The effect of pH on colchicine conformation and structure

Area of Science:

• Biochemistry
• Chemical Biology
• Spectroscopy

Background:

• Colchicine is a known bioactive alkaloid with applications in medicine.
• Understanding its structural stability across different pH levels is crucial for its biological activity and formulation.
• Previous studies have not fully elucidated colchicine's conformational behavior in aqueous solutions under varying pH conditions.

Purpose of the Study:

• To investigate the structural and conformational changes of colchicine across a wide pH range (0-14).
• To determine the optimal pH conditions for colchicine stability, particularly under thermal stress.
• To provide insights into colchicine's behavior relevant to its metabolism and interactions with biological macromolecules.

Main Methods:

• UV-vis spectrophotometry was employed to analyze colchicine structure at 1.7 x 10(-5) M.
• Nuclear Magnetic Resonance (NMR) spectroscopy was utilized to study colchicine conformation at a 0.1 M concentration in D2O.
• Stability assessments were conducted at varying pH values and temperatures (40 degrees C).

Main Results:

• Colchicine exhibited a stable molecular structure in aqueous solutions within the pH range of 2 to 12.
• A complete interpretation of the colchicine NMR spectrum in deuterium oxide (D2O) was achieved.
• Colchicine stability was compromised at elevated temperatures (40 degrees C) outside the pH range of 2 to 10.

Conclusions:

• Colchicine demonstrates significant structural stability in aqueous solutions across a broad physiological pH range (2-12).
• Thermal stress necessitates a narrower pH range (2-10) for maintaining colchicine's structural integrity.
• These findings are vital for understanding colchicine's reactivity in biological systems, including metabolism and macromolecular binding.