Quantitative Structure-Property Relationship Modeling of the Octanol/Water Partition Coefficient of a Series of Alkylpyridines Using Quantum Chemical Descriptors

Lipophilicity is therefore the characteristic of certain substances of "liking" fatty substances. From a chemical standpoint, lipophilicity is a substance's affinity for non-polar solvents such as lipids. Lipophilicity is intimately linked to the concept of the partitioning of a molecule between an aqueous phase and a lipid phase. In this study, we modeled the octanol/water partition coefficient of a family of alkylpyridines using quantum-chemical molecular descriptors. Two molecular descriptors were calculated in this context: electronic energy (E T ) and the energy gap (ΔE gap ). QSPR (Quantitative Structure-Property Relationship) methods enabled us to correlate the octanol/water partition coefficient with these two molecular descriptors. The statistical and validation parameters are satisfactory. Statistical indicators have demonstrated a strong correlation between the octanol/water partition coefficient and these two independent variables. Validation parameters confirm that the established model is valid and performs effectively in predicting the octanol/water partition coefficient for the family of alkylpyridines studied. Consequently, it can be used to reliably predict the octanol/water partition coefficient for alkylpyridines within this same family provided they fall within the model's applicability domain at a 95% confidence level. From now on, designing new alkylpyridines with specific octanol/water partition coefficients requires only adjusting the two parameters of this model: electronic energy (E T ) and the energy gap (ΔEgap). This work will thus simplify the task for experimental chemists synthesizing this family of molecules, provided they fall within the applicability domain of the developed QSPR model.