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With diabetes being the 7th leading cause of death worldwide, overcoming issues limiting the oral administration of insulin is of global significance. The development of imine-linked-covalent organic framework (nCOF) nanoparticles for oral insulin delivery to overcome these delivery barriers is herein reported. A gastro-resistant nCOF was prepared from layered nanosheets with insulin loaded between the nanosheet layers. The insulin-loaded nCOF exhibited insulin protection in digestive fluids in vitro as well as glucose-responsive release, and this hyperglycemia-induced release was confirmed in vivo in diabetic rats without noticeable toxic effects. This is strong evidence that nCOF-based oral insulin delivery systems could replace traditional subcutaneous injections easing insulin therapy., We report the successful use of a gastro-resistant covalent organic framework for in vivo oral delivery of insulin.

The presence of carcinogenic bromate (BrO3−) in drinking water became a global concern and efforts towards its removal mainly focused on addressing the source. Herein, we rationally designed a porphyrin-based covalent organic framework (PV-COF) with a cationic surface to provide electrostatic interactions and a porphyrin core to induce hydrogen bonding interactions for the efficient removal of BrO3− from water. Through H-bonding and electrostatic interactions, PV-COF exhibited an exceptional bromate removal efficiency (maximum adsorption capacity, Qmax: 203.8 mg g−1) with the fastest uptake rate (kads) of 191.45 g mg−1 min−1. The bromate concentration was reduced to far below the allowed concentration in drinking water (10 ppb) within 20 minutes. We studied the relationship between bromate adsorption and COF surface modification by metalation of the porphyrinic core or neutralization of the viologen linkers by chemical reduction. The bromate adsorption mechanism was studied by EDAX mapping and molecular simulations, and it was found that ion exchange and hydrogen bonding formation drive the adsorption. Importantly, PV-COF could be easily recycled several times without compromising its adsorption efficiency., A cationic COF removes carcinogenic bromate with a remarkable rate constant of 191.45 g mg−1 min−1.

Herbicide paraquat (dimethylviologen) is a major water pollutant threatening ecosystems and human health. Therefore, it is crucial to develop materials to remove it from water. Three calix[n]arene-based (n = 4, 6, 8) porous organic polymers with different cavity sizes of the backbone macrocycle (CX4P, CX6P, CX8P) were synthesized and tested for their potential use in toxic paraquat removal. These polymers reached some of the highest reported maximum uptake capacities (Qmax up to 419 mg g−1) and showed high adsorption rate constants (kobs up to 0.179 g mg−1 min−1). Importantly, the materials could be easily regenerated by simple washing methods and reused without significant losses in their efficiency while still outperforming commercial activated carbon currently used in water purification.

Herein we report an aqueous polymerization strategy, assisted by dual-purpose supramolecular templates, for the formation of polyhydrazones and their subsequent hydrogelation. In this approach, donor–acceptor charge transfer interactions between small molecule templates and bipyridinium-based dialdehyde monomers facilitated monomer–monomer and polymer–monomer preorganization. The template-assisted polymerizations thus experienced augmented Mw and Mn values by up to 68 and 84% respectively as compared to the untemplated protocol. In this capacity, the presence of the templates and the increased molecular weight of the polymers effectively decreased the minimum monomer concentration needed for hydrogelation, enhanced the mechanical strength of the hydrogel microstructure, and increased the recovery velocity of the gel following shear-induced breakdown. The hydrogels were processed into colored films and highly crystalline ultra-light aerogels with a sheet-like morphology, as revealed by cross-polarized light, scanning electron, and transmission electron microscopies. The aerogels exhibited the ability to uptake gaseous iodine and iodine from solution with removal efficiencies and uptake capacities up to ∼91% and ∼363 wt% respectively.

A set of metal–organic trefoil knots (M-TKs) generated by metal-templated self-assembly of a simple pair of chelating ligands were well tolerated in vitro by non-cancer cells but were significantly more potent than cisplatin in both human cancer cells––including those resistant to cisplatin––and in zebrafish embryos. In cultured cells, M-TKs generated reactive oxygen species that triggered apoptosis via the mitochondrial pathway without directly disrupting the cell-membrane or damaging nuclear DNA. The cytotoxicity and wide scope for structural variation of M-TKs indicate the potential of synthetic metal–organic knots as a new field of chemical space for pharmaceutical design and development.

