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Programmable operation of a molecular machine, 1, that synthesizes different products by moving a substrate between different activating sites a, Flow chart showing the programmable synthesis of any one of four stereoisomers by molecular machine 1. The stereochemistry of each chiral centre in the product was anticipated to show dependence on the handedness of the activating site used in the step that forms that centre. However, the results (Fig. 2) show that while the absolute configuration is determined by the activating site handedness (R or S) during iminium activation (stage IV), the relative configuration (syn or anti) is determined by the switch state (E or Z) during enamine activation (stage VI). Inset, switching process. b, The molecular machine’s response to command inputs in program D. PowerPoint slide
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It has been convincingly argued that molecular machines that manipulate individual atoms, or highly reactive clusters of atoms, with Ångström precision are unlikely to be realized. However, biological molecular machines routinely position rather less reactive substrates in order to direct chemical reaction sequences, from sequence-specific synthesi...
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... Hence, sequential addition of multiple stimuli (e. g., acid and base) is the prime requirement for the complete operation. Moreover, isomerization induced large geometrical change, easy modularity, and bistability bring forth access to unprecedented opportunities e. g., actuation of liquid crystalline material, [26] switchable cascade of reactions, [27,28] negative feedback loops, [29] cargo delivery, [30] intermolecular communication, [31] and programmable molecular assembler, [32] etc. However, reversible switching proceeds via concomitant accumulation of salts upon subsequent addition of acid and base that results in poor cycling performance. ...
The chemically triggered reversible switching of pH‐responsive hydrazones involves rotary motion‐induced configurational changes, serving as a prototype for constructing an array of molecular machines. Typically, the configurational isomerization of such switches into two distinct forms (E/Z) occurs through the alteration of the pH the medium, achieved by successive additions of acid and base stimuli. However, this process results in intermittent operation due to the concomitant accumulation of salt after each cycle, limiting switching performance to only a few cycles (5–6). In this context, we introduce a novel strategy for the autonomous E/Z isomerization of hydrazones in acetonitrile using pulses of trichloroacetic acid as a chemical fuel. The use of this transient acid enabled reversible switching of hydrazones even after 50 cycles without causing significant fatigue. To test the broad viability of the fuel, a series of ortho/para‐substituted hydrazones were synthesized and their switching performance was investigated. The analysis of kinetic data showed a strong dependency of switching operations including the lifetime of transient state, on the electronic properties of substituents. Finally, a distinct color change from yellow to orange due to reversible switching of the para‐methoxy substituted hydrazone was employed for the creation of rewritable messages on commercially available paper.
... Alternative strategies have been pursued by the Leigh group 21-23 for which two pseudo-enantiomeric catalysts are present from the beginning in the reaction mixture. This yields an elegant example of stereodivergency in which a stoichiometric amount of a substrate anchored to a molecular machine is sequentially transformed by the catalyst pseudo-enantiomers (Fig. 1b) 22 . In a different design, the simultaneous operation of a pair of enantioselective switchable catalysts was prevented by mutual inhibition 21 . ...
... These switchable asymmetric catalysts have been exclusively employed for the generation of chiral molecules having opposite configurations, i.e. enantiodivergency. Alternative strategies have been pursued by the Leigh group [21][22][23] for which two pseudo-enantiomeric catalysts are present from the beginning in the reaction mixture. This yields an elegant example of stereodivergency in which a stoichiometric amount of a substrate anchored to a molecular machine is sequentially transformed by the catalyst pseudo-enantiomers (Fig. 1b) 22 . ...
... Alternative strategies have been pursued by the Leigh group [21][22][23] for which two pseudo-enantiomeric catalysts are present from the beginning in the reaction mixture. This yields an elegant example of stereodivergency in which a stoichiometric amount of a substrate anchored to a molecular machine is sequentially transformed by the catalyst pseudo-enantiomers (Fig. 1b) 22 . In a different design, the simultaneous operation of a pair of enantioselective switchable catalysts was prevented by mutual inhibition 21 . ...
