Molecular machines, or nanomachines, are one of the most intriguing and promising outcomes of scientific research in the last century. The Nobel Prize in Chemistry 2016 was awarded to Jean-Pierre Sauvage, Sir J. Fraser Stoddart and Bernard L. Feringa for their design and production of molecular machines. But what do they consist of? Professor Vincenzo Balzani, a pioneer and leading expert in the field of molecular devices, proposed a very explicative definition: “a molecular-level machine can be defined as an assembly of a discrete number of molecular components designed to perform mechanical-like movements (output) as a consequence of appropriate external stimuli (input)”.1
Generally speaking, these tiny machines consist of mechanically interlocking molecules, which move and can be controlled by external triggers. These features, combined with a unique structural versatility, make them extremely powerful in a wide range of technological applications. Molecular machines have a great potential, from working as tiny robots detecting disease or serving as smart materials in sensors. One of the most promising advance in the development and use of molecular device is their application in photopharmacology. Molecular devices are currently used for medicine purposes, for example in Photodynamic therapy for skin cancer treatment. But the new frontier in this field is the design of a new class of smart devices with therapeutic activity, which is regulated by the application of an external light stimulus. The group of Prof. Szymanski modifies different well-known antibiotics by inserting a photosensitive moiety in the molecular structure, which make them active only after UV light irradiation.2 This represents a simple and effective strategy to enhance their activity and prevent the antimicrobial resistance. A similar approach is used to develop photo-modulated anticancer drugs: in this case the activation through a light input modifies the drug structure, enabling the interaction with the target proteins on the cancer cells.3 Another promising application of molecular devices is related to vision restoration in humans: several light-activated nanomachines are currently tested in cell culture and animals, and according to Trauner, one of the leading experts in this field, these device will represent an authentic revolution in the cure of blindness in the next few years.4
Despite all these extraordinary outbreaks there are still some problems that researchers must face. The main limitation is related to the use of an appropriate wavelength for the photo-triggering, since the light should penetrate in depth with a sufficient energy to induce the device activation. On the other hand, the inactive form of the molecular device or the photo-induced reaction byproducts should be non-toxic for the organism.
It’s not so easy to find a compromise, there is a long road ahead, but the potential of molecular devices is truly unlimited.
[1] Artificial Molecular-Level Machines: Which Energy To Make Them Work?
Roberto Ballardini,Vincenzo Balzani,Alberto Credi, Maria Teresa Gandolfi and Margherita Venturi
Accounts of Chemical Research 2001 34 (6), 445-455. DOI: 10.1021/ar000170g
[2] Photocontrol of Antibacterial Activity: Shifting from UV to Red Light Activation
Michael Wegener, Mickel J. Hansen, Arnold J. M. Driessen, Wiktor Szymanski, and Ben L. Feringa
Journal of the American Chemical Society 2017 139 (49), 17979-17986. DOI: 10.1021/jacs.7b09281
[3] Photoswitchable Inhibitors of Microtubule Dynamics Optically Control Mitosis and Cell Death Malgorzata Borowiak, Wallis Nahaboo, Martin Reynders, Katharina Nekolla, Pierre Jalinot, Jens Hasserodt, Markus Rehberg, Marie Delattre, Stefan Zahler, Angelika Vollmar, Dirk Trauner, Oliver Thorn-Seshold
Cell 2015, 162 (2), 403-411. https://doi.org/10.1016/j.cell.2015.06.049.
[4] Photochemical restoration of visual responses in blind mice.
Aleksandra Polosukhina, Jeffrey Litt, Ivan Tochitsky, Joseph Nemargut, Yivgeny Sychev, Ivan De Kouchkovsky, Tracy Huang, Katharine Borges, Dirk Trauner, Russell N. Van Gelder and Richard H. Kramer. Neuron 2012, 75 (2), 271-282. https://doi.org/10.1016/j.neuron.2012.05.022.
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