The Potential of Mechanically Interlocked Molecules (MIMs) as OFF/ON Catalysts

Mechanically interlocked molecules (MIMs), characterized by their interlocked molecular architecture, have been a subject of extensive research, primarily driven by the development of efficient methods for their synthesis. In a recent study published in the peer-reviewed Journal Angewandte Chemie International Edition, Adrien Bessaguet, Quentin Blancart-Remaury, Pauline Poinot, Dr. Isabelle Opalinski, and led by Professor Sébastien Papot from the University of Poitiers focused on MIMs, such as rotaxanes, catenanes, and molecular knots, which exhibit unique properties due to the presence of mechanical bonds within their structures. While the synthetic challenges associated with MIMs have been extensively addressed in previous studies, the researchers took a pioneering step by shifting the focus towards the controlled disassembly of MIMs for potential applications in catalysis and sensing. Previously, MIMs have been explored for various biomedical applications, such as drug delivery systems and disease detection. Nanovalves grafted onto mesoporous silica nanoparticles, biodegradable polyrotaxanes, and light- and enzyme-responsive rotaxane-based prodrugs are some notable examples. The controlled disassembly of MIMs has emerged as a crucial feature for these applications. The new study presents a novel approach that leverages the controlled breakdown of mechanical bonds within MIMs to develop OFF/ON catalysts. Specifically, the study focuses on the design of CuI-complexed catenanes, including stimuli-sensitive triggers and phenanthroline-derived self-opening macrocycles.

The authors innovative idea revolves around encapsulating CuI inside the cavity formed by two interlocked macrocycles, rendering it inactive for the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. However, the triggers can be activated by appropriate external chemical stimuli, resulting in the formation of a dianiline intermediate that undergoes spontaneous eliminations. This process leads to the cleavage of the mechanical bond, making CuI accessible to alkyne and azide reactants, thus restoring its catalytic activity for the CuAAC reaction. They found stimuli-responsive catenane-based catalysts to be involved in signal amplification processes. This property allows for the detection of analytes at remarkably low concentrations, as low as 1 part per billion (ppb). The ability to amplify signals is a crucial aspect of catalysis and sensing, and the study demonstrated how MIMs can excel in this regard.

The key step in the synthesis of these stimuli-responsive catenanes relies on the construction of the interlocked architecture via a CuI-directed passive metal template strategy. This straightforward synthetic approach offers the potential for versatile access to a wide range of stimuli-responsive catenanes containing various trigger types, including redox-, light-, and enzyme-sensitive triggers. The research team conducted detailed investigations into the mechanism of self-decomposition of the catenanes in the presence of appropriate chemical stimuli. The experiments involved the use of piperidine and Pd(PPh₃)₄ for different catenanes. The results demonstrated that the disassembly of the interlocked molecular architecture proceeded through controlled mechanisms, ultimately leading to the activation of the CuI catalyst. Furthermore, the authors explored the possibility of achieving efficient catalyst activation through a double-catalyst cascade. In their approach, a catalytic amount of piperidine was used as an activator for the CuI catalyst, leading to an amplification process that can be harnessed for sensing purposes.

It is noteworthy to mention the observation of the inhibition of CuI to catalyze the CuAAC reaction within the structure of catenanes due to the catenand effect. The stability of the catenanes in the presence of cyanide ions was evaluated to illustrate this effect. The results confirmed that the catenand effect was responsible for inhibiting CuI catalytic activity, highlighting the unique behavior of MIMs in modulating metal catalysts. The authors demonstrated that the catenand effect allows versatile modulation of CuI catalytic activity in various chemical reactions. This finding opens up exciting possibilities for the development of a wide range of catalysts with finely-tuned properties, making MIMs highly promising candidates for catalysis research. The authors also explored the potential of Alloc-protected catenanes for the detection of low palladium concentrations. They successfully demonstrated the efficiency of Alloc-protected catenanes as OFF/ON catalysts, enabling the sensitive detection of palladium at concentrations as low as 1 ppb. This sensing strategy, based on a double-catalyst amplification methodology, holds promise for various sensing applications. In conclusion, Professor Sébastien Papot and colleagues study represents a significant milestone in the field of MIMs and catalysis. Their innovative approach to using mechanically interlocked molecules as OFF/ON catalysts by controlled disassembly of the mechanical bond opens up new avenues for research in catalysis, sensing, and signal amplification. As an extension of this study, Professor Papot’s team plans to adapt this approach to the detection of enzymes present at very low concentrations in biological fluids for the early diagnosis of certain diseases.