Physical and chemical studies related to the development of m-THPC (FOSCAN®) for the photodynamic therapy (PDT) of tumours

✍ Scribed by Raymond Bonnett; Birgul D. Djelal; Angelina Nguyen

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 149 KB
• Volume: 05
• Category: Article
• ISSN: 1088-4246
• DOI: 10.1002/jpp.377

✦ Synopsis

Aggregation of 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (m-THPC) is observed not to occur in methanol or in ethanol:polyethyleneglycol 300:water = 2:3:5 (v/v) in the concentration range of 0.46–73.4 × 10^-5^M and 0.92–29.4 × 10^-5^M , respectively. However, aggregation occurs for 4.59 × 10^-5^M solutions in methanol–water mixtures for compositions >50% water (v/v). The Soret band broadens and ε~max~decreases; λ~max~shows a red shift, consistent with a J-type structure. Possible aggregate structures are considered based on the known hydrogen bonding patterns in crystalline solvates of the closely related 5,10,15,20-tetrakis(3,5-dihydroxyphenyl)porphyrin. Spectrophotometric titration of m-THPC in methanol–buffer mixtures gives apparent p K~a~values of p K~3~= 3.45 and p K~4~= 1.45. The phenolic groups have p K~a~= 10.0. Comparisons are made with the corresponding porphyrin and with literature values on related systems. Singlet oxygen chemistry. The photobleaching of bilirubin is shown to be accelerated fivefold in the presence of a 0.05 mol proportion of m-THPC. The accelerated reaction is slowed down in the presence of 2,5-dimethylfuran and of β-carotene, providing further evidence by chemical reaction for the ability of m-THPC to photogenerate singlet oxygen. The relevance of these observations to clinical usage is discussed briefly.