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Harnessing the Energy of Molecular Recognition in a Nanomachine Having a Photochemical On/Off Switch
Abstract
6A-Deoxy-6A-(N-methyl-3-phenylpropionamido)-beta-cyclodextrin operates as a molecular machine, where the amide group serves as a torsion bar to harness the work output resulting from extraction of 1-adamantanol and consequent complexation of the aryl substituent by the cyclodextrin, when the latter behave as the piston and cylinder, respectively, of a molecular pump. At 25 degrees C, the complexation changes the ratio of the amide (Z)- and (E)-isomers from 2.4:1 to 25:1, on which basis the work performed on the amide bond is calculated to be 1.4 kcal mol-1. trans-6A-Deoxy-6A-(N-methylcinnamido)-beta-cyclodextrin and the cis isomer function as a more advanced version of the machine, with the alkene moiety serving as a photochemical on/off switch. Irradiation at 300 nm converts the trans cinnamide to the cis isomer, while the reverse process occurs at 254 nm. With the cis isomer there is little interaction of the phenyl group with the cyclodextrin cavity, so in that mode the machine is turned off. By contrast, complexation of the aryl substituent by the cyclodextrin occurs with the trans cinnamide and changes the ratio of the amide (Z)- and (E)-isomers from 2.6:1 to 100:1. Consequently, in this mode the machine is turned on, and the work harnessed by the amide bond is 2.1 kcal mol-1.
... [2,3] They have also been used to facilitate chemical transformations, [4] as well as in separation science [5] and the development of new materials. [6] In supramolecular chemistry, they have provided the foundation for a diverse range of molecular devices, including rachets, [7] switches, [8,9] muscles, [10] and machines, [11,12] that perform specific functions in response to external stimuli. ...
... Previously, we found that the 6 A -trans-cinnamido-b-cyclodextrin 3 ( Figure 1) formed a self-inclusion complex in water, that was disrupted by organic solvents and competitive guests, whereas the corresponding cis-isomer 4 did not. [11] The cis--trans photoisomerization therefore enabled the water-dependent substituent complexation. With the 3 A -trans-cinnamidocyclodextrin 1, the substituent is included in the cyclodextrin annulus irrespective of the solvent or the presence of potentially competitive guests. ...
... the synthetic procedures (Scheme 2). Accordingly, treatment of b-cyclodextrin with the nitrophenyl toluenesulfonate 5 gave the cyclodextrin tosylate 7, [14] which reacted with 40 % methylamine in water to give 3 A -deoxy-3 A -methylamino-altro-b-cyclodextrin (11). A previous study by Murakami et al. [15] established that treatment of the tosylate 7 with base produces the mannoepoxide 9, which undergoes nucleophilic ring-opening in the presence of aqueous ammonia to afford 3 A -amino-3 Adeoxy-altro-b-cyclodextrin. ...
The photoinduced interconversion between cinnamido-substituted cyclodextrins constitutes a gating switch through which the substituent moves to open or block access to the cyclodextrin cavity. Most unusually for a cyclodextrin-based device, the operation of this gate is solvent-independent and unaffected by potentially competitive guests. It occurs in MeOH and DMSO, as well as in water. This contrasts with other cyclodextrin inclusion phenomena that are usually driven by hydrophobic effects and limited to aqueous media.
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
... Other authors utilize the reaction of the secondary amino-β-CD derivative with acyl chloride, as Coulston et al. [232] who did to synthesize molecular machines prototypes. Based on phenylpropionamido and cinnamido-β-CDs, these machines can repeatedly form complexes with adamantanol. ...
Cyclodextrins are well known supramolecular hosts used in a wide range of applications. Monosubstitution of native cyclodextrins in the position C-6 of a glucose unit represents the simplest method how to achieve covalent binding of a well-defined host unit into the more complicated systems. These derivatives are relatively easy to prepare; that is why the number of publications describing their preparations exceeds 1400, and the reported synthetic methods are often very similar. Nevertheless, it might be very demanding to decide which of the published methods is the best one for the intended purpose. In the review, we aim to present only the most useful and well-described methods for preparing different types of mono-6-substituted derivatives. We also discuss the common problems encountered during their syntheses and suggest their optimal solutions.
... Another quite interesting example of applicability for b-CDbased pseudo[1]rotaxanes is the molecular pumps developed by Easton and co-workers (Scheme 21). 172 The first prototype of the nanomachine comprises an N-methyl-3-phenylpropanamido pendant as a piston, connected to a b-CD moiety as the cylinder molecule 26, which is fuelled by inclusion of 1-adamantanol (AD). The compression and decompression strokes involve the binding processes of the amide (Z)-isomer with AD, and the amide (E)-isomer with AD in a reverse sequence, with the difference in the binding-free energies being the work generated by and stored within the engine. ...
Synthetic supramolecular chemistry pursues not only the construction of new matter, but also control over its inherently dynamic behaviour. In this context, classic host–guest chemistry, based on the development of a myriad of macrocyclic receptors with fine-tuned affinities and selectivities, has enormously contributed to the discovery of new chemical function under self-assembly conditions. In turn, the use of molecular switches as control units within host–guest assemblies opened the door for the regulation of their dynamic interactional behaviour, which can be translated into controlled aggregation. In this review, we will focus on different strategies developed for the regulated binding of organic molecules by switchable macrocyclic hosts. As we will see, an appropriate design using stimuli-responsive versions of well-known organic receptors allows the molecular switches implemented within their structures to transform their regulated behaviour from the molecular to the supramolecular level.
... At the early stages of the development of synthetic rotary molecular machines, the machine depends on Brownian ratchets system. At the later stage of developments, for the reasons discussed later in the chapter, unidirectional rotaries uses different stimulants such as electromagnetic spectrum(53,243,244), thermal fluctuation(184,245,246) and chemical fuel(247,248) to power molecular rotors. Further theoretical approaches such as electron tunnelling(249) and coulomb interaction driven motors(250) were mentioned as a potential fuel source for the rotary motor. ...
