Study of the Predicted Variation of the Acidity Constant (pKa) of a Family of Chlorophenols as a Function of 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. The concept of lipophilicity, while easy to define, is nevertheless not easy to quantify. In this study, we conducted a predictive analysis of the acidity constant of sixteen (16) chlorophenols based on quantum-chemical molecular descriptors. The results obtained are satisfactory and promising regarding the prediction and explanation of the acidity constant for this family of molecules. A QSPR (Quantitative Structure-Property Relationship) model linking the acidity constant (pKa) to three molecular descriptors was developed. These molecular descriptors namely ionization energy (IE), standard entropy of formation (∆ f S 0 ), and the sum of the absolute values of Mulliken charges (Q) enable the explanation and prediction of the acidity constant for this family of molecules. This model exhibited highly satisfactory statistical and validation parameters. They indicate that the developed QSPR model is validated and performs well in predicting the acidity constant. It can therefore be used to effectively predict the acidity constant of other molecules within its applicability domain at a 95% confidence level.