Talk by Frances H. Arnold

Frances H. Arnold, Professor at the California Institute of Technology (Caltech), Pasadena, CA, USA, said, she fell in love with enzymes because they can do chemistry better than human chemists and do it cleanly and effectively with only a few waste products.

“We can read DNA, we can write DNA, but we still do not know how to compose it.” If we want to make a new enzyme or make an existing one work under non-natural conditions, we have to be able to compose that sequence of DNA that encodes that capability.

Nature has done this through evolution, through mutation and natural selection, and over a long period. Similar to this, Frances Arnold and her team are designing new enzymes. They use evolution to randomly mutate the DNA towards a desired aim. The process is similar to the selective breeding of plants and animals by which humans have modified the biological world to serve our needs. “We have done this in an iterative process without understanding the underlying mechanism.”, Arnold said.

In 2016, Frances Arnold and coworkers created, for example, an enzyme that could create a Si–C bond [1]. Using cytochrome c from Rhodothermus marinus, they improved the reaction to be 15 times more efficient than industrial catalysts. Their recent work uses directed evolution, simulation, and machine learning to optimize and develop enzymes, applied to biocatalysis in pharmaceuticals, biofuels, sensors, and diagnostics.

First Enzyme to Break a Si–C Bond

In a recent publication [2], Frances Arnold and her team identified and evolved a cytochrome P450 enzyme to efficiently hydroxylate and cleave the carbon-silicon bonds of methylsiloxanes. These are human-made organosilicon compounds that are resistant to biodegradation and may bioaccumulate. Their enzyme is the first to break a silicon-carbon bond, including both linear and cyclic forms.

Beyond Science

In addition to her research, Frances Arnold shared her scientific journey and role as an advisor to the Biden administration, emphasizing the importance of promoting values such as “hope over fear, unity over division, science over fiction, and truths over lies.” She also portrayed herself in an episode of the TV show The Big Bang Theory.

References

[1] S. B. Jennifer Kan, Russell D. Lewis, Kai Chen, Frances H. Arnold, Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life, Science 2016, 354(6315),1048-1051. https://doi.org/10.1126/science.aah6219

[2] Nicholas S. Sarai, Tyler J. Fulton, Ryen L. O’Meara, Kadina E. Johnston, Sabine Brinkmann-Chen, Ryan R. Maar, Ron E. Tecklenburg, John M. Roberts, Jordan C. T. Reddel, Dimitris E. Katsoulis, Frances H. Arnold, Directed evolution of enzymatic silicon-carbon bond cleavage in siloxanes, Science 2024, 383(6681), 438-443. https://doi.org/10.1126/science.adi5554

Talk by David Leigh

David Leigh, Professor at the University of Manchester, UK, accompanied his lecture on molecular machines with magic tricks involving rings, scarves, and newspapers.

Ratchet Mechanisms in Chemistry

David Leigh’s work focuses on ratchet mechanisms, which control the movement of molecules in a directed way, rather than relying on random motion. There are two principal types applicable to chemistry:

1. In biomolecular systems, ratcheting often occurs through a chemical engine’s catalysis of an accompanying ‘fuel’-to-‘waste’ reaction, typically adenosine triphosphate (ATP) + H₂O to adenosine diphosphate (ADP) + phosphate.
2. Ratcheting can create directional movement by repeatedly switching between different energy states, altering the relative depths of energy lows and heights of energy highs. This ensures consistent directional transport without the substrate’s position needing to influence the machine’s speed.

First Autonomous Chemically Fueled Synthetic Molecular Motor

The first autonomous chemically fuelled synthetic molecular motor was presented in 2016 [1,2]. David Leigh describes a system where a small macrocycle moves continuously and directionally around a larger molecular track, powered by the chemical fuel fluorenylmethyloxycarbonyl chloride (Fmoc-Cl). The mechanism is illustrated by a Wollit and Gromit movie [2].

The motor operates as long as unreacted fuel remains, achieving directionality through asymmetric reaction rates that prevent the macrocycle from reversing direction. Specifically, the chemical fuel reacts faster when the macrocycle is farther from the reactive site and slower when it is closer. This difference in reaction rates creates a bias that propels the macrocycle in one consistent direction, preventing it from moving backward and ensuring continuous, directional motion around the track.

First Autonomous Unidirectional 360° Single-Bond Rotation

In 2022, the Leigh group developed an autonomous single-bond rotary motor that operates through an information ratchet mechanism. 1-phenylpyrrole 2,2′-dicarboxylic acid is a catalysis-driven motor that can continuously convert a chemical fuel into energy to induce repetitive 360° directional rotation of the two aromatic rings around the covalent N–C bond that connects them [3].

The biaryl motor features carboxylic acid groups on each ring that cannot pass each other via rotation around the C−N biaryl bond; instead, interconversion of atropisomeric conformations occurs through rotation in the opposite direction. When fueled with a carbodiimide, however, a cyclic anhydride forms, enabling the carboxyl groups to pass each other through a low-energy ring flip, allowing effective rotation past each other.

Applications and Potential

David Leigh’s research has shown that these mechanisms can be applied not only to synthetic molecular machines and motors but also to various chemical exchange processes. This is leading to the creation of advanced functional molecules and the first examples of molecular robots.

