Determining microscopic dissociation constants of polyprotic polyphenols using NMR spectroscopy

Area of Science:

• Organic Chemistry
• Analytical Chemistry
• Biochemistry

Background:

• Protolytic equilibrium is key to compound properties like reactivity, bioavailability, and pharmacokinetics.
• Ellagitannin deprotonation influences metal chelation, oxidation, and antibacterial activity.
• Existing methods for determining microscopic pK_as of polyprotic acids are limited in providing deprotonation site information.

Purpose of the Study:

• To determine microscopic pK_a values and deprotonation positions in ellagitannins.
• To investigate the impact of structural motifs and stereoconfiguration on ellagitannin pK_a values.
• To establish a reliable method for analyzing polyprotic acid deprotonation.

Main Methods:

• Utilized NMR spectroscopy (specifically ¹³C chemical shift pH-dependence) on methyl gallate and four ellagitannins.
• Determined microscopic pK_a values for acidic hydroxyl groups in aromatic rings.
• Established deprotonation positions by comparing experimental NMR spectra with Density Functional Theory (DFT) calculations.

Main Results:

• Successfully determined microscopic pK_a values and deprotonation sites for model compound methyl gallate and four ellagitannins.
• Identified how structural features and stereochemistry influence ellagitannin pK_a values.
• Provided insights into the oxidative and metal-chelating properties of ellagitannins based on deprotonation characteristics.

Conclusions:

• Developed a method to accurately determine microscopic pK_a values and deprotonation sites in ellagitannins.
• This method is vital for understanding the biological activity of ellagitannins.
• The approach is applicable to a broad range of polyprotic compounds for pK_a and deprotonation site determination.