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Abstract Rotaxanes equipped with actuators hold great potential for developing highly functional molecular machines. Such systems could significantly enhance our ability to study and manipulate biological and artificial membranes. Here, we introduce a rotaxane with a ring featuring two azobenzene photoswitches, which retain their photoreversibility and can be stochastically shuttled along the axle in solution. Studies in model bilayers, supported by molecular dynamics simulations, show how azobenzene photoswitching alters the interaction of rotaxanes with surrounding lipids, leading to changes in lipid packing. Such changes in the lipid bilayer were leveraged to induce the light-triggered release of sulforhodamine B from large unilamellar vesicles. Additionally, light activation of the rotaxanes is shown to induce reversible contraction and expansion of giant unilamellar vesicles. The results provide novel insights into the interactions and operation of rotaxanes in lipid bilayers and their impact on membrane properties. This will aid in developing systems for precise membrane manipulation for applications in biomedicine and bioengineering.

Abstract Rotaxanes are mechanically interlocked molecules where a ring (macrocycle) is threaded onto a linear molecule (thread). The position of the macrocycle on different stations on the thread can be controlled in response to external stimuli, making rotaxanes applicable as molecular switches. Here we show that bistable rotaxanes based on the combination of a Zn(II) tetraphenylporphyrin photosensitizer, attached to the macrocycle, and a black-hole-quencher, attached to the thread, are capable of singlet oxygen production which can be switched on/off by the addition of base/acid. However, we found that only a sufficiently long linker between both stations on the thread enabled switchability, and that the direction of switching was inversed with regard to the original design. This unexpected behavior was attributed to intramolecular folding of the rotaxanes, as indicated by extensive theoretical calculations. This evidences the importance to take into account the conformational flexibility of large molecular structures when designing functional switchable systems.

Rotaxanes are mechanically interlocked molecules where a ring (macrocycle) is threaded onto a linear molecule (thread). The position of the macrocycle on different stations on the thread can be controlled in response to external stimuli, making rotaxanes applicable as molecular switches. Here we show that bistable rotaxanes based on the combination of a Zn(II) tetraphenylporphyrin photosensitizer, attached to the macrocycle, and a black-hole-quencher, attached to the thread, are capable of singlet oxygen production which can be switched on/off by the addition of base/acid. However, we found that only a sufficiently long linker between both stations on the thread enabled switchability, and that the direction of switching was inversed with regard to the original design. This unexpected behavior was attributed to intramolecular folding of the rotaxanes, as indicated by extensive theoretical calculations. This evidences the importance to take into account the conformational flexibility of large molecular structures when designing functional switchable systems. Singlet oxygen is a highly useful reagent for organic synthesis, disinfection and photodynamic therapy, but its high reactivity calls for systems where its photochemical generation can be switched on and off on demand. Here, the authors report porphyrin-decorated pH-switchable [2]rotaxanes for singlet oxygen photoproduction, finding that molecular folding of the rotaxanes influences the on/off switching in an unforeseen way. [ABSTRACT FROM AUTHOR]

Rotaxanes equipped with actuators hold great potential for developing highly functional molecular machines. Such systems could significantly enhance our ability to study and manipulate biological and artificial membranes. Here, we introduce a rotaxane with a ring featuring two azobenzene photoswitches, which retain their photoreversibility and can be stochastically shuttled along the axle in solution. Studies in model bilayers, supported by molecular dynamics simulations, show how azobenzene photoswitching alters the interaction of rotaxanes with surrounding lipids, leading to changes in lipid packing. Such changes in the lipid bilayer were leveraged to induce the light-triggered release of sulforhodamine B from large unilamellar vesicles. Additionally, light activation of the rotaxanes is shown to induce reversible contraction and expansion of giant unilamellar vesicles. The results provide novel insights into the interactions and operation of rotaxanes in lipid bilayers and their impact on membrane properties. This will aid in developing systems for precise membrane manipulation for applications in biomedicine and bioengineering., (© 2024. The Author(s).)

We report the synthesis of two rotaxanes (1 and 2) whose rings have appended thiourea units for the selective recognition of Cl - anions. Rotaxane 1 transports Cl - across synthetic lipid bilayers more efficiently than 2, exhibiting EC 50 values of 0.243 mol% versus 0.736 mol%, respectively. A control rotaxane (3) without the thiourea units and the individual axle (4) also showed Cl - transport, although with much lower efficiency (EC 50 values of 4.044 mol% and 4.986 mol%). The unthreaded ring (5) showed the lowest transport activity. This trend highlights the advantage of the interlocked system with a ring containing thiourea units. We also investigated how the membrane composition of liposomes influences the transport activity of 1 and 2, observing higher Cl - transport in membranes with higher fluidity. Additionally, we demonstrated that rotaxane 1 can kill drug-resistant and osmotolerant Staphylococcus aureus when used in combination with NaCl or arachidonic acid. The latter is known to increase the fluidity of the membrane in S. aureus , highlighting cooperative behavior. This work provides new insights into how various structural features and the membrane environment influence the anion transport activity of rotaxanes, offering important design principles for optimizing future rotaxanes for biomedical and other applications., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

The development of efficient methods for the synthesis of mechanically interlocked compounds is currently considered a major challenge in supramolecular chemistry. Twofold vinylogous fumaramides, a class of conjugated bis(enaminones), successfully achieve the assembly of hydrogen-bonded amide-based rotaxanes, with a templating ability comparable to that of their parent fumaramide-based systems, showcasing full conversions and impressive yields up to 92%. Computational calculations offer a compelling explanation for the remarkable efficiency of these bis(enaminones) in driving the synthesis of unprecedented rotaxanes. The reactivity of these interlocked species was thoroughly investigated, revealing that a one-step double stopper-exchange process can be successfully performed while preserving the mechanical bond. This approach facilitates the formation of controllable rotaxanes, including a three-station molecular shuttle, whose assembly via a clipping methodology is highly unselective. The internal translational motion of this latter species has been successfully controlled in a reversible way by means of a cycloaddition/retrocycloaddition sequence. Many templates for accessing hydrogen-bonded amide-based rotaxanes have resulted in modest yields, but a novel templating method has shown significant promise. Conjugated bis(enaminones) serve as an effective template for the formation of rotaxanes, and a post-synthetic double stopper-exchange method further enables the preparation of versatile and complex rotaxane structures. [ABSTRACT FROM AUTHOR]

