Screening Substrates
Another common use of AARON is to make predictions for a given ligand/catalyst for different substrates. This can be done for any substrate that can be formed by performing substitutions on the substrate present in the TS template library. The substitutions are specified within the a '&Substrates' section of the AARON input file.
We will again use the bipyridine-N,N'-dioxide catalyzed allylation of aromatic aldehydes as an example. This time, however, we'll consider benzaldehydes with substitutions at atom 14:
Note that you need always to specify at least one ligand. This ligand can be just the ligand present in the TS library ('None') or some new ligand or substituted ligand.
The input file below will request all TS structures be computed for the allylation of substituted benzaldehyde for substrates constructed by replacing atom 14 with CN and F using the ligand present in the TS library (bipyridine-N,N'-dioxide):
reaction_type=Allylation template=NN-dioxide_example charge=1 method=b97d denfit=true basis=6-31G &Ligands Cat1: None & &Substrates Sub1: 14=CN Sub2: 14=F &
AARON can also screen multiple catalysts/ligands over multiple substrates.
We will consider the same two substrates as in Example 1, but now we will make predictions for bi-isoquinoline-N,N'-dioxide and a fluorinated analogue.
reaction_type=Allylation template=NN-dioxide_example charge=1 method=b97d denfit=true basis=6-31G &Ligands Cat3: ligand=bi-isoquinoline-NN-dioxide Cat4: ligand=bi-isoquinoline-NN-dioxide 14=F 17=F & &Substrates Sub1: 14=CN Sub2: 14=F &
Note that AARON will actually make predictions for six different systems. First, it will compute all TS structures for the new catalysts with the original substrate found in the TS library:
Cat3/Cat3 Cat4/Cat4
It will then use these structures as templates for the two new catalysts applied to the two new substrates formed by performing the requested substitutions:
Cat3/Cat3-Sub1 Cat3/Cat3-Sub2 Cat4/Cat4-Sub1 Cat4/Cat4-Sub2
In general, AARON will also automatically detect and rotate any rotatable substituent on the catalyst/ligand (regardless of whether you added it or not!).
For the substrate, however, only newly added substituents will be rotated. This has important implications when you replace equivalent hydrogens.
For instance, suppose you have a TS library with a Me group on the substrate. If you want to make predictions for a benzyl group at this position, your first instinct might be to request that AARON replace one of the hydrogens of the Me group with Ph. However, this will result in AARON only considering rotamers of the added Ph group. In reality, you will want to consider the rotamers of the new benzyl group. As such, in such cases you should request that AARON replace the Me group with Bn.