A new 3D molecular structure representation using quantum topology with application to structure–property relationships

Abstract

We present a new 3D molecular structure representation based on Richard F.W. Bader's quantum topological atoms in molecules (AIM) theory for use in quantitative structure–property/activity relationship (QSPR/QSAR) modeling. Central to this structure representation using quantum topology (StruQT) are critical points located on the electron density distribution of the molecules. Other gradient fields such as the Laplacian of the electron density distribution can also be used. The type of critical point of particular interest is the bond critical point (BCP) which is here characterized by using the following three parameters: electron density ρ, the Laplacian ∇ 2 ρ and the ellipticity ϵ. This representation has the advantage that there is no need to probe a large number of lattice points in 3D space to capture the important parts of the 3D electronic structure as is necessary in, e.g. comparative field analysis (CoMFA). We tested the new structure representation by predicting the wavelength of the lowest UV transition for a system of 18 anthocyanidins. Different quantitative structure–property relationship (QSPR) models are constructed using several chemometric/machine learning methods such as standard partial least squares regression (PLS), truncated PLS variable selection, genetic algorithm-based variable selection and genetic programming (GP). These models identified bonds that either take part in decreasing or increasing the dominant excitation wavelength. The models also correctly emphasized on the involvement of the conjugated π system for predicting the wavelength through flagging the BCP ellipticity parameters as important for this particular data set.