Force-controlled release of small molecules offers great promise for the delivery of drugs and the release of healing or reporting agents in a medical or materials context 1-3 . In polymer mechanochemistry, polymers are used as actuators to stretch mechanosensitive molecules (mechanophores) 4 . This technique has enabled the release of molecular cargo by rearrangement, as a direct 5,6 or indirect 7-10 consequence of bond scission in a mechanophore, or by dissociation of cage 11 , supramolecular 12 or metal complexes 13,14 , and even by 'flex activation' 15,16 . However, the systems described so far are limited in the diversity and/or quantity of the molecules released per stretching event 1,2 . This is due to the difficulty in iteratively activating scissile mechanophores, as the actuating polymers will dissociate after the first activation. Physical encapsulation strategies can be used to deliver a larger cargo load, but these are often subject to non-specific (that is, non-mechanical) release 3 . Here we show that a rotaxane (an interlocked molecule in which a macrocycle is trapped on a stoppered axle) acts as an efficient actuator to trigger the release of cargo molecules appended to its axle. The release of up to five cargo molecules per rotaxane actuator was demonstrated in solution, by ultrasonication, and in bulk, by compression, achieving a release efficiency of up to 71% and 30%, respectively, which places this rotaxane device among the most efficient release systems achieved so far 1 . We also demonstrate the release of three representative functional molecules (a drug, a fluorescent tag and an organocatalyst), and we anticipate that a large variety of cargo molecules could be released with this device. This rotaxane actuator provides a versatile platform for various force-controlled release applications., (© 2024. The Author(s).)

Aza-Pechmann derivatives have emerged as interesting building blocks for the preparation of organic electronic devices. The development of methodologies aimed to enhance their chemical stability and modulate their physical and chemical properties constitutes an interesting goal. Here we report the synthesis of mechanically interlocked aza-Pechmann dyes with benzylic amide macrocycles, along with the study of how the mechanical bond impacts their stability, photophysical and redox properties. Rotaxanes composed of Pechmann dilactams as threads exhibit one of the highest energy barriers for macrocyclic ring rotation, highlighting the strength of the attractive interactions ring-thread within the interlocked structure. Their enhanced thermal stability, compared to the non-interlocked counterparts, evidences the protective role of the macrocycle. Computational and electrochemical analyses indicate that the benzylic amide macrocycle improves the stability of the HOMO and LUMO orbitals of the interlocked dyes. Finally, spectroscopic and electrochemical data reveal that the macrocycle subtly modulates the optoelectronic and redox behaviour of the Pechmann dilactams., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We previously reported that acid-degradable methylated β-cyclodextrins (Me-β-CDs)-threaded polyrotaxanes (Me-PRXs) can induce autophagic cell death through endoplasmic reticulum (ER) stress-related autophagy, even in apoptosis-resistant cells. Hence, Me-PRXs show great potential as anticancer therapeutics. In this study, peptide-supermolecule conjugates were designed to achieve the targeted delivery of Me-PRX to malignant tumors. Arg-Gly-Asp peptides are well-known binding motifs of integrin α v β 3 , which is overexpressed on angiogenic sites and many malignant tumors. The tumor-targeted cyclic Arg-Gly-Asp (cRGD) peptide was orthogonally post-modified to Me-PRX via click chemistry. Surface plasmon resonance (SPR) results indicated that cRGD-Me-PRX strongly binds to integrin α v β 3 , whereas non-targeted cyclic Arg-Ala-Glu (cRGE) peptide conjugated to Me-PRX (cRGE-Me-PRX) failed to interact with integrins α v β 3 . In vitro, cRGD-Me-PRX demonstrated enhanced cellular internalization and antitumor activity in 4T1 cells than that of unmodified Me-PRX and non-targeted cRGE-Me-PRX, due to its ability to recognize integrin α v β 3 . Furthermore, cRGD-Me-PRX accumulated effectively in tumors, leading to antitumor effects, and exhibited excellent biocompatibility and safety in vivo. Therefore, cRGD conjugation to enhance selectivity for integrin α v β 3 -positive cancer cells is a promising design strategy for Me-PRXs in antitumor therapy.

Rotaxanes are typically prepared using covalent bonds to trap a wheel component onto an axle molecule, and rotaxane-type wheel–axle assembly using only noncovalent interactions has been far less explored. Here we show that a dinickel(II) metallomacrocycle forms two different types of wheel–axle assemblies with a dibenzylammonium axle molecule based only on noncovalent interactions. The non-threaded assembly was obtained by introduction of Ni2+ into the macrocycle before the complexation with the axle molecule (metal-first method). The non-threaded assembly was in rapid equilibrium with each of the components in solution. The threaded assembly was obtained by introduction of Ni2+ after the formation of a pseudorotaxane from the non-metalated wheel and the axle molecule (axle-first method). The threaded assembly was not in equilibrium with the dissociated species even though it was maintained only by noncovalent interactions. Thus, formation of one of the non-threaded and threaded wheel–axle assemblies over the other is governed by the assembly pathway. Mechanically interlocked rotaxanes are typically prepared using covalent bonds to trap a wheel component onto an axle molecule, and rotaxane-type wheel–axle assembly using only noncovalent interactions has been far less explored. Here, a dinickel(II) metallomacrocycle is found to form two different types of wheel–axle assemblies, with a dibenzylammonium axle molecule forming both non-threaded and rotaxane-type threaded assemblies, based only on noncovalent interactions, with formation of one over the other governed by the assembly pathway. [ABSTRACT FROM AUTHOR]

