Molecular Ratchets and Kinetic Asymmetry: Giving Chemistry Direction.

Over the last two decades ratchet mechanisms have transformed the understanding and design of stochastic molecular systems-biological, chemical and physical-in a move away from the mechanical macroscopic analogies that dominated thinking regarding molecular dynamics in the 1990s and early 2000s (e.g. pistons, springs, etc), to the more scale-relevant concepts that underpin out-of-equilibrium research in the molecular sciences today.

A Minimalistic Covalent Bond-Forming Chemical Reaction Cycle that Consumes Adenosine Diphosphate.

The development of synthetic active matter requires the ability to design materials capable of harnessing energy from a source to carry out work. Nature achieves this using chemical reaction cycles in which energy released from an exergonic chemical reaction is used to drive biochemical processes. Although many chemically fuelled synthetic reaction cycles that control transient responses, such as self-assembly, have been reported, the generally high complexity of the reported systems hampers a full understanding of how the available chemical energy is actually exploited by these systems.

Ratcheting synthesis.

Synthetic chemistry has traditionally relied on reactions between reactants of high chemical potential and transformations that proceed energetically downhill to either a global or local minimum (thermodynamic or kinetic control). Catalysts can be used to manipulate kinetic control, lowering activation energies to influence reaction outcomes. However, such chemistry is still constrained by the shape of one-dimensional reaction coordinates.

Using Catalysis to Drive Chemistry Away from Equilibrium: Relating Kinetic Asymmetry, Power Strokes, and the Curtin-Hammett Principle in Brownian Ratchets.

Chemically fueled autonomous molecular machines are catalysis-driven systems governed by Brownian information ratchet mechanisms. One fundamental principle behind their operation is kinetic asymmetry, which quantifies the directionality of molecular motors. However, it is difficult for synthetic chemists to apply this concept to molecular design because kinetic asymmetry is usually introduced in abstract mathematical terms involving experimentally inaccessible parameters.

Tuning the Force, Speed, and Efficiency of an Autonomous Chemically Fueled Information Ratchet.

Autonomous chemically fueled molecular machines that function through information ratchet mechanisms underpin the nonequilibrium processes that sustain life. These biomolecular motors have evolved to be well-suited to the tasks they perform. Synthetic systems that function through similar mechanisms have recently been developed, and their minimalist structures enable the influence of structural changes on machine performance to be assessed.

Chemical fuels for molecular machinery.

Chemical reaction networks that transform out-of-equilibrium 'fuel' to 'waste' are the engines that power the biomolecular machinery of the cell. Inspired by such systems, autonomous artificial molecular machinery is being developed that functions by catalysing the decomposition of chemical fuels, exploiting kinetic asymmetry to harness energy released from the fuel-to-waste reaction to drive non-equilibrium structures and dynamics. Different aspects of chemical fuels profoundly influence their ability to power molecular machines.

Autonomous fuelled directional rotation about a covalent single bond.

Biology operates through autonomous chemically fuelled molecular machinery, including rotary motors such as adenosine triphosphate synthase and the bacterial flagellar motor. Chemists have long sought to create analogous molecular structures with chemically powered, directionally rotating, components. However, synthetic motor molecules capable of autonomous 360° directional rotation about a single bond have proved elusive, with previous designs lacking either autonomous fuelling or directionality.

Insights from an information thermodynamics analysis of a synthetic molecular motor.

Information is physical, a realization that has transformed the physics of measurement and communication. However, the flow between information, energy and mechanics in chemical systems remains largely unexplored. Here we analyse a minimalist autonomous chemically driven molecular motor in terms of information thermodynamics, a framework that quantitatively relates information to other thermodynamic parameters.

A Doubly Kinetically-Gated Information Ratchet Autonomously Driven by Carbodiimide Hydration.

We report a rotaxane-based information ratchet in which the macrocycle distribution is pumped away from equilibrium using a carbodiimide fuel. A carboxylate group on the axle, nonequidistant between two macrocycle binding sites, efficiently catalyzes the hydration of a carbodiimide fuel to the corresponding urea waste, with >80% of the fuel molecules reacting through the machine-catalyzed pathway. The energy of the reaction is harnessed by kinetic differentiation of the mechanical states of the machine driving the macrocycle to the binding site distal to the catalyst.