A [5]Rotaxane‐Based Photosensitizer for Photodynamic Therapy

Abstract

A [5]rotaxane was synthesized through a catalytically self‐threading reaction in which CB6 serves as a macrocycle and acts as a catalyst for the 1,3‐dipolar cycloaddition reaction between the alkyne substituted porphyrin core and azide functionalized stopper groups by forming triazole. Application of this rotaxane as a photosensitizer in photodynamic therapy against cancer cells and in bacteria inactivation have also been demonstrated. This photosensitizer has an excellent water solubility and remains stable in biological media at physiological pH (7.4) for prolonged times. It has the ability to generate singlet oxygen efficiently; while it shows no dark cytotoxicity up to 300 µm to the MCF7 cancer cell line, it is photocytotoxic even at 2 µm and reduces the cell viability to around 70 % when exposed to white light. It also displays light‐triggered biocidal activity both against gram‐negative bacteria (Escherichia coli, E. coli) and gram‐positive bacteria (Bacillus subtilis). Upon white light irradiation for 1 min with a flux of 22 mW/cm2 of E. coli suspension incubated with [5]rotaxane (3.5 µm), a killing efficiency of 96 % is achieved, whereas in the dark the effect is recorded as only around 9 %.

Development and advancement of rotaxane dendrimers as switchable macromolecular machines

“…5). 55 The CB [6]-based rotaxane gave excellent water solubility of the porphyrin, and exhibited antibacterial properties towards E. coli, B. subtilis and the MCF7 cell line upon white light radiation.…”

Azides and Porphyrinoids: Synthetic Approaches and Applications. Part 1—Azides, Porphyrins and Corroles

“…The obtained [2]rotaxane peripherally decorated with porphyrin units presents adequate features to act as an antenna for a light-harvesting device, able to transfer energy from the Zn(II) porphyrin moieties to the core [26]. More recently, Tuncel and co-workers reported the synthesis of a cucurbit [6]uril (CB6) [5]rotaxane P20 bearing a tetracationic porphyrin decorated with triazole units [27]. The [5]rotaxane P20 was synthesized as depicted in Scheme 8; the tetracationic porphyrin derivative P19 was reacted with tert-butyl azidoethylammonium chloride and CB6 in water for 24 h at 40 • C (Scheme 8).…”

“…In this reaction the CB6 has a dual function; it is the catalyst for the 1,3-dipolar cycloaddition between the azido and the alkynyl groups, leading to the formation of the 1,2,3-triazole ring, and it is the macrocycle for the inclusion of the four triazole rings. The porphyrin-core [5]rotaxane P20 was obtained at an 87% yield [27].…”

“…The photosensitizing properties of the water-soluble compound P20 was assessed on the photoinactivation of Escherichia coli (E. coli), a Gram-negative bacterial strain, Bacillus subtilis (B. subtilis), a Gram-positive bacterium, and breast cancer cell line MCF7. It displayed no cytotoxicity in the dark but under light P20 showed to be an efficient photosensitizer, even at low concentrations, demonstrating the potential for being used in both cancer photodynamic therapy (PDT) and photodynamic inactivation of microorganisms (PDI) [27]. Scheme 8.…”

Glycosylated porphyrin-cucurbituril conjugate for photodynamic inactivation of bacteria and doxorubicin carriage for anticancer drug delivery

“…Recently, a supramolecular approach started to emerge as an attractive way to design an ideal photosensitizer because using this approach it would be possible to regulate the photosensitizer's cytotoxicity, solubility and optical properties [13][14][15][16][17][18]. In this regard, we reported a highly water-soluble supramolecular photosensitizer based on [5]rotaxane which was prepared by a 1,3-dipolar cycloaddition reaction between the alkyne substituted porphyrin core and azide functionalized stopper groups in the presence of cucurbit [6]uril (CB6) [19]. This rotaxane-based photosensitizer shows negligible toxicity in the dark and has been proven to be a very efficient photosensitizer for photodynamic bacteria inactivation and cancer therapy.…”