Brønsted basicity is a fundamental chemical property featured by several kinds of inorganic and organic compounds. In this Review, we treat a particularly high basicity resulting from the mechanical entanglement involving two or more molecular subunits in catenanes and rotaxanes. Such entanglement allows a number of basic sites to be in close proximity with each other, highly increasing the proton affinity in comparison with the corresponding, non-entangled counterparts up to obtain superbases, properly defined as mechanically interlocked superbases. In the following pages, the development of this kind of superbases will be described with a historical perusal, starting from the initial, serendipitous findings up to the most recent reports where the strong basic property of entangled molecular units is the object of a rational design. Brønsted basicity can be greatly enhanced by the mechanical entanglement of two or more interlocked molecular subunits within catenanes and rotaxanes. Here, the authors discuss the development of such mechanically interlocked superbases, and outline challenges and opportunities for future directions of research. [ABSTRACT FROM AUTHOR]

Mechanically interlocked polymers (MIPs) are promising candidates for the construction of elastomeric materials with desirable mechanical performance on account of their abilities to undergo inherent rotational and translational mechanical movements at the molecular level. However, the investigations on their mechanical properties are lagging far behind their structural fabrication, especially for linear polyrotaxanes in bulk. Herein, we report stretchable poly[2]rotaxane elastomers (PREs) which integrate numerous mechanical bonds in the polymeric backbone to boost macroscopic mechanical properties. Specifically, we have synthesized a hydroxyfunctionalized [2]rotaxane that subsequently participates in the condensation polymerization with diisocyanate to form PREs. Benefitting from the peculiar structural and dynamic characteristics of the poly[2]rotaxane, the representative PRE exhibits favorable mechanical performance in terms of stretchability (∼1200%), Young's modulus (24.6 MPa), and toughness (49.5 MJ/m3). Moreover, we present our poly[2]rotaxanes as model systems to understand the relationship between mechanical bonds and macroscopic mechanical properties. It is concluded that the mechanical properties of our PREs are mainly determined by the unique topological architectures which possess a consecutive energy dissipation pathway including the dissociation of host-guest interaction and consequential sliding motion of the wheel along the axle in the [2]rotaxane motif. [ABSTRACT FROM AUTHOR]

Abstract A supramolecular photovoltaic strategy is applied to enhance power conversion efficiencies (PCE) of photoelectrochemical devices by suppressing electron–hole recombination after photoinduced electron transfer (PET). Here, the author exploit supramolecular localization of the redox mediator—in close proximity to the dye—through a rotaxane topology, reducing electron–hole recombination in p‐type dye‐sensitized solar cells (p‐DSSCs). Dye PRotaxane features 1,5‐dioxynaphthalene recognition sites (DNP‐arms) with a mechanically‐interlocked macrocyclic redox mediator naphthalene diimide macrocycle (3‐NDI‐ring), stoppering synthetically via click chemistry. The control molecule PStopper has stoppered DNP‐arms, preventing rotaxane formation with the 3‐NDI‐ring. Transient absorption and time‐resolved fluorescence spectroscopy studies show ultrafast (211 ± 7 fs and 2.92 ± 0.05 ps) PET from the dye‐moiety of PRotaxane to its mechanically interlocked 3‐NDI‐ring‐acceptor, slowing down the electron–hole recombination on NiO surfaces compared to the analogue . p‐DSSCs employing PRotaxane (PCE = 0.07%) demonstrate a 30% PCE increase compared to PStopper (PCE = 0.05%) devices, combining enhancements in both open‐circuit voltages (VOC = 0.43 vs 0.36 V) and short‐circuit photocurrent density (JSC = −0.39 vs −0.34 mA cm−2). Electrochemical impedance spectroscopy shows that PRotaxane devices exhibit hole lifetimes (τh) approaching 1 s, a 16‐fold improvement compared to traditional I−/I3−‐based systems (τh = 50 ms), demonstrating the benefits obtained upon nanoengineering of interfacial dye‐regeneration at the photocathode.

Anion exchange membranes (AEMs) with high selective conductivity and low surface resistance are important for the development of electrodialysis desalination industry. In this work, we design and synthesize a rotaxane of β-cyclodextrin (CD)-alkyldiamine inclusion complex (CDIC) via a host-guest molecular recognition mechanism; the resulting CDIC rotaxane is employed for cross-linking chloromethylated, hydroxy quaternized polysulfone (HQPSf) to make AEMs. β-CD is inherently hydrophilic and its –OH on the outer surface can hydrogen-bond with HQPSf to promote ionic cluster aggregation, leading to enhanced microphase-separated morphology and improved conductivity; the rotaxane-cross-linked structure guarantees good ductility and ion selectivity of the membrane. Therefore, the optimized HQPSf-CDIC membrane gives the most excellent current efficiency discharge current efficiency (92.04 %), the lowest energy consumption (4.68 kWh kg−1), and the maximum Cl− mobility (75.38 mg m−2 s−1) in the electrodialysis tests, significantly better than the un-crosslinked HQPSf membrane (86.41 %, 5.17 kWh kg−1 and 71.29 mg m−2 s−1). Our work demonstrates that introducing CDIC rotaxane cross-linked structure can help to enhance microphase separation and improve the performance of AEMs for electrodialysis. The microphase separation mechanism of anion exchange membrane HQPSf-CDIC-x. [Display omitted] • Anion exchange membranes (AEMs) with high selective conductivity and low surface resistance are important for the development of electrodialysis desalination industry. In this work, we design and synthesize a rotaxane of β-cyclodextrin (CD) - alkyldiamine inclusion complex (CDIC) via a host-guest molecular recognition mechanism; the resulting CDIC rotaxane is employed for cross-linking chloromethylated, hydroxy quaternized polysulfone (HQPSf) to make AEMs. β-CD is inherently hydrophilic and its –OH on the outer surface can hydrogen-bond with HQPSf to promote ionic cluster aggregation, leading to enhanced microphase-separated morphology and improved conductivity; the rotaxane-cross-linked structure guarantees good ductility and ion selectivity of the membrane. Therefore, the optimized HQPSf-CDIC membrane gives the most excellent current efficiency discharge current efficiency (92.04 %), the lowest energy consumption (4.68 KWh kg 1), and the maximum Cl− mobility (75.38 mg m−2 s−1) in the electrodialysis tests, significantly better than the un-crosslinked HQPSf membrane (86.41 %, 5.17 kWh kg−1 and 71.29 mg m−2 s−1). Our work demonstrates that introducing CDIC rotaxane cross-linked structure can help to enhance microphase separation and improve the performance of AEMs for electrodialysis. [ABSTRACT FROM AUTHOR]