Metal-Organic Frameworks (MOFs) are new remarkable nano-porous materials that exhibit exceptional thermal and chemical stabilities. They have a broad range of applications ranging from, not limited to, gas storage/separation, molecular separations, sensor, catalysis, drug delivery and removal of toxic chemicals and detoxification of warfare agents. The properties of the materials are highly dependent on the nature of the atomic interactions and structural arrangement of the crystallise material. This thesis focused on the MOFs that respond to stimuli where the structure will undergo reversible transformation in which it can lead to remarkable sorption properties that enhance the material performance. The selected MOFs, ZIF-8 and Mg-MOF-74 were studied in this thesis. The materials were evaluated at atomistic and quantum levels. Here, we proposed a new theoretical concept regarding controlling molecular movements by implanting molecular machines in Mg-MOF-74. We designed the molecular machines to respond to external electric field and the machines are anchored within the onedimensional pore channel of Mg-MOF-74. The pore opening and closing was simultaneously controlled by the induced electric field; thus, the flow directions of methane can be controlled at molecular level. Moreover, this thesis moved onto the study regarding mechanical ‘gate’ opening movements in ZIF-8 which are stimulated by introduction of water molecules to the system. First, we examined with water models response in ZIF-8. Five types of different water models and six different ZIF-8 force fields were chosen and simulated with Grand Canonical Monte Carlo method. We found that the simulated adsorption isotherms are significant diverse in relation to water models. Afterward, we mimicked experimental water adsorption set up through the use of a graphene piston in molecular dynamics simulation. Here, we demonstrated through the use of water that we witnessed experimental ‘gate’ effect. However, we also found that current atomics force fields in literature were unable to replicate the adsorption isotherm at experimental conditions, resulting in the development and modifications for new force field that tune to water responses in ZIF-8.
... Thus, both amide and alkene isomerizations and intermolecular host-guest complexation of 1-adamantol are exploited in the operation of the molecular device based on E-6 A -deoxy-6 A -(N-methylcinnamido)β-CD shown in Figure 32. 73 The thermal E to Z isomerization about the amide bond controls the equilibrium between isomeric 124E and 124Z in which 1-adamantol, Figure 32 The 124E , 124Z , 124E , and 124Z equilibrium system in which intermolecular host-guest complexation of 1-adamantol competes with cinnamate self-complexation in 124Z and E to Z isomerization about the amide bond occurs while the E stereochemistry about the cinnamate alkene bond is retained. Photoisomerization by irradiating at 300 nm switches the stereochemistry about the cinnamate alkene bond to Z to produce the 125E , 125Z , 125E , and 125Z system in which no competitive cinnamate self-complexation occurs. ...
Cyclodextrins (CDs) are naturally occurring homochiral macrocycles composed of α-1,4-linked d-glucopyranose in the 4C1 conformation. The three smallest α-, β-, and γ-CDs are composed of 6, 7, and 8 glucopyranoses, and as a class constitute one of the most widely used molecular components in supramolecular chemistry. This usage is based on the ability of CDs to complex a vast range of guests in their hydrophobic annuli in water. In this brief review, CD supramolecular chemistry is explored from simple CD complexes to increasingly complex assemblies. The modification of CDs to give desirable properties is also examined along with their supramolecular chemistry. This exploration encompasses CD host–guest complexes, enantioselectivity, polymers, catalysis, metallocyclodextrins, rotaxanes and catenanes, and molecular devices and nanomachines, some of which mimic Nature and all of which represent a fascinating aspect of supramolecular chemistry with some extraordinary possibilities for further advances and practical application.Keywords:cyclodextrin;enantioselectivity;host–guest complex;molecular device;nanomachine;rotaxane;supramolecular
... The interaction of these two groups has been considered in many of the systems reviewed above. A more recent study based of plug/socket designs was conducted by Coulston et al. [98]. In this experimental study it was proposed that these types of systems could work as molecular pistons by photoisomerization. ...
... Although the redox-controlled 17 and pH-controlled 18 guest complexation of CB [7] has been investigated, the guest complexation and decomplexation of CB[7] triggered by light has not been studied. Cinnamamide (Scheme 1), whose photoisomerization properties such as transform efficiency, wavelength-dependence, and thermal stability have been well studied, is an attractive photoresponsive component for molecular switch systems, 19 because of the high conformational thermal stability of the Z isomer Scheme 1 Photo-switchable "on-off" host-guest system. after E to Z photoisomerization. ...
A new photo-switchable "on-off" host-guest system comprising cucurbit[7]uril (CB[7]) and a photoresponsive cinnamamide derivative (trans-(3-phenyl-acryloylamino)-acetic acid, E-1) is studied. The cinnamamide derivative and CB[7] forms a stable 1 : 1 host-guest complex (CB[7]·E-1) with a high binding constant (K = 2.1 × 10(4) M(-1)). Irradiation of UV light (300 nm) to an aqueous solution of CB[7]·E-1 induces the E- to Z-conformational change of the cinnamamide derivative, which then leads to the dissociation of the complex as evidenced by UV-visible and (1)H-NMR spectroscopy. The reverse process, photo-induced host-guest complex formation between CB[7] and Z-1 is achieved by irradiation of UV light at 254 nm. The photo-switchable "on-off" host-guest system shows high reversibility and switching efficiency, which makes it potentially useful in designing photoresponsive gating systems.
... Thus if changes in the geometry around the amide bond are used as a reference point, then this system could be regarded as a type of molecular machine. 37 Another example that highlighted the overlap between ''molecular machines'' and ''molecular switches'' used a semi-biological approach to create ''molecular cage'' that can enclose proteins. Genetically engineered chaperonin GroEL was functionalised with azobenzene derivatives at both entrances to the cavity; when the azobenzene moieties were in the trans-state, the entrance to the cavity was blocked. ...
This annual report describes a selection of contributions from researchers who, using organic chemistry tools and inspiration from biomolecular systems have developed new techniques, approaches and applications. The report is divided in four sections. The first three sections deal with progress in organic chemistry inspired by the major classes of biomolecules. The fourth section focuses on recent developments in organic chemistry inspired by the complexity of biomolecular systems, and notes that, more than a decade after the first artificial self-replicators were described, a discipline that deals with complexity in artificial chemical systems is beginning to take shape, under the name of Systems Chemistry.
