Photophysical properties and photodynamic activity of a novel menthol–zinc phthalocyanine conjugate incorporated in micelles

The synthesis, photophysical properties, and photodynamic activity of the lipophilic tetra-menthyl-substituted zinc phthalocyanine (ZnMintPc, main regioisomer {2,9,16,23-tetrakis{[(1S,2R,5S)-5-methyl-2-(1-methylethyl)cyclohexyl]oxy}-phthalocyaninato}zinc(II)) are described. This compound was synthesized under cyclotetramerization conditions by reaction of substituted phthalonitrile prepared from 4-nitrophthalonitrile with natural l-menthol. This new phthalocyanine presented remarkable structural and photophysical features with potential application in photodynamic therapy (PDT) involving hydrophobic membrane regions. This photosensitizer was incorporated in micelles of 12 different surfactants, namely ionic detergents SDS, CTAB, and HPS, the non-ionic detergents Tween® 20, Tween® 80, C12E9, Brij® 30, Brij® 35, Brij® 97, and Brij® 98, and the triblock copolymers Pluronic F-68 and Pluronic F-127. Solubilization or aggregation in the lipophilic compartment of the micelles was assessed by UV–vis absorption and photoluminescence spectroscopies. Singlet oxygen was produced by irradiation of the micelles with light from red LEDs, peaked at 635 nm, and the quantum yields were obtained using 1,3-diphenylisobenzofuran (DPBF) as probe. Two micellar systems, more specifically Brij® 30 and Pluronic® F-127, displayed excellent ability to generate singlet oxygen. Photobleaching rates of the ZnMintPc incorporated into the micelles were also obtained. The results demonstrated the lipophilic ZnMintPc is suitable for PDT applications and suggest the use of Pluronic® F-127 in the formulation of adequate drug delivery systems for this photosensitizer.

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► A novel menthol derivative of zinc phthalocyanine (ZnMintPc) was synthesized.
► Red light irradiation of ZnMintPc produces singlet oxygen in different micelles.
► Micelles of non-ionic surfactants presented better singlet oxygen quantum yields.
► Properties of ZnMintPc indicate that it is suitable for PDT in membranes.
► Best sensitization was found in non toxic Pluronic® F-127 micelles.