Synthesis, photophysical properties, and in vitro photodynamic activities of new silicon(IV) phthalocyanines

This thesis describes the synthesis, spectroscopic characterisation, and photo-physical and biological properties of a series of novel silicon(IV) phthalocyanines which are potentially useful as second-generation photosensitisers for photodynamic therapy.; Chapter 1 presents an overview of photodynamic therapy, including its historical development, current clinical status, and photophysical and biological mechanisms. Some representative photosensitisers are also reviewed.; Chapter 2 describes two silicon(IV) phthalocyanines containing poly(ethylene glycol) chains at the axial positions, including their synthesis, spectroscopic characteristics and photophysical properties. Their complexation with bovine serum albumin and in vitro photodynamic activities towards HepG2 human hepatocarcinoma cells and J774 mouse macrophage are also reported.; A novel series of silicon(IV) phthalocyanines substituted axially with one or two 1,3-bis(dimethylamino)-2-propoxy group(s) are described in Chapter 3. These compounds are essentially non-aggregated in common organic solvents and show a weak fluorescence emission, while their methylated derivatives are also non-aggregated even in aqueous media and exhibit a strong fluorescence emission.{09}The photocytotoxicities of these compounds against HepG2 and J774 cells have also been investigated. These new phthalocyanines, in particular the unsymmetrical and amphiphilic analogues, are highly potent with IC50 values down to 20 nM. The cellular uptake and subcellular localisation of these compounds have also been studied by fluorescence microscopy. The unsymmetric phthalocyanine SiPc[OC3H5(NMe2 )2](OMe) has a high and selective affinity to the mitochondria of HepG2 cells.; Chapter 4 discusses the photodynamic effects of a series of silicon(IV) phthalocyanines with different axial substituents against HT29 and T84 human colon adenocarcinoma cells, with the long-term goal of developing efficient photosensitising agents for colorectal cancer.{09} While these compounds are not cytotoxic in the absence of light, they exhibit high photocytotoxicities with IC50 values as low as 17 nM.; Chapter 5 reports the synthesis and characterisation of a series of halogenated silicon(IV) phthalocyanines substituted axially with poly(ethylene glycol), 1,3-bis(dimethylamino)-2-propoxy or isopropylidene-protected galactose groups, with the goal of enhancing the photosensitising properties by heavy atom effect. (Abstract shortened by UMI.)...