Here we report template-free synthesis of imine-linked calix[4]arene hollow nanocapsules and their utility in the effective delivery of a poorly soluble cancer drug into tumor cells. These stimuli-responsive nanocapsules show high drug loading and release which resulted in a 40-fold higher cytotoxicity for breast cancer cell line over normal cells.

The development of novel materials for removal of organic contaminants from water is of global importance for the preservation of the environment. Here, we describe the synthesis and characterization of the first porous covalent calix[4]arene-based polymer (CalP) and its use for water purification. CalP has a high surface area, large pore volume and excellent sorption capacity for a range of organic solvents, oils, and toxic dyes. The polymer can selectively absorb up to seven times its weight of oil from oil/water mixtures. From aqueous solutions, it can adsorb both anionic and cationic dyes in under 15 minutes. Its uptake capacity is significantly higher than those of the most adsorbent materials reported to date, including commercial activated carbon. Additionally, the polymer can be easily regenerated using mild washing procedures and reused several times with no loss of absorption efficiency.

[Abstract] Cucurbit[7]uril-modified iron-oxide nanoparticles (CB[7]NPs) were loaded with doxorubicin hydrochloride (Dox) and tested as a drug delivery system. Dox was found to interact with the carbonyl-rich rims of the CB[7] macrocycles adsorbed on the surface of the nanoparticles. The Dox-loaded nanoparticles (Dox@CB[7]NPs) were stable at room temperature and physiological pH and released their Dox cargo under acidic conditions, in the presence of glutathione, or with heating. Dox@CB[7]NPs reduced the viability of HeLa and three other cancer-derived cell lines in vitro at lower IC50 than free Dox. They were also nontoxic to C. elegans. The sensitivity of HeLa cells to Dox@CB[7]NPs was enhanced when the temperature was elevated by application of an alternating magnetic field. Thus, Dox@CB[7]NPs show promise as agents for the intracellular delivery of Dox to cancer cells, for the selective and controlled release of the drug, and, more generally, as a possible means of combining chemotherapeutic and hyperthermic treatment modalities. Al Jalila Foundation; AJF 201425 Al Jalila Foundation; AJF 201538

We report the efficient synthesis of a viologen-based covalent organic polymer by a microwave-assisted Menshutkin reaction. The polymer's viologen sub-units were synthesized in the 4,4′-bipyridinium dicationic state but could be reduced to radical-cationic and neutral forms. Regardless of the redox state of its viologens, the polymer was found to be thermally stable and capable of removing three dyes of differing polarities—fluorescein (FL), rhodamine B (RhB), and Nile red (NR)—from aqueous solutions. With its viologens in the dicationic state, the polymer was most efficient at removing FL, which is hydrophilic. With its viologens in the neutral state, it was most efficient at removing NR, which is hydrophobic. This strategy of using a single redox-tunable material for adsorbing multiple contaminants of different polarities represents a unique approach to water purification.

The immobilization of molecular switches within materials can give rise to new bulk properties that are useful for a variety of applications. Here, we report the synthesis and characterization of covalent organic polymers composed of cyclotriphosphazene core moieties linked together by redox-switchable viologen units. The polymers are isolated as non-porous, micro- and nano-sized spherical particles whose constituent viologens allow access to three distinct redox states: dicationic, radical-cationic and neutral. With viologens in their dicationic state, the particles were used for magic printing, gaseous ammonia sensing, and efficient oxoanion capture. With viologens in any oxidation state, the polymers were capable of capturing 200 to 380% of their weight of iodine vapor. Iodine capture within all of the viologen-based polymers was fast, requiring minutes, as compared to capture by previously reported polymers, which requires hours. With viologens in their neutral state, the polymers exhibited the highest iodine loadings reported to date. Upon one and two-electron reduction, the polymers partially or completely lost their cationic character and, concomitantly, their anion removal capability.

