Systems and methods for bistable oligomer machines

Abstract

In some embodiments, molecules and / or oligomeric machines comprising oligomeric modules are selected and linked to exhibit conformational bistability, where the relative orientation between the oligomeric modules can change from a first orientation to a second orientation in response to one or more stimuli.

Description

[0001] Cross - reference to related applications

[0002] This application claims the benefit of priority of U.S. Provisional Patent Application No. 62,824,610, filed Mar. 27, 2019, the content of which is hereby incorporated by reference in its entirety. Technical Field

[0003] The present application is directed to nanomechanical devices whose operation involves conformational bistability of nanoscale oligomer structures and / or their nanoscale components (compositions). Background Art

[0004] Industrial miniaturization of devices and machines typically proceeds through top-down design. The creation of ever-smaller components and devices is desired, and manufacturing moves from the micron scale to the nanoscale. At dimensions approaching about 10 nm through top-down design, the cost of using precise manipulation of macroscopic devices typically increases and can become prohibitively expensive. Alternatively, a bottom-up strategy of designing functional devices at the nanoscale from sub-nanometer (atomic) scale building blocks (elements) may prove beneficial. Oligomer machines that exhibit conformational bistability can provide nanomechanical functionality, provide stimulus-responsive control, and enable nanoscale manipulation for a variety of applications, including, but not limited to, energy harvesting, stimulus-responsive mechanical actuation, sensing, drug delivery (administration), and biotherapeutic agents. Summary of the Invention

[0005] In some embodiments, molecules and / or oligomer machines comprising oligomer modules are selected and joined (assembled) to exhibit conformational bistability, wherein the relative orientation between the oligomer modules can change from a first orientation to a second orientation in response to one or more stimuli.

[0006] In some embodiments, an oligomer machine includes: a synthetic material that includes a first oligomer module and a second oligomer module coupled to the first oligomer module to form an oligomer chain; at least one flexure or hinge site at a co - connection (co - junction) location between the first oligomer module and the second oligomer module, the flexure or hinge site allowing relative buckling (bending, flexing) between the first oligomer module and the second oligomer module; at least one power - generating element; a substrate configured with respect to the at least one power - generating element and the oligomer chain such that relative buckling between the first oligomer module and the second oligomer module results in a mechanical interaction between at least the second oligomer module of the oligomer chain and the at least one power - generating element, and wherein the oligomer chain is formed such that in response to a stimulus, relative buckling occurs between the first oligomer module and the second oligomer module in a manner that causes a mechanical interaction between the second oligomer module and the power - generating element, and wherein the mechanical interaction produces a change in voltage associated with the at least one power - generating element.

[0007] In some embodiments, an oligomer drug - delivery machine includes: a first oligomer module; a second oligomer module coupled to the first oligomer module at a flexure or hinge site to form an oligomer chain; and a therapeutic agent captured between the first oligomer module and the second oligomer module, wherein the oligomer chain is configured such that upon application of energy thereto, relative movement occurs between the first oligomer module and the second oligomer module such that the captured therapeutic agent is released.

[0008] In some embodiments, an oligomer machine includes: an arrangement of molecules configured to be introduced into a mammalian body, the molecules being arranged and selected such that when exposed to a prescribed temperature, the arrangement performs at least one mechanical function selected from the group consisting of: vibrating, stretching (elongating), rotating, lifting, compressing, ratcheting, bouncing, and buckling, wherein the prescribed temperature is normal mammalian body temperature and is below a temperature that causes necrosis of mammalian cells, such that upon introduction of the arrangement of molecules into the mammalian body, the arrangement of molecules does not perform the mechanical function until the arrangement of molecules is exposed to a temperature that is at least equal to the prescribed temperature.

[0009] In some embodiments, the oligomer machine includes: a synthetic material that includes a first oligomer module and a second oligomer module connected to the first oligomer module to form an oligomer chain; at least one bend or hinge portion at a co - connection location between the first oligomer module and the second oligomer module, the bend or hinge portion allowing relative buckling between the first oligomer module and the second oligomer module; a first chemical reagent attached to the first oligomer module; a second chemical reagent attached to the second oligomer module, and wherein the oligomer chain is formed such that in response to a prescribed amount of energy applied thereto, the first chemical reagent and the second chemical reagent are caused to come into contact with each other and undergo a chemical reaction.

[0010] In some embodiments, the oligomer machine includes: a synthetic material that includes a first oligomer module and a second oligomer module connected to the first oligomer module to form an oligomer chain; at least one bend or hinge portion at a co - connection location between the first oligomer module and the second oligomer module, the bend or hinge portion allowing relative buckling between the first oligomer module and the second oligomer module; at least one piston element; a substrate configured with respect to the at least one piston element and the oligomer chain such that relative buckling between the first oligomer module and the second oligomer module results in a mechanical interaction between at least the second oligomer module of the oligomer chain and the at least one piston element, and wherein the oligomer chain is formed such that in response to a prescribed amount of energy applied thereto, relative buckling occurs between the first oligomer module and the second oligomer module in a manner that causes a mechanical interaction between the second oligomer module and the piston element, and wherein the mechanical interaction generates a mechanical force. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 Illustrate two conformational states of oligo - NIPAm - 20a.

[0012] Figure 2 Illustrate the radius of gyration versus temperature for an exemplary oligo - NIPAm - 20 embodiment.

[0013] Figure 3 Illustrate the end - to - end distance d versus compressive force F for an exemplary oligo - NIPMAm - 30 embodiment, where Fc is the critical pressure.

[0014] Figure 4 Illustrate the Euler arch (arc) related to some aspects of the presently disclosed embodiments.

[0015] Figure 5 Illustrate the bifurcation diagram of the cusp catastrophe model represented by the distance d between the edges of the Euler arch versus the tensile force F.

[0016] Figure 6Describes an exemplary embodiment for simulating an applied force, where one edge of a bent oligomer chain is fixed and a force F is applied to the other edge of the chain.

[0017] Figure 7 Depicts the time series of the edge-to-edge distance of an exemplary NIPMAm-30 oligomer.

[0018] Figure 8 Depicts the spontaneous vibration of an exemplary oligomeric-NIPMAm-30 (top picture) and the statistical weights of the number of "open" and "closed" state visits when the pulling force F passes through a critical value.

[0019] Figure 9 Depicts the stochastic resonance of an exemplary NIPMAm-30 oligomer controlled by a weak oscillating force.

[0020] Figure 10 Depicts a bistable system capable of vibrating spontaneously between two conformations.

[0021] Figure 11 Depicts the time dependence of the edge-to-edge distance in an exemplary oligomeric-NIPMAm-30 embodiment in the vibration mechanism (state) near the critical pulling force.

[0022] Figure 12 Depicts the statistical data of the number of visits to the bent and stretched states normalized by the maximum value for exemplary oligomeric-NIPMAm-30 embodiments near (left) and far from (right) the critical pulling force.

[0023] Figure 13 Depicts the time dependence of the number of hydrogen bonds around the hinge site and the edge-to-edge distance of an exemplary NIPMAm-30 embodiment for a pulling force Fc = 400 pN (left picture) and F = 500 pN (right picture).

[0024] Figure 14 depicts exemplary: ( 1400 ) A bistable oligomer having a single-molecule load attached to the oligomer surface; ( 1401 ) Oligomeric-NIPMAm-30 having attached load molecules; a compressive force is applied to control the spontaneous vibration and stochastic resonance of the oligomer; and ( 1402 - 1405 ) Samples of the tested molecular loads: dye ATTO-390, hormone, amino acid tryptophan, estradinol, and triiodothyronine.

[0025] Figure 15 Depicts the spontaneous vibration of exemplary oligomers with and without attached load molecules.

[0026] Figure 16 Depict the statistical weight distribution of the number of accesses to the "open" and "closed" states of an exemplary oligomer composition having a single tryptophan molecule versus compressive force.

[0027] Figure 17 Depict the shift of the spontaneous vibration region of an exemplary oligo-NIPMAm-30 embodiment caused by the attachment of different load molecules to the exemplary embodiment.

[0028] Figure 18 depicts an exemplary embodiment in which ( 1800 ) stochastic resonance of the oligo-NIPMAm-30 composition can be induced (caused) in the vibration mechanism by a weak applied oscillatory force; and ( 1801 ) the attachment of a single tryptophan molecule alters the vibration mechanism and stochastic resonance can be transformed into ordinary forced oscillation.

[0029] Figure 19 Depict an exemplary nanomachine embodiment that functions like a piston-type engine, comprising a bistable oligomer machine connected to two nanotubes, one of the two nanotubes moving reversibly within the other.

[0030] Figure 20 Depict the unfolding ( 2000 ) and folding ( 2002 ) shapes of an exemplary NIPAm-20i embodiment.

[0031] Figure 21 Depict the radius of gyration of an exemplary NIPMAm-30s embodiment versus simulation time.

[0032] Figure 22 Depict the unfolding ( 2200 ) and folding ( 2201 ) shapes of an exemplary NIPMAm-30s embodiment.

[0033] Figure 23 Depict the unfolding ( 2300 ) and folding ( 2301 ) shapes of an exemplary NIPMAm-30i embodiment.

[0034] Figure 24 Depict the radius of gyration of an exemplary NIPMAm 30i embodiment versus simulation time.

[0035] Figure 25 Depict the radius of gyration of an exemplary NIPAm-21i-19s diblock embodiment versus simulation time.

[0036] Figure 26 Depict the unfolding ( 2600) and folding ( 2601 ) shape.

[0037] Figure 27 Radius of gyration versus simulation time for an exemplary 21i-19a NIPAm diblock embodiment.

[0038] Figure 28 Unfolding ( 2800 ) and folding ( 2801 ) shape for an exemplary NIPAm-12i-4s-12i triblock embodiment.

[0039] Figure 29 Radius of gyration versus simulation time for an exemplary 12i-6s-12i NIPAm triblock embodiment.

[0040] Figure 30 Radius of gyration versus simulation time for an exemplary oligo-NIPAm-12i-8s-12i triblock embodiment.

[0041] Figure 31 Unfolding ( 3100 ), folding ( 3101 ) and semi-folded ( 3102 ) states for an exemplary NIPAm-12i-8s-12i triblock embodiment.

[0042] Figure 32 Unfolding ( 3200 ) and folding ( 3201 ) shape for an exemplary oligo-NIPMAm-12i-7s-12i triblock embodiment.

[0043] Figure 33 depicts an exemplary 10-7-10-NMIPAm-NIPMAm-NMIPAm chimeric component: ( 3300 ) and ( 3302 ) are the shapes of the chimeric component in the open and closed conformational states; ( 3301 ) temperature-induced bistability of the chimeric component; and ( 3103 ) spontaneous vibration of the component at T = 320K.

[0044] Figure 34 Depicts an exemplary poly(p-phenylene) component.

[0045] Figure 35 Initial (open) ( 3500 ) and final (closed) ( 3501 ) states of an exemplary nano tweezer (nanoplier) embodiment.

[0046] Figure 36Depict the distance between the ends of the rod-like segments connected by PNIPAm over time in an exemplary embodiment.