Despite recent developments on the design of dynamic catalysts, none of them have been exploited for the in-situ control of multiple stereogenic centers in a single molecular scaffold. We report herein that it is possible to obtain in majority any amongst the four possible stereoisomers of an amino alcohol by means of a switchable asymmetric catalyst built on supramolecular helices. Hydrogen-bonded assemblies between a benzene-1,3,5-tricarboxamide (BTA) achiral phosphine ligand coordinated to copper and a chiral BTA comonomer are engaged in a copper-hydride catalyzed hydrosilylation and hydroamination cascade process. The nature of the product stereoisomer is related to the handedness of the helices and can thus be directed in a predictable way by changing the nature of the major enantiomer of the BTA comonomer present in the assemblies. The strategy allows all stereoisomers to be obtained one-pot with similar selectivities by conducting the cascade reaction in a concomitant manner, i.e. without inverting the handedness of the helices, or sequentially, i.e. by switching the handedness of the supramolecular helices between the hydrosilylation and hydroamination steps. Supramolecular helical catalysts appear as a unique and versatile platform to control the configuration of molecules or polymers embedding several stereogenic centers.
... sequence-specific synthesis 33,34,58,59 , dissipative materials 40,48,49,52,60,61 and endergonic supramolecular structures [17][18][19] . The simplicity of the reactants and fuelling cycle of 5 provides a minimalist demonstration of chemically fuelled ratcheted synthesis that aids its understanding in biology and potential utility in synthesis. ...
Spontaneous chemical reactions proceed energetically downhill to either a local or global minimum, limiting possible transformations to those that are exergonic. Endergonic reactions do not proceed spontaneously and require an input of energy. Light has been used to drive a number of deracemizations and thermodynamically unfavourable bond-forming reactions, but is restricted to substrates that can absorb, directly or indirectly, energy provided by photons. In contrast, anabolism involves energetically uphill transformations powered by chemical fuels. Here we report on the transduction of energy from an artificial chemical fuel to drive a thermodynamically unfavourable Diels–Alder reaction. Carboxylic acid catalysed carbodiimide-to-urea formation is chemically orthogonal to the reaction of the diene and dienophile, but transiently brings the functional groups into close proximity, causing the otherwise prohibited cycloaddition to proceed in modest yield (15% after two fuelling cycles) and with high levels of regio- (>99%) and stereoselectivity (92:8 exo : endo ). Kinetic asymmetry in the fuelling cycle ratchets the Diels–Alder reaction away from the equilibrium distribution of the Diels–Alder:retro-Diels–Alder products. The driving of the endergonic reaction occurs through a ratchet mechanism (an energy or information ratchet, depending on the synthetic protocol), reminiscent of how molecular machines directionally bias motion. Ratcheting synthesis has the potential to expand the synthetic chemistry toolbox in terms of reactivity, complexity and control.
... Leigh and co-workers described a motorized system capable of moving a substrate to different sites, leading to different diastereoisomer products in a chemical transformation. 174 This system comprises terminal alkene incorporated acyl hydrazone rotor and quinoline stator bearing two prolinol silyl ethers connected by triazole linkages. The novelty of this machine is that it can stereoselectively produce one diastereomer in excess over the four products, which could not achieve via the conventional method. ...
... In chemical synthesis, the motors may act as a robot that controls the production of different products in a programmed way. 174 The reports have been published on switching chirality, yet issues associated with the systems, such as the recyclability of a motor or switching activity, need to be addressed. Thereby, many reactions will be benefited from the forthcoming rotary motor-based robotic systems. ...
Molecular machines are nanoscale devices capable of performing mechanical works at molecular level. These systems could be a single molecule or a collection of component molecules that interrelate with one another to produce nanomechanical movements and resulting performances. The design of the components of molecular machine with bioinspired traits results in various nanomechanical motions. Some known molecular machines are rotors, motors, nanocars, gears, elevators, and so on based on their nanomechanical motion. The conversion of these individual nanomechanical motions to collective motions via integration into suitable platforms yields impressive macroscopic output at varied sizes. Instead of limited experimental acquaintances, the researchers demonstrated several applications of molecular machines in chemical transformation, energy conversion, gas/liquid separation, biomedical use, and soft material fabrication. As a result, the development of new molecular machines and their applications has accelerated over the previous two decades. This review highlights the design principles and application scopes of several rotors and rotary motor systems because these machines are used in real applications. This review also offers a systematic and thorough overview of current advancements in rotary motors, providing in-depth knowledge and predicting future problems and goals in this area.
