[Various properties of erythromycin basicity]

Area of Science:

• Pharmaceutical Chemistry
• Physical Chemistry

Background:

• Erythromycin (Er) is a weak base with unique solution properties.
• Its basicity decreases upon storage, particularly at elevated temperatures.

Purpose of the Study:

• To investigate the degradation of erythromycin's basicity in aqueous solutions.
• To explore methods for restoring the lost basic properties of erythromycin.

Main Methods:

• Monitoring pH changes in erythromycin solutions over time and temperature.
• Assessing the effect of adding Lewis bases (e.g., DMSO, DMF) on stored erythromycin solutions.
• Comparing erythromycin's behavior in aqueous vs. chloroform solutions.

Main Results:

• Aqueous erythromycin solutions exhibit a decrease in basicity (dpH/dt = -0.03 between 10-25°C).
• Addition of Lewis bases partially restored the basicity of stored erythromycin.
• Erythromycin protonization in chloroform showed normal thermodynamic and kinetic behavior.

Conclusions:

• Aqueous erythromycin undergoes a transformation, likely involving intramolecular or intermolecular interactions.
• These interactions may shield the tertiary nitrogen atom, forming a nitrogen linkage and reducing basicity.
• The observed changes are specific to aqueous solutions and are reversible with certain additives.