[0047] Figure 37 Depict an exemplary embodiment of a nano tweezer constructed with a rod-like poly(p-phenylene) segment having 15 monomer units and oligo-NIPAm-30s as the power unit: Left: In this exemplary embodiment, oligo-NIPAm-30s can compress the rod with a degree of protonation of 33%; Right: In this exemplary embodiment, oligo-NIPAm-30s cannot compress the rod with a degree of protonation of 50%. Detailed embodiments

[0048] Oligomers and / or molecular machines may include devices capable of exhibiting controlled motion at the nanoscale. Some oligomers and / or molecular machines exhibit conformational bistability, where these machines may be capable of changing between at least two conformations upon application of one or more stimuli under some conditions. Some oligomers and / or molecular machines may include multiple components such as oligomer modules, bending and / or hinge regions, and extenders. Upon application or de-application of one or more stimuli, some molecular machines are configured to perform multiple mechanical motions, such as vibration, folding, bending, and / or stretching. In some embodiments, the mechanical motions can be used for a variety of applications, especially in sensing, energy harvesting, drug delivery, and chemical reactions, for example.

[0049] Bistable oligomers and / or molecular machines

[0050] The oligomeric machine can be configured to exhibit conformational bistability and can include oligomeric modules that are selected and connected to exhibit controllable and / or reproducible conformational changes in response to one or more stimuli. Conformational bistability can be characterized by the presence of at least two distinguishable conformational states, where the spontaneous or reproducible transitions between such states can be controlled by stimuli such as externally controllable parameters. Non-limiting examples of conformational states include the spatial shape or arrangement of molecular, oligomeric, and / or polymeric materials. For example, an oligomeric chain can have a stretched shape, or it can be folded into a bent shape. Bistability means that for a desired process or application, at least two conformational states are sufficiently stable or metastable. For example, an oligomeric chain having a stretched state and a bent state can be repeatedly (repeatedly) switched back and forth between the stretched state and the bent state by a stimulus. An oligomeric machine that exhibits conformational bistability can be used for nanomechanical operations. Nanomechanics (nanomechanics) refers to the motion at the nanoscale by material structures such as molecular, oligomeric, and / or polymeric structures. The atomic fluctuations of such structures are typically much smaller than the size of the structure and its motion. Currently, the industrial miniaturization of devices and machines is based on top-down design. At present, scales of a few tens of nanometers are industrially achievable. At the same time, it becomes clear that when approaching dimensions of about 10 nm by top-down design, the cost of precise manipulation using "macroscopic" devices increases sharply and becomes too expensive in typical mass production. Instead, the manipulation of objects with dimensions of a few (a few) nanometers should use "molecular machines" of approximately the same size. Nanomechanics enables the realization of machine-like motion at the nanoscale using rigid nanoscale materials. Machine-like motion can mean the motion of "hard" units, i.e., the motion of rigid structures, where the atomic fluctuations are much smaller than the characteristic size of the structure and the scale of its motion. Since the atomic fluctuations at room temperature are on the order of 1 angstrom, the minimum size of the functional unit will generally not be significantly less than 1 nanometer.

[0051] Oligomers include few and / or many repeating monomer units. Oligomers can include one or many types of monomer units. For example, oligomers can include one, two, three, or more types of monomer units. The type of monomer can be not particularly limited as long as the oligomer machine exhibits conformational bistability. For example, monomers can include acrylamide, methacrylamide, acrylate, methacrylate, styrenics, olefins, conjugated monomers, thiophenes, peptides, 2-isopropyl-N-methacrylamide, and / or peptidomimetics. In a preferred embodiment, the monomer units include N-isopropylacrylamide (NIPAm) and / or N-isopropylmethacrylamide (NIPMAm). Some oligomers can include isomers of NIPAm (NMIPAm) in which the methyl and isopropyl groups are replaced with each other. Oligomers can be synthesized by a variety of methods. The synthesis of oligomers is not particularly limited and some exemplary techniques include iterative synthesis, step-growth synthesis, polymerization reactions, living polymerization, living radical polymerization, atom transfer radical polymerization, anionic polymerization, cationic polymerization, reversible addition-fragmentation chain transfer polymerization, ring-opening polymerization, metathesis reactions, and / or solid-supported synthesis. Oligomers can be synthesized in a single reaction or multiple reactions. Purification techniques can be used to fractionate and / or separate oligomers by, for example, molecular weight, functionality, tacticity, stereochemistry, and / or regiochemistry. Oligomers can contain more than one monomer type and can have various architectures such as block copolymer oligomers, branched oligomers, random copolymer oligomers, and / or gradient oligomers. Oligomers can be coupled together by a variety of means (e.g., click chemistry, azo-alkyne chemistry, thiol-ene chemistry, epoxy chemistry, Diels-Alder reaction, chain-end substitution), and / or can be synthesized together in single and / or multiple reaction steps. Oligomers can be telechelic. The tacticity can be controlled by a variety of means such as catalyst selection, solvent selection, reaction temperature, ligand selection, and / or polymerization reaction selection. The molecular weight of oligomers can be controlled by: controlling the reaction temperature, monomer concentration, initiator concentration, inhibitor concentration, reaction duration, post-synthesis separation, and / or terminating the reaction. Some exemplary embodiments include oligomers containing N-isopropylacrylamide (NIPAm) and / or N-isopropylmethacrylamide (NIPMAm). Some exemplary embodiments include block copolymer oligomers of N-isopropylacrylamide and / or N-isopropylmethacrylamide. Some exemplary embodiments include block copolymer oligomers of N-isopropylacrylamide and / or N-isopropylmethacrylamide having one or more isotactic, atactic, and / or syndiotactic blocks. Some oligomers include at least 10, at least 15, at least 20, at least 25, and / or at least 30 monomer units. Some oligomers have a persistence length of at least 0.5 nm, at least 1 nm, and / or at least 2 nm.Some oligomers can be at least 0.5 nm, at least 1 nm, at least 2 nm, at least 5 nm, and / or at least 10 nm in length. Some oligomers can have a lower critical solution temperature (LCST). Some oligomers can have an upper critical solution temperature (UCST). Bulk poly(N-isopropylacrylamide) (PNIPAm) exhibits an LCST. The LCST of an oligomer can be different from the LCST of a longer polymer made from the same monomer units. The LCST of an oligomer can be changed by varying the composition of the oligomer. The LCST of an oligomer can be changed by adjusting the ratio of comonomers in the oligomer. Some oligomers can be polydisperse. Some oligomers can be monodisperse. Some oligomers may not have any significant polydispersity. Some exemplary embodiments can include oligomer fragments of PNIPAm of 20 - 30 units and PNIPMAm (poly-N-isopropylmethacrylamide) of the same length. Some embodiments include block copolymer oligomer components having a central PNIPAm fragment of 5 - 15 units and two terminal PNMIPAm fragments of 5 - 20 units. Such exemplary embodiments can be configured to exhibit two clearly distinguishable conformational states, one corresponding to an extended, stretched form of the oligomer fragment and the other having a folded, bent form. The transition between these conformational states in these exemplary embodiments implements a mechanical-like nanoscale motion of the fragment portions.

[0052] Oligomer modules can be joined together. Oligomer modules can be joined together during the synthesis of the oligomer modules. Oligomer modules can be joined together in subsequent reactions. Oligomer modules can be joined together at bending and / or hinge regions. The bending and / or hinge regions can be inherent to the oligomer structure. The bending and / or hinge regions can include additional molecules and / or oligomer structures. The bending and / or hinge regions can include residues from joining reactions such as click reactions, chain end modification reactions, thiol-ene reactions, azide-alkyne reactions, Diels-Alder reactions, epoxy reactions, esterification reactions, and / or cycloaddition reactions. The bending and / or hinge regions can be flexible. The bending and / or hinge regions can include, for example, acrylamide residues, methacrylamide residues, ether linkers, oxyethylene units, peptides, and / or peptidomimetics.

[0053] The oligomeric machine can be configured to exhibit conformational bistability and can include oligomeric modules that are selected and connected to exhibit controllable and / or reproducible conformational changes in response to one or more stimuli. Such stimuli can include, for example, one or more of the following: changes in temperature, set temperature, electric field, magnetic field, changes in pH, applied forces of at least 10 piconewtons, defined amounts of energy, addition of compounds capable of associating and / or binding to the oligomeric machine, changes in solvents and / or co-solvents (cosolvents), and / or changes in ionic strength. One or more stimuli can induce fluctuations back and forth between a first and a second conformation. One or more stimuli can induce a transition from the first conformation to the second conformation. One or more stimuli can induce a transition from the first conformation to the second conformation, and one or more additional stimuli can induce a transition from the second conformation back to the first conformation. One or more stimuli can induce a transition from the first conformation to the second conformation, and upon cessation of the one or more stimuli, the conformation can transition back from the second conformation to the first conformation. The oligomeric machine can be configured to vibrate randomly at or near a transition point, such as a transition temperature. The oligomeric machine can be configured to vibrate randomly at or near a critical load and / or power load. The transition temperature can be between 250K - 400K, 275K - 375K, and / or 300K - 350K. The change in pH can be an increase or a decrease in pH. The change in temperature can be an increase or a decrease in temperature. Some exemplary embodiments can include oligomers of N-isopropylacrylamide (oligo-NIPAm) having a length of about 10 - 15 monomer units, oligomers containing isomers of NIPAm (NMIPAm) in which the methyl and isopropyl groups are replaced with each other, oligomers of poly-N-isopropylmethacrylamide (oligo-NIPMAm), and / or block copolymer oligomers. In some embodiments, the nanomechanical motion of the structural element can be achieved by initiating a transition between an open conformation and a folded or closed conformation accompanied by the motion of rigid molecular segments. This phenomenon is different from the coil-to-globule phase transition in some PNIPAm polymers. Some exemplary embodiments exhibit conformational bistability of fairly short oligomers along with the advantages of reproducibility and mechanically-like motion.

[0054] Figure 1 Exemplary embodiments illustrating two distinguishable conformational states of poly-N-isopropylacrylamide (oligo-NIPAm-20) having a length of 20 units, which have a temperature-controlled transition between an open ( 100 ) and a closed ( 101 ) conformational state. Some embodiments can be configured as nanomechanical power units that include two structural elements of oligo-NIPAm having a persistence Kuhn segment of about 1 nanometer. Figure 2 Illustrating the open ( 200) and closing 201 ) a temperature-controlled transition between states. Figure 3 Illustrates the control of conformational transitions in an exemplary embodiment including oligo-NIPMAm-30 (element 303), where a compressive force (304) is applied to the end of oligo-NIPMAm-30 with one end fixed (302). In this exemplary embodiment, at a pressure (compression) close to 400 pN, the open conformational state (305) becomes unstable and the oligomer abruptly transitions to the closed state (306).

