Monomerization of Phthalocyanines in Water via Their Supramolecular Interactions with Cucurbiturils

Abstract

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.

Overcoming barriers with non-covalent interactions: supramolecular recognition of adamantyl cucurbit[n]uril assemblies for medical applications

“…However, one must carefully design the system in which ADA/CB[ n ] will be incorporated and estimate whether the final assembly would be too bulky and/or hydrophilic to enter the cells in sufficient amount as it was demonstrated in the case of four CB[7]s that were non-covalently attached to aminoadamantyl-substituted phthalocyanines (Pcs). 159 The study in question showed that supramolecular interaction between CB[7] with Pcs in water improved both fluorescence and singlet oxygen production. On the other hand, bioactivity decreased for at least an order of magnitude after host–guest interaction with CB[7], which was attributed to much lower uptake by cells due to the aforementioned reasons.…”

BODIPY-cucurbituril complexes: supramolecular approach toward improvement of photodynamic activity

“…Highly hydrophilic cyclodextrins and cucurbit[n]urils (CB[n]) were mostly utilized for the solubilization of various PS. 8 For example, CB [7], known to form stable inclusion complexes with organic cations, was used to increase water solubility and reduce aggregation of phthalocyanine, 9 porphyrin, 10 or methylene blue 11 PSs with various consequences (positive or negative) for the final photodynamic activity. Also, an opposite approach in delivering AIEgens (aggregationinduced emission fluorophores) attached to CB [7] was recently reported.…”

“…(c) 1-Aminoadamantane and its analogues substituted on nitrogen atoms are known to form strong host-guest complexes with CB [7] having K a values in the range of 10 12 -10 15 M À1 . 9,21,22 Therefore, adamantyl (Ad) substituents have been placed on either meso position (1-3, one Ad) or on both styryl substituents (4 and 5, two Ads). This allowed us to evaluate the effect of one or two bulky and hydrophilic CB [7] molecules on the final BODIPY properties after the inclusion of Ad inside the macrocycle (Fig.…”