Hi all,

I am trying to locate the transition state of a transimination reaction in DMol³ (Materials Studio) using an explicit amine proton shuttle.

The system consists of:

• an imine 
• a nucleophilic amine
• a second amine acting as a proton shuttle

The target is the TS leading first to a proton-transferred aminoaminal intermediate (pictures) or even simulate the "whole" Transimination in one step if possible somehow. Final goal is to determine the Ea of the reaction. 

So far I have:

• optimized reactant and product minima,
• performed multiple Reactant Preview and Product Preview LST/QST searches,
• tested manually preorganized reactant complexes,
• performed constrained geometry optimizations along the forming C–N bond.

The problem is that Reactant Preview and Product Preview consistently converge to essentially the same region of the PES. The resulting TS candidates show several imaginary frequencies rather than a single one, and the corresponding modes mainly describe intermolecular reorganization of the amine/shuttle complex rather than the expected bond-forming reaction coordinate.

I also constrained the forming C–N distance (2.5, 2.0, and 1.5 Å) and optimized the remaining geometry. Even with an almost fully formed C–N bond, the rest of the system reorganized only slightly, suggesting that the reaction coordinate is not described by C–N formation alone.

At this point I suspect that the actual mechanism may involve multiple elementary steps and that DMol³ is repeatedly finding a preorganization/reorientation saddle point rather than the chemical TS.

How would you proceed?

• Separate the mechanism into multiple steps?
• Search for a proton-transfer TS first?
• Use TS optimization from a manually constructed TS guess?

Any suggestions or similar experiences would be greatly appreciated.