In nature, molecular environments in proteins can sterically protect and stabilize reactive species such as organic radicals through non-covalent interactions. Here, we report a near-infrared fluorescent rotaxane in which the stabilization of a chemically labile squaraine fluorophore by the coordination of a tetralactam macrocycle can be controlled chemically and electrochemically. The rotaxane can be switched between two co-conformations in which the wheel either stabilizes or exposes the fluorophore. Coordination by the wheel affects the squaraine's stability across four redox states and renders the radical anion significantly more stable—by a factor of 6.7—than without protection by a mechanically bonded wheel. Furthermore, the fluorescence properties can be tuned by the redox reactions in a stepwise manner. Mechanically interlocked molecules provide an excellent scaffold to stabilize and selectively expose reactive species in a co-conformational switching process controlled by external stimuli. Incorporating sensitive chromophores into interlocked systems that are mechanically responsive to external stimuli is attractive for tuning of the dye's optical properties and stability. Here, the authors report the mechanically controlled protection and deprotection of a squaraine dye within a [2]rotaxane, governed by macrocycle shielding/de-shielding upon chloride addition or oxidation. [ABSTRACT FROM AUTHOR]

Abstract The development of efficient methods for the synthesis of mechanically interlocked compounds is currently considered a major challenge in supramolecular chemistry. Twofold vinylogous fumaramides, a class of conjugated bis(enaminones), successfully achieve the assembly of hydrogen-bonded amide-based rotaxanes, with a templating ability comparable to that of their parent fumaramide-based systems, showcasing full conversions and impressive yields up to 92%. Computational calculations offer a compelling explanation for the remarkable efficiency of these bis(enaminones) in driving the synthesis of unprecedented rotaxanes. The reactivity of these interlocked species was thoroughly investigated, revealing that a one-step double stopper-exchange process can be successfully performed while preserving the mechanical bond. This approach facilitates the formation of controllable rotaxanes, including a three-station molecular shuttle, whose assembly via a clipping methodology is highly unselective. The internal translational motion of this latter species has been successfully controlled in a reversible way by means of a cycloaddition/retrocycloaddition sequence.

Responsive synthetic receptors for adaptive recognition of different ionic guests in a competitive environment are valuable molecular tools for not only ion sensing and transport, but also the development of ion-responsive smart materials and related technologies. By virtue of the mechanical chelation and ability to undergo large-amplitude co-conformational changes, described herein is the discovery of a chameleon-like [2]catenane that selectively binds copper(I) or sulfate ions and its associated co-conformational mechanostereochemical switching. This work highlights not only the advantages and versatility of catenane as a molecular skeleton in receptor design, but also its potential in constructing complex responsive systems with multiple inputs and outputs., (© 2024. The Author(s).)

• Supramolecular binding strategy was developed to prepare novel COFs. • β-CD inclusion was used as building block for the preparation of COFs. • Por-CD-COF could greatly reduce the use of photoactive ingredients. • The threading of CD could significantly enhance the photoactivity of COFs. • Por-CD-COF exerted cyclodextrin enhanced PTT and PDT. As an emerging artificial porous material, covalent organic frameworks (COFs) with customizable structure and function, have always been the focus of polymer science. Controllable fabrication of COFs with brand-new structure is the top priority for its development. Here, the 'supramolecular binding' strategy is developed as a simple but efficient method to prepare COFs with novel structures and functions. By this means, polymeric rotaxanes threaded COFs, denoted as Por-CD-COF, was facilely prepared via the combination of dynamic covalent imine-bond formation with supramolecular self-assembly, in which the polyrotaxane formed via inclusion of aromatic linker with bactericidal active β-cyclodextrin macrocycle (CD) was condensed with the photosensitive porphyrin via the combination of mechanical grinding and solvothermal synthesis. The formation of polyrotaxane could change the distance between layers, avoiding the quench of photoactivity caused by the severe aggregation of layered structure. Under the same molar amount of reaction monomers, the weight of the Por-CD-COF is approaching five times of the CD-free COF, which could greatly reduce the use of photoactive ingredients. Further experiments demonstrated the introduction of CDs could also significantly improve the biocompatibility. Impressively, this special porphyrin-involved CD-COF, displays excellent photo activity, which could act as an efficient broad spectrum antibacterial agents realizing the combinational action of cyclodextrin enhanced photothermal and photodynamic antimicrobial at an extremely low quality of the effective photosensitizer (Porphyrin). Meanwhile, even at the same dose of fungicide, the bactericidal effect of Por-CD-COF is far exceeding the CD-free therapeutic agent. This novel synthetic strategy allows the incorporation of mechanically interlocked CDs (MIMs) into the porous polymeric materials, providing an easy access to low-cost preparation of COFs for the specific applications. [ABSTRACT FROM AUTHOR]

Using mechanical energy to drive chemical transformations is an exciting prospect to improve the sustainability of chemical reactions and to produce products not achievable by more traditional methods. In-situ monitoring of reaction pathways and chemical transformations is vital to deliver the reproducible results required for scale up to realize the potential of mechanochemistry beyond the chemistry lab. This mini review will discuss the recent advances in in-situ monitoring of ball milling and polymer mechanochemistry, highlighting the potential for shared knowledge for scale up. [ABSTRACT FROM AUTHOR]

