Hi all,
I am looking at calculating transition state energies of triazoline degradation in the prodrugs I am synthesizing. It is the step between step 2 and step 3 (in the attached figure).
The protocol I am following at the moment is to use Avogadro to conduct a systematic rotor search (conformer search) to find the conformers at local minima and subsequently conduct a optimization and frequency calculations on Gaussian 09.
I am having issues with finding a suitable conformer. As Avogardo does not provide the same set of conformer every single time I conduct the "systematic rotor search". And also on conducting an energy minimization on the obtained local minima conformers the energy drops further leading to a totally new conformer.
Can you suggest any better way of doing this?
Thank you.
Regards,
Siddharth.
Dear Siddharth Sai Matikonda,
In order to calculate the activation energy of a process, you should first find the global minimum structure (GM) and NOT a local minimum.
The best way for searching the global minimum structure (GM) is by conducting a "reaction coordinate method" for some of the important dihedral angles that by changing their values the conformation of the molecule is changed and thus its energy.
I have looked at the attached figure. You should be looking on the contraction of the 8-membered ring to 7-membered ring step. Therefore, the first step in the calculation is to find the GM of the 8-membered ring entity using the reaction coordinate method. The second step is to calculate the energy for bond cleavage and bond formation (it might be that this NOT only one step; it can be two steps) and to assign the rate-limiting step according to the calculated values.
The mechanism of the reaction may be a radical one and not an ionic. Please search the literature on similar reactions in which the 8-membered ring is contracted to 7-membered ring. This may help you to assign how many steps are involved in the contraction process.
Hoping this will be helpful,
Rafik
Hoping this will be helpful,
Rafik
If you are just trying to locate the TS, there are two strategies - if you can draw a reasonable TS, then do that and use opt=(ts,calcfc,noeigentest) in G09 and that should find the TS - if you can't draw what would be a reasonable looking TS, then you can use the structure of the reactant and the structure of the products in the G09 input file along with opt=(qst2,calcfc,noeigentest) and that will find a TS along a path from reactant to products - I hope this helps -
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