Molecular machines: understanding how molecules move and work

What is it about?

Can a molecule behave like a machine? At the nanoscale, the answer is yes. Over the past decades, chemists have learned to construct artificial molecular systems capable of performing controlled movements in response to external stimuli. Among the most fascinating examples are mechanically interlocked molecules (MIMs), including rotaxanes, whose components are mechanically linked but not necessarily connected by conventional covalent bonds. These molecular architectures can be designed to perform movements such as the controlled displacement of a ring along a molecular thread, in a process known as translocation. Understanding what controls this movement is essential for transforming molecular motion into useful functions.

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Photo by BoliviaInteligente on Unsplash

Photo by BoliviaInteligente on Unsplash

Why is it important?

A typical [2]rotaxane consists of a molecular thread terminated by bulky groups, preventing a macrocyclic ring from escaping. The ring can nevertheless move along the thread and, depending on the chemical structure of the system, preferentially occupy different recognition sites. This simple architecture can therefore behave as a molecular shuttle or switch. A chemical stimulus, for example, can modify the affinity between the ring and one of the stations along the thread, causing the macrocycle to move from one position to another. As the architecture becomes more sophisticated, the possibilities increase: systems can contain multiple stations, respond to different stimuli, and perform increasingly complex sequences of molecular movements. But there is a fundamental question: what actually drives and controls these movements at the molecular level? Answering this question experimentally can be challenging because molecular machines operate through a complex network of interactions. Hydrogen bonds, electrostatic forces, π–π interactions, dispersion forces, metal–ligand coordination and interactions with the surrounding solvent can all contribute to determining which molecular conformation is preferred. Computational chemistry provides a powerful way to investigate these processes. A series of recent computational studies has combined density functional theory (DFT) and all-atom molecular dynamics (MD) simulations with advanced tools for analysing chemical interactions, including the Quantum Theory of Atoms in Molecules (QTAIM) and the Independent Gradient Model based on Hirshfeld partitioning (IGMH). The combination is particularly valuable because the different approaches answer complementary questions. DFT calculations provide information about the electronic structure and the energetic features of specific molecular arrangements. Molecular dynamics, instead, allows the behaviour of the entire molecular system to be followed at finite temperature and in the presence of solvent. This is crucial because molecular machines do not operate in isolation: their movements are strongly influenced by their dynamic environment.

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