Supramolecular polymers possess great potential in catalysis owing to their distinctive molecular recognition and dynamic crosslinking features. However, investigating supramolecular electrocatalysts with high efficiency in oxygen reduction reaction to hydrogen peroxide (ORHP) remains an unexplored frontier. Herein, we present organic polymers for ORHP by introducing cyclodextrin-containing noncovalent building blocks, affording these supramolecules with abundant dynamic bonds. The electronic states and reaction kinetics are further well-modulated via a host-guest strategy, resulting in appropriate regional electron binding force and controllable chemical activity. Notably, integrating supramolecular units into phenyl group-containing model covalent polymer achieves a production rate of 9.14 mol g−1cat h−1, with 98.01% Faraday efficiency, surpassing most reported metal-free electrocatalysts. Moreover, the dynamic bonds in supramolecular catalysts can effectively regulate the binding ability of oxygen intermediates, leading to high reactivity and selectivity for the 2e− pathway. Supported by theory calculation and in situ experiment, C atoms (site–1) adjacent to the –C = N (N) group are potential active sites. This work pioneers host-guest strategy and provides inspiring ideas for the ORHP process. Dynamic bonds offer unique advantages of adaptability and selectivity, yet, supramolecular electrocatalysts specifically tailored for 2e− pathway remain unexplored. Here, the authors report a host-guest strategy that employs dynamic bonds to adjust electronic states through dual-channel regulation. [ABSTRACT FROM AUTHOR]

Achieving light-induced manipulation of controlled self-assembly in nanosized structures is essential for developing artificially dynamic smart materials. Herein, we demonstrate an approach using a non-photoresponsive hydrogen-bonded (H-bonded) macrocycle to control the self-assembly and disassembly of nanostructures in response to light. The present system comprises a photoacid (merocyanine, 1-MEH), a pseudorotaxane formed by two H-bonded macrocycles, dipyridinyl acetylene, and zinc ions. The operation of such a system is examined according to the alternation of self-assembly through proton transfer, which is mediated by the photoacid upon exposure to visible light. The host–guest complexation between the macrocycle and bipyridium guests was investigated by NMR spectroscopy, and one of the guests with the highest affinity for the ring was selected for use as one of the components of the system, which forms the host–guest complex with the ring in a 2:1 stoichiometry. In solution, a dipyridine and the ring, having no interaction with each other, rapidly form a complex in the presence of 1-MEH when exposed to light and thermally relax back to the free ring without entrapped guests after 4 h. Furthermore, the addition of zinc ions to the solution above leads to the formation of a polypseudorotaxane with its morphology responsive to photoirradiation. This work exemplifies the light-controlled alteration of self-assembly in non-photoresponsive systems based on interactions between the guest and the H-bonded macrocycle in the presence of a photoacid. [ABSTRACT FROM AUTHOR]

Aggregation-induced emission dyes (AIEs) have gained significant interest due to their unique optical properties. Upon aggregation, AIEs can exhibit remarkable fluorescence enhancement. These systems are ideal candidates for applications in bioimaging, such as image-guided drug delivery or surgery. Encapsulation of AIEs in polymeric nanocarriers can result in biocompatible and efficient nanosystems. Herein, we report the fabrication of novel nanoaggregates formulated by amino terpolymer and tetraphenylethylene (TPE) AIE in aqueous media. Poly(di(ethylene glycol) methyl ether methacrylate-co-2-(dimethylamino)ethylmethacrylate-co-oligoethylene glycol methyl ether methacrylate), P(DEGMA-co-DMAEMA-co-OEGMA) hydrophilic terpolymer was utilized for the complexation of the sodium tetraphenylethylene 4,4′,4″,4‴-tetrasulfonate AIE dye. Fluorescence spectroscopy, physicochemical studies, and self-assembly in aqueous and fetal bovine serum media were carried out. The finely dispersed nanoparticles exhibited enhanced fluorescence compared to the pure dye. To investigate the role of tertiary amino groups in the aggregation phenomenon, the polymer was quaternized, and quaternized polymer nanocarriers were fabricated. The increase in fluorescence intensity indicated stronger interaction between the cationic polymer analog and the dye. A stronger interaction between the nanoparticles and fetal bovine serum was observed in the case of the quaternized polymer. Thus, P(DEGMA-co-DMAEMA-co-OEGMA) formulations are better candidates for bioimaging applications than the quaternized ones, presenting both aggregation-induced emission and less interaction with fetal bovine serum. [ABSTRACT FROM AUTHOR]

Cobaltocenium-containing (co)polysiloxanes (Cc-PDMSs) with terminal and side groups were synthesized by the reaction of catalyst-free hydroamination between ethynylcobaltocenium hexafluorophosphate and polysiloxanes comprising amino moieties as terminal and side groups. The conversion of NH2 groups in the polymers reaches 85%. The obtained (co)polysiloxanes "gelate" due to an increase in their molecular weight by approx. 30 times, when stored at room temperature over one week. "Gelated" Cc-PDMSs remain soluble in most polar solvents. The structure of Cc-PDMSs and the mechanism of "gelation" were established by 1H, 13C{1H}, 29Si{1H}, 19F{1H}, 31P{1H} nuclear magnetic resonance, infrared, ultraviolet–visible, and X-ray photoelectron spectroscopies. As determined by cyclic voltammetry, Cc-PDMSs possess redox properties (CoII/CoIII transitions at E1/2 = −1.8 and −1.3 V before and after "gelation", respectively). This synthetic approach allows to increase the molecular weights of the synthesized polysiloxanes functionalized with cobaltocenium groups easily, leading to their higher film-forming ability, which is desirable for some electronic applications. Cc-PDMSs can be utilized as redox-active polymer films in modified electrodes, electrochromic devices, redox-active coatings, and components for batteries. [ABSTRACT FROM AUTHOR]

A chiral sodium glycerophosphate is successfully exploited as a catalyst in the Michael addition of methyl malonate to a number of chalcones. The reactions supplied the target adducts in satisfactory yields and good enantiomeric excesses. A tentative computational study is presented, aiming to understand the reaction mechanism. [ABSTRACT FROM AUTHOR]