... One of the aims of nanotechnology is to obtain artificial nanoscale machines that obey external orders directed to a technological goal (e.g., to transduce the presence of an analyte into electrical signals measured by a sensor, to deliver a molecular cargo at a specific location or under specific physiological conditions, or to exert minute forces and very precise displacements on nanoscale objects). Although synthetic approaches to molecular machine design with a mechanical inspiration are leading to considerable advances (3,9,11,37), the emerging field of bionanotechnology is taking a shortcut: developing nanotechnological devices based on biomolecules (2). Indeed, proteins can be viewed as highly efficient machines capable of performing many important classes of function, ranging from that of motors to structural elements, catalysts, and electronic and molecular carriers to information repositories. ...
Chemical modification with photoisomerizable tethered ligands endows proteins with sensitivity to light. These optically actuated proteins are revolutionizing research in biology by making it possible to manipulate biological processes noninvasively and with unprecedented spatiotemporal resolution.
Chemical substituents hold the potential to markedly influence the photochemical behavior in molecular systems and assist in gaining a comprehensive understanding of nonadiabatic phenomena. In this study, we have conducted a comparative analysis of the influence of chemical substituents on the photochemical ring-opening of 1,3-cyclohexadiene (CHD), considering four systems: CHD, 2,3-dimethylcyclohexadiene (CHD-Me2-1), 1,4-dimethylcyclohexadiene (CHD-Me2-2), and 1,2,3,4-tetramethylcyclohexadiene (CHD-Me4), using electronic structure theory calculations and nonadiabatic molecular dynamics simulations. Employing extended multistate complete active space second-order perturbation (XMS-CASPT2) theory, we optimized reactants, S1 states, conical intersections (CIns), and products, revealing structural and energetic variations consistent with prior research. Nonadiabatic molecular dynamics simulation was used to gain insights into photochemical dynamics at state-averaged complete active space self-consistent field (SA-CASSCF) theory. CHD-Me4 exhibited reduced carbon–carbon single bond rupture rates, responsible for ring-opening, due to substituent proximity. Further, CHD-Me2-2 and CHD-Me4 displayed prolonged excited-state relaxation times, highlighting notable substituents’ impact. Analysis of kinetic energy profiles of specific carbon atoms also revealed restrained atomic displacements, particularly in CHD-Me2-2 and CHD-Me4. These findings advance our understanding of how substituents modulate photochemical reactions in cyclohexadiene derivatives, guiding new molecular design and future research.
Structures and UV-vis absorption spectra of the host-guest interaction of the methoxy cinnamic acid (MCA) derivatives and cyclodextrins (CDs) were performed by using the density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. All geometries of MCA derivatives (4-MCA, 245-MCA, 246-MCA), three types of CD (αCD, βCD, γCD), and five host-guest inclusion complexes between MCA and CD consisting of 4-MCA/αCD (1), 4-MCA/βCD (2), 245-MCA/βCD (3), 246-MCA/βCD (4), and 246-MCA/γCD (5) were fully optimized by using the M06-2X/6-31G (d,p) levels of theory. Two orientations (A and B) of the MCA guest molecule were considered. Upon examining the optimized geometry, five complexes of the methoxy cinnamic acid molecules are located inside the cavity of CD. Orientation B was more stable than orientation A because of the stronger intermolecular hydrogen bonds between the hydroxyl group of CD and the carboxylic group of MCA. The results indicated that the intermolecular hydrogen bond is mainly the driving force of formation between methoxy cinnamic acid and cyclodextrins. To reveal the host-guest interaction that is relevant to UV-filter compounds, the UV-vis absorption spectra were performed using TD-DFT calculations. The obtained results confirmed that orientation B is the most stable orientation and can absorb in both UVB and UVA regions which is similar to the parent MCA. Therefore, this knowledge will bring to understand the host-guest interaction between methoxy cinnamic acid and cyclodextrin complexes. The theoretical results are expected to provide valuable information for improving the stability of further UV-filter compounds.
With the benefit of the increasing nanodevice techniques today, the molecular‐level probe of the more complicated systems (supramolecular systems) offered the opportunity to explore the interaction in the supramolecular system. Graphene‐molecule‐graphene single molecule junctions (GMG‐SMJs) has been employed in hydrogen bond investigations. The quadrupolar hydrogen‐bond dimer increased the strength of hydrogen bonds and device conductivity, which led to better performance and afforded more profound dynamic information in real‐time electrical detection. Host–guest complexes are the assembly of the supramolecular lock‐and‐key image. The pronounced conception for these complexes is that the host molecule provides a large hydrophobic cavity to the guest molecule with a microenvironment for chemical reactions. Supramolecular donor–acceptor dyads constitute a versatile kind of molecular assemblies with a variety of active electronic properties of molecular devices via donor–acceptor interactions. The intermolecular charge‐transfer interactions for supramolecules are also discussed.
In this study we report synthesis of modified oligonucleotides consisting of benzoic acid or isophthalic acid residues as new nucleobases. As evaluated by UV thermal denaturation analysis at different pH conditions (5.0, 6.0, 7.0, and 8.0), these modified oligonucleotides exhibited pH-dependent recognition of natural nucleobases and one is first found to be capable of base pair switching in response to a pH change. The isophthalic acid residue incorporated into the oligonucleotide on a D-threoninol backbone could preferentially bind with adenine but with guanine in response to a change in the pH conditions from pH 5 to pH 7 (or 8) without significant difference in duplex stability. These findings would be valuable for further developing pH-responsive DNA-based molecular devices.
