Abstract
The COSMO project (“COntrolled Shuttling inside artificial MOlecular tubes”), coordinated by Prof. Alberto Credi at the University of Bologna, focuses on developing a new class of molecular shuttles, which are a most common type of artificial molecular machines. Unlike traditional designs, where a ring-like molecule moves between specific sites along an axle on rotaxanes, the proposed shuttles will feature a mobile component fully enclosed within a tubular molecule. These artificial nanotubes will be chemically tailored to recognize and interact with the guest molecule via non-covalent forces, with external stimuli used to control its movement. The project will initially investigate nanotubes with two active compartments, but these could evolve into longer, directional molecular motors. The systems will be analyzed in solution using spectroscopic and electrochemical techniques to understand their thermodynamic and kinetic properties. The tubular confinement is expected to influence the motion of the guest in unique ways. Furthermore, the nanotubes will be embedded in lipid membranes, potentially enabling controlled molecular or ionic transport across biomimetic membranes. These experiments could pave the way to innovative applications in control of biological functions and drug delivery.
Results achieved
The COSMO project successfully achieved its main scientific objectives, advancing the design and understanding of artificial supramolecular systems capable of controlled molecular motion and selective guest transport within confined nanoscale environments. The project was carried out through the close collaboration of the University of Bologna, the University of Parma and the University of Insubria, integrating synthesis, spectroscopy, photophysics and computational modelling. A major achievement was the identification and study of responsive molecular guests, including bipyridinium, azoarene, azoheteroarene, stilbazolium and cyanine derivatives, designed to respond to external stimuli such as light, pH or redox input. In particular, the University of Bologna demonstrated the first light-driven ratcheted formation of cyclodextrin inclusion complexes in water, showing that supramolecular host–guest systems can be driven away from thermodynamic equilibrium by light and enabling directional control over the formation of orientational isomers. The University of Parma designed and synthesized new calix[6]arene-based cages and tubular hosts, including rigid covalent systems, dynamic imine-linked architectures and hybrid structures combining rigidity and responsiveness. These molecular containers displayed tunable cavities suitable for the inclusion of different organic guests. Their study showed that confinement inside calixarene cavities can significantly modify the behaviour of guest molecules, enhancing fluorescence emission and altering spectroscopic properties. The University of Insubria provided key theoretical insight through molecular dynamics and metadynamics simulations, clarifying the energetics and mechanisms of threading and dethreading processes. Computational work was also extended to calix[6]arene-based systems embedded in lipid bilayers, offering valuable design criteria for future supramolecular channels and biomimetic transport systems. Additional results broadened the scientific impact of COSMO. Photoactive stilbazolium–calixarene pseudorotaxanes exhibited orientational isomerism, reversible threading behaviour and enhanced fluorescence upon encapsulation, opening perspectives for functional optical materials and molecular sensors. The project also led to the discovery of a new family of light-driven molecular rotary motors based on arylazoimidazolium derivatives, whose preferred direction of rotation can be inverted by changing the irradiation wavelength. This result extends COSMO from linear shuttling to rotary molecular motion and contributes to the development of artificial molecular machines. Furthermore, photoswitchable amphiphilic guests were incorporated into liposome membranes, where light-induced molecular isomerisation enabled reversible control of supramolecular aggregation and vesicle assembly across multiple length scales. COSMO generated significant dissemination outputs. At the time of the final report, the project had produced 5 scientific papers in peer-reviewed international journals, including one manuscript published in Nature Chemistry, and 4 additional manuscripts under review or in preparation. The results were presented through 9 scientific communications, including 3 oral presentations and 6 posters, at 8 national and international conferences. The project was also disseminated to a broader public through participation in two outreach events: the Cagliari FestivalScienza 2024, with the participation of the Principal Investigator in a roundtable discussion, and the European Researchers’ Night 2025 in Bologna. Overall, COSMO established new design principles for controlling molecular motion, transport and optical response in confined environments. Its outcomes provide a foundation for future artificial nanodevices capable of regulated transport, signalling and light-controlled functions, with prospective applications in adaptive materials, molecular sensing, nanotechnology and nanomedicine. All activities were conducted in compliance with the Do No Significant Harm principle, Open Access policies, and principles of gender equality, generational balance and equal opportunities. The project received financial support from the European Union within the framework of PRIN 2022, under the National Recovery and Resilience Plan - Mission 4, Component 2, Investment 1.1.Dettagli del progetto
Responsabile scientifico: Alberto Credi
Strutture Unibo coinvolte:
Dipartimento di Chimica Industriale "Toso Montanari"
Coordinatore:
ALMA MATER STUDIORUM - Università di Bologna(Italy)
Contributo totale di progetto: Euro (EUR) 203.089,00
Contributo totale Unibo: Euro (EUR) 72.746,00
Durata del progetto in mesi: 24
Data di inizio
16/10/2023
Data di fine:
15/10/2025
