[Hydrogen bond and acid-base interactions in erythromycin solutions]

Area of Science:

• Spectroscopy
• Physical Chemistry
• Organic Chemistry

Context:

• Erythromycin's conformational structure and association behavior in various solvents (CCl4, C2Cl4, CHCl3) were investigated.
• Infrared (IR) spectroscopy was employed to study the hydroxyl (v OH) and carbonyl (vC=O) stretching regions.

Purpose:

• To elucidate the nature of erythromycin association in solution.
• To characterize the role of hydrogen bonding in erythromycin's structure and interactions.
• To understand erythromycin's behavior in the presence of proton acceptors and acids.

Summary:

• Erythromycin association in solution is primarily mediated by hydrogen linkages between hydroxyl groups and the ester carbonyl group.
• Monomeric erythromycin exhibits intramolecular hydrogen bonding involving all hydroxyl groups, forming various ring structures.
• Association involves the disruption of some intramolecular hydrogen bonds. Strong proton acceptors (hexamethanol, trioctylphosphinoxide) interact with erythromycin, altering its IR spectrum.
• Protonization of erythromycin by monochloroacetic acid in CHCl3 occurs at the nitrogen atom, with the acid existing as an anion up to a 1:1 ratio.
• Titration with propionic acid shows different behavior in methanol versus CHCl3, indicating solvent-dependent acid-base interactions.

Impact:

• Provides fundamental insights into the solution-state behavior of erythromycin, crucial for understanding its stability, formulation, and drug delivery.
• Characterizes the specific hydrogen bonding networks that dictate erythromycin's conformation and aggregation.
• Demonstrates the influence of solvent polarity and the presence of acidic/basic species on erythromycin's structural integrity and interactions.