Millisecond-scale conformational transitions represent a seminal challenge for traditional molecular dynamics simulations, even with the help of high-end supercomputer architectures. Such events are particularly relevant to the study of molecular motors — proteins or abiological constructs that convert chemical energy into mechanical work. Here, we present a hybrid--simulation scheme combining an array of methods including elastic network models, transition path sampling and advanced free-energy methods possibly in conjunction with generalized-ensemble schemes to deliver a viable option for capturing the millisecond-scale motor steps of biological motors. The methodology is already implemented in large measure in popular molecular dynamics programs, and can leverage the massively parallel capabilities of petascale computers. Applicability of the hybrid method is demonstrated with two examples, namely cyclodextrin-based motors and V-type ATPases.
A polymer (4) bearing heptamethylene (C7) and azobenzene (Azo) was synthesized. Based on the different association constants between the cyclodextrins and the hydrophobic moieties C7 and Azo, a side-chain polypseudorotaxane was prepared. In the first step, α-cyclodextrin (α-CD) was added to the polymer 4 solution to form the side-chain polypseudorotaxane, in which the C7 and Azo was both included by the α-CD. In the second step, the trans-Azo at the end of the side chain of the polymer 4 was isomerized to the cis-Azo under the irradiation of the 365 nm UV light to form the side-chain polyrotaxane, in which α-CD was interlocked on the side chain. In the final step, β-cyclodextrin (β-CD) was added to the side-chain polyrotaxane to form the side-chain polypseudorotaxane.
The balances of interactions were studied by computational methods in the translational isomers of a solvent switchable fullerene-stoppered [2]rotaxane (1) manifesting unexpected behavior, namely that due to favorable dispersion interactions the fullerene stopper becomes the second station upon change of the solvent. For comparison, another system, a pH switchable molecular shuttle (2), was also examined as an example of prevailing electrostatic interactions. Tested for 1 were five global hybrid Generalized Gradient Approximation functionals (B3LYP, B3LYP-D3, B3LYP-D3BJ, PBEh1PBE and APFD), one long-range corrected, range-separated functional with D2 empirical dispersion correction, ωB97XD, the Zhao-Truhlar's hybrid meta-GGA functional M06 with double the amount of nonlocal exchange (2X), and a pure functional, B97, with the Grimme's D3BJ dispersion (B97D3). The molecular mechanics method qualitatively correctly reproduced the behavior of the [2]rotaxanes, whereas the DFT models, except for M06-2X to some extent, failed in the case of significant dispersion interactions with participation of the fulleropyrrolidine stopper (rotaxane 1). Unexpectedly, the benzylic amide macrocycle tends to adopt preferentially 'boat'-like conformation in most of the cases. Four hydrogen bonds interconnect the axle with the wheel for the translational isomer with the macroring at the succinamide station (station II), whereas the number of hydrogen bonds vary for the isomer with the macroring at the fulleropyrrolidine stopper (station I) depending of the computational model used. The B3LYP and the PBEh1PBE results show strong preference of station II in the gas phase and in the model solvent DMSO. After including empirical dispersion correction, the translational isomer with the macroring at station I has the lower energy with B3LYP, both in the gas phase and in DMSO. The same result, but with higher preference of station I, was estimated with APFD, ωB97XD and B97D3. Only M06-2X presented qualitatively correct behavior for the relative stability of the two translational isomers, namely, slight preference of station II for the isolated molecule and higher relative energy of the same isomer with the model solvent DMSO. The electrostatic interactions in 2 have the decisive contribution both when the macroring is positioned at the dipeptide residue for the neutral form, and at the N-benzylalanine fragment after protonation, and the observed behavior of the [2]rotaxane is correctly reproduced by the methods used.
Manufacturing machines converting energy to mechanical work at the molecular level is a vital pathway to explore the microscopic world. A kind of operable molecular engines, composed of β-cyclodextrin (β-CD), aryl, alkene and amide moiety was investigated using molecular dynamics simulations combined with free-energy calculations. To understand how the integrated alkene double bond controls the work performed on the engines, two alkene isomers of the prototype were considered as two molecular engines. The free-energy profiles delineating the binding process of the amide (Z)- and (E)-isomers for each alkene isomer with 1-adamantanol indicate that for the alkene (E)-isomer, the apparent work performed on the amide bond is 1.6 kcal/mol, while the alkene (Z)-isomer is incapable to perform work. Direct switch on/off of engines caused by the isomerization of the alkene bond was, therefore, witnessed, in line with experimental measurements. Decomposition of the free-energy profile into different components and structural analyses suggest that the isomerization of the alkene bond controls the position of the aryl unit relative to the cavity of the CD, resulting in the difference among the free-energy profiles and the stark contrast of the work performed on engines.
6-O-monotosyl-deoxy-β-cyclodextrin (6-OTs-β-CD) was prepared by literature method, and analyzed by IR and 1HNMR. The analytic results show that the goal material is reliable. The inclusion complex was acquired by the reaction of 6-OTs-β-CD and N, N'-diphenyl thiourea with the mole ratio of 2:1, and then the comprehensive thermal analysis spectrum was used to study the thermal stability of inclusion complex. The adsorption behaviors of the inclusion complex and N, N'-diphenyl thiourea to Th4+ were studied with the method of visible spectrophotometry. The experimental results indicate that the adsorption equilibrium of inclusion complex is shorten greatly comparing with N, N'-diphenyl thiourea. The best adsorption conditions are as follows: pH=4, shaking for 10 min and the sorbent mass is 0.025 g, the adsorption capacity is 27.46 mg/g, and the adsorption rate is up to 91.5%.
Manufacturing at the molecular level engines to power nanocars represents a challenge in the development of nanomachines. A molecular engine formed of β-cyclodextrin (β-CD), aryl, and amide moiety has been studied by means of molecular dynamics simulations combined with free-energy calculations. The compression and decompression strokes involving the binding processes of the (Z)- and (E)-isomers of this engine with 1-adamantanol (AD) have been elucidated by determining the underlying potentials of mean force (PMFs). The difference in the binding-free energies, considered as the work generated by and stored within this engine, is calculated to be +1.5 kcal/mol, in remarkable agreement with the experimentally measured quantity. Partitioning the PMFs into physically meaningful free-energy components suggests that the two binding processes are primarily controlled by the favorable inclusion of AD by the β-CD. The work generated by the engine is harnessed to push the alkyl moiety from the hydrophobic cavity of the CD to water, to modify a dihedral angle by a twisting motion about the C–Cα bond, and to increase the tilt angle between the mean plane of the sugar unit, which connects the amide moiety, and the mean plane of the CD. By deciphering the intricate mechanism whereby the present molecular engine operates, our understanding of how similar nanomachines work is expected to be improved significantly, helping in turn the design of novel, more effective ones.