[0055] In some embodiments, the mechanical properties can be analogous to the action of classical non-linear mechanical systems such as the Euler arch or the Zeeman catastrophe machine. A catastrophe machine is a mechanical device with dynamics that exhibit a "catastrophe". Figure 4 Depicts an Euler arch, which is one of the simplest mechanical constructs with "catastrophe" behavior and consists of two rigid rods (403 and 405) connected by an elastic hinge (404). To exhibit a "catastrophe", one edge of the Euler arch is fixed (402) and the other edge is compressed by an external force. As the compressive force reaches a critical value, the Euler arch suddenly straightens. When the compressive force increases, the Euler arch shows bistability, with a jump transition from the tensile state to the bent state ( 400 and 401 depicting two different bent states). For small tensile forces, the Euler arch remains in tension. However, once the compressive force crosses the critical value, the Euler arch suddenly bends. In the theory of dynamical systems, such a sharp change is called a "catastrophe". Thus, the Euler arch is called a "catastrophe machine". The same catastrophe can be demonstrated by applying a tensile force to the bent arch. The bistability of the Euler arch is described by the bifurcation diagram of the cusp catastrophe model as depicted by Figure 5 In Figure 5In regions I and V, the potential energy has a single minimum associated with the bent and the straight Euler arches, respectively. In regions II and IV, there are two energy minima, one of which dominates, while in region III, the two local energy minima are symmetric and neither state dominates. Some exemplary embodiments include nanoscale oligomeric machine components configured to exhibit "mutant" mechanical behavior. A preferred embodiment of a nanomechanical device acting as a mutant machine can be an oligomeric component consisting of two persistent Kuhn segments connected by a bent or hinge site. Such an embodiment surprisingly demonstrates the kinetic behavior of oligomeric components on the order of a few nanometers in size. This can be confirmed by two exemplary oligomeric components (oligo-NIPAm-20, oligo-NIPMAm-30) subjected to tensile forces studied by computer simulation methods. The GROMACS molecular dynamics package was used to perform atomic simulations of the kinetics of the oligomeric components in water at temperatures below and above the critical temperature for the transition from the bent state to the stretched state. The OPLS-AA force field combined with the TIP3P explicit water model was used to describe intermolecular and intramolecular interactions. In such an exemplary embodiment, an oligomeric component in a bent (folded) conformation (600) at a constant temperature is subjected to an applied force (603) at one edge of the chain and the other edge of the chain is fixed (602), inducing a transition to a straight (unfolded) conformation (601). Figure 6 This configuration is depicted in. By varying the tensile force F that triggers the transition from the bent state to the straight state, it was found that the threshold force is approximately 400 pN (piconewtons) for the NIPMAm-30 oligomer and 120 pN for the oligo-NIPAm-20 oligomer. In Figure 7 , a time series of the edge-to-edge distance of the NIPMAm-30 oligomer is shown. Curve (701) corresponds to a tensile force below the threshold, and curve (703) corresponds to a tensile force above the threshold. A tensile force below the threshold does not stimulate the transition from the bent conformation to the stretched conformation. A force above the threshold stimulates the transition for a relatively short time. When the external force crosses the threshold, the kinetics of the component exhibit conformational bistability. Figure 8 Conformational bistability of some exemplary embodiments is demonstrated. In Figure 8Among them, curve (802) corresponds to a force of 325 pN, curve (803) corresponds to a force of 350 pN, curve (804) corresponds to a force of 375 pN, curve (805) corresponds to a force of 400 pN, and curve (806) corresponds to a force of 425 pN. In these exemplary systems, near the threshold force, oligo-NIPMAm-30 and oligo-NIPAm-20 alternately access the bent and stretched states. With a small deviation of up to 20 pN, conformational bistability is exhibited near 390 pN for oligo-NIPMAm-30 and near 120 pN for oligo-NIPAm-20. For larger deviations, the oligomer components have well-defined states, either bent or stretched. Thus, bistability can be demonstrated by the kinetic exemplary embodiments. In this sense, oligo-NIPMAm-30 and oligo-NIPAm-20 can be configured to exhibit "mutant" nanomechanical dynamics.

[0056] In some embodiments, the periodic (cyclic) variation of the control parameters near the threshold can be demonstrated by using all-atom computer simulations in a stochastic vibration mechanism as follows: applying an additional weak oscillatory force to simulate stochastic resonance. The periodic variation of the pulling force near the threshold Fc = 400 pN is carried out by applying a weak oscillatory electric field having an amplitude E in the range of 0.01 - 1.00 V / nm 0 and a frequency varying from 50 to 500 MHz. Stochastic resonance is clearly observed under these variations of the control parameters. In Figure 9 exemplary embodiments are illustrated, where the stochastic resonance of NIPMAm-30 oligomers controlled by a weak oscillatory force is depicted. Figure ( 900 ) and ( 901 ) show the frequency spectra of the vibration between the two states and the vibration when no oscillatory force is applied to the oligomers. Figure ( 902 ) and ( 903 ) show the frequency spectra of the spontaneous resonance effect and the transition when a weak oscillatory force controls the oligomer vibration. In some embodiments, the nanoscale allows thermal fluctuations to directly enter the bistability mechanism. In some embodiments, a new class of nanomechanical devices, namely nanovibrators, can be constructed by taking advantage of the unexpected effect of thermally activated vibrations of bistable oligomer components. Figure 10 is an illustration of this principle, where ( 1000 ) depicts the energy distribution diagram of a bistable system vibrating between the bent (1001) and stretched (1002) states. Figure 10The elements (1003), (1004), (1005), (1006), (1007), (1008), and (1009) depict a stretched conformation, a fixed edge, a rigid element, a bending or hinge region, a rigid element, an applied force, and a vibrational action, respectively. Preferred nanomechanical embodiments may be oligomeric-NIPMA-30 or oligomeric-NIPAm-20 compositions, which consist of two persistent Kuhn segments of about 1 nanometer in length connected by a bending or hinge site. The dynamics of the oligomeric composition subjected to a tensile force are studied by computer simulation methods. The GROMACS molecular dynamics package is used to perform atomic simulations of the oligomeric composition in water at temperatures above the transition temperature. The OPLS-AA force field combined with the TIP3P explicit water model is used to describe intermolecular and intramolecular interactions. The dynamics of the oligomeric composition are characterized by the time dependence of the edge-to-edge distance in the chain. The thermally induced vibrations of the oligomeric composition are established by fine-tuning the tensile force near the threshold. Figure 11 Illustrates an exemplary embodiment and shows the time dependence of the edge-to-edge distance in the oligomeric-NIPMAm-30 oligomer in the vibrational regime near the critical tensile force Fc = 400 pN. Near the threshold of the tensile force for the exemplary embodiments of oligomeric-NIPMAm-30 and NIPAm-20, the oligomers alternately access two states, open and closed. With a rather small tensile force deviation of up to 10 pN, vibrations between these states occur for oligomeric-NIPMAm-30 starting from 400 pN and for NIPAm-20 oligomers starting from 120 pN. Figure 12 For these exemplary embodiments, it is shown that for larger deviations, such as when the bistable potential is very asymmetric, the oligomeric composition gets trapped in one of the two states and does not produce vibrations. Figure 12 Illustrates near ( 1200 ) and far from ( 1201 ) the critical tensile force, the statistical data of the number of accesses to the bent and stretched states normalized by the maximum value for an exemplary oligomeric-NIPMAm-30 embodiment. The curves (1202), (1203), (1204), (1205), (1206), and (1207) correspond to forces of 280 pN, 300 pN, 320 pN, 230 pN, 250 pN, and 280 pN, respectively. In some exemplary embodiments, non-covalent interactions can be used to modulate (tune) this bistable vibrational behavior. Figure 13 Illustrates an exemplary embodiment in which the hydrogen bond bonding along the chain of oligomeric-NIPMAm-30 and between oligomeric-NIPMAm-30 and around water modulates the vibrations. Surprisingly, in these exemplary embodiments, no correlation is observed between the number of hydrogen bonds around the edge portion of the NIPMAm-30 chain and the vibrations.Figure 13 depicts an exemplary embodiment of the NIPMAm-30 oligomer, and in the left pictures ( 1300 and 1301 ) for a pulling force of Fc = 400 pN and in the right pictures ( 1302 and 1303 ) for a pulling force of F = 500 pN, the top curves ( 1300 and 1302 ) show the time dependence of the number of hydrogen bonds around the hinge site and the bottom curves ( 1301 and 1303 ) show the time dependence of the edge-to-edge distance of the chain. Such an embodiment shows that the hydrogen bonds around the hinge site of the NIPMAm-30 oligomer play a dominant role in the mechanical-like vibrations of the oligomer components. In this embodiment, the oligomer components alternately access two states at an average time interval of about 5 nanoseconds, which corresponds to skipping an activation barrier of about 10 k B T, and the vibrations are modulated by the compensation of about 1 hydrogen bond in the hinge site region. The thermally induced vibrations reveal important features of some embodiments of the molecular and / or oligomer machines. The mechanical-like motion of such an embodiment is well-distinguished from thermal fluctuations, but at the same time, the machine action can be activated even by the thermal energy of low potential.

[0057] The oligomer machine may include one or more extender elements. One or more extender elements may be attached to one end of the first oligomer module. One or more extender elements may be attached to one end of the second oligomer module. One or more extender elements may be attached to one end of the first oligomer module and one end of the second oligomer module. One or more extender elements may be attached to an oligomer chain including one or more oligomer modules. The extender element may be rigid. The extender element may be a rigid molecular structure. The extender element may be more rigid than the oligomer module. The extender element may have a persistence length of at least 1 nm, at least 2 nm, at least 5 nm, at least 10 nm, and / or at least 20 nm. The extender element may be, for example, a DNA fragment, a nanotube, an ionomer, a cationic polymer and / or oligomer, and / or an anionic polymer and / or oligomer. The extender element may be attached to the oligomer module via a covalent bond. The extender element may be attached to the oligomer module using, for example, click chemistry, nitrene reaction, thiol-ene reaction, azide-alkyne reaction, Diels-Alder reaction, nucleophilic reaction, and / or amide formation reaction. The extender element may be polymerized by an oligomer initiator. The extender element may include an initiator by which the oligomer element is polymerized.

[0058] Applications of bistable oligomers and / or molecular machines

[0059] An oligomeric machine capable of exhibiting conformational bistability may include a power generation element and may be configured to actuate the power generation element. The power generation element may be, for example, a piezoelectric element, nanoparticles, nanolayers, and / or nanotubes. The oligomeric machine may be configured such that when the oligomeric machine transitions from a first conformation to a second conformation, the oligomeric machine applies a stress to the power generation element, such as a piezoelectric element. The stress may include a compressive force, a tensile force, or a shear force. The oligomeric machine may be configured to apply a stress to the power generation element in a variety of ways. The oligomeric machine may be configured such that when the oligomeric machine transitions from a first conformation to a second conformation, it applies a compressive stress to the piezoelectric element, thereby generating a voltage. The power generation element may be attached to the oligomeric machine covalently or non-covalently. The power generation element may be attached to the oligomeric machine covalently or non-covalently at a bend and / or hinge site. The power generation element may be attached to the oligomeric machine covalently or non-covalently at a bend and / or hinge site such that when the oligomeric machine transitions from an open conformation to a closed or folded conformation, the oligomeric machine applies a stress to the power generation element.

