Synthesis and electrochemistry of photoantimicrobial agents based on the azine chromophore

Abstract

Photodynamic Therapy (PDT) is a ôancer treatment involving selective retention of a photoactive drug in tumour cells and tissue. Subsequent illumination with light of the correct wavelength can result in tumour destruction, generally assumed to be mediated by singlet oxygen ( 102) generated by the light-excited drug. Among such compounds, the biological stains methylene blue and toluidine blue 0, both phenothiazinium derivatives, have been widely studied with respect to their use in PDT and potential antimicrobial applications. However, studies of novel methylene blue derivatives (MBD) for PDT are scarce in the literature. We have synthesised a range of novel phenothiazinium derivatives, in particular 3,7-disubstituted analogues and explored the use of electrochemical methods in assessing their potential efficacy in PDT.
A range of phenothiaziniums were synthesised by oxidation of the appropriate precursor phenothiazines by iodine and were characterised for synthetic purposes by infrared spectroscopy, nuclear magnetic resonance, ultravioletvisible spectroscopy, mass spectrometry and thin layer chromatographic techniques.
The ability of the photosensitiser to resist reduction to the colourless Leuco form by tumour cells means that the efficiency of photosensitisation is maximised. The thermodynamic and kinetic susceptibilities of the synthesised phenothiaziniums to reductive bleaching was assessed using cyclic voltammetric and electrogravimetric methods.