... Though this kind of assembler would represent a broadly revolutionary machine for manufacturing, developing and scaling such a complex piece of technology could take several decades. Existing examples of molecular assemblers 53 are not nearly as broadly applicable as the hypothetical one shown here. (B) Many of the goals associated with nanotechnology can be more easily achieved using synthetic biology, especially when seeking biomolecular products. ...
Gene therapy has demonstrated enormous potential for changing how we combat disease. By directly engineering the genetic composition of cells, it provides a broad range of options for improving human health. Adeno-associated viruses (AAVs) represent a leading gene therapy vector and are expected to address a wide range of conditions in the coming decade. Three AAV therapies have already been approved by the FDA to treat Leber's congenital amaurosis, spinal muscular atrophy, and hemophilia B. Yet these therapies cost around $850,000, $2,100,000, and $3,500,000, respectively. Such prices limit the broad applicability of AAV gene therapy and make it inaccessible to most patients. Much of this problem arises from the high manufacturing costs of AAVs. At the same time, the field of synthetic biology has grown rapidly and has displayed a special aptitude for addressing biomanufacturing problems. Here, we discuss emerging efforts to apply synthetic biology design to decrease the price of AAV production, and we propose that such efforts could play a major role in making gene therapy much more widely accessible.
... [1,2] The molecules that change their shape in response to external stimuli can work as mechanical materials in very small regions at the molecular level. [3,4] On the other hand, to construct the materials working in the macroscopic region, in general, it is necessary to utilize polymer materials. [5,6] However, in many cases, since the free volume around the molecule is large in polymer materials, it is difficult for the movement of each molecule to be directly linked to the macroscopic deformation of the material. ...
Photomechanical molecular crystals are promising materials for photon‐powered artificial actuators. To interpret the photomechanical responses, the spatiotemporal distribution of photoproducts in crystals could be an important role in addition to molecular structures, molecular packings, illumination conditions, crystal morphology, crystal size, and so on. In this study, we have found that single crystals of 2,5‐distyrylpyrazine show a smooth single‐crystal‐to‐single‐crystal photomechanical expansion, and the photochemical reaction propagates from the edge to the center of the single crystal. We revealed that the surface effect (special reactivity at the crystal surface) in addition to the cooperative effect (the reaction is facilitated by neighboring molecules) is essential for the edge‐to‐center propagation of the photochemical reaction. Our results would provide a foundation for future studies of the photochemical reaction dynamics in photomechanical molecular crystals.
... Taking BMMs as an example, a key challenge for artificial molecular machines (AMMs) [3][4][5][6][7][8][9] is to perform work on a coupled system, i.e. transducing the energy that is put into the system into other forms of energy, by avoiding heat dissipation as efficiently as possible. [5,8,10,11] In recent years, molecular machinists developed AMMs that can execute more and more sophisticated tasks, such as multifunctional catalysis, [12][13][14] contracting or moving macroscopic objects, [15][16][17][18][19][20][21][22] penetrating and affecting cell walls, [23][24][25] transporting and assembling molecular entities, [26][27][28][29] shifting chemical equilibria, [30,31] performing coupled motions [32][33][34][35][36][37] or pumping molecular entities. [38][39][40][41][42][43] As demonstrated in the examples above, photochemical molecular motors [44][45][46][47][48][49][50] can be crucial components in AMMs. ...
In artificial small‐molecule machines, molecular motors can be used to perform work on coupled systems by applying a mechanical load—such as strain—that allows for energy transduction. Here, we report how ring strain influences the rotation of a rotary molecular motor. Bridging the two halves of the motor with alkyl tethers of varying sizes yields macrocycles that constrain the motor's movement. Increasing the ring size by two methylene increments increases the mobility of the motor stepwise and allows for fine‐tuning of strain in the system. Small macrocycles (8–14 methylene units) only undergo a photochemical E/Z isomerization. Larger macrocycles (16–22 methylene units) can perform a full rotational cycle, but thermal helix inversion is strongly dependent on the ring size. This study provides systematic and quantitative insight into the behavior of molecular motors under a mechanical load, paving the way for the development of complex coupled nanomachinery.
... The Smalley-Drexler debate introduced the fat and sticky fingers problem to nanotechnology that molecular assemblers cannot manipulate atoms because they are themselves constructed from multiple atoms and cannot be positioned with arbitrary position and atoms stick together due to van der Waal forces (Tourney, 2018)biology overcomes this through molecular recognition and enzymes in a solvent that facilitates self-assembly. However, a molecular assembler has been demonstrated that reversibly rotary switches between two activating sites of opposing chirality controlled by the addition or deletion of a proton (Kassem et al., 2017;Kelly and Snapper, 2017). This suggests that nanotechnology-scale self-replication is feasible but we do not consider it here. ...