Cyclodextrins (CDs) are ubiquitous excipients, constituted of cyclic glucopyranose units, and possess a unique dual nature, that of a hydrophobic interior and a hydrophilic exterior. This enables their interaction with lipid-affinitive compounds and hydrophilic compounds, thereby augmenting their application in pharmaceutical formulations as agents for improving solubility, as well as fundamental elements of advanced drug delivery systems. Additionally, CDs, upon suitable modification, can strategically participate in the interaction with cellular components and physical barriers, such as the blood–brain barrier, where their intricate and multifunctional engagement leads to various biological impacts. This review consolidates the crucial features of CDs and their derivatives, and summarizes the applications of them as drug delivery systems in neurodegenerative disorders, emphasizing their notable potentials. [ABSTRACT FROM AUTHOR]

The chemistry of heterometallic metal complexes continues to attract the interest of molecular inorganic chemists mainly because of the properties that different metal ions can bring to compounds. Contrary to the plethora of 3d–4f- and 3d–3d′-metal complexes, complexes containing both 3d- and 4d-metal ions are much less studied. The choice of the bridging organic ligand is of paramount importance for the synthesis of such species. In the present work, we describe the use of the potentially tetradentate NOO′O″ Schiff bases N-(2-carboxyphenyl)salicylideneimine (saphHCOOH) and N-(4-chloro-carboxyphenyl)salicylideneimine (4ClsaphHCOOH) in CdII-MIII (M = Fe, Cr) chemistry. The complexes [Cd2Fe2(saphCOO)4(NO3)2(H2O)2] (1), [Cd2Cr2(saphCOO)4(NO3)2(H2O)2] (2), [Cd2Fe2(4ClsaphCOO)4(NO3)2(H2O)2] (3) and [CdCr2(4ClsaphCOO)4(H2O)3(EtOH)] (4) have been structurally characterized, the quality of the structure of the latter being poor but, permitting the knowledge of the connectivity and the main structural features. Complexes 1–3 are isostructural, but not isomorphous, possessing a variety of lattice solvent molecules (EtOH, MeCN, CH2Cl2, H2O). The metal topology can be described as two isosceles triangles sharing a common CdII...CdII edge. The two CdII atoms are doubly bridged by two μ-aqua groups. The MIII...CdII sides of the triangles are each asymmetrically bridged by one carboxylate oxygen atom of a 2.2111 saphCOO2−/4ClsaphCOO2− ligand. The core of the molecules is {Cd2M2(μ-Oaqua)2(μ-OR)4}6+, where the OR oxygen atoms are the bridging carboxylate oxygens. The coordination spheres of the metal ions in the centrosymmetric molecules are [Cd(Oaqua)2(Ocarboxylato)4(Onitrato)2] and [M(Nimino)2(Ocarboxylato)2(Ophenolato)2]. The biaugmented trigonal prism is the most appropriate for the description of the coordination geometry of the CdII atoms in 1 and 3, while the geometry of these metal ions in 2 is best described as distorted triangular dodecahedral. A combination of H-bonding and π–π stacking interactions give interesting supramolecular patterns in the three tetranuclear compounds. The three metal ions in 4 define an isosceles triangle with two almost equal CdII...CrIII sides. The CdII center is linked to each CrIII atom through one carboxylato oxygen of a 2.2111 4ClsaphCOO2− ligand. The core of the molecule is {CdCr2(μ-OR)2}6+, where the OR oxygen atoms are the bridging carboxylato oxygens. A tridentate chelating 1.1101 4ClsaphCOO2− ligand is bonded to each CrIII. The coordination spheres are [Cd(Oaqua)3(Oethanol)(Obridging carboxylato)2(Oterminal carboxylate)2] and [Cr(Obridging carboxylato)(Oterminal carboxylato)(Ophenolato)2(Nimino)2]. Complexes 1–4 are the first heterometallic 3d–4d complexes based on saphHCOOH and 4ClsaphCOOH. The structures are critically compared with those of previous reported ZnII-MIII (M = Fe, Cr) complexes. The IR and Raman spectra of the complexes are discussed in terms of the coordination modes of the ligands involved. UV/VIS spectra in CH2Cl2 are also reported, and the bands are assigned to the corresponding transitions. The δ and ΔEQ57Fe-Mössbauer parameters of 1 and 3 at room temperature and 80 K suggest the presence of isolated high-spin FeIII centers. Variable-temperature (1.8–310 K) and variable-field (0–50 kOe) magnetic studies for 1 and 2 indicate the absence of MIII...MIII exchange interactions, in agreement with the long distances (~8 Å) between the paramagnetic metal ions. The combined work demonstrates the ability of saphCOO2− and 4ClsaphCOO2− to give 3d–4d metal complexes. [ABSTRACT FROM AUTHOR]

Bis-triazoles separated by a symmetrical linking group are joined at C4 of each triazole or at N1 of each triazole. Preparation of a series of bis-1H-1,2,3-triazoles derived from o-bis(azidomethyl)benzene and an alkyne is reported with use of copper N-heterocyclic carbene catalysis with microwave-assisted heating in an aqueous solvent. The products were symmetrical N1–N1′-bis-1H-1,2,3-triazoles. Additional syntheses utilized dialkynes and organic azides to prepare symmetrical C4–C4′-bis-1H-1,2,3-triazoles. Pure products were often obtained directly when water was used as the solvent with microwave-assisted heating. Results are given for experiments using conventional heating or no heating. Sonication results are given for a reaction where microwave-assisted heating was unsatisfactory. [ABSTRACT FROM AUTHOR]