[Abstract] Two synthetic approaches—temperature variation and anion templation—allowed for the selective formation of a [2]catenane ([2]C4+) or a trefoil knot (TK6+), or for the enhanced formation of a Solomon link (SL8+), all from a simple set of starting materials (Zn(II) acetate, diformylpyridine (DFP) and a diamino-2,2′-bipyridine (DAB)) in mixed aqueous solutions. The catenane formed exclusively at 90 °C in a 1 : 1 mixed solvent of D2O and MeOD. In the presence of bromide ion as template, TK6+ formed exclusively at 50 °C in the same solvent. In the solid state, TK6+ hosts two bromide ions in its central cavity by forming six Csp2–H hydrogen bonds. In D2O, TK6+, which was originally prepared as a trifluoroacetate (TFA) salt, was found to exchange two TFA counterions for two monovalent anions of different sizes and shapes, which lodged within the knot's central cavity. In contrast to bromide, the larger triflate anion (CF3SO3−) promoted the formation of SL8+, which was characterized by 1H NMR spectroscopy and mass spectrometry. Two dimensional heteronuclear 19F-1H-HOSEY NMR experiments detected CH⋯F interactions inside the cavity of SL8+. Thus, the product distribution of this dynamic link forming system is sensitive to temperature and the size and shape of the anion template, and one of the products, TK6+, is capable of binding a variety of monovalent anions in D2O with high affinity (with log β2 values of 4 to 6 being typical).

Three topologically non-trivial cadmium(ii)-based complexes-Cd-[2]C, Cd-TK and Cd-SL-were simultaneously self-assembled in a dynamic library, individually isolated and fully characterized using solid-state, gas-phase and solution-phase techniques. Post-synthetic modifications, including reduction and transmetalation, were subsequently achieved. Imine bond reduction followed by demetallation led to the isolation of the corresponding organic molecules [2]C, TK and SL. Transmetalation of Cd-TK and Cd-SL with the zinc(ii) cation resulted in isolation of the corresponding zinc(ii)-containing complexes Zn-TK and Zn-SL.

Stereoisomerization and the unprecedented phenomenon of metal translocation in the absence of redox processes were probed in two inherently chiral bimetallic [2]catenanes by using a combination of variable-temperature 1H NMR and CD spectroscopies, X-ray crystallography, and DFT calculations.

The synthesis and the dynamic behavior of a bistable [2]rotaxane, based on a reverse donor–acceptor motif containing naphthalene diimide (NpI) and 4,4′-bipyridinium (BIPY2+) as two electron-deficient stations and bis-1,5-dioxynaphthalene[38]crown-10 (BDNP38C10) as the electron-rich ring, is described. A functionalized tetraarylmethane moiety has been incorporated between the two stations in order to control the free energy barrier for the shuttling of the BDNP38C10 on the dumbbell component. The bistable [2]rotaxane was synthesized using the so-called “threading-followed-by-stoppering” approach and characterized by NMR spectroscopy and mass spectrometry. Initially, the BDNP38C10 ring resides on the NpI station on account of the synthetic approach employed in the synthesis of the bistable [2]rotaxane. 1H NMR spectroscopy was used to follow the equilibration process between the two translational isomers of the bistable [2]rotaxane—namely, NpI ⊂ BDNP38C10 and BIPY2+ ⊂ BDNP38C10. After 72 h, equilibrium was reached with a 3 : 2 ratio of the two translational isomers in favor of the NpI ⊂ BDNP38C10 co-conformation in CD3CN. The rate of relaxation of the crown ether from NpI ⊂ BDNP38C10 back to BIPY2+ ⊂ BDNP38C10 was associated with a rate constant of 2.2 ± 0.3 × 10−5 s−1 (t1/2 = 3.4 h), corresponding to a free energy of activation of 23.8 ± 0.1 kcal mol−1. Cyclic voltammetry (CV) reveals that the BDNP38C10 ring can be enticed to pass over the speed bump onto the neutral BIPY0 unit upon the generation of the NpI2− dianion, even although the neutral BIPY0 has presumably little or no affinity for the BDNP38C10 ring.

The redox chemistry of a newly synthesized small dendrimer containing six peripheral viologen units and a phosphazene core is described. The one-electron reduction of each viologen (total six electrons) leads to intermolecular dimerization of the reduced viologens borne by the same phosphorous atom, resulting in a color change from colourless to purple providing it with potential electrochromic applications.

