Community Research and Development Information Service - CORDIS

PDT photosensitisers derived from chlorophyll and bacteriochlorophyll

This joint chemical project concerns the development of new photosensitisers suitable for use in the treatment of tumours using photodynamic therapy. A feature of the work is to use naturally-occurring substances, chlorophyll and bacteriochlorophyll, as the starting materials, and this direction rests on the experience in the Moscow laboratory in the isolation of photosensitisers from these sources.

On the synthetic side, several new photosynthesisers have been made, revealing new aspects of chlorophyll and bacteriochlorophyll chemistry. Thus the regioselective reduction of the exocyclic anhydride ring of compounds of the purpurin 18 series gives δ-lactones, whereas oxidative cyclization of purpurin 18 free acid gives a product with a δ-lactone fused onto ring D. Reactions at the C-3 vinyl group have been examined, and the formation of novel cyclic imides and cyclic hydroxamic acids from purpurin 18 derivatives has been explored.

On the biological side, preliminary in vivo and in vitro bioassays have now been carried out in Moscow on purpurin 18 derivatives with spacer groups.
Photophysical studies have continued in Minsk on a series of compounds provided by the London and Moscow Laboratories. Work on porphyrin-chlorin dimers has been published.

Photophysical studies have been carried out on a series of purpurin derivatives and related compounds (provided by Moscow) and on a series of benzoporphyrin derivatives and related compounds (provided by London). Work has also been done on porphyrin dimers with ether links and with phenyl spacer groups. The results show several features of interest. For example the red shift of the Q(00) band of the porphyrin nucleus in absorption and emission by about 40nm on sequential annelation of benzene rings is the first experimental verification of theoretical predictions.

Treatment of purpurin 18 free acid with DDQ leads to the formation of a δ-lactone ring fused to ring D by an oxidative cyclisation. The lactone can be opened to give the 18-hydroxychlorin, which suffers elimination to give the corresponding pophyrin. Again, the treatment of purpurin 18 methyl ester with hydroxylamine opens the anhydride ring to give the corresponding cyclic hydroxamic acid in 90% yield. The N-hydroxy group has been functionatised to give a range of potentially useful sensitisers. This and some related work has been carried out in close collaboration with the London laboratory, which has provided various spectroscopic techniques to substantiate the novel structures and chemistry being discovered.

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Queen Mary and Westfield College
Mile End Road
E1 4NS London
United Kingdom
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