Acetylenic quinoxalinoporphyrazines as photosensitisers for photodynamic therapy.
A range of lipo- and hydrophilic derivatives of the new class of octaalkynyl tetra-[6,7]-quinoxalinoporphyrazines (TQuiPors), analogues of the naphthalocyanines, were prepared in two steps starting from functionalised hexa-1,5-diyne-3,4-diones. Divalent zinc and magnesium ions were introduced into the macrocyclic core. Whereas the triisopropylsilyl-, 3,5-di-tert-butylphenyl- and 4-triisopropylsilyloxyphenyl-terminated acetylenic TQuiPors are lipophilic and hence soluble in standard organic solvents, a polyethylene glycol-substituted derivative was found to dissolve in DMSO as well as in ethanol/water mixtures. The new chromophores are characterised by intense UV/Vis/NIR absorptions, most notably by bands at 770 nm with extinction coefficients exceeding 500 000 M(-1) cm(-1). With a view to possible photodynamic therapy applications, the potency of the chromophores to sensitise the formation of singlet oxygen was examined, both qualitatively using a 1,3-diphenylisobenzofuran assay, and quantitatively by the determination of the singlet oxygen quantum yields. It was found that all TQuiPors produce singlet oxygen when irradiated in the presence of air. In particular, the octaalkynyl Zn-TQuiPor generates singlet oxygen with a quantum yield of 56 %, thereby rivalling, and, in conjunction with its absorption profile, even exceeding the standards set by established PDT agents. The photostabilities of the TQuiPors were assessed and generally found to be satisfactory, but dependent on the solvent and the wavelength of the incident light.
Mitzel
Frieder
F
Christopher-Ingold-Laboratories Department of Chemistry University College London 20 Gordon Street, London WC1H 0AJ, UK.
FitzGerald
Simon
S
Beeby
Andrew
A
Faust
Rüdiger
R
D007211:Indoles; D054833:Isoindoles; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D026082:Singlet Oxygen / Q000737:chemistry; D012995:Solubility; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
D007211:Indoles; D054833:Isoindoles; D017319:Photosensitizing Agents; D011166:Porphyrins; D011810:Quinoxalines; D026082:Singlet Oxygen; C013647:phthalocyanine