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The composition of Photofrin II
C J Byrne1, L V Marshallsay, A D Ward
1Department of Organic Chemistry, University of Adelaide, Australia.
Summary
Photofrin II contains an acid-stable oligomer, not dihaematoporphyrin ester. This oligomer, comprising 40% of the sample, is formed during sodium hydroxide polymerization, with dimer and trimer structures identified.
Area of Science:
- Biochemistry
- Organic Chemistry
- Photodynamic Therapy
Background:
- Photofrin II is a widely used photosensitizer in photodynamic therapy.
- Understanding its precise chemical composition is crucial for optimizing its efficacy and safety.
- Previous studies suggested the presence of various porphyrin derivatives, but a detailed structural analysis was lacking.
Purpose of the Study:
- To elucidate the exact chemical composition of Photofrin II.
- To identify and characterize the major components, particularly the acid-stable oligomeric fraction.
- To determine the structural basis of Photofrin II's properties.
Main Methods:
- High-performance liquid chromatography (HPLC) for component separation.
- Acid hydrolysis to analyze the stability and structure of components.
- Synthesis of dihaematoporphyrin ester for comparison.
- Nuclear magnetic resonance (NMR) and fast atom bombardment (FAB) mass spectrometry for structural elucidation.
- Isolation and characterization of dimer and trimer derivatives.
Main Results:
- Dihaematoporphyrin ester was confirmed as a minor component, not a significant part of Photofrin II.
- An acid-stable oligomeric material constituted approximately 40% of Photofrin II.
- A dimer and a trimer, linked by a three-carbon bridge, were isolated and structurally characterized.
- The structures of hydroxyl-containing precursors and the oligomeric material were proposed.
- The acid-stable oligomer is a product of the sodium hydroxide polymerization step in Photofrin II preparation.
Conclusions:
- Photofrin II's composition is primarily an acid-stable oligomer, not previously identified ester derivatives.
- The identified dimer and trimer structures provide insights into the aggregation of porphyrins in Photofrin II.
- The findings clarify the chemical makeup of Photofrin II, aiding in the understanding of its photodynamic therapy applications.
- The sodium hydroxide polymerization process is identified as the key step for oligomer formation.