Quantum Molecular Similarity. 1. BCP Space

Abstract

We propose a new similarity measure operating in an abstract space spanned by properties evaluated at bond critical points defined by the theory of Atoms in Molecules. Consequently, we represent molecules compactly and reliably, extracting the relevant information from their ab initio wave function. Typical problems of continuous quantum similarity measures are thereby avoided. The practical use of this novel method is adequately illustrated via the Hammett equation for para and meta substituted benzoic acids. On the basis of our definition of distances between molecules in BCP (Bond Critical Point) space, we are able to reproduce the experimental sequence of acidities determined by the well-known σ constant of a set of substituted congeners. Moreover, our approach points out where the common reactive center of the molecules is. Due to these promising results we embark on a research program systematically addressing further issues outlined in this work. The generality and feasibility of our approach will enable predictions in medically related QSARs.

Special issue: Philosophical aspects and implications of the quantum theory of atoms in molecules (QTAIM)

“…The delocalization indices have been used to construct predictive physical models that accurately predict proton-proton (Matta et al 2002) and fluorine-fluorine (Castillo et al 2005) NMR coupling constants. A brilliant research program termed the quantum topological molecular similarity (QTMS), developed by Popelier, has demonstrated the exceptional capability of bond properties to encode and summarize molecular properties and predict not only drug activity but even pinpoint the location of the active site within the molecule (Popelier 1999;O'Brien and Popelier 2001).…”

“…Since the theory affords predictions that can be tested by experiment then QTAIM is a falsifiable theory in Popper's (1959) sense. Furthermore, the theory has never been falsified, despite the occasional claims based on either improper application, lack of understanding, or over-interpretation.…”

An alignment‐free methodology for modelling field‐based 3D‐structure activity relationships using inductive logic programming

“…A detailed description of these critical points is beyond the scope of this discussion, but as an example the bond critical point is the AIM definition of a bond between two atoms. The properties of these critical points are a very useful representation of molecular structure [48][49][50][51][52] as they both contain a lot of information and relate to classical chemical concepts. StruQT-ILP uses the critical points in the electron density and its connections along with a set of high-level background programs defining for instance chemical substructures (benzene ring, nitro group etc.)…”

Molecular Quantum Similarity: Theory and Applications

“…Popelier et al [155][156][157][158][159] proposed a new similarity measure operating in an abstract space spanned by properties evaluated at bond critical points defined by the theory of AIM. This measure gives rise to a field known as quantum toplogical molecular similarity, and is used, among others, to develop QSP/AR models such as toxicity predictors.…”