Nipagin-Functionalized Porphyrazine and Phthalocyanine-Synthesis, Physicochemical Characterization and Toxicity Study after Deposition on Titanium Dioxide Nanoparticles P25

Abstract

Aza-porphyrinoids exhibit distinct spectral properties in UV-Vis, and they are studied in applications such as photosensitizers in medicine and catalysts in technology. The use of appropriate peripheral substituents allows the modulation of their physicochemical properties. Phthalocyanine and sulfanyl porphyrazine octa-substituted with 4-(butoxycarbonyl)phenyloxy moieties were synthesized and characterized using UV-Vis and NMR spectroscopy, as well as mass spectrometry. A comparison of porphyrazine with phthalocyanine aza-porphyrinoids revealed that phthalocyanine macrocycle exhibits higher singlet oxygen generation quantum yields, reaching the value of 0.29 in DMF. After both macrocycles had been deposited on titanium dioxide nanoparticles P25, the cytotoxicities and photocytotoxicities of the prepared materials were studied using a Microtox^® acute toxicity test. The highest cytotoxicity occurred after irradiation with a red light for the material composed of phthalocyanine deposited on titania nanoparticles.

Keywords: Linstead macrocyclization; Microtox; phthalocyanine; porphyrazine; singlet oxygen; titanium dioxide.

Scheme 1

Synthetic route leading to symmetrical phthalocyanine derivative 3: (i) 1,4-dibromobutane, K₂CO₃, DMF, rt, 72 h; (ii) 3,6-dihydroxybenzene-1,2-dicarbonitrile, K₂CO₃, DMF, rt, 20 h; (iii) Mg(BuO)₂, BuOH, 120 °C, 20 h.

Scheme 2

Synthetic route leading to sulfanyl porphyrazine: (i) 1,4-dibromobutane, K₂CO₃, DMF, rt, 72 h; (ii) dimercaptomaleonitrile sodium salt hydrate, K₂CO₃, DMF, 50 °C, 20 h; (iii) Mg(BuO)₂, BuOH, 120 °C, 20 h.

Scheme 3

Synthetic route leading to novel sulfanyl porphyrazine 7: (i) 1,4-dibromobutane, K₂CO₃, DMF, rt, 72 h; (ii) dimercaptomaleonitrile sodium salt hydrate, K₂CO₃, DMF, 50 °C, 20 h; (iii) Mg(BuO)₂, BuOH, 120 °C, 20 h.

Scheme 4

Alternative synthetic route leading to 3: (i) 3,6-dihydroxybenzene-1,2-dicarbonitrile, K₂CO₃, DMF, rt, 20 h; (ii) Mg(BuO)₂, BuOH, 120 °C, 20 h.

Figure 1

Solvatochromic effects observed in the UV-Vis spectra in various solvents for (a) 3; (b) 7; AcOH—acetic acid, DCM—dichloromethane, DMF—N,N-dimethylformamide.

Figure 2

Effect of solvents used on the color of the solution of 3: (a) pyridine, (b) N,N-dimethylformamide, (c) dichloromethane, (d) dichloromethane + 1% of acetic acid, (e) acetone, (f) ethyl acetate.

Figure 3

Chemical structures of macrocycles 3, 7 and 9–12.

Figure 4

Changes in A. fischeri cell viability after 15 min of the experiment when incubated with different materials (P25, 3@P25, 7@P25) or compounds (3, 7). The addition of water served as the control experiment (H₂O).