Monomerization of Phthalocyanines in Water via Their Supramolecular Interactions with Cucurbiturils

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 in α- or β-positions by aminoadamantyl substituent (with different level of alkylation of nitrogen) was prepared from the corresponding phthalonitriles. ¹H NMR study of the interaction of phthalonitriles with CB[7] in water confirmed the formation of an inclusion complex with aminoadamantyl moiety with K_a values of about 10¹² M^-1. The interaction of CB[7] with Pcs in water substantially reduced H-type aggregation and improved both fluorescence and singlet oxygen production, confirming that this approach is efficient in 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 much lower uptake by cells due to very bulky and hydrophilic character of the of the Pc-CB[7] assembly.