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Synthesis of new tripyridyl amphiphilic porphyrins for PDT via methylation and N- oxidation of 3- and 4-pyridyl Groups

Photosensitisers are compounds whose activation by light of a specific wavelength can lead to the destruction of tumour cells and of various microorganisms through oxidative stress. Among the most common photosensitisers are compounds with porphyrin structure that can generate cytotoxic singlet oxygen and other reactive oxygen species, as well as release fluorescence. Therefore, they have significant theranostics potential with possible applications in photodynamic therapy (PDT) and in diagnostics for molecular imaging [1]. Porphyrin photosensitisers selectively accumulate in tumour tissue thanks to the mechanism known as the “enhanced permeability and retention effects”, and it has been suggested that compounds with amphiphilic properties could facilitate this process [2, 3]. Recently we reported the synthesis of 5-(4- octadecanamidophenyl)-10, 15, 20-tris(N- methylpyridinium-3-yl)porphyrin trichloride and evaluation of in vitro PDT activity of this amphiphilic porphyrin on HeLa cells [4]. The lipophilic part of the molecule proved to be important for the overall PDT activity, but also for the indicated bifunctional activity. Therefore, in order to investigate further the effect of the lipophilic moiety, several amphiphilic porphyrins, with saturated and unsaturated long alkyl chain (C18), were prepared. The amphiphilicity was achieved in the last synthetic step by methylation of 3- and 4-pyridyl groups. Another series of amphiphilic zwitterionic porphyrins was prepared by N-oxidation of 3- and 4-pyridyl groups. Porphyrin N-oxides have been previously investigated as potential hypoxia-selective agents [5], but derivatives with long alkyl chains have not yet been reported. All prepared porphyrins were characterised by 1H and 13C NMR one- and two-dimensional spectroscopy, ESI-Q- TOF and MALDI-TOF/TOF mass spectrometry, and their photophysical properties evaluated by UV- visible and fluorescence spectroscopy. Their synthesis will be described, and the distinct features of their characterisations will be presented and discussed.

Photodynamic therapy ; Photosensitiser ; Porphyrin ; Methylation ; N-oxidation

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