vitalys 发表于 2024-1-22 11:29
Thank you very much for the valuable informations, It's really helpful.
Considering what you expl ...

You can calculate the non-covalent complex in the same way as you calculate any molecule: just draw the structure of the complex, optimize it, calculate frequencies, and calculate the single point energy. But note that you will probably have to do a configurational search, if you don't already know what the binding configuration is.
With so large negative activation energies, I would recommend you to try to locate the non-covalent reactant complex. Then, if you still observe negative activation energies whose magnitude is within e.g. 1 kcal/mol, you can explain it away by my explanation (2), and this is normally accepted.

Negative activation energies are actually possible, for example when:
(1) A and B forms a non-covalent complex exothermically, and the barrier from the non-covalent complex to the TS is smaller than the energy released upon forming the non-covalent complex. In this case, if you calculate the activation energy from the energies of the separate reactants A and B, you get a negative activation energy.
Or
(2) you are not using the same level of theory for the geometry optimization and single point energy calculations. Even if the activation energy is positive at the level of theory used in the geometry optimization, there is clearly no guarantee that it is still positive at the level of theory used in the single point energy calculations, because you changed the level of theory.