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

Abstract

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.

Towards universal substituent constants: Parameterizing bond critical point properties with electronegativity descriptors

“…Applied to substituents, when bonded to a substrate, BCP properties at the critical point joining the two fragments give insight into the character of the substituent [25]. Group and critical point properties have been related to traditional substituent effect proxies [26]. Delocalization indices between pairs of atoms can also be calculated, Equation ().…”