Synthesis, spectroscopic, and cellular properties of α-pegylated cis-A₂B₂- and A₃B-types ZnPcs

Abstract

A series of pegylated cis-A2B2- or A3B-type ZnPcs, substituted on the α-positions with tri(ethylene glycol) and hydroxyl groups, were synthesized from a new bis-phthalonitrile. A clamshell-type bis-phthalocyanine was also obtained as a byproduct. The hydroxyl group of one ZnPc was alkylated with 3-dimethylaminopropyl chloride to afford a pegylated ZnPc functionalized with an amine group. All mononuclear ZnPcs were soluble in polar organic solvents, showed intense Q absorptions in DMF, and had fluorescence quantum yields in the range 0.10–0.23. The clamshell-type bis-phthalocyanine adopts mainly open shell conformations in DMF, and closed clamshell conformations in chloroform. All ZnPcs were highly phototoxic to human carcinoma HEp2 cells, particularly the amino-ZnPc mainly protonated under physiological conditions, which showed the highest phototoxicity (IC50 = 0.5 μM at 1.5 J/cm2) and dark cytotoxicity (IC50 = 22 μM), in part due to its high cellular uptake. The ZnPcs localized in multiple organelles, including mitochondria, lysosomes, Golgi and ER.

Phthalocyanines and Tetrapyrazinoporphyrazines with Two Cationic Donuts: High Photodynamic Activity as a Result of Rigid Spatial Arrangement of Peripheral Substituents

“…Several strategies on how to resolve this obstacle have been developed by various research groups. The strategies include the use of surfactants/cosolvents , or delivery systems − to dissolve the lipophilic compounds or substitution by highly hydrophilic substituents axially on the central metal , or on the Pc core. − …”

Biotinylated-cationic zinc(II) phthalocyanine towards photodynamic therapy

“…The p-p stacking interaction process that takes place between the macrocyclic planes is wellknown to reduce the singlet oxygen production, and therefore, limits their PDT efficiency. Consequently, several strategies have been adopted, for example, adding surfactants/cosolvents [28,29], attaching the to delivery systems [30][31][32], dissolving the lipophilic compounds or axial substituents on the central metal [33,34], or on the Pc core specially with biocompatible units [24,35] or bulky groups [36][37][38][39] in order to improve the macrocycles' hydrophilicity and biocompatibility, which are necessary for this particular type of application.…”

Synthesis and investigation of phthalocyanine-biotin conjugates

“…In particular, isomerically pure Pcs bearing versatile functional groups can be used as templates to produce functionalized Pcs via, for example, esterification, substitution and acylation reactions [11][12][13][14][15][16][17][18][19]. The Pc templates can be conjugated to hydrophilic and cell-targeting moieties, yielding amphiphilic compounds with enhanced solubility, serum life, and specificity towards receptors overexpressed on cancer cells [11,14,[20][21][22]. This strategy is particularly useful when the required precursors bearing targeting moieties are not readily available or are unstable under cyclization conditions [23][24].…”