Transducing chemical energy through catalysis by an artificial molecular motor.

Cells display a range of mechanical activities generated by motor proteins powered through catalysis. This raises the fundamental question of how the acceleration of a chemical reaction can enable the energy released from that reaction to be transduced (and, consequently, work to be done) by a molecular catalyst. Here we demonstrate the molecular-level transduction of chemical energy to mechanical force in the form of the powered contraction and powered re-expansion of a cross-linked polymer gel driven by the directional rotation of artificial catalysis-driven molecular motors.

Active template synthesis.

The active template synthesis of mechanically interlocked molecular architectures exploits the dual ability of various structural elements (metals or, in the case of metal-free active template synthesis, particular arrangements of functional groups) to serve as both a template for the organisation of building blocks and as a catalyst to facilitate the formation of covalent bonds between them. This enables the entwined or threaded intermediate structure to be covalently captured under kinetic control. Unlike classical passive template synthesis, the intercomponent interactions transiently used to promote the assembly typically do not 'live on' in the interlocked product, meaning that active template synthesis can be traceless and used for constructing mechanically interlocked molecules that do not feature strong binding interactions between the components.

Work-related slip, trip and fall injuries reported by National Health Service staff in Great Britain: how many are due to slipping?

Background: Workplace injuries due to a slip, trip or fall on the level (STF) are often reported together, making the potential impact of targeted interventions, such as slip-resistant footwear, difficult to assess. The objective of this research was to review workplace non-fatal injuries reported as STFs under the Reporting of Injuries, Diseases and Dangerous Occurrences Regulations 2013 to determine what proportion of staff STF injuries reported by the National Health Service (NHS) in Great Britain were caused specifically by a slip.

Methods: The free text descriptions of all 1004 STF injuries reported by NHS staff in summer 2018 and winter 2018/2019 were independently reviewed by two researchers to determine whether a slip was the primary cause or not.

Mechanical scission of a knotted polymer.

Molecular knots and entanglements form randomly and spontaneously in both biological and synthetic polymer chains. It is known that macroscopic materials, such as ropes, are substantially weakened by the presence of knots, but until now it has been unclear whether similar behaviour occurs on a molecular level. Here we show that the presence of a well-defined overhand knot in a polymer chain substantially increases the rate of scission of the polymer under tension (≥2.

The role of the Pin1- P-tau axis in the development and treatment of vascular contribution to cognitive impairment and dementia and preeclampsia.

Tauopathies are neurodegenerative diseases characterized by deposits of abnormal Tau protein in the brain. Conventional tauopathies are often defined by a limited number of Tau epitopes, notably neurofibrillary tangles, but emerging evidence suggests structural heterogeneity among tauopathies. The prolyl isomerase Pin1 isomerizes P-tau to inhibit the development of oligomers, tangles and neurodegeneration in multiple neurodegenerative diseases such as Alzheimer's disease, traumatic brain injury, vascular contribution to cognitive impairment and dementia (VCID) and preeclampsia (PE).

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.

Changing Liquid Crystal Helical Pitch with a Reversible Rotaxane Switch.

The transmission of chiral information between the molecular, meso and microscopic scales is a facet of biology that remains challenging to understand mechanistically and to mimic with artificial systems. Here we demonstrate that the dynamic change in the expression of the chirality of a rotaxane can be transduced into a change in pitch of a soft matter system. Shuttling the position of the macrocycle from far-away-from to close-to a point-chiral center on the rotaxane axle changes the expression of the chiral information that is transmitted across length scales; from nanometer scale constitutional chirality that affects the conformation of the macrocycle, to the centimeter scale chirality of the liquid crystal phase, significantly changing the pitch length of the chiral nematic structure.

Stepwise Operation of a Molecular Rotary Motor Driven by an Appel Reaction.

To date, only a small number of chemistries and chemical fueling strategies have been successfully used to operate artificial molecular motors. Here, we report the 360° directionally biased rotation of phenyl groups about a C-C bond, driven by a stepwise Appel reaction sequence. The motor molecule consists of a biaryl-embedded phosphine oxide and phenol, in which full rotation around the biaryl bond is blocked by the P-O oxygen atom on the rotor being too bulky to pass the oxygen atom on the stator.