[0060] An oligomeric machine capable of exhibiting conformational bistability may include a light absorption element and may be configured to change conformation upon absorption of light energy. The light absorption element may include, for example, one or more dye molecules, conjugated molecules, aromatic molecules, semiconductor oligomers and / or polymers, quantum dots, nanoparticles, stilbene moieties, azobenzene moieties, and / or bonds configured for cis-trans isomerization. An oligomeric machine capable of exhibiting conformational bistability may include a light absorption element at one or more bend and / or hinge regions. An oligomeric machine capable of exhibiting conformational bistability may include bonds configured for cis-trans isomerization at one or more bend and / or hinge regions such that upon absorption of light, the bonds configured for cis-trans isomerization isomerize, thereby inducing a conformational change of the oligomeric machine. The bonds configured for cis-trans isomerization may be introduced into the oligomeric machine, for example, by a polymerization reaction of a bifunctional initiator including the bonds configured for cis-trans isomerization.

[0061] An oligomeric machine capable of exhibiting conformational bistability may be configured for sensing an analyte. The oligomeric machine may be configured such that upon binding and / or associating with the analyte, the oligomeric machine changes from a first conformation to a second conformation. The oligomeric machine may be configured such that upon binding and / or associating with the analyte, the frequency of the oligomeric machine fluctuating between the first and second conformations is modulated. The frequency of the oligomeric machine fluctuating between the first and second conformations may be decreased or increased. The analyte may be and / or include small molecules, amino acids, saccharides, hormones, oligomers, peptides, metabolites, coordinating groups, ions, aromatic groups, hydrogen bond donors, and / or hydrogen bond acceptors. The oligomeric machine may include Resonance energy transfer (FRET) donors and / or FRET acceptors. The oligomeric machine can be configured such that non-covalent interactions between the bending and / or hinge regions of the oligomeric machine and the analyte induce a conformational change in the oligomeric machine, causing a change in the spectral properties of the oligomeric machine. The binding and / or association of the analyte with the oligomeric machine can modulate the FRET signal. Oligomeric components on the order of a few nanometers in size with conformational bistability properties related to thermally activated spontaneous vibrations and stochastic resonance can be used as detection units in the design of sensors. The physical mechanism of detection can be based on the sensitivity of the spontaneous vibrations and stochastic resonance of the bistable oligomeric components to the physical or chemical binding of the analyte to the oligomeric components. In an exemplary embodiment, the spontaneous vibrations and stochastic resonance of two oligomeric components (oligo-NIPMAm-30 and oligo-NIPAm-20) subjected to the attachment of molecular loads were studied by computer simulation methods. The exemplary embodiment is illustrated in FIG. 14, where ( 1400 ) depicts load molecules (1406 and 1408) bound to an oligomeric machine assembly (1407). Exemplary load molecules include ATTO-390 ( 1402 ), tryptophan ( 1403 ), estradiol ( 1404 ), and triiodothyronine ( 1405 ). The GROMACS molecular dynamics package was used to perform atomic simulations of the spontaneous vibrations and stochastic resonance dynamics of the oligomeric components in aqueous solution at temperatures below and above the critical temperature for the transition from the bent state to the stretched state. The OPLS-AA force field combined with the TIP3P explicit water model was used to describe intermolecular and intramolecular interactions. The dynamics of the oligomeric components were characterized by the time series of the distance between the chain ends. Figure 15 And Figure 16 depict an exemplary embodiment where the spontaneous vibrations of the oligo-NIPMAm-30 oligomeric component respond to the attachment of a load molecule. It can be clearly seen that in the absence of a load molecule, the spontaneous vibrations of oligo-NIPMAm-30 occur near a critical pressure equal to about 375 pN. However, when a load molecule attaches to the oligomer subjected to the same compressive force, the oligomer completely leaves the vibrational mode. Single molecule detection by thermally activated spontaneous vibrations of an exemplary oligo-NIPMAm-30 oligomeric component is depicted in Figure 15 and Figure 16 , where Figure 15 depicts the spontaneous vibrations (1502) of the oligomer without an attached load molecule, which does not vibrate under these conditions when molecules (1501) of ATTO-390, tryptophan, and estradiol are attached. In Figure 16Among them, for the compressive forces of 380 pN (1601), 390 pN (1603), and 400 pN (1602) respectively, the statistical weight distributions of the number of accesses to the "open" and "closed" states of the oligomer component with a single tryptophan molecule are depicted against the compressive force. The bimodal distribution corresponds to the spontaneous vibration mode. The control parameter such as the compressive force can be adjusted to the following value: at this value, along with the attachment load, the spontaneous oscillation of the oligomer occurs. Figure 17 Shows the shift of the spontaneous vibration region when the load molecule attaches. When the load molecule attaches to the oligo-NIPMAm-30 oligomer component, the spontaneous vibration region shifts towards a higher compressive force value. For example, the spontaneous vibration of the oligo-NIPMAm-30 oligomer component with a single attached tryptophan molecule occurs at about F c 色氨酸 = 390 pN compressive force, while the spontaneous vibration of the oligo-NIPMAm-30 itself occurs at about F c 色氨酸 = 375 pN compressive force. The shift of the spontaneous vibration region when the load molecule attaches indicates the corresponding shift of the stochastic resonance characteristics, as depicted in, for example, Figure 18. The shift of the spontaneous vibration and the stochastic resonance mode is sensitive not only to the type of molecule but also to the number of detected molecules. The detection unit based on the spontaneous vibration of the bistable oligomer component is highly sensitive and can show a detection effect even for a single organic molecule.

[0062] The oligomeric machine can be configured for drug delivery. The oligomeric machine can include an imaging agent, a contrast agent, a therapeutic agent, and / or a theranostic agent. The therapeutic agent can include a small molecule therapeutic agent, a chemotherapeutic agent, and / or other therapeutic agents. Such therapeutic agents can be covalently bound to the oligomeric machine, non-covalently bound to the oligomeric machine, and / or encapsulated and bound to the oligomeric machine. The oligomeric machine can be configured for administering a drug to a patient. The patient can be a human or a non-human mammal. The oligomeric machine can be configured to modulate the biodistribution, pharmacodynamics, pharmacokinetics, and / or accumulation of the oligomeric machine in a specific organ and / or tissue of the patient. Such a configuration can include the enhanced permeability and retention (EPR) effect, antibody targeting, peptide fragments, peptidomimetic fragments, and / or nucleic acid fragments. The oligomeric machine can be configured for controlled release of a therapeutic agent. The controlled release of the agent can include mechanical forces and / or solvolysis of bonds accompanied by conformational changes. For example, the therapeutic agent can be encapsulated in polylactic acid and / or polyglactic acid. The therapeutic agent can be bound to the oligomeric machine by a hydrolyzable bond such as an ester bond. The oligomeric machine can include a light absorber, such as a dye, a quantum dot, and / or a nanoparticle. The oligomeric machine including the absorber can generate local heating when absorbing light. The oligomeric machine including the absorber capable of generating local heating when absorbing light can be configured such that a local temperature change induces a change in the conformation and / or the frequency of conformational changes in the oligomeric machine. The oligomeric machine can be configured such that the conformational change enables the oligomeric machine to capture and / or bind to a target structure such as a molecule.

[0063] The oligomeric machine can be configured to induce, catalyze, and / or inhibit a chemical reaction. The oligomeric machine can be configured such that a conformational change brings two or more substrates into a preferred relative orientation for a chemical reaction. The oligomeric machine can be configured to activate a bond to break. The oligomeric machine can catalyze bond formation. The oligomeric machine can be configured such that a change in conformation exposes and / or blocks a catalytically active site. The oligomeric machine can be configured such that a first conformation exposes the catalytically active site and a second conformation sterically blocks the catalytically active site. The catalytically active site can include a transition metal catalyst and / or an organic catalyst. The oligomeric machine can include a catalytic triad, wherein a first conformation is configured such that the catalytic triad is in a preferred conformation for catalytic activity, and in a second conformation the catalytic triad is in a less preferred conformation for catalytic activity. The oligomeric machine can be configured such that a conformational change causes a bond to be stressed and / or more exposed. The stressed and / or more exposed bond can be activated to undergo a further chemical reaction. For example, a stressed and / or more exposed ester bond can be more prone to hydrolysis.

[0064] The oligomer machine may include a piston-type element. The piston-type element may be a rigid molecular structure, such as a molecular structure having a persistence length greater than 10 nm and / or a nanotube. The oligomer machine may be attached to a surface at one end and to a rigid molecular structure at a second end. The oligomer machine may be configured such that a conformational change results in mechanical actuation of the rigid molecular structure. The oligomer machine may be attached to the surface using, for example, thiol chemistry, silane chemistry, and / or nitrene chemistry. The oligomer machine may be synthesized on a solid support. The oligomer machine may be attached to the rigid molecular structure using, for example, thiol chemistry, click chemistry, and / or nitrene chemistry. The oligomer machine may be synthesized on the rigid molecular structure. The oligomer machine may be synthesized on and / or attached to a solid support and may include terminal functional groups configured to bind to the rigid molecular structure. The rigid molecular structure may be configured to bind and / or react with the terminally functionalized oligomer machine. In some embodiments, an oligomer component having a size of a few nanometers with conformational bistability properties may be used as a power unit in the oligomer machine. In Figure 19 A piston-engine type nanomechanical device with a bistable oligomer component serving as a power unit is depicted in, where (1900) depicts an exemplary attachment point to the surface, (1901) depicts an exemplary oligomer machine assembly, (1902) depicts an exemplary piston-type element, (1903) depicts an exemplary actuation cycle, and ( 1904 ) depicts an exemplary radius of gyration versus time. Such an embodiment may include a composite component constructed from three structural elements. Two elements may be two nanotubes coaxially inserted one into the other like a piston in a cylinder. The inner nanotube is movable and serves as the piston, while the outer nanotube is stationary and serves as the cylinder. The third functional element of the nanomechanical device may include a bistable oligomer with one end fixed and the other end connected to the inner nanotube of the piston-nanotube structure.

[0065] Non - limiting exemplary embodiments of oligomers and / or molecular machines and their applications

[0066] In some embodiments, when the solute temperature crosses the LCST, a PNIPAm oligomer having a length of approximately two linked Kuhn segments can undergo a reversible conformational change, whereby the mutual orientation of the Kuhn segments can be reproducibly altered in response to an external stimulus. This can be demonstrated using a series of computational experiments. The all-atom GROMACS molecular dynamics package was used to perform atomic simulations of NIPAm oligomers in aqueous solution at temperatures below and above the LCST. The OPLS-AA force field combined with the TIP3P explicit water model was used to describe intermolecular and intramolecular interactions. The conformation of the chain is characterized by its radius of gyration and / or the distance between the chain ends. In an exemplary embodiment, the oligomer can include 20 NIPAm monomer units linked isotactically (named oligo-NIPAm-20). Figure 20 An exemplary embodiment of oligo-NIPAm-20i is depicted, where the chain unfolds at a temperature of 280K with an average radius of gyration of 1.15nm ( 2000 and 2001 ), and it folds to a state with an average radius of gyration of 0.55nm at a temperature of 320K ( 2002 and 2003 ).