Using artificial molecular ratchets for practical applications is still early in development. They have been integrated into various materials such as surfaces, gels, and metal-organic frameworks (MOFs). Light-driven motors have shown potential in twisting polymer chains to contract gels and disrupt cell membranes, yet broader applications interfacing with bulk materials remain unexplored, and molecular motors have primarily functioned as switches. Exploring synthetic ratchets interfaced with membranes holds promise, mimicking biological machines that pump species across membranes and maintain non-equilibrium states. Challenges persist in their robustness and versatility compared to biological counterparts.

The recognition of molecular ratchet mechanisms in biology, and their invention in synthetic systems, is proving significant in areas as diverse as supramolecular chemistry, systems chemistry, dynamic covalent chemistry, DNA nanotechnology, polymer and materials science, molecular biology, heterogeneous catalysis, endergonic synthesis, the origin of life, and many other branches of chemical science.

References

[1] Miriam R. Wilson, Jordi Solà, Armando Carlone, Stephen M. Goldup, Nathalie Lebrasseur, David A. Leigh, An autonomous chemically fuelled small-molecule motor, Nature 2016, 534, 235–240. https://doi.org/10.1038/nature18013

[2] Cracking Nanomotor, Gromit!, Leigh group website (accessed July 17, 2024)

[3] Stefan Borsley, Elisabeth Kreidt, David A. Leigh, Benjamin M. W. Roberts, Autonomous fuelled directional rotation about a covalent single bond, Nature 2022, 604, 80–85. https://doi.org/10.1038/s41586-022-04450-5
-> ChemistryViews News on this research

[4] Stefan Borsley, David A. Leigh, Benjamin M. W. Roberts, Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction, Angew. Chem. Int. Ed. 2024. https://doi.org/10.1002/anie.202400495

Chemistry Europe

Founded in 1995, Chemistry Europe is an association of 16 European chemical societies, all members of EuChemS. It publishes a family of high-quality scientific chemistry journals covering a wide range of disciplines, as well as the science news magazine ChemistryViews. The EuChemS Chemistry Congress, along with the Chemistry Europe Councils and Representatives Meetings, is one of the main meeting places for members of Chemistry Europe.

Flagship Journal – ChemistryEurope

At a Chemistry Europe Mini-Symposium Luisa de Cola, Professor at Università degli Studi di Milano Statale, Italy, and Lars C. Grabow, Professor at the University of Houston, TX, USA, and both editors of the new, high-impact journal ChemistryEurope, reported on their research.

Lars C. Grabow during his talk at the Chemistry Europe Mini-Symposium and group photo. (Photos © Josefa Fernandez and Sonja Kwiatkowskyj)
From left: Gianluca Maria Farinola, President of the Società Chimica Italiana (SCI), Professor at Università degli Studi di Bari “Aldo Moro”, Italy, and Chemistry Europe Council Member, Luisa de Cola, Haymo Ross, Anne Nijs, and Lars C. Grabow, all involved in the flagship journal ChemistryEurope.

ChemElectroChem Quiz in ChemistryViews

To celebrate the 10th anniversary of ChemElectroChem, a quiz was held at the Wiley booth and on ChemistryViews. Many participants had fun trying to match cover images and article titles from the journal and win a prize at the booth.

The quiz runs until July 21, 2024. A book voucher will be raffled among all participants. So, join in quickly 😊

The ChemistryViews quiz on the 10th anniversary of ChemElectroChem at the booth, in the foro with Sonja Kwiatkowskyj and Haymo Ross, and on social media (Photos © Sonja Kwiatkowskyj)

Fellows Reception

The Chemistry Europe Fellows Reception took place in the nearby Epic Museum, a museum about immigration, with about 60 invited guests. Every two years, Chemistry Europe recognizes innovative ideas and outstanding support for its publication activities by awarding the title of Chemistry Europe Fellow.

The European Chemical Societies participating in Chemistry Europe award their Fellows with certificates and trophies at a national meeting. Traditionally, the entire class of new Fellows is also honored with a reception at the ECC. And we love celebrating with our authors, readers, supporters, and, in the meantime, many friends. Thank you all for the great party and support!

The next round of Fellow nominations will begin next spring. We are currently accepting nominations for the Chemistry Europe Award.

Chemistry Europe Fellows and Representatives at the Reception. (Photo © Drew Gwilliams)
From left: Péter G. Szalay, Professor at Eötvös Loránd University, Budapest, Hungary, Izabela Nowak, Professor at Adam Mickiewicz University (AMU), Poznań, Poland, Anne Nijs, European Journal of Organic Chemistry/ChemistryEurope, Aaron McCormack, Chairperson ICI Young Chemists’ Network (YCN), Ireland, Haymo Ross, Chemistry – A European Journal, Gianluca Maria Farinola, Università degli Studi di Bari Aldo Moro in Bari, Italy, Josefa Fernandez, Head of Executive Office, Chemistry Europe, Christoforos Kokotos, University of Athens, Greece, Stefanie Dehnen, Professor at KIT, Germany, Kristof Van Hecke, Professor at Ghent University, Belgium, Alessandro Abbotto, Professor at Università di Milano-Bicocca, Italy, Sonja Kwiatkowskyj, Chemistry Europe Marketing Manager, João Borges, University of Aveiro, Portugal, Joaquim Faria, Universidade do Porto, Portugal, Vera Koester, ChemistryViews, Federico Bella, Politecnico di Torino, Italy.

Snapshots of the Chemistry Europe Fellows reception (Photos © Chemistry Europe).