In the early 1980s, the Sagan-Tipler debate raged regarding the interpretation of the Fermi paradox but no clear winner emerged. Sagan favoured the existence of ETI on the basis of the Copernican principle and Tipler favoured the non-existence of ETI on the basis of the Occam's razor principle. Tipler's stance was an expansion of the similar but earlier Hart declaration. However, crucial to the Tipler argument was the role played by self-replicating interstellar robot probes. Any technologically capable species will develop self-replication technology as the most economical means of exploring space and the Galaxy as a whole with minimal investment. There is no evidence of such probes in our solar system including the asteroid belt, ergo, ETI do not exist. This is a powerful and cogent argument. Counter-arguments have been weak including Sagan's sociological explanations. We present a Copernican argument that ETI do not exist – humans are developing self-replication technology today. We are developing the ability to 3D print entire robotic machines from extraterrestrial resources including electric motors and electronics as part of a general in-situ resource utilization (ISRU) capability. We have 3D-printed electric motors which can be potentially leveraged from extraterrestrial material that should be available in every star system. From a similar range of materials, we have identified a means to 3D print neural network circuitry. From our industrial ecology, self-replicating machines and indeed universal constructors are feasible. We describe in some detail how a self-replicating interstellar spacecraft may be constricted from asteroidal resources. We describe technological signatures of the processing of asteroidal material (which is expected to be common to most star systems), and the excess production of certain types of clay and other detritus materials. Self-replication technology is under development and imminent – if humans are pursuing self-replication technology, then by the Copernican principle, so would any technologically savvy species elsewhere. There is no evidence that they have.
... Artificial machines composed of a molecule or molecular assembly has inspired many scientists, and they have made large efforts to design and control the mechanical movement 1,2 . The molecules that change their shape in response to external stimulus can work as mechanical materials in very small regions at the molecular level 3,4 . On the other hand, to construct the materials working in the macroscopic region, in general, it is necessary to utilize polymer materials 5,6 . ...
Photomechanical molecular crystals are promising materials as photon-powered artificial actuators. To design and control the photomechanical responses, the spatiotemporal distribution of photoproducts in crystal could be a key factor in addition to molecular structures, molecular packings, illumination conditions, crystal morphology, crystal size, and so on. In this study, we have found that single crystals of 2,5-distyrylpyrazine shows a smooth photomechanical expansion, and the photochemical reaction proceeds heterogeneously on the optical length scale by observation of the changes in color, fluorescence, and birefringence. Moreover, we have performed a numerical simulation to reproduce the experimental results and revealed that both the cooperativity effect and the surface effect in crystal are essential for the heterogeneous progress of the photochemical reaction. Our results would provide a framework for analyzing the heterogeneous reaction dynamics on optical length scale in photoresponsive molecular crystals and a benchmark for future studies of photomechanical molecular crystals.
... Artificial machines composed of a molecule or molecular assembly has inspired many scientists, and they have made large efforts to design and control the mechanical movement 1,2 . The molecules that change their shape in response to external stimulus can work as mechanical materials in very small regions at the molecular level 3,4 . On the other hand, to construct the materials working in the macroscopic region, in general, it is necessary to utilize polymer materials 5,6 . ...
Photomechanical molecular crystals are promising materials as photon-powered artificial actuators. To design and control the photomechanical responses, the spatiotemporal distribution of photoproducts in crystal could be a key factor in addition to molecular structures, molecular packings, illumination conditions, crystal morphology, crystal size, and so on. In this study, we have found that single crystals of 2,5-distyrylpyrazine show a smooth photomechanical expansion, and the photochemical reaction proceeds heterogeneously on the optical length scale by observation of the changes in color, fluorescence, and birefringence. Moreover, we have performed a numerical simulation to reproduce the experimental results and revealed that both the cooperativity effect and the surface effect in crystal are essential for the heterogeneous progress of the photochemical reaction. Our results would provide a framework for analyzing the heterogeneous reaction dynamics on optical length scale in photoresponsive molecular crystals and a benchmark for future studies of photomechanical molecular crystals.