[0067] For some embodiments, 25 - 30 syndiotactically-linked monomer units are optimal, and it appears to correspond to approximately two persistent Kuhn segments. For example, an oligomer composed of 15 syndiotactically-linked NIPAm monomers (named oligo-NIPAm-15s) does not exhibit conformational bistability in response to temperature changes, having a radius of gyration of 0.97nm at 280K and 0.98nm at 320K.

[0068] Poly(N-isopropyl)methacrylamide (PNIPMAm) is also a thermosensitive polymer having an LCST at approximately 315K (42C / 108F). In some embodiments, a PNIPMAm oligomer having a length of approximately two linked persistent Kuhn segments can be configured to undergo a conformational change from an unfolded to a folded state when the solute temperature crosses the transition point. The GROMACS molecular dynamics package was used to perform all-atom simulations of a single PNIPMAm oligomer in water at temperatures below and above the LCST. The OPLS-AA force field combined with the TIP3P explicit water model was used to describe intermolecular and intramolecular interactions. The transition temperature of some oligomers is below the LCST of the bulk polymer. In some embodiments, it is expected to be between 305K and 310K. Figure 21 and Figure 22Depicts an exemplary oligomer embodiment (named oligo-NIPMAm-30s) comprising 30 NIPMAm monomers connected syndiotactically, and exhibits an extended chain (2101) with an average radius of gyration of 1.35 nm at a temperature of 290 K, and it folds (2102) with an average radius of gyration of 1.15 nm at a temperature of 310 K. Figure 22 Depicts the conformational change of an exemplary oligomer from a worm-like extended shape ( 2200 ) to a V-shaped hairpin-like folded structure ( 2200 ).

[0069] In an exemplary embodiment, Figure 23 Depicts an oligomer (named oligo-NIPMAm-30i) comprising 30 NIPMAm monomers connected isotactically. In this embodiment, Figure 24 It shows that the chain unfolds (2401) with an average radius of gyration of 1.37 nm at a temperature of 290 K, and it folds (2402) with an average radius of gyration of 1 nm at a temperature of 310 K. In this embodiment, the conformation of the oligomer chain changes from a stretched worm-like shape (2300) to a folded hairpin-like shape (2301).

[0070] It can be confirmed that some oligomer structures do not exhibit conformational bistability. For example, an oligomer (named oligo-NIPAm-21i-19s) composed of a block of 21 NIPAm monomers connected isotactically and a block of 19 NIPAm monomers connected syndiotactically does not exhibit thermosensitive folding, as Figure 25As shown. In simulations of oligomers of NIPMAm consisting of 20 monomers connected atactic (named oligo-NIPMAm-20a) and oligomers of NIPMAm consisting of 20 monomers connected syndiotactically (named oligo-NIPMAm-20s), neither of the two oligomers showed conformational bistability. At temperatures below and above the LCST, they had an average radius of gyration of 1 nm for oligo-NIPMAm-20a and 0.8 nm for oligo-NIPMAm-20s. An oligomer consisting of 30 NIPMAm monomers connected atactic (named oligo-NIPMAm-30a) adopted a stretched unfolded shape with an average radius of gyration of 1.57 nm at a temperature of 290 K, while at a temperature of 310 K, it had a slightly more compact worm-like shape with an average radius of gyration of 1.35 nm. Simulations were also carried out on an oligomer of NIPMAm consisting of 20 monomers connected atactic (named oligo-NIPMAm-20a) and an oligomer of NIPMAm consisting of 20 monomers connected syndiotactically (named oligo-NIPMAm-20s). Neither of the two oligomers showed conformational bistability, and at temperatures below and above the LCST, they had an average radius of gyration of 1 nm for oligo-NIPMAm-20a and 0.8 nm for oligo-NIPMAm-20s.

[0071] In Figure 26 In some exemplary embodiments shown, the oligomer may include two connected continuous blocks (here named oligo-NIPAm-21i-19a), the two connected continuous blocks being different in stereoregularity and including a block of 21 NIPAm monomers connected isotactically and a block of 19 NIPAm monomers connected atactically. The structure exhibits conformational bistability in response to temperature changes, where below the LCST, it adopts an unfolded extended shape with an average radius of gyration of 1.37 nm ( 2600 ), and above the LCST, the oligomer folds into a horseshoe-like shape with an average radius of gyration of 1.1 nm ( 2601 ). Figure 27 To further illustrate this exemplary embodiment, small fluctuations in the radius of gyration with respect to (about) its variation in the folded (2702) and unfolded (2701) states indicate that these states are well-defined.

[0072] In another exemplary embodiment, an oligomeric machine assembly is shown that includes hard segments of two approximately 10 isotactic NIPAm units connected by a syndiotactic NIPAm bend or hinge region. In a preferred triblock oligomer composition that includes two end blocks each having 12 isotactically connected NIPAm monomers connected by a bend region consisting of 4 syndiotactically connected NIPAm monomers, the composition is designated as oligo-NIPAm-12i-4s-12i. Below the LCST, the oligo-NIPAm-12i-4s-12i composition predominantly exists in a stretched rod-like structure with an average radius of gyration of 1.3 nm. Above the LCST, the triblock oligomer composition folds into an L-shaped lever-like form with an average radius of gyration of 1.05 nm. Figure 28 The oligo-NIPAm-12i-4s-12i composition is depicted, which exhibits two well-separated conformational states, an extended ( 2800 ) state and a folded ( 2801 ) state, with a reproducible reversible transition between the stretched form and the L-shaped lever-like form in response to an external stimulus. In Figure 28 , element (2803) depicts the bend or hinge subassembly, and element (2802) depicts the rigid subassembly.

[0073] In another exemplary embodiment, the triblock oligomer composition consists of two end blocks connected by a bend or hinge region and is designated as oligo-NIPAm-15i-10s-15i, where the two end blocks each have 15 isotactically connected NIPAm monomers and the bend or hinge region consists of 10 syndiotactically connected NIPAm monomers. Below the LCST, the composition exists as a stretched rod-like structure with an average radius of gyration of 1.5 nm, while above the LCST, it folds into a V-shaped hairpin-like form with an average radius of gyration of 1.25 nm. Figure 29 The extended and folded shapes of the oligo-NIPAm-15i-10s-15i triblock oligomer composition are depicted. The oligo-NIPAm-15i-10s-15i composition also exhibits two well-separated conformational states, an extended state and a folded state, with a reproducible reversible transition between the rod-like stretched form and the V-shaped hairpin-like form in response to an external stimulus. Figure 30The results of all-atom computer simulations of three oligo-NIPAm-compositions 12s-8i-12s, 9i-6s-9i, and 12i-6s-12i are depicted. Changing the order of the blocks (i.e., changing from 12i-8s-12i to 12s-8i-12s) results in the absence of bistability, where the system has the same conformational state at 290 K and at 320 K, with an average radius of gyration of 1.25 nm. Due to the lower likelihood of forming hydrogen bonds along the chain that causes the persistence length to decrease sharply, the relatively short isotactic blocks (in the 9i-6s-9i oligomer) seem to be less stiff. As a result, the oligomer compositions fold with an average radius of gyration of 1 nm for both 290 K and 320 K. The oligomer composition named 12i-6s-12i shows different conformational states at temperatures below and above the LCST, and the folded state fluctuates strongly. In some exemplary embodiments, other selections of triblock compositions may have two conformational states, but may exhibit less controllability in terms of the change in the mutual orientation of the rigid edges of the chain when it folds in response to an external stimulus. Such an exemplary embodiment may be a triblock oligomer composition consisting of two edge blocks connected by a bent site, each of the two edge blocks having 12 NIPAm monomers connected isotactically, and the bent site consisting of 8 NIPAm monomers connected syndiotactically. This exemplary embodiment is named oligo-NIPAm-12i-8s-12i. Figure 31 A series of simulations at different temperatures with a step of 10 K are depicted. At 280 K, the structure behaves as a rigid rod ( 3100 ). At 310 K, it collapses into a well-folded S-shaped state ( 3101 ). At 330 K, due to the high temperature, entropy dominates over hydrophobic interactions, making the folded S-shape unstable ( 3102 ). Note that the shape of the composition does not change during a large amount of simulation time. In some embodiments, additional triblock oligomers of NIPMAm are shown. Isotactic segments showing high stiffness can be used as edge blocks, and syndiotactic segments can be flexible and syndiotactic segments can be introduced as bent and hinge sites. A preferred triblock oligomer comprising two edge blocks each having 12 NIPMAm monomers connected isotactically can be connected by a bent site consisting of 7 NIPMAm monomers connected syndiotactically and this exemplary embodiment is represented by oligo-NIPMAm-12i-7s-12i. This oligomer composition has conformational bistability with a transition temperature close to 300 K. Below the transition temperature, it exists as a stretched rod-like structure with an average radius of gyration of 1.26 nm, while above the transition temperature, it folds into a Γ-shaped lever-like conformation with an average radius of gyration of 1.12 nm. As Figure 32As depicted, the oligo-NIPMAm-12i-7s-12i component exhibits two well-separated conformational states, an extended ( 3200 ) state and a folded ( 3201 ) state, with a reproducible reversible transition between a stretched form and a Г-shaped lever-like form in response to external stimuli.

[0074] In another embodiment, a triblock copolymeric oligomer comprising two rigid blocks is connected by a bent third block. In some embodiments, the oligo-NMIPAm fragment, a stereoisomer of NIPAm in which its methyl and isopropyl groups are replaced with each other, exhibits high rigidity and can be used as a rigid edge block in the component, while the oligo-NIPAm fragment is bendable and can be positioned at the bent or hinge site. For example, a preferred triblock chimeric oligomer may include two edge NMIPMAm-blocks each having 10 monomers and is connected by a bent site consisting of 7 NIPMAm monomers in an isotactic configuration. The component of this embodiment is designated 10-7-10-NMIPMA-NIPMA-NMIPMA. In Figure 33, elements (3305 and 3306) depict the bent or hinge subassembly, and elements (3304 and 3307) depict the rigid subassembly. Figure 33( 3300 ) depicts the open conformation of this embodiment. Figure 33( 3302) ) depicts the closed conformation of this embodiment. Figure 33( 3301 ) depicts the conformational bistability exhibited by this embodiment. Figure 33( 3303 ) depicts the spontaneous vibration exhibited by this embodiment at 320K. This chimeric embodiment has a conformational transition above 300K. Below the transition temperature, it exists as an "open" stretched structure with an average end-to-end distance of about 4nm, while above the transition temperature, it semi-folds into a "closed" conformation with an average end-to-end distance of about 1nm. Near the transition temperature, the 10-7-10-NMIPMA-NIPMA-NMIPMA component exhibits a spontaneous transition between the open and closed states, thereby reproducibly altering the mutual orientation of the rigid NMIPMAm fragments in response to external stimuli. A series of computational experiments were performed on this embodiment. The all-atom GROMACS molecular dynamics package was used to perform atomic simulations of the NMIPMA-NIPMA-NMIPMA oligomer in aqueous solution at temperatures ranging from 290K to 360K. The OPLS-AA force field combined with the TIP3P explicit water model was used to describe intermolecular and intramolecular interactions. The conformation of the chain was characterized by its radius of gyration and the distance between the ends of the oligomer.

