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

RAYMOND BONNETT

Department of Chemistry, Queen Mary and Westfield College, Mile End Road, London E1 4NS, UK

Corresponding author, Department of Chemistry, Queen Mary and Westfield College, Mile End Road, London E1 4NS, UK.

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BIRGUL D. DJELAL

Department of Chemistry, Queen Mary and Westfield College, Mile End Road, London E1 4NS, UK

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, and

ANGELINA NGUYEN

Department of Chemistry, Queen Mary and Westfield College, Mile End Road, London E1 4NS, UK

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https://doi.org/10.1002/jpp.377Cited by:56 (Source: Crossref)

Abstract

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^-5M and 0.92–29.4 × 10^-5M, respectively. However, aggregation occurs for 4.59 × 10^-5M 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 pK_a values of pK₃ = 3.45 and pK₄ = 1.45. The phenolic groups have pK_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.

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