Chromatographic hydrophobicity index: pH profile for polyprotic compounds

Area of Science:

• Analytical Chemistry
• Physical Chemistry
• Biochemistry

Background:

• Hydrophobicity is a critical parameter in drug discovery and chemical analysis.
• Measuring hydrophobicity across different pH values is challenging for ionizable compounds.
• The Chromatographic Hydrophobicity Index (CHI) is a key metric for quantifying hydrophobicity.

Purpose of the Study:

• To develop a general equation for modeling the pH-dependent variation of CHI in polyprotic compounds.
• To assess the applicability of the proposed model to various diprotic solutes.
• To provide a simplified method for calculating CHI at any pH.

Main Methods:

• Experimental measurement of CHI for selected diprotic compounds.
• Development and application of a general equation for polyprotic compounds.
• Analysis of model fits for neutral acids, neutral bases, and amphiprotic compounds (zwitterionic and non-zwitterionic).

Main Results:

• The proposed model accurately fits the experimental CHI data for all tested solute types.
• The neutral form of compounds generally exhibits the highest hydrophobicity, with exceptions like zwitterionic phenylalanine.
• The derived equation and parameters enable straightforward CHI calculation at any given pH.

Conclusions:

• The developed model offers a robust approach for predicting CHI across a pH range for polyprotic compounds.
• This method enhances the understanding of hydrophobicity variations in complex chemical systems.
• The model facilitates the accurate estimation of compound hydrophobicity, crucial for various scientific disciplines.