The molecular binding behaviors of mono-[6-deoxy-6-(1-piperazinyl)]-β-cyclodextrin (1), piperazine/β-cyclodextrin complex (2), and dioxane/β-cyclodextrin complex (3) were systematically investigated by NMR spectroscopy, mass spectrometry, dynamic light scattering, viscosity measurements, microcalorimetry, crystallography, and electron microscopic observations, displaying that the self-aggregation of piperazine-modified cyclodextrin 1 in both aqueous solution and the solid state produced a head-to-tail polymeric helical structure. In contrast, the cyclodextrin units in piperazine/β-cyclodextrin complex 2 were located in a staggered pattern, which was strikingly distinctive from the reported results by slow solvent evaporation method. Despite the fact that piperazinyl moiety was introduced by covalent and noncovalent chemical bonds in compound 1 and complex 2, respectively, these two superstructures have the same crystal systems and space groups, which was clearly distinguished from the crystal structure of complex 3 and native β-cyclodextrin. These results indicated that the hydrogen bonding interconnection was a crucial and basic factor to govern the unique aggregation structures of supramolecular assemblies.
This chapter overviews molecular machines based on cyclodextrins (CDs). The categories of CD-based molecular machines, external stimuli for CD-based molecular machines, and typical examples of CD-based molecular machines are briefly described.
A couple of analogues of azobenzenyl beta-cyclodextrins 1 and 2 with self-locked and self-unlocked conformations have been synthesized via the Huisgen cycloaddition from the same reactants, but in distinct reaction conditions (i.e., the hydrothermal synthesis and the "click" reaction, respectively), their conformations were sufficiently proved by X-ray crystal structural analysis, molecular modeling study, and 2D NMR spectroscopy, and their self-assembly behaviors in aqueous solution were also investigated by NMR spectroscopy. Interestingly, the self-locked conformer 1, which could be regarded as a new type of [1]rotaxane, self-assembled to a novel bimolecular capsule, where its azobenzene substituent was included in both its own cavity and the counterpart's cavity, in aqueous solution and in the solid state. In contrast, by adjusting the conformation of 1 to a self-unlocked one, the resulting conformer 2 was found to self-assemble to a linear supramolecule. These studies have shown the stronger impact of the reaction condition changing in cyclodextrin's modification products and will provide a new access to control the structure of supramolecular assemblies by tuning the conformation of building blocks.
The design and fabrication of new type viscosity sensor on molecular scale will enrich the detection means in both physical and life sciences. In this work, a rotor-containing fluorescent dye was prepared, which can reveal a typical viscosity-sensitive behavior due to the environment-induced non-radiative decay. The viscosity-sensitive behavior of this dye could be tunable (locked and activated) in aqueous environment, either with the reversible light-driven trans/cis-photoisomerization of the cyanostilbene moiety, or with the reversible assembly/disassembly process of β-cyclodextrin (β-CD) to the rotor part. Such dual-mode tunable viscosity sensitivity can be well distinguished by fluorescent spectra. A slope method, on double-logarithmic plots of the fluorescent signal to the corresponding environmental viscosity, makes a quantitative estimation to the tunable viscosity sensitivity, featuring the ‘Activated’ and the ‘Locked’ state in this molecular-scale viscometer.
The design and construction of functional supramolecular systems capable of digital information processing is very important. In this work, we synthesized two fluorescent guest compounds (OVN and MVN) for supramolecular bindings at different sites with cucurbit[7]uril (CB7) and α-cyclodextrin (α-CD). The selective host–guest formation was employed to control the systems’ fluorescent signal for different-mode performances. The structural characterizations were conducted by 1H NMR, HRMS, and 2D NOESY 1H NMR spectroscopy. Specifically, the selective supramolecular bindings of CB7 and α-CD will cause a stepwise variation of the fluorescent signal output in OVN guest system. This signal can also be stepwise reset by introduction of different competing substances. On the other hand, supramolecular bindings can only lead to a binary signal change in MVN guest system.
Various cyclodextrins, alpha, beta and gamma, were esterified with 4-methoxy-, 2,4,5- and 2,4,6-trimethoxycinnamic acids. Upon esterification with β-cyclodextrin, the photostability of 2,4,5-trimethoxycinnamate increased while no improvement was observed for 4-methoxycinnamate and 2,4,6-trimethoxycinnamate. However, increase in the photostability of 4-methoxycinnamoyl moiety could be observed when esterified with α-CD and that of 2,4,6-trimethoxycinnamoyl moiety could be observed after being esterified with γ-CD. These photostability data together with the 2D NMR analyses indicated that the 4-methoxycinnamoyl, 2,4,5-trimethoxycinnamoyl and 2,4,6-trimethoxy cinnamoyl moieties could enter the α-CD, the β-CD, and the γ-CD cavities, respectively.
Cyclodextrins belong to the most important and promising macrocyclic hosts, since they are
inexpensive, water-soluble natural products, non-toxic, readily functionalized and commercially
available. Cyclodextrin chemistry creates lots of research areas. The present review focuses on
investigations of cyclodextrins in polymer chemistry and their applications in drug delivery systems.
Click reactions as a possibility to obtain polymer chains with covalently attached cyclodextrins are
described, and examples for the application of such polymers in drug delivery are shown.