The long-lived room-temperature phosphorescence (RTP) originating from thiophene boronate polyvinyl alcohol (PVA) has enabled the creation of metal-ion-responsive RTP films doped with spirolactam ring-containing rhodamine 6G (1). In this study, RTP-active PVA films, namely, TDB@PVA and ATB@PVA, were prepared through boronate esterification of thiophene-2,5-diboronic acid (TDB) and 5-acetylthiophene-2-boronic acid (ATB) with the diol units of PVA. The delayed emission properties were evaluated, revealing an emission band at 477 nm with a turquoise afterglow for TDB@PVA and at 510 nm with a green afterglow for ATB@PVA after UV light irradiation ceased. The photophysical properties were assessed using TD-DFT and DFT calculations at the B3LYP/cc-pVDZ level. N-(rhodamine-6G)lactam dye with a salicylimine unit (1) was doped into the RTP-based PVA films, producing a multicolored afterglow upon the addition of metal ions. This phenomenon is explained by a triplet-tosinglet Förster-type resonance energy transfer process from the cross-linked thiophene boronate in PVA to the metal-ion-activated colored form of 1. This photophysical feature finds applicability in encryption techniques. Notably, the reversible metal-ligand coordination of 1 in the PVA system enabled a write/erase information process. [ABSTRACT FROM AUTHOR]

Amino acids with unusual types of chirality and their derivatives have recently attracted attention as precursors in the synthesis of chiral catalysts and peptide analogues with unique properties. In this study, we have synthesized a new nido-carborane-based planar-chiral amino acid, in the molecule of which the amino group is directly bonded to the B(3) atom, and the carboxyl group is attached to the B(9) atom through the CH2S+(Me) fragment. 3-Amino-9-dimethylsulfonio-nido-carborane, prepared in three steps from 3-amino-closo-carborane in a high yield, was a key intermediate in the synthesis of the target planar-chiral amino acid. The carboxymethyl group at the sulfur atom was introduced by the demethylation reaction of the dimethylsulfonio derivative, followed by S-alkylation. The structure of new 3,9-disubstituted nido-carboranes was studied for the first time using NMR spectroscopy. The resonances of all boron atoms in the 11B NMR spectrum of 3-amino-9-dimethylsulfonio-nido-carborane were assigned based on the 2D NMR correlation experiments. The nido-carborane-based planar-chiral amino acid and related compounds are of interest as a basis for peptide-like compounds and chiral ligands. [ABSTRACT FROM AUTHOR]

Most chemotherapeutic agents are poorly soluble in water, have low selectivity, and cannot reach the tumor in the desired therapeutic concentration. On the other hand, sensitive hydrophilic therapeutics like nucleic acids and proteins suffer from poor bioavailability and cell internalization. To solve this problem, new types of controlled release systems based on nano-sized self-assemblies of cyclodextrins able to control the speed, timing, and location of therapeutic release are being developed. Cyclodextrins are macrocyclic oligosaccharides characterized by a high synthetic plasticity and potential for derivatization. Introduction of new hydrophobic and/or hydrophilic domains and/or formation of nano-assemblies with therapeutic load extends the use of CDs beyond the tried-and-tested CD-drug host–guest inclusion complexes. The recent advances in nano drug delivery have indicated the benefits of the hybrid amphiphilic CD nanosystems over individual CD and polymer components. This review provides a comprehensive overview of the most recent advances in the design of CDs self-assemblies and their use for delivery of a wide range of therapeutic molecules. It aims to offer a valuable insight into the many roles of CDs within this class of drug nanocarriers as well as current challenges and future perspectives. [ABSTRACT FROM AUTHOR]

This work focuses on the first use of ultrasonic phenol-ene coupling as a polymer analogous transformation. The ultrasonic reaction was introduced into chitin chemistry, resulting in the fast and convenient preparation of new water-soluble cationic chitin derivatives. Since water-soluble derivatives of fully deacetylated chitin are poorly described in the literature, the synthesis of each new type of these derivatives is a significant event in polysaccharide chemistry. Polycations, or cationic polymers, are of particular interest as antibacterial agents. Consequently, the resulting polymers were tested for their antibacterial activity and toxicity. We found that the highly substituted polymer of medium molecular weight exhibited the most pronounced in vitro antibacterial effect. We prepared nanoparticles using the ionic gelation technique. The most effective in vitro antibacterial chitin-based systems were tested in vivo in rats. These tests demonstrated outstanding antibacterial effects combined with an absence of toxicity. Additionally, we found that the resulting polymers, unlike their nanoparticle counterparts, also exhibited strong antioxidant effects. In summary, we demonstrated the effectiveness of ultrasound in polymer chemistry and highlighted the importance of the sonochemical approach in the chemical modification of polysaccharides. This approach enables the synthesis of derivatives with improved physicochemical and biological properties. [ABSTRACT FROM AUTHOR]

Nanoscale systems that release small molecules have potential therapeutic and industrial uses, but can result in low numbers of molecules reaching their target. A release system triggered by mechanical force offers a fresh approach.System of interlocked molecules releases cargo on demand. [ABSTRACT FROM AUTHOR]

Abstract Rotaxanes are typically prepared using covalent bonds to trap a wheel component onto an axle molecule, and rotaxane-type wheel–axle assembly using only noncovalent interactions has been far less explored. Here we show that a dinickel(II) metallomacrocycle forms two different types of wheel–axle assemblies with a dibenzylammonium axle molecule based only on noncovalent interactions. The non-threaded assembly was obtained by introduction of Ni2+ into the macrocycle before the complexation with the axle molecule (metal-first method). The non-threaded assembly was in rapid equilibrium with each of the components in solution. The threaded assembly was obtained by introduction of Ni2+ after the formation of a pseudorotaxane from the non-metalated wheel and the axle molecule (axle-first method). The threaded assembly was not in equilibrium with the dissociated species even though it was maintained only by noncovalent interactions. Thus, formation of one of the non-threaded and threaded wheel–axle assemblies over the other is governed by the assembly pathway.