[0075] The nanomechanical device can be configured to act as nanoscopic tweezers or molecular forceps, where the oligomeric component acts as the power unit. An exemplary embodiment of the nanomechanical device can include four oligomeric elements, where two of the elements include poly(p-phenylene) rod-like segments of 10-20 monomer units, and each phenyl ring in the poly(p-phenylene) is modified with a short aliphatic chain having an amine group at its terminus. The amine group in the short aliphatic chain attached to the phenyl ring can be protonated and / or deprotonated. Figure 34 Depicted is an exemplary poly(p-phenylene) (3402) modified with an aliphatic amine group (3401). By varying the pH of the solvent, or by using a photoacid (photoacid generator) and / or a photobase (photobase generator) to vary the degree of protonation, the electrostatic repulsion between the rod elements can be controlled. Short (about 3 monomers) flexible polyoxyethylene segments can tether (constrain) two poly(p-phenylene) elements close to each other, and the NIPAm-30s oligomer can be configured to act as the power unit. The distance between the edges of the rod segments connected by the NIPAm-30s oligomer can vary due to the competition between the electrostatic repulsion in the rod segments and the mechanical compressive force formed by the NIPAm-30s during the conformational transition. The NIPAm-30s oligomer capable of undergoing a reversible conformational transition can provide sufficient mechanical force for the compression of the rod segments, as Figure 35 depicted in. A series of computational experiments were conducted. Atomic simulations of the NIPAm-30s oligomer in aqueous solution were performed using the GROMACS molecular dynamics package at temperatures below and above the transition temperature of the oligomeric-NIPAm-30s conformational bistability. The OPLS-AA force field combined with the TIP3P explicit water model was used to describe the intermolecular and intramolecular interactions. The operation of the exemplary nanomechanical device is characterized by the distance between the edges of the NIPAm-30s oligomer. In some embodiments, at temperatures below the transition temperature of the oligomeric-NIPAm-30s, a 10-monomer unit poly(p-phenylene) rod segment with 70% protonated amine groups, which results in the maximum distance between the edges of the rod segments, is connected by an extended and stretched PNIPAm-30s oligomer. Figure 35 Illustrates an exemplary embodiment where the temperature is set at 320K to induce a conformational transition of the PNIPAm-30s. In Figure 35 ( 3500 ) depicts an exemplary nanoscopic tweezer in an open configuration, ( 3501) ) depicts the nanoscopic tweezer in a closed configuration, and element (3503) depicts a rigid unit including poly(p-phenylene), and (3502) depicts the oligomeric machine assembly. Figure 36In this exemplary embodiment, it is shown that the NIPAm-30s oligomer can provide sufficient mechanical force for the compression of the loaded rod-like segments of the modified poly(p-phenylene) with 50% protonated amine groups. The unfolded conformational transition of the oligo-NIPAm-30s fragment to the folded state occurs. In this embodiment, the oligo-NIPAm-30s fragment resists the electrostatic repulsive interaction of the protonated amines to compress the rod-like segments towards each other. A variant of this embodiment with longer phenylene rod-like segments of 15 monomer units can be shown. Changing the degree of protonation in the exemplary embodiment shows control of the nanomechanical actuation in response to pH. Figure 37 Describe such an exemplary embodiment, where the nano tweezer structure can be actuated at a lower degree of protonation of about 33% rather than at a higher degree of protonation of about 50%. In Figure 37 , ( 3700 ) depicts an exemplary nano tweezer in a closed configuration, ( 3501 ) depicts a nano tweezer in an open configuration, and the element (3503) depicts a rigid unit including poly(p-phenylene), and (3502) depicts an oligomer machine component.

[0076] In a first non-limiting exemplary embodiment, two linked oligomer modules have conformational bistability with a controlled conformational change. The molecular and / or oligomer machine assembly includes a first oligomer module having a first end and a second end and a second oligomer module having a first end and a second end. The first end of the first oligomer module is connected to the first end of the second oligomer module to form an oligomer chain, and the second end of the first oligomer module is disconnected from the second end of the second oligomer module. The first oligomer module and the second oligomer module are selected and connected such that the pair of linked oligomer modules has conformational bistability. In response to a random perturbation (disturbance) applied to the linked oligomer modules, the relative orientation of the first oligomer module and the second oligomer module spontaneously changes from a first orientation to a second orientation. In response to energy applied to the linked oligomer modules, the relative orientation of the first oligomer module and the second oligomer module repeatedly changes from the first orientation to the second orientation. The oligomer module can have a length between 0.5 nm and 20 nm. The relative orientation of the first and second oligomer modules can define a conformation, and there can be two such stable or metastable conformations. The transition between the first conformation and the second conformation can include relative movement of the first and second oligomer modules. The oligomer module can include at least 5 repeating units. The oligomer module can include at least 10 repeating units. The oligomer module can include at least 15 repeating units. The oligomer module can include at least 20 repeating units. The oligomer module can include at least 25 repeating units. The oligomer module can include at least 30 repeating units. The oligomer module can include poly-N-isopropylacrylamide. The oligomer module can include poly-N-isopropylmethacrylamide. The oligomer and / or molecular machine assembly can be configured to exhibit a conformational transition point within 250 K to 400 K. The oligomer and / or molecular machine assembly can be configured to exhibit a conformational transition point within 275 K to 375 K. The oligomer and / or molecular machine assembly can be configured to exhibit a conformational transition point within 300 K to 350 K. The oligomer module can include a single monomer unit. The oligomer module can include NIPAm residues. The oligomer module can include NIPMAm residues. The relative orientation of the first and second oligomer modules can change in response to the application of light energy. The relative orientation of the first and second oligomer modules can change in response to the application of an electric field. The relative orientation of the first and second oligomer modules can change in response to the application of a magnetic field. The relative orientation of the first and second oligomer modules can change in response to a reversible or irreversible chemical reaction. The relative orientation of the first and second oligomer modules can change in response to non-covalent interactions. The relative orientation of the first and second oligomer modules can change in response to ligand binding, ionic interactions, and / or hydrogen bonding. The relative orientation of the first and second oligomer modules can change in response to a change in pH. The relative orientation of the first and second oligomer modules can change in response to the application of heat and / or a change in temperature.The relative orientation of the first and second oligomer modules can vary in response to thermal fluctuations in the surrounding environment. The first and second oligomer modules can be selected and connected such that buckling along the length of each oligomer module is no more than 50%. In some embodiments, the buckling can be comparable to fluctuations in the atomic structure. In some embodiments, the difference between the first and second orientations of the oligomer module is a change in the distance between the disconnected ends of the module of at least 0.2 nm. In some embodiments, a force of at least 10 piconewtons can be applied to cause the oligomer and / or molecular machine to transition between the first and second conformations. In some embodiments, the transition between the first and second conformations can be configured to apply a force of at least 10 piconewtons.

[0077] In a second non-limiting exemplary embodiment, co-connected bistable oligomer modules below 50 nm enable variable buckling. The bistable oligomer machine can include a synthetic material that includes at least two co-connected oligomer modules forming an oligomer chain. Each oligomer module can be a continuous oligomer chain segment having a length from 0.5 nm to 15 nm. A bending and / or hinge element can be located at at least one co-connection position between two co-connected oligomer modules. The synthetic material can be selected such that applying a predetermined amount of energy to the oligomer chain causes the oligomer modules to predictably buckle relative to each other at the at least one bending or hinge site. Applying a predetermined amount of energy can include applying a variable predetermined amount of energy to cause a variety of different mechanical-like motions. The variety of different mechanical-like motions can include buckling in a first direction and reverse buckling in a second direction and / or opposite the first direction. The variable energy application can be binary, and the value of one energy level is positive. The variable energy application can be binary, and the value of one energy level is positive and the other is approximately 0. The synthetic material can be selected such that applying a predetermined amount of energy to the oligomer chain causes buckling about a bending or hinge site in a first direction, and wherein applying a further portion of the predetermined amount of energy to the oligomer chain causes reversal of the buckling about the bending or hinge site. The synthetic material can be selected such that applying a predetermined amount of energy to the oligomer chain causes buckling about a bending or hinge site in a first direction, and wherein stopping applying the predetermined amount of energy to the oligomer chain causes reversal of the buckling about the hinge site. The synthetic material can be selected such that alternating application of energy levels causes repeated buckling at the bending or hinge site. The length of each oligomer module can be between 0.5 nm and 20 nm. The bending or hinge site can be located at a weakened site in the oligomer chain. The synthetic material can be an oligomer and / or a polymer. The synthetic material can be selected such that applying a predetermined amount of energy to the oligomer chain causes buckling about a bending or hinge site in a first direction, and wherein stopping applying the predetermined amount of energy to the oligomer chain causes reversal of the buckling about the hinge site. The synthetic material can be selected such that applying a predetermined amount of random perturbation to the oligomer chain causes spontaneous buckling about a bending or hinge site in a first direction and in a second direction, and wherein stopping applying the predetermined amount of random perturbation to the oligomer chain causes cessation of the spontaneous buckling about the hinge site. The synthetic material can be selected such that applying a predetermined amount of energy to the oligomer chain causes buckling about a bending or hinge site in a first direction, and wherein applying a further portion of the predetermined amount of energy to the oligomer chain causes reversal of the buckling about the bending or hinge site. The oligomer modules can predictably buckle relative to each other at at least one bending or hinge site. Some molecules and / or oligomer machines can have variable and / or fixed Kuhn segment lengths, and may not require the relative motion to be repeatable.

[0078] In a third non-limiting exemplary embodiment, periodic (cyclic) application and removal of energy causes periodic oligomer module buckling. The molecule and / or oligomer machine can include: a synthetic material that includes at least two co-connected oligomer modules forming an oligomer chain, and at least one bend or hinge site at at least one co-connection location between the at least two co-connected oligomer modules. The oligomer chain can be formed such that in response to a specified amount of energy applied to the chain, a specified amount of relative buckling occurs between the at least two co-connected oligomer modules about the at least one bend or hinge site to cause a change from a first orientation to a second orientation, and when the specified amount of applied energy is stopped, the at least two co-connected oligomer modules return from the second orientation to the first orientation. The oligomer chain can be formed such that in response to repeated periodic application and stopping of a specified amount of energy, the oligomer chain repeatedly buckles from the first orientation to the second orientation. At least one of the co-connected oligomer modules can include NIPAm residues. At least one of the co-connected oligomer modules can include NIPMAm residues. At least one of the co-connected NIPAm oligomer modules can be bound to a rigid molecular structure such as a nanotube or DNA. At least one of the co-connected NIPMAm oligomer modules can be bound to a rigid molecular structure such as a nanotube or DNA. Periodic application of energy can cause the oligomer module to buckle when the energy is applied and return to its original position when the energy is released or dissipated.