The photophysical properties of a multicomponent [1]rotaxane bearing a β-cyclodextrin ring covalently connected to an axle comprising an azobenzene photoisomerisable moiety and a naphthalimide-type fluorescent stopper are investigated by a combined experimental and computational study. The absorption and fluorescence spectra, and particularly the induced circular dichroism (ICD) signal, are determined. The latter shows a sign relation that cannot be rationalised in terms of the simple general rules commonly employed to analyse the ICD spectra of achiral guests encircled by chiral hosts. To assist the interpretation of experimental results, DFT and time-dependent (TD) DFT calculations are performed to explore the availability of low-energy conformations and to model their spectroscopic response. Molecular dynamics simulations performed in water show the interconversion of a number of conformers, the contribution of which to the ICD signal is in agreement with the observation.
IntroductionIn and Out SwitchingBack and Forth SwitchingDisplacement SwitchingCoordination SwitchingRearrangement SwitchingConclusion and PerspectiveAcknowledgementReferences
By combining the features of photochromic spiropyran and the host–guest inclusion complex between the adamantyl (AD) and β-cyclodextrin (β-CD) derivatives, we report a temperature-gated molecular fluorescence switch.
The design, synthesis and study of the photophysical and photochemical properties of the first biomimetic cyclodextrin (CD) model of photoactive yellow protein (PYP) are described. This model bears a deprotonated trans-p-coumaric acid chromophore, covalently linked via a cysteine moiety to a permethylated 6-monoamino β-CD. NMR and UV/Visible spectroscopy studies showed the formation of strong self-inclusion complexes in water at basic pH. Steady-state photolysis demonstrated that, unlike the free chromophore in solution, excitation of the model molecule leads to the formation of a photoproduct identified as the cis isomer by NMR spectroscopy. These observations provide evidence that the restricted CD cavity offers a promising framework for the design of biomimetic models of the PYP hydrophobic pocket.
Two Janus [2]rotaxanes, 5a and 5b, with α-cyclodextrin (α-CD) derivatives substituted on the 6-position with two recognition sites (azobenzene and heptamethylene (C7)) that were linked with linkers of different lengths (oligo(ethylene glycol) with a degree of polymerization equal to 2 or approximately 21) were synthesized and characterized. 2D ROESY NMR spectroscopy and circular dichroism (cd) spectra demonstrated that the recognition site of the α-CD moiety was switched by photoisomerization of the azobenzene moiety in 5a and 5b. The different size changes of 5a and 5b in hydrodynamic radius (R(H)) owing to the different length of linker between two recognition sites were observed by pulse-field-gradient spin-echo NMR spectroscopy. The kinetic results indicated that the different length of linker had no or a weak effect for the photoisomerization process of 5a and 5b.
An efficient strategy toward the synthesis of large-ring cyclodextrin (CD) analogs alternating alpha,alpha'-trehalose disaccharide subunits and pseudoamide segments (cyclotrehalans, CTs), involving a bimolecular macrocyclization reaction as the key step, is reported. NMR and molecular modeling confirmed that the eight and ten alpha-d-glucopyranoside subunits in tetrameric and pentameric CT homologues (CT4 and CT5, respectively) are magnetically equivalent, as in the gamma and epsilonCD counterparts. Yet, the orientation of the monosaccharide constituents is reversed in CTs as compared with CDs, the beta-face being directed to the inside of the nanometric cavity while the alpha-face remains in contact with the bulk solvent. Molecular mechanics and dynamics experiments revealed that the cyclooligosaccharide architecture in CT4 and CT5 is relatively flexible, which is in contrast to that previously observed for the first members of the CT series (CT2 and CT3 oligomers). Thus, although in their fully expanded conformation their cavity size is close to that of gammaCD, the higher mobility of the pseudoamide bridges as compared with classical glycosidic linkages endows these hosts with induced fitting capabilities toward smaller guests.
An efficient general strategy for the incorporation of functional elements onto the secondary hydroxyl rim of beta-cyclodextrin has been developed and applied to the synthesis of a novel series of C7-symmetric homogeneous macromolecular polycations with improved DNA complexing and delivery properties.
The rotaxane 3(E,E) serves as the basis of a light driven molecular muscle, where reversible photoisomerisation of the stilbene units causes the cyclodextrins to move off and on the stilbene units, contracting and extending the distance between the blocking groups.
The alpha,alpha'-dibromo-o-xylylene cap has been installed at the secondary hydroxyls of a single glucopyranosyl residue in cyclodextrins in one pot and with total regioselectivity; the resulting cyclic ether acts as a removable hinge, allowing selective elaboration of the secondary face and modulating both the self-association and the inclusion capabilities of the hosts.
Although the current array of nanomachines mostly comprises simple devices (at least from a mechanical viewpoint), the underlying physical and chemical interactions that play key roles in the 'assembly' of these machines have required decades of research to ascertain a fundamental understanding of how such processes can be manipulated at the nanoscale. In this review, we wish to convey a realistic picture of the current developments in the design and implementation of nanomachines, with an emphasis on how these developments are leading to practical applications in medicine, including a sense of how such simple devices are rapidly becoming the building blocks for assembling the nanorobots of tomorrow.
Concise and efficient strategies toward the synthesis of D2h- and D3h-symmetric cyclodextrin analogues alternating alpha,alpha'-trehalose disaccharide subunits and pseudoamide segments (cyclotrehalans, CTs) are reported. The conformational properties of these cyclooligosaccharides are governed by the rigidity of the alpha,alpha'-trehalose disaccharide repeating unit and the partial double-bond character of the N-(C=X) linkages. In contrast to the typical concave-shaped cavity of cyclodextrins (CDs), CTs feature a convex-shaped hydrophobic cavity in which the beta-face of the monosaccharide subunits is oriented toward the inner side, as supported by NMR and modeling (molecular mechanics and dynamics) studies. In the case of cyclodimeric CTs (CT2s), the existence of intramolecular hydrogen bonds results in collapsed cavities, too small to allow the formation of inclusion complexes with organic molecules. Cyclotrimeric CTs (CT3s) display cavity sizes that are intermediate between those of alphaCD and betaCD, ideally suited for the complexation of complementary guests with ternary symmetry such as adamantane 1-carboxylate (AC). The higher flexibility of the pseudoamide bridges as compared with classical glycosidic linkages endow these glyconanocavities with some conformational adaptability properties, making them better suited than CDs for complexation of angular guests, as seen from comparative inclusion capability experiments against the fluorescent probes 6-p-toluidinonaphthalene-2-sulfonate (TNS; linear) and 8-anilinonaphthalene-1-sulfonate (ANS; angular).
