(a) pEC3 predicted based on its SNAr
potential (pEC3 = -0.31*SNAr barrier +
4.90)[54] b pEC3
predicted using ACD logP
As highlighted by other researchers the prediction of skin sensitization
is a highly challenging process and that the concordance between
different in vivo , in vitro and in chemico based
methods is often no more than 60-80% in agreement with gold-standard
methods such as the LLNA assay.[8,
15, 16]
This is in part due to the fact that the LLNA response is not always a
result of direct sensitization the molecule itself, potentially arising
as a function of reactive
metabolites.[21,
64] In this case we report a purely
theoretical approach to predict a diverse set of Schiff base chemicals
– using just two relatively simple and interpretable descriptors. The
observation that the model can explain ~50-60% of the
variance in the dataset is therefore not surprising.