[0079] A fourth non-limiting exemplary embodiment can include a bistable oligomer machine having three connected parts, where only the central part buckles. The molecule and / or oligomer machine can include an oligomer chain having a first part, a second part, and a third part, where the second part is located between the first part and the third part and the second part has a significantly greater flexibility than the flexibility of each of the first part and the third part. The first part and the third part can be oligomer modules, and the second co-connected oligomer part can be configured such that when exposed to a specified amount of energy, the second part is caused to buckle while the first part and the third part remain substantially unbuckled. The first part and the third part can be oligomer modules, and the second co-connected oligomer part can be a pair of co-connected oligomer modules configured such that when exposed to a specified amount of energy, the second part is caused to buckle while the first part and the third part remain substantially unbuckled. The molecules of the second oligomer module can be selected and arranged to predictably and repeatedly buckle and recover in response to the application and removal of energy. The molecule and / or oligomer machine can include three molecular segments arranged end-to-end, where only the central segment is flexible.

[0080] In a fifth non-limiting exemplary embodiment, a bistable oligomer machine may include a buckling portion and an extender formed of different materials. The molecular and / or oligomer machine assembly may include: a synthetic material comprising at least a first oligomer module and a second oligomer module connected to the first oligomer module to form an oligomer chain; at least one bend or hinge site at a co-connection location between the first oligomer module and the second oligomer module, the bend or hinge site allowing relative buckling between the first oligomer module and the second oligomer module; and at least one extender attached to the connected oligomer modules, the extender being formed of a material different from the material of the oligomer modules. The material of the extender may be less flexible than the material of the oligomer modules. The extender may be connected to the distal end of the second oligomer module. The extender may be formed of a material different from both the first oligomer module and the second oligomer module. The materials of the first oligomer module and the second oligomer module may be selected such that upon application of a prescribed amount of energy to the oligomer chain, relative buckling occurs at the bend or hinge site. The extender may have a length greater than the length of the second oligomer module. The molecular and / or oligomer machine may further include an additional extender connected to the first oligomer module, wherein the extender has a helical configuration. The extender segment may be attached to at least one end of the flexible oligomer module to enhance the functionality of the molecular and / or oligomer machine. The extender may be formed of a material different from the flexible oligomer module to allow variability in length, rigidity, and / or chemical functionalization.

[0081] In a sixth non-limiting exemplary embodiment, the bistable oligomer machine may include poly(N-isopropylacrylamide). The synthetic oligomer for the bistable oligomer machine may include a segment of poly(N-isopropylacrylamide) (PNIPAm) having at least 15 repeat units. The PNIPAm oligomer may be stereoregular or stereoirregular. The PNIPAm oligomer may include isotactic, syndiotactic, and / or atactic regions. The PNIPAm oligomer may be such that at least one-third portion of the PNIPAm oligomer does not bend by more than 50% along the length of the at least one-third portion. The PNIPAm oligomer may have conformational bistability with a reproducible change in the relative displacement of the ends of the oligomer segments in response to applied energy. The PNIPAm oligomer may exhibit thermally activated spontaneous vibration with a reproducible change in the relative displacement of the ends of the oligomer segments in response to applied random perturbations. The PNIPAm oligomer may exhibit stochastic resonance with a reproducible change in the relative displacement of the ends of the oligomer segments in response to applied energy. The PNIPAm oligomer may be a block copolymer oligomer. The block copolymer oligomer may be composed of portions each in isotactic, syndiotactic, or atactic form. The PNIPAm copolymer oligomer may be selected such that each block of the PNIPAm copolymer oligomer composition does not bend by more than 50% along the length of the block. The PNIPAm copolymer oligomer may have conformational bistability with a reproducible change in the relative arrangement of the blocks in response to applied energy. The oligomer may include 20 NIPAm units. The oligomer may include 25 NIPAm units. The oligomer may include 30 NIPAm units.

[0082] In a seventh non-limiting, exemplary embodiment, the bistable oligomer machine may include poly(N-isopropylmethacrylamide). The synthetic oligomer for the bistable oligomer machine may include a segment of poly(N-isopropylmethacrylamide) (PNIPMAm) having at least 15 repeat units. The PNIPMAm oligomer may be stereoregular or stereoirregular. The PNIPMAm oligomer may include isotactic, syndiotactic, and / or atactic regions. The PNIPMAm oligomer may be such that at least one-third portion of the PNIPMAm oligomer does not bend by more than 50% along the length of the at least one-third portion. The PNIPMAm oligomer may have conformational bistability with a reproducible change in the relative displacement of the ends of the oligomer segments in response to an applied energy. The PNIPMAm oligomer may exhibit thermally activated spontaneous vibrations with a reproducible change in the relative displacement of the ends of the oligomer segments in response to an applied random perturbation. The PNIPMAm oligomer may exhibit stochastic resonance with a reproducible change in the relative displacement of the ends of the oligomer segments in response to an applied energy. The PNIPMAm oligomer may be a block copolymer oligomer. The block copolymer oligomer may be composed of portions each in isotactic, syndiotactic, or atactic form. The PNIPMAm copolymer oligomer may be selected such that each block of the PNIPMAm copolymer oligomer composition does not bend by more than 50% along the length of the block. The PNIPMAm copolymer oligomer may have conformational bistability with a reproducible change in the relative arrangement of the blocks in response to an applied energy. The oligomer may include 20 NIPMAm units. The oligomer may include 25 NIPMAm units. The oligomer may include 30 NIPMAm units.

[0083] The eighth non-limiting exemplary embodiment may include a chimeric bistable oligomer machine. Synthetic oligomers for molecular and / or oligomer machines may include segments of poly(N-isopropylacrylamide) (PNIPAm) of at least 5 repeat units in isotactic or syndiotactic form and at least one other oligomer segment different from PNIPAm having a length of at least 0.5 nm and / or a persistence length of at least 0.5 nm. At least a portion of the PNIPAm may be such that it does not bend more than 50% along the length of the at least one portion of the PNIPAm oligomer and does not bend more than 50% along at least one-third of the length. The oligomer segment may exhibit conformational stability with a reproducible change in the spatial arrangement of the segment ends in response to an applied energy. The oligomer composition may include three oligomer modules having two edge NMIPAm modules each having 10 monomers connected by a bending site consisting of 7 NIPMAm monomers in an isotactic configuration. The chimeric composition may allow for meaningful customization of the structure and function of the molecular and / or oligomer machine such as length, rigidity, and / or chemical functionalization. The oligomer composition may include three modules having two edge NMIPAm modules each having 8 monomers connected by a bending site consisting of 5 NIPMAm monomers in an isotactic configuration.

[0084] Another non-limiting exemplary embodiment may include a bistable oligomer machine configured to generate mechanical force. The molecular and / or oligomer machine may include: a synthetic material comprising a first oligomer module and a second oligomer module connected to the first oligomer module to form an oligomer chain, at least one bending or hinge site at a co-connection position between the first oligomer module and the second oligomer module, the bending or hinge site allowing relative buckling between the first oligomer module and the second oligomer module; at least one piston-type element; and a substrate configured with the piston element and the oligomer chain such that the second oligomer module of the oligomer chain can mechanically actuate the piston element. The piston element may be any suitable rigid molecule and / or nanostructured body such as a graphene nanotube, a nanowire, and / or a DNA fragment. The bistable oligomer machine may generate mechanical force by transferring the motion of the bistable oligomer machine to a periodic motion of the piston-type element.

[0085] Another non-limiting exemplary embodiment may include a bistable oligomer machine for an electromechanical nanodevice. The molecular and / or oligomer machine may include: a synthetic material that includes a first oligomer module and a second oligomer module connected to the first oligomer module to form an oligomer chain, at least one bending or hinge site at a co-connection position between the first oligomer module and the second oligomer module, the bending or hinge site allowing relative buckling between the first oligomer module and the second oligomer module; at least one power generation element; and a substrate configured with the power generation element and the oligomer chain such that the second oligomer module of the oligomer chain can mechanically actuate the power generation element. The oligomer chain may be formed such that in response to a specified amount of energy applied thereto, relative movement occurs between the first oligomer module and the second oligomer module in a manner that causes the second oligomer module to mechanically act on the power generation element to generate a voltage and / or current. The power generation element may be a piezoelectric element, nanoparticle, nanowire, and / or nanolayer. The molecular and / or oligomer machine may be configured to generate a voltage by mechanically acting on the piezoelectric element.

[0086] Other exemplary embodiments may include a bistable oligomer machine for energy harvesting. The molecular and / or oligomer machine may include: a synthetic material that includes a first oligomer module and a second oligomer module connected to the first oligomer module to form an oligomer chain, at least one bending or hinge site at a co-connection position between the first oligomer module and the second oligomer module, the bending or hinge site allowing relative buckling between the first oligomer module and the second oligomer module; at least one light absorption element attached to the oligomer chain at the bending or hinge site; at least one power generation element; and a substrate configured with the power generation element and the oligomer chain such that the second oligomer module of the oligomer chain ensures mechanical action on the power generation element. The oligomer chain may be formed such that in response to a specified amount of energy applied thereto, relative movement occurs between the first oligomer module and the second oligomer module in a manner that causes the second oligomer module to mechanically act on the power generation element to generate a voltage and / or current. The power generation element may be a piezoelectric element, nanoparticle, nanowire, and / or nanolayer. The molecular and / or oligomer machine may be configured to generate a voltage by mechanically acting on the piezoelectric element. The light absorption element may be a dye, a compound including an aromatic group, a conjugated compound, and / or a semiconductor element.

[0087] Other exemplary embodiments may include bistable oligomer machines for sensing. The molecular and / or oligomer machines may include: a synthetic material comprising a first oligomer module and a second oligomer module connected to the first oligomer module to form an oligomer chain, at least one flexure or hinge site at a co - connection position between the first oligomer module and the second oligomer module, the flexure or hinge site allowing relative buckling between the first oligomer module and the second oligomer module; at least one chemically specific site disposed in the flexure or hinge site of the oligomer chain for selectively binding a detectable molecule; at least one power - generating element; and a substrate configured with the power - generating element and the oligomer chain such that the second oligomer module of the oligomer chain ensures a mechanical action on the power - generating element. The oligomer chain may be formed such that in response to a prescribed amount of energy applied thereto, relative movement occurs between the first oligomer module and the second oligomer module in a manner that causes the second oligomer module to mechanically act on the power - generating element to generate a voltage and / or current. The power - generating element may be a piezoelectric element, nanoparticle, nanowire, and / or nanolayer. The oligomer chain having a chemically specific site may be formed such that in response to the binding of a detectable molecule, relative movement occurs between the first oligomer module and the second oligomer module in a manner that causes pressure of the second oligomer module on the power - generating element to generate a voltage. The synthetic material comprising the first oligomer module and the second oligomer module connected to the first oligomer module to form an oligomer chain may have thermally activated spontaneous vibrations with reproducible variations in the relative displacement of the oligomer modules in response to random perturbations. The detection unit may include a NIPAm - 20 oligomer component. The detection unit may include a NIPMAm - 30 oligomer component.