Light excitation powers the reversible shuttling movement of the ring component of a rotaxane between two stations located at a 1.3-nm distance on its dumbbell-shaped component. The photoinduced shuttling movement, which occurs in solution, is based on a "four-stroke" synchronized sequence of electronic and nuclear processes. At room temperature the deactivation time of the high-energy charge-transfer state obtained by light excitation is approximately 10 micros, and the time period required for the ring-displacement process is on the order of 100 micros. The rotaxane behaves as an autonomous linear motor and operates with a quantum efficiency up to approximately 12%. The investigated system is a unique example of an artificial linear nanomotor because it gathers together the following features: (i) it is powered by visible light (e.g., sunlight); (ii) it exhibits autonomous behavior, like motor proteins; (iii) it does not generate waste products; (iv) its operation can rely only on intramolecular processes, allowing in principle operation at the single-molecule level; (v) it can be driven at a frequency of 1 kHz; (vi) it works in mild environmental conditions (i.e., fluid solution at ambient temperature); and (vii) it is stable for at least 10(3) cycles.
Nanomachines of the future will require molecular-scale motors that can perform work and collectively induce controlled motion of much larger objects. We have designed a synthetic, light-driven molecular motor that is embedded in a liquid-crystal film and can rotate objects placed on the film that exceed the size of the motor molecule by a factor of 10,000. The changes in shape of the motor during the rotary steps cause a remarkable rotational reorganization of the liquid-crystal film and its surface relief, which ultimately causes the rotation of submillimetre-sized particles on the film.
Technology is omnipresent in our modern-day society and it is hard to imagine a world without machines, computers or robots. One of the main current scientific challenges is the bottom-up construction of systems that represent nanosize analogues of switches, devices and motors. Our efforts in this area have focussed on the construction of devices based on sterically overcrowded alkenes. In this paper, we present our ongoing research on the construction of binary molecular switches, which has recently led to genuine molecular motors. The control of chirality in a molecular switching system allows interconversion between molecules of opposite helicity using different wavelengths of light. Such bistable chiral switches are of potential use in optical data storage and processing at the molecular level. The control of molecular chirality is even more subtle in the case of molecular motor systems. The exquisite control of chirality using light as an energy source has resulted in a controlled, repetitive 360° unidirectional rotation in two generations of molecular motor systems.
The design and synthesis of a ruthenium complex are described, together with its physico-chemical properties, showing its potential to work as a single molecule rotary motor.
Three different multicomponent molecular systems have been synthesized by means of the three-dimensional template effect of copper(I). These systems incorporate both a coordinating ring (2,9-diphenyl-1,10-phenanthroline-containing 30-membered ring) and a molecular string which consists of two different coordination sites (2,9-disubstituted-1,10-phenanthroline and 5,5‘ ‘-disubstituted-2,2‘:6‘,2‘ ‘-terpyridine unit). Each end of the string could be functionnalyzed by a small group or by a bulky stopper (tris(p-tert-butylphenyl)(4-hydroxyphenyl)methane), leading to an unstoppered compound, to a semi-rotaxane, or to a real rotaxane. As in the case of a disymmetrical copper [2]-catenane, large reversible molecular motions have been induced both electrochemically and photochemically. The driving force of the rearrangement processes is the high stability of two markedly different coordination environments for the copper(I) and copper(II) ions. In the copper(I) state, two phenanthroline units (one of the ring, one of the string) interact with the metal ion in a tetrahedral geometry (CuI(4)), whereas in the copper(II) state, one phenanthroline belonging to the ring and the terpyridine of the string afford a five-coordinate geometry (CuII(5)). The rates of the molecular motion processes (from CuII(4) to CuII(5) and from CuI(5) to CuI(4)) are respectively faster and slower (minutes time scale) as compared to those for the catenane species. This result could be interpreted on the basis of structural differences between the rotaxane and catenane systems.
The molecular shuttle described in this communication is the prototype for the construction of more intricate molecular assemblies where the components will be designed to receive, store, transfer, and transmit information in a highly controllable manner, following their spontaneous self-assembly at the supramolecular level. Increasingly, we can look forward to a «bottom-up» approach to nanotechnology which is targeted toward the development of molecular-scale information processing systems
[structure: see text]. The pictured rotaxane is assembled in water by capping a substituted cyclodextrin composed of the wheel and axle components. The unusual dimeric structure of the rotaxane reflects the thermodynamics of the assembly process. In N,N-dimethylformamide, the corresponding monomer is the predominant product.
Eight new [2]rotaxanes have been prepared, incorporating an alpha-cyclodextrin as the rotor, a stilbene as the axle, and trinitrophenyl substituents as capping groups. Strategies have been devised to elaborate these by linking the rotor to the axle, to produce two new [1]rotaxanes. Rotational motion in a selection of these rotaxanes has been investigated through the application of two-dimensional NMR spectroscopy by performing TOCSY, DQF-COSY, ROESY and HMQC experiments. This has shown that a methoxyl group incorporated on the stilbene and a succinamide joining the stilbene and the cyclodextrin behave analogously to a ratchet tooth and pawl, respectively, to restrict rotation.
Molecular reactors are miniature vessels for the assembly of reactants at the molecular level, in order to change the nature of chemical transformations. It seems probable that those that will find most immediate applications are those that change product ratios or give products which would not readily form in the absence of the reactors, and thereby afford easy access to materials that are otherwise difficult to obtain. Molecular machines consist of interrelated parts with separate functions and perform some kind of work, at the molecular level. Practical examples are likely to be relatively uncomplicated and not based on individual functions of single-molecule devices. Instead they will probably rely on extensive redundancy of the molecular components and their interactions and reactions, as well as of the machines themselves.
The spinning rate of an encapsulated cyclophane guest is affected by the "size" of the coguests.
