is that M06-2X has higher HF% than B3LYP and then you will always get lower energies. Anyway, thank you very much.