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

Aggregation of 5,10,15,20-tetrakis(m-hydroxyphenyl)chl (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 x 10(-5) M and 0.92-29.4 x 10 -5 M, respectively. However, aggregation occurs for 4.59 x 10-5 M solutions in methanol-water mixtures for compositions > 50% wafer (v/v). The Soret b and broadens and epsilon (max) decreases; lambda (max) shows a red shift, c onsistent with a S-type structure, Possible aggregate structures are consid ered based on the known hydrogen bonding patterns in crystalline solvates o f the closely related 5,10,15,20-tetrakis(3,5-dihydroxyphenyl) Spectrophoto metric titration of m-THPC in methanol-buffer mixtures gives apparent pK(a) values of pK(3) = 3.45 and pK(4) = 1.45. The phenolic groups have pK(a) 10 .0. Comparisons are made with the corresponding porphyrin and with literatu re values on related systems. Singlet oxygen chemistry The photobleaching o f bilirubin is shown to be accelerated fivefold in the presence of a 0.05 m ol proportion of m-THPC. The accelerated reaction is slowed down in the pre sence of 2,5-dimethylfuran and of beta -carotene, providing further evidenc e by chemical reaction for the ability of m-THPC to photogenerate singlet o xygen. The relevance of these observations to clinical usage is discussed b riefly. Copyright (C) 2001 John Wiley & Sons, Ltd.