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.

Switched "On" Transient Fluorescence Output from a Pulsed-Fuel Molecular Ratchet.

We report the synthesis and operation of a molecular energy ratchet that transports a crown ether from solution onto a thread, along the axle, over a fluorophore, and off the other end of the thread back into bulk solution, all in response to a single pulse of a chemical fuel (CClCOH). The fluorophore is a pyrene residue whose fluorescence is normally prevented by photoinduced electron transfer (PET) to a nearby -methyltriazolium group. However, crown ether binding to the -methyltriazolium site inhibits the PET, switching on pyrene fluorescence under UV irradiation.

In Search of Wasserman's Catenane.

We repeat the earliest claimed [2]catenane synthesis, reported by Wasserman over 60 years ago, in order to ascertain whether or not a nontemplate, statistical synthesis by acyloin macrocyclization does indeed form mechanically interlocked rings. The lack of direct experimental evidence for Wasserman's catenane has led to it being described as a "prophetic compound", a technical term used in patents for claimed molecules that have not yet been synthesized. Contemporary synthetic methods were used to reconstruct Wasserman's deuterium-labeled macrocycle and other building blocks on the 10-100 g reaction scale necessary to generate, in principle, ∼1 mg of catenane.

Compact Rotaxane Superbases.

Challenges for the development of efficacious new superbases include their ease of synthesis, chemical stability, and high basicity, while minimizing nucleophilicity is important for reducing unwanted side reactions. Here, we introduce a new family of organic superbases, compact amine-crown ether rotaxanes, which show desirable characteristics in all these respects. Metal-free active template synthesis provides access to a range of rotaxanes with as little as three atoms between the stoppering groups, locking the location of a small crown ether (21C7 and 24C8 derivatives) over the amine group of the axle.

Decorating polymer beads with 10 inorganic-organic [2]rotaxanes as shown by spin counting.

Polymer beads have been used as the core of magnetic particles for around twenty years. Here we report studies to attach polymetallic complexes to polymer beads for the first time, producing beads of around 115 microns diameter that are attached to 10 hybrid inorganic-organic [2]rotaxanes. The bead is then formally a [10] rotaxane.

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.

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We report the synthesis of molecular prime and composite knots by social self-sorting of 2,6-pyridinedicarboxamide (pdc) ligands of differing topicity and stereochemistry. Upon mixing achiral monotopic and ditopic pdc-ligand strands in a 1:1:1 ratio with Lu(III), a well-defined heteromeric complex featuring one of each ligand strand and the metal ion is selectively formed. Introducing point-chiral centers into the ligands leads to single-sense helical stereochemistry of the resulting coordination complex.

Transamidation-Driven Molecular Pumps.

We report a new class of synthetic molecular pumps that use a stepwise information ratchet mechanism to achieve the kinetic gating required to sequester their macrocyclic substrates from bulk solution. Threading occurs as a result of active template reactions between the pump terminus amine and an acyl electrophile, whereby the bond-forming reaction is accelerated through the cavity of a crown ether. Carboxylation of the resulting amide results in displacement of the ring to the collection region of the thread.

Knotting matters: orderly molecular entanglements.

Entangling strands in a well-ordered manner can produce useful effects, from shoelaces and fishing nets to brown paper packages tied up with strings. At the nanoscale, non-crystalline polymer chains of sufficient length and flexibility randomly form tangled mixtures containing open knots of different sizes, shapes and complexity. However, discrete molecular knots of precise topology can also be obtained by controlling the number, sequence and stereochemistry of strand crossings: orderly molecular entanglements.

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.

Pumping between phases with a pulsed-fuel molecular ratchet.

The sorption of species from a solution into and onto solids underpins the sequestering of waste and pollutants, precious metal recovery, heterogeneous catalysis, analysis and separation science, and other technologies. The transfer between phases tends to proceed spontaneously in the direction of equilibrium. For example, alkyl ammonium groups mounted on silica nanoparticles are used to chemisorb cucurbituril macrocycles from solution through host-guest binding.

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.