Toward Universal Substituent Constants: Relating QTAIM Functional Group Descriptors to Substituent Effect Proxies

Substituents modulate reactions, but their effects are
commonly
described by using proxies to their functional group properties. Substituent
descriptors from the quantum theory of atoms in molecules, which are
true functional group properties, are related here to these proxies,
which have historically had chemically relevant meaning. Due to the
large number of descriptors, multivariate analysis is used to intuit
their significance. Multiple linear regression, principal component,
and partial least squares regression analyses highlight that these
substituent descriptors contain similar information to the proxies
while being intrinsic, predictable substituent properties. Sources
of error limiting quantitative reproduction of the proxy data include
transferability, experimental accuracy, and solvation issues.