In recent years computational methods for molecular modeling have become a prime focus of computational biology and cheminformatics. Many dedicated systems exist for modeling specific classes of molecules such as proteins or small drug-like ligands. These are often heavily tailored toward the automated generation of molecular structures based on some meta-input by the user and are not intended for expert-driven structure assembly. Dedicated manual or semi-automated assembly software tools exist for a variety of molecule classes but are limited in the scope of structures they can produce. In this work we present BuildAMol, a highly flexible and extendable, general-purpose fragment-based molecular assembly toolkit. Written in Python and featuring a well-documented, user-friendly API, BuildAMol empowers researchers with a framework for detailed manual or semi-automated construction of diverse molecular models. Unlike specialized software, BuildAMol caters to a broad range of applications. We demonstrate its versatility across various use cases, encompassing generating metal complexes or the modeling of dendrimers or integrated into a drug discovery pipeline. By providing a robust foundation for expert-driven model building, BuildAMol holds promise as a valuable tool for the continuous integration and advancement of powerful deep learning techniques. Scientific contribution BuildAMol introduces a cutting-edge framework for molecular modeling that seamlessly blends versatility with user-friendly accessibility. This innovative toolkit integrates modeling, modification, optimization, and visualization functions within a unified API, and facilitates collaboration with other cheminformatics libraries. BuildAMol, with its shallow learning curve, serves as a versatile tool for various molecular applications while also laying the groundwork for the development of specialized software tools, contributing to the progress of molecular research and innovation. [ABSTRACT FROM AUTHOR]

Cilostazol is a phosphodiesterase III inhibitor characterized by poor solubility. This limitation can be overcome by using a drug carrier capable of delivering the drug to the target site. Cyclodextrins are essential as drug carriers because of their outstanding complexation abilities and their capacity to improve drug bioavailability. This study comprises two stages: The first involves verifying different cyclodextrins and their complexation abilities towards cilostazol. This was accomplished using molecular docking simulations (MDS) and density functional theory (DFT). Both techniques indicate that the largest Sulfobutyl Ether-β-Cyclodextrin forms the most stable complex with cilostazol. Additionally, other important parameters of the complex are described, including binding sites, dominant interactions, and thermodynamic parameters such as complexation enthalpy, Gibbs free energy, and Gibbs free energy of solvation. The second stage involves a binding study between cilostazol and Phosphodiesterse3 (PDE3). This study was conducted using molecular docking simulations, and the most important energetic parameters are detailed. This is the first such report, and we believe that the results of our predictions will pave the way for future drug development efforts using cyclodextrin–cilostazol complexes as potential therapeutics. [ABSTRACT FROM AUTHOR]

The separation and purification of chemical raw materials, particularly neutral compounds with similar physical and chemical properties, represents an ongoing challenge. In this study, we introduce a class of water-soluble macrocycle compound, calix[2]azolium[2]benzimidazolone (H), comprising two azolium and two benzimidazolone subunits. The heterocycle subunits form a hydrophobic binding pocket that enables H1 to encapsulate a series of neutral guests in water with 1:1 or 2:1 stoichiometry, including aldehydes, ketones, and nitrile compounds. The host-guest complexation in the solid state was further confirmed through X-ray crystallography. Remarkably, H1 was shown to be a nonporous adaptive crystal material to separate valeraldehyde from the mixture of valeraldehyde/2-methylbutanal/pentanol with high selectivity and recyclability in the solid states. This work not only demonstrates that azolium-based macrocycles are promising candidates for the encapsulation of organic molecules but also shows the potential application in separation science. The separation and purification of particularly neutral compounds with similar physical and chemical properties remains challenging. Here, the authors introduce a water-soluble macrocyclic calixarene compound as nonporous adaptive crystalline material to separate valeraldehyde from the mixture of valeraldehyde/2-methylbutanal/pentanol with high selectivity and recyclability in the solid state. [ABSTRACT FROM AUTHOR]

Macrocyclic conformations play a crucial role in regulating their properties. Our understanding of the determinants to control macrocyclic conformation interconversion is still in its infancy. Here we present a macrocycle, octamethyl cyclo[4](1,3-(4,6)-dimethylbenzene)[4]((4,6-benzene)(1,3-dicarboxylate) (OC-4), that can exist at 298 K as two stable atropisomers with C2v and C4v symmetry denoted as C2v-OC-4 and C4v-OC-4, respectively. Heating induces the efficient stepwise conversion of C2v- to C4v-OC-4 via a Cs-symmetric intermediate (Cs-OC-4). It differs from the typical transition state-mediated processes of simple C–C single bond rotations. Hydrolysis and further esterification with a countercation dependence promote the generation of C2v- and Cs-OC-4 from C4v-OC-4. In contrast to C2v-OC-4, C4v-OC-4 can bind linear guests to form pseudo-rotaxans, or bind C60 or C70 efficiently. The present study highlights the differences in recognition behavior that can result from conformational interconversion, as well as providing insights into the basic parameters that govern coupled molecular rotations. The three-dimensional conformation of macrocycles determine their chemical and recognition properties and the factors that influence the interconversion between macrocyclic forms are poorly understood. Here the authors describe a macrocycle existing as two stable atropisomers and the mechanism behind the thermally-induced transition between them. [ABSTRACT FROM AUTHOR]

Supramolecular chemistry is a relatively new field of study that utilizes conventional chemical knowledge to produce new edges of smart materials. One such material use of supramolecular chemistry is the development of sensing platforms. Biologically relevant molecules need frequent assessment both qualitatively and quantitatively to explore several biological processes. In this review, we have discussed supramolecular sensing techniques with key examples of sensing several kinds of bio-analytes and tried to cast light on how molecular design can help in making smart materials. Moreover, how these smart materials have been finally used as sensing platforms has been discussed as well. Several useful spectroscopic, microscopic, visible, and electronic outcomes of sensor materials have been discussed, with a special emphasis on device-based applications. This kind of comprehensive discussion is necessary to widen the scope of sensing technology. [ABSTRACT FROM AUTHOR]

The diversity of cyclodextrins and their derivatives is increasing with continuous research. In addition to monomolecular cyclodextrins with different branched chains, cyclodextrin-based polymers have emerged. The aim of this review is to summarize these innovations, with a special focus on the study of applications of cyclodextrins and their derivatives in nano-delivery systems. The areas covered include nanospheres, nano-sponges, nanogels, cyclodextrin metal–organic frameworks, liposomes, and emulsions, providing a comprehensive and in-depth understanding of the design and development of nano-delivery systems. [ABSTRACT FROM AUTHOR]