A limited range of redox-active, rotaxane-based, molecular switches exist, despite numerous potential applications for them as components of nanoscale devices. We have designed and synthesised a neutral, redox-active [2]rotaxane, which incorporates an electron-deficient pyromellitic diimide (PmI)-containing ring encircling two electron-rich recognition sites in the form of dioxynaphthalene (DNP) and tetrathiafulvalene (TTF) units positioned along the rod section of its dumbbell component. Molecular modeling using MacroModel guided the design of the mechanically interlocked molecular switch. The binding affinities in CH(2)Cl(2) at 298 K between the free ring and two electron-rich guests--one (K(a) = 5.8 × 10(2) M(-1)) containing a DNP unit and the other (K(a) = 6.3 × 10(3) M(-1)) containing a TTF unit--are strong: the one order of magnitude difference in their affinities favouring the TTF unit suggested to us the feasibility of integrating these three building blocks into a bistable [2]rotaxane switch. The [2]rotaxane was obtained in 34% yield by relying on neutral donor-acceptor templation and a double copper-catalysed azide-alkyne cycloaddition (CuAAC). Cyclic voltammetry (CV) and spectroelectrochemistry (SEC) were employed to stimulate and observe switching by this neutral bistable rotaxane in solution at 298 K, while (1)H NMR spectroscopy was enlisted to investigate switching upon chemical oxidation. The neutral [2]rotaxane is a chemically robust and functional switch with potential for applications in device settings.

We report a variety of [c2]daisy chain molecules which undergo quantitative, efficient, and fully reversible molecular movements upon the addition of base/acid in organic solvents. Such externally triggered molecular movements can induce the contraction and extension of the [c2]daisy chain molecule as a whole. A linear polymer of such a bistable [c2]daisy chain exerts similar types of movements and can be looked upon as a candidate for the development of artificial muscles. The spectrophotometric investigations of both the monomeric and polymeric bistable [c2]daisy chains, as well as the corresponding model compounds, were performed in MeCN at room temperature, in order to obtain the thermodynamic parameters for these mechanically interlocked molecules. Based on their spectrophotometric and thermodynamic characteristics, kinetic analysis of the acid/base-induced contraction and extension of the [c2]daisy chain monomer and polymer were conducted by employing a stopped-flow technique. These kinetic data suggest that the rates of contraction and extension for these [c2]daisy chain molecules are determined by the thermodynamic stabilities of the corresponding kinetic intermediates. Faster switching rates for both the contraction and extension processes of the polymeric [c2]daisy chain were observed when compared to those of its monomeric counterpart. These kinetic and thermodynamic investigations on [c2]daisy chain-based muscle-like compounds provide important information for those seeking an understanding of the mechanisms of actuation in mechanically interlocked macromolecules.

A [2]pseudorotaxane-based mechanised nanoparticle system, which operates within an aqueous acidic environment, has been prepared and characterised; this integrated system affords both water-soluble stalk and ring components in an effort to improve the biocompatibility of these promising new drug delivery vehicles.

A switchable donor–acceptor pretzelane composed of a crown ether containing tetrathiafulvalene and 1,5-dihydroxynaphthalene recognition units and a covalently tethered cyclobis(paraquat-pphenylene) ring exhibits unidirectional motion on both oxidation (forwards) and reduction (backwards). Accepted version

Two donor–acceptor thread-like compounds incorporating viologen (V2+) units and 1,5-dihydroxynaphthalene (DNP) stations have been prepared. Their ability to form self-assembled charge-transfer (CT) complexes with cucurbit[8]uril (CB[8]) is evidenced by UV-Vis and NMR spectroscopies, as well as by mass spectrometry. Binding studies show the formation of 1 : 1 and 2 : 1 complexes between CB[8] and a thread-like compound containing two viologen units, while only a 1 : 1 inclusion complex was observed between CB[8] and a thread-like compound containing only a single viologen unit. The switching behavior of the threads within their pseudorotaxane frameworks was investigated by using cyclic voltammetry (CV) and UV-Vis spectroscopy.