[0088] Additional exemplary embodiments may include bistable oligomer machines configured for drug encapsulation and delivery. The molecular drug delivery machine may include: a first oligomer module; a second oligomer module connected to the first oligomer module at a bend or hinge site and forming an oligomer chain; and a therapeutic agent captured between the first oligomer module and the second oligomer module. The oligomer chain may be configured such that upon application of energy thereto, relative movement occurs between the first oligomer module and the second oligomer module in a manner that releases the captured therapeutic agent. The therapeutic agent may be captured between the first oligomer module and the second oligomer module in a manner that impedes degradation (decomposition) of the therapeutic agent. The therapeutic agent may have a lower affinity for at least one organ in the mammalian body than the first and second oligomer modules, thereby enabling accumulation of the therapeutic agent in the at least one organ. The molecular and / or oligomer machine may further include a targeting agent that targets the therapeutic agent for delivery to at least one organ in the mammalian body. The therapeutic agent may be captured between the first oligomer module and the oligomer module segment by covalent and / or non-covalent bonds between the therapeutic agent and the molecular drug delivery machine. The non-covalent bond may be a mechanical bond, a van der Waals bond, and / or a hydrogen bond. The therapeutic agent may be captured between the first oligomer module and the second oligomer module by a chemical bond between the therapeutic agent and the oligomer drug delivery machine. The chemical bond may be a hydrolyzable bond, and when relative movement occurs between the first oligomer module and the second oligomer module, the hydrolyzable bond is exposed to a solvent, thereby breaking the hydrolyzable bond and releasing the captured therapeutic agent. The oligomer chain may be configured such that upon application of heat thereto, the therapeutic agent is released. The therapeutic agent may be a negative regulator of the mammalian heat shock response such that release of the therapeutic agent after application of heat reduces the mammalian heat shock response. The therapeutic agent may be an agent that induces mammalian cell death. The molecular and / or oligomer machine may be configured for precise drug delivery and release at a targeted site. For example, the therapeutic agent may be encapsulated within the bistable oligomer machine, which may release the therapeutic agent upon actuation of the oligomer machine.

[0089] Yet another non-limiting exemplary embodiment may include a bistable oligomer machine for the controlled release of a therapeutic agent. The molecular drug delivery machine may include: a first oligomer module, a second oligomer module connected to the first oligomer module at a bend or hinge site and forming an oligomer chain, an encapsulation structure arranged to be joined by the oligomer chain, and a therapeutic agent within the encapsulation structure. The oligomer chain may be configured such that upon application of energy thereto, relative movement occurs between the first oligomer module and the second oligomer module in a manner that causes joining with the encapsulation structure in a way that results in rupture of the encapsulation structure and release of the therapeutic agent. The therapeutic agent may include at least two molecules. The molecule and / or the oligomer machine may include an additional therapeutic agent for co-delivery with the therapeutic agent within the encapsulation structure. The molecule and / or the oligomer machine may include at least one targeting agent for targeting the delivery of the therapeutic agent to at least one organ in a mammalian body. The molecular and / or oligomeric drug delivery machine may be configured for irreversible destruction upon rupture of the encapsulation structure, thereby allowing the components of the encapsulation structure to be metabolized by the mammalian body. The encapsulation structure may include at least 2 oligomer chains. The molecule and / or the oligomer machine may be configured to rupture a vesicle containing the therapeutic agent.

[0090] Other non-limiting exemplary embodiments may include thermally activated bistable oligomer machines. The molecule and / or the oligomer machine may include a molecular arrangement configured for introduction into a mammalian body, the molecules being arranged and selected such that when exposed to a specified temperature, the arrangement performs at least one mechanical function selected from: vibration, stretching, rotation, lifting, pressing, meshing, snapping back, and buckling. The specified temperature may be normal mammalian body temperature and below the temperature that causes necrosis of mammalian cells. The molecule and / or the oligomer machine may be configured such that upon introduction of the molecular arrangement into the mammalian body, the molecular arrangement does not perform the mechanical function until the molecular arrangement is exposed to a temperature of at least the specified temperature. The molecular arrangement may include a polymeric material. The molecule and / or the oligomer machine may include a sensitizer configured to increase the local temperature. The sensitizer may be chemically attached to the molecular arrangement. The sensitizer may include at least one nanoparticle and / or an organic dye. The sensitizer may be configured to absorb light in the infrared spectrum. The molecule and / or the oligomer machine may be configured as a drug delivery machine. The molecule and / or the oligomer machine may be chemically attached to a payload, and the molecule and / or the oligomer machine may be configured as a molecular shuttle to move the payload. The molecule and / or the oligomer machine may be configured as a molecular linear actuator. The molecule and / or the oligomer machine may be configured as a molecular sensor. The molecule and / or the oligomer machine may include at least one imaging agent that is activated after the molecule and / or the oligomer machine performs the mechanical function. The molecule and / or the oligomer machine may be configured as a molecular clamp, wherein at least one mechanical function causes at least two distal ends of the molecule and / or the oligomer machine to contract to grasp an object between the distal ends of the molecule and / or the oligomer machine.

[0091] Yet another non-limiting exemplary embodiment may include an oligomer machine configured to facilitate a chemical reaction. The molecule and / or oligomer machine may include: a synthetic material including a first oligomer module and a second oligomer module connected to the first module to form an oligomer chain; at least one bend or hinge site at a co-connection location between the first oligomer module and the second oligomer module, the bend or hinge site allowing relative buckling between the first oligomer module and the second oligomer module; a first chemical reagent attached to the first oligomer module; and a second chemical reagent attached to the second oligomer module. The oligomer chain may be formed such that in response to a prescribed amount of energy applied thereto, the first chemical reagent and the second chemical reagent are caused to come into contact with each other and undergo a chemical reaction. The oligomer chain may be formed such that in response to a prescribed amount of energy applied thereto, the first chemical reagent and the second chemical reagent are caused to come into contact with each other and undergo a chemical reaction. The chemical reaction may include a chemical bond. The chemical reaction may include electrons from the second chemical reagent being received by the first chemical reagent. The molecule and / or oligomer machine may be configured to act as a chemical catalyst, a molecular assembly and / or destructor capable of synthesizing polymeric materials, and / or an energy concentrator. The molecule and / or oligomer machine may be configured to facilitate a chemical reaction by bringing reaction reagents into proximity with each other or by transporting high-energy / charged reaction reagents.

[0092] Other exemplary embodiments may include a bistable oligomer machine configured to respond to a variety of different stimuli. The molecule and / or oligomer machine may include: a molecular arrangement configured to perform a mechanical function in response to the application of a first stimulus, where the mechanical function is selected from rotation, lifting, pressing, engaging, springing back, and buckling; and a receptor associated with the molecular arrangement, the receptor being configured to receive a second stimulus different from the first stimulus and, in response to the second stimulus, render the mechanical function ineffective (inactivate) despite the continued application of the first stimulus. The first and second stimuli may be independently selected to include any one of the following: a change in temperature and / or a compound configured to bind to the receptor and thereby render the mechanical function ineffective. The molecule and / or oligomer machine may be configured to be irreversibly inoperable when bound by a deactivating compound. The receptor may be configured to make the molecule and / or oligomer machine more readily excretable from a mammalian body. The receptor may be configured such that when triggered, the molecule and / or oligomer machine becomes more polar.

[0093] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In case of conflict, the present document, including definitions, will control. Preferred methods and materials are described herein, although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present disclosure. The materials, methods, and examples disclosed herein are illustrative only and not intended to be limiting. As used herein, the terms "comprising," "including," "having," "can," "contain," and variations thereof are intended to be open transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures. The singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. The present disclosure also contemplates other embodiments that "comprise" the embodiments or elements presented herein, "consist of," and "consist essentially of," whether or not explicitly set forth. The conjunctive term "or" can include any and all combinations of one or more of the listed elements associated by that conjunctive term. For example, the phrase "a device including a or b" can refer to a device including a where b may be absent, a device including b where a may be absent, or a device where both a and b are present. The phrase "at least one of a, b, … and n" or "at least one of a, b, … n, or combinations thereof" is defined in the broadest sense to mean one or more elements selected from the group consisting of a, b, … and n, that is, any combination of one or more of the elements a, b, … or n, including any one of the elements alone or in combination with one or more of the other elements, which may also include additional elements not listed in combination form. As used herein, the terms "first," "second," "third," etc. do not denote any order, quantity, or importance, but are used to distinguish one element from another. As used herein, the term "substantially" represents the degree of inherent uncertainty that can be attributed to any quantitative comparison, value, measurement, or other representation. The term "substantially" can also be used herein to denote the degree to which a quantitative representation can vary from the stated reference by that degree without resulting in a change in the basic function of the subject matter being discussed. The term "at least one flexure site or one hinge site" refers to at least one co-connection location between at least two oligomer modules that permits the at least two oligomer modules to predictably flex relative to each other about the flexure or hinge site.

Claims

1. An oligomer machine, comprising: a synthetic material comprising a first oligomer module and a second oligomer module connected to the first oligomer module to form an oligomer chain; at least one bending or hinge site at a co - connection position between the first oligomer module and the second oligomer module, the bending or hinge site allowing relative buckling between the first oligomer module and the second oligomer module; at least one power - generating element; a substrate configured with respect to the at least one power - generating element and the oligomer chain such that relative buckling between the first oligomer module and the second oligomer module results in a mechanical interaction between at least the second oligomer module of the oligomer chain and the at least one power - generating element; wherein the oligomer chain is formed such that in response to a stimulus, relative buckling occurs between the first oligomer module and the second oligomer module in a manner that causes a mechanical interaction between the second oligomer module and the power - generating element, and wherein the mechanical interaction produces a change in voltage related to the at least one power - generating element; wherein the first oligomer module and the second oligomer module are independently selected from poly(N - isopropylacrylamide), poly(2 - isopropyl - N - methylacrylamide), and / or poly(N - isopropylmethylacrylamide).

2. The oligomer machine according to claim 1, further comprising at least one light - absorbing element attached to the oligomer chain at the at least one bending or hinge site, wherein the oligomer chain having the light - absorbing element is formed such that in response to a specified amount of light energy applied to the light - absorbing element, relative buckling occurs between the first oligomer module and the second oligomer module in a manner that causes a mechanical interaction between the second oligomer module and the at least one power - generating element to produce a change in voltage related to the at least one power - generating element.

3. The oligomer machine according to claim 1, further comprising at least one chemical - specific site disposed at the at least one bending or hinge site of the oligomer chain for selectively binding a molecule capable of being detected, wherein the oligomer chain having the chemical - specific site is formed such that in response to the binding of the molecule capable of being detected, relative buckling occurs between the first oligomer module and the second oligomer module in a manner that causes a mechanical interaction between the second oligomer module and the at least one power - generating element to produce a change in voltage related to the at least one power - generating element.

4. The oligomer machine according to claim 1, wherein the power - generating element comprises at least one of the following: a piezoelectric element, nanoparticles, nanowires, or nanolayers.

5. The oligomer machine according to claim 1, wherein the at least one bending or hinge site is selected from acrylamide residues, methacrylamide residues, ether linkers, oxyethylene units, peptides, and / or peptidomimetics.

6. The oligomer machine according to claim 1, wherein the oligomer chain comprises a poly(N - isopropylmethylacrylamide) block between two poly(2 - isopropyl - N - methylacrylamide) blocks.

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