The formation of inclusion complexes between drugs and macrocycles has proven to be an effective strategy to increase solubilization and stabilization of the drug, while in several cases improving their biological activity. In this context, we explored the formation of an inclusion complex between chemotherapeutic drug Melphalan (Mel) and cucurbit[7]uril (CB[7]), and studied its effect on Mel alkylating activity, hydrolysis, and cytotoxicity. The formation of the inclusion complex (Mel@CB[7]) was proven by absorption and fluorescence spectroscopy, NMR, docking studies, and molecular dynamics simulations. The binding constant for Mel and CB[7] was fairly high at pH 1 ((1.7 ± 0.7) × 106 M–1), whereas no binding was observed at neutral pH. The Mel@CB[7] complex showed a slightly decreased alkylating activity, whereas the cytotoxicity on the HL-60 cell line was maintained. The formation of the complex did not protect Mel from hydrolysis, and this result is discussed based on the simulated structure for the complex.

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Supramolecular control of singlet oxygen generation is incredibly valuable for several fields with broad applications and thus still challenging. However, macrocyclic inclusion complexes inherently restrict the interaction of photosensitizers with surrounding oxygen in the media. To circumvent this issue, we turned our attention in this work to acyclic cucurbituril-like containers and uncover their properties as supramolecular hosts for photosensitizers with extraordinary control of their photophysics, including singlet oxygen generation. Thermodynamic and photophysical studies were carried out showing that these acyclic containers compare very favorably to benchmark macrocycles such as cucurbiturils and cyclodextrins in terms of their binding affinities and supramolecular control of singlet oxygen generation. Acyclic container with terminal naphthalene walls offers a similar cavity to cucurbit[7]­uril and the same carbonyl-lined portals for a tight binding of phenothiazinium dye methylene blue and stabilizing its singlet and triplet excited states. Thus, generation of singlet oxygen for this container is higher than for other macrocycles and even higher than the free photosensitizer. While the acyclic container with smaller terminal benzene walls, stacks over the dye through sulfur−π and π–π interactions deactivating the singlet and triplet excited states, thus showing the lowest generation of singlet oxygen out of all of the studied systems. Due to the great water solubility and biocompatibility of these systems, they possess great potential for novel applications in photocatalysis, synthesis, and biomedical fields, among others.

A new toluidine blue-myristic acid photosensitizer derivate (TBOMyr) was investigated as a design molecule to bind simultaneously to cucurbit[7]uril (CB[7]) and human serum albumin (HSA) with the aim of constructing...