Photophysical evaluation of substituted zinc phthalocyanines as sensitisers for photodynamic therapy

Abstract

Zinc phthalocyanines (ZnPc) are currently being investigated in relation to their use as sensitisers for Photodynamic Therapy (PDT). In particular, the photophysical properties of these dyes are of interest since then- ability to generate the cytotoxic species, singlet oxygen ((^1)O(_2)), is believed to be central to their role in causing tumour necrosis. In this study, a detailed investigation of the photophysical properties of substituted zinc phthalocyanines under various conditions is described. Two novel β-tetra substituted zinc phthalocyanines have been synthesised, ZnPc(CMe(C0(_2)Me)(_2))(_4) and ZnPc(CHMeCO(_2)H)(_4). The nature of peripheral substituents has little effect on triplet state or singlet oxygen production by ZnPc, however, ZnPc(CHMeCO(_2)H)(_4) displays a remarkable sensitivity to the ionic strength of non aqueous solutions. Ion concentrations below 10(^-4) mol dm(^-3) induce dimerisation whilst concentrations greater than this promote monomerisation. This behaviour is attributed to ion pairing effects. Photophysical properties of substituted zinc phthalocyanines in heterogenous media and on solid substrates are also described. The temperature and pH of solvent media greatly influence the photophysical properties of phtiialocyanines. Octadecyl zinc phthalocyanine (C10) aggregates upon cooling to 77 K in ether-pentane-alcohol (5:5:2) solution. Additional structure in the absorption spectrum is observed, accompanied by the appearance of a fluorescence emission band at 760 nm. Aluminium phthalocyanine chloride in methanol dimerises upon addition of 2.5 x 10(^-5) mol dm(^-3) fluoride ions. Dimer species are characterised by a blue shifted peak in the absorption spectrum and are non-fluorescent. These results are ascribed to different aggregate geometries and discussed in terms of exciton theory. Low pH induces stepwise protonation of the azomethine bridges of the phthalocyanme ring, Pc + nH(^+) PcH(_n)(^n+)+, where n = 0 to 4. Protonation results in significant changes in absorption, fluorescence and triplet state properties of the phthalocyanine. A dramatic decrease in singlet oxygen generation by the phthalocyanine (ɸ∆ (n = 0) = 0.54, ɸ∆ (n = 1) = 0.075) is reported, and occurs under surprisingly mild conditions (pK(_a) of ZnPcS(_2) in 1% Triton X-100/H(_2)O = 4.4). The propensity of ZnPc's to bind to serum protein and to participate in electron transfer reactions with potential electron donors is discussed.