A [2]rotaxane capped by a beta-cyclodextrin and a 2,4,6-trinitrophenyl group has been prepared by dissolving 6-aminocinnamoyl beta-cyclodextrin in water with 1-adamantane carboxylic acid and complexation with alpha-cyclodextrin followed by the reaction with 2,4,6-trinitrobenzene sulfonic acid sodium salt. The [2]rotaxane has been found to form supramolecular polymers by host-guest interactions.
alpha-Cyclodextrin with a p-t-butoxyaminocinnamoylamino group in the 3-position (3-p-(t)()BocCiNH-alpha-CD) has been found to form a supramolecular polymer in an aqueous solution. The degree of polymerization of the supramolecular polymer is higher than 15 at 20 mM, as proved by VPO (vapor pressure osmometry) measurements and turbo ion spray TOF MS measurements. The existence of substitution/substitution interactions between adjacent monomers of the supramolecular polymer have been confirmed by the observation of positive and negative Cotton bands in circular dichroism spectra. The mechanism for the induction of the chirality was confirmed using model compounds. The substituents were found to exist as a left-handed anti configuration in supramolecular polymers. The supramolecular polymer was found to take a helical structure. The structure of the supramolecular polymer was observed by STM measurements.
Nature uses molecular motors and machines in virtually every significant biological process, but demonstrating that simpler artificial structures operating through the same gross mechanisms can be interfaced with-and perform physical tasks in-the macroscopic world represents a significant hurdle for molecular nanotechnology. Here we describe a wholly synthetic molecular system that converts an external energy source (light) into biased brownian motion to transport a macroscopic cargo and do measurable work. The millimetre-scale directional transport of a liquid on a surface is achieved by using the biased brownian motion of stimuli-responsive rotaxanes ('molecular shuttles') to expose or conceal fluoroalkane residues and thereby modify surface tension. The collective operation of a monolayer of the molecular shuttles is sufficient to power the movement of a microlitre droplet of diiodomethane up a twelve-degree incline.
The cis-trans isomerization of prolyl amide bonds results in large structural and functional changes in proteins and is a rate-determining step in protein folding. We describe a novel electronic strategy to control cis-trans isomerization, based on the demonstration that interactions between aromatic residues and proline are tunable by aromatic electronics. A series of peptides of sequence TXPN, X = Trp, pyridylalanine, pentafluorophenylalanine, or 4-Z-phenylalanine derivatives (Z = electron-donating, electron-withdrawing, or electron-neutral substituents), was synthesized and Ktrans/cis analyzed by NMR. Electron-rich aromatic residues stabilized cis amide bond formation, while electron-poor aromatics relatively favored trans amide bond formation. A Hammett correlation between aromatic electronics and cis-trans isomerization was observed. These results indicate that the interaction between aromatic residues and proline, which is observed to stabilize cis amide bonds and is also a general stabilizing interaction ubiquitous in proteins and protein-protein complexes, is not stabilized exclusively by a classical hydrophobic effect. To a large extent, the aromatic-prolyl interaction is driven and controllable by an electronic effect between the aromatic ring pi-electrons and the proline ring, consistent with a C-H-pi interaction as the key stabilizing force. The aromatic-prolyl interaction is electronically tunable by 0.9 kcal/mol and is enthalpic in nature. In addition, by combining aromatic ring electronics and stereoelectronic effects using 4-fluoroprolines, we demonstrate broad tuning (2.0 kcal/mol) of cis-trans isomerism in tetrapeptides. We demonstrate a simple tetrapeptide, TWflpN, that exhibits 60% cis amide bond and adopts a type VIa1 beta-turn conformation.
Here we correlate chemical (covalent), physical (thermodynamic), and statistical (population distribution) descriptions of behavior with the way that two new types of simple molecular machines (the threads of rotaxanes) perform the task of transporting a Brownian substrate (the rotaxane macrocycle) between two distinguishable binding sites. The first machine-substrate ensemble is a [2]rotaxane that operates through a mechanism that intrinsically causes it to change the average position of the macrocycle irreversibly. This contrasts with the behavior of classic stimuli-responsive molecular shuttles that act as reversible molecular switches. The second system is a compartmentalized molecular machine that is able to pump its substrate energetically uphill using the energy provided by a photon by means of an olefin photoisomerization. Resetting this compartmentalized molecular machine does not undo the work it has carried out or the task performed, a significant difference to a simple molecular switch and a characteristic we recognize as "ratcheting" (see Scheme 8). The ratcheting mechanism allows the [2]rotaxane to carry out the transport function envisaged for the historical thought-machines, Smoluchowski's Trapdoor and Maxwell's Pressure Demon, albeit via an unrelated mechanism and using an input of energy. We define and exemplify the terms "ratcheting" and "escapement" in mechanical terms for the molecular level and outline the fundamental phenomenological differences that exist between what constitutes a two-state Brownian switch, a two-state Brownian memory or "flip-flop", and a (two-stroke) Brownian motor. We also suggest that considering the relationship between the parts of a molecular machine and a substrate in terms of "statistical balance" and "linkage" could be useful in the design of more complex systems and in helping to understand the role of individual amino acids and peptide fragments during the directional transport of substrates by biological pumps and motors.
[structure: see text] With the eventual goal of demonstrating a motorized nanocar, the key structure has been synthesized which bears a light-activated unidirectional molecular motor and an oligo(phenylene ethynylene) chassis and axle system with four carboranes to serve as the wheels. Kinetics studies in solution show that the motor indeed rotates upon irradiation with 365 nm light, and the fullerene-free carborane wheel system is an essential design feature for motor operation.
Complex molecular machinery may be envisioned as densely packed, multicomponent, self-assembling systems built with high structural precision to control the dynamics of one or more internal degrees of freedom. With molecular gyroscopes as a test, we describe a general strategy to design crystals capable of supporting structurally programmed molecular motions, a practical approach to their synthesis, convenient strategies to characterize their solid-state dynamics, and potential applications based on polar structures responding collectively to external fields.