Predicting thermochemical parameters of oxygen-containing heterocycles using simple QSPR models

Abstract

Quantitative structure–property relationships for the prediction of standard enthalpies and entropies of formation as well as standard molar heat capacities for small oxygen heterocyclic compounds were developed, using 1D, 2D and 3D descriptors and experimental or computed thermochemical data. To develop the models, the data set was split into test and training sets using D-optimal experimental design to generate a diverse training set. Internal (R ² _{cross-validated} = 0.898 − 0.998) and external (R ² _{cross-validated} = 0.847 − 0.996) validation showed the models to be both stable and highly predictive. Enthalpies of formation were best described by electrotopological, atomic composition and molecular refractivity descriptors, while Kier and Hall χ and κ descriptors as well as the number of rotatable bonds appear frequently in models describing the entropy of formation of these compounds. Heat capacity models often feature the molecular area descriptor as well as the Kier and Hall ⁰χ descriptor and the number of methyl groups present in the molecule.

Keywords:

• Thermochemistry
• QSPR
• Enthalpy of formation
• Entropy of formation
• Heat capacity
• Heterocycles

Acknowledgements

The authors wish to acknowledge the Dutch Polymer Institute (DPI), Project #500, for financial support of this work. Furthermore, Brian Pauw is gratefully acknowledged for help with MatLab programming.