Non-peripherally substituted metal-free and zinc phthalocyanines (Pcs) bearing four diethylamino groups and four Br atoms were prepared. Optimal conditions for synthesis of corresponding precursor ([Formula: see text] 3-bromo-6-(diethylamino)phthalonitrile) either by nucleophilic substitution or by Buchwald–Hartwig coupling were studied. Noteworthy, 3,6-bis(diethylamino)phthalonitrile was also formed, nevertheless only at low yield (typically below 1%) and all attempts for its cyclotetramerization failed. Q bands of prepared Pcs were strongly red shifted up to the near-IR region (769 and 800 nm in THF for zinc and metal-free Pc, respectively). Unusually large hypsochromic shifts of the Q bands, 130 and 80 nm for metal-free and zinc Pc, respectively, were observed upon treating these Pcs with trifluoroacetic acid, which was attributed to the protonation of non-peripheral amines. Treatment with sulfuric acid led to subsequent protonation on the azomethine nitrogens as well. Photophysical study revealed low fluorescence emission of both derivatives ([Formula: see text] <0.03, in THF) and efficient singlet oxygen production only for zinc Pc ([Formula: see text] 0.77 in THF and 0.60 in DMF).

Aggregation of phthalocyanines (Pcs) represents a problematic feature that decreases the potential of these macrocycles in a number of applications. In this work, we present a supramolecular approach based on the interaction of aminoadamantyl-substituted Pcs with bulky and hydrophilic cucurbit[7]uril (CB[7]) to increase the levels of Pc monomers in water. A series of zinc(II) Pcs substituted at positions α or β by an aminoadamantyl substituent (with a different level of alkylation of nitrogen) were prepared from the corresponding phthalonitriles. A 1H nuclear magnetic resonance study of the interaction of phthalonitriles with CB[7] in water confirmed the formation of an inclusion complex with an aminoadamantyl moiety with K a values of ∼1012 M–1. The interaction of CB[7] with Pcs in water substantially weakened H-type aggregation and improved both fluorescence and singlet oxygen production, confirming that this approach is efficient for the monomerization of Pcs. In vitro evaluation of the photodynamic activity of prepared Pcs led to EC50 values in the submicromolar range on HeLa and SK-MEL-28 cells. However, the activity decreased for at least an order of magnitude after host–guest interaction with CB[7] despite better photophysical properties. This was attributed to a much lower uptake by cells due to the very bulky and hydrophilic character of the Pc-CB[7] assembly.

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