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A tetracationic macrocycle can include clinically used photodynamic agents, alleviating their posttreatment phototoxicity and maintaining their photodynamic efficacy.

Excess bilirubin accumulates in the bodies of patients suffering from acute liver failure (ALF) to cause much irreversible damage and bring about serious clinical symptoms such as kernicterus, hepatic coma, or even death. Hemoperfusion is a widely used method for removing bilirubin from the blood, but clinically used adsorbents have unsatisfactory adsorption capacity and kinetics. In this study, we prepared four supramolecular organic framework microcrystals

Since 1995, photodynamic therapy (PDT) has been utilized as an effective method for cancer treatment. However, the residues of photosensitizers in the normal tissues after PDT can be activated by sunlight to cause severe skin phototoxicity, for which currently there are no clinical solutions. As a result, post-PDT patients need to remain out of sunlight for up to five weeks, which produces great living and mental burdens for patients. Herein, we report that a biocompatible porous organic polymer (POP) with average 3.1 nm porosity is able to suppress the skin phototoxicity of clinically used porphyrin-based photodynamic agents (PDAs), including Photofrin, Talaporfin and Hiporfin, through an adsorption-elimination mechanism. Fluorescence titration and dialysis experiments show that POP can adsorb and retain the PDAs at a micromolar concentration. In vivo experiments demonstrate that POP can significantly suppress the skin phototoxicity caused by all the three PDAs without reducing their PDT efficacy. STATEMENT OF SIGNIFICANCE: Up to now, no efficient clinical treatment for the inhibition of post-PDT phototoxicity of clinically used porphyrin-based PDAs is available. In the manuscript, a water-soluble cationic porous organic polymer has been revealed to include three clinically used PDAs. In vivo experiments show that this inclusion remarkably reduces the content of PDAs in mouse skins, leading to significant alleviation of their post-PDT phototoxicity without no negative effect on their PDT efficacy. Thus, this work provides a strategy for overcoming the drawback of clinically used photodynamic agents.

ConspectusIn past decades, regular porous architectures have received a great amount of attention because of their versatile functions and applications derived from their efficient adsorption of various guests. However, most reported porous architectures exist only in the solid state. Therefore, their applications as biomaterials may face several challenges, such as phase separation, slow degradation, and long-term accumulation in the body. This Account summarizes our efforts with respect to the development and biomedical applications of water-soluble 3D diamondoid supramolecular organic frameworks (

A three-dimensional flexible organic framework FOF-1 has been synthesized from the condensation of a tetratopic acylhydrazine and a rigid 4,4′-diphenyl-4,4′-bipyridinium dialdehyde in water through the quantitative formation of hydrazone bond. FOF-1 is further applied to construct a polycatenane framework FOF-pc-1 through the quantitative cucurbit[7]uril encapsulation for the diphenylbipyridinium subunits of the framework by making use of the dynamic nature of the hydrazone bond in water. The bipyridinium subunits in both frameworks can be reduced their radical cation counterparts to produce conjugated radical cation-linked dynamic organic frameworks rc-FOF-1 or rc-FOF-pc-1. Polycatenation is revealed to enhance the stability of the dynamic frameworks in water, whereas depolycatenation can be reached for both FOF-pc-1 and rc-FOF-pc-1 by using a ferrocene guest to form a more stable complex with CB[7].

Bacterial lipopolysaccharides (LPS, endotoxins) cause sepsis that is responsible for a huge amount of mortality globally. However, their neutralization or detoxification remains an unmet medical need. We envisaged that cationic organic frameworks with persistent hydrophobic porosity may adsorb and thus neutralize LPS through a combination of cooperative ion-pairing electrostatic attraction and hydrophobicity. We here report the preparation of two water-soluble flexible organic frameworks (FOF-1 and FOF-2) from tetratopic and ditopic precursors through quantitative formation of hydrazone bonds at room temperature. The two FOFs are revealed to possess hydrodynamic diameters, which range from 20 to 120 nm, depending on the concentrations. Dynamic light scattering and isothermal titration calorimetric and chromogenic limulus amebocyte lysate experiments indicate that both frameworks are able to adsorb and thus reduce the concentration of free LPS molecules in aqueous solution, whereas cytokine inhibition experiments with RAW264.7 support that this adsorption can significantly decrease the toxicity of LPS. In vivo experiments with mice (five males per group) show that the injection of FOF-1 at a dose of 0.6 mg/kg realizes the survival of all of the mice administrated with LPS of the d-galactosamine (d-Gal)-sensitized absolute lethal dose (LD

Heparins are natural and partially degraded polyelectrolytes that consist of sulfated polysaccharide backbones. However, as clinically used anticoagulants, heparins are associated with clinical bleeding risks and thus require rapid neutralization. Protamine sulfate is the only clinically approved antidote for unfractionated heparin (UFH), which not only may cause severe adverse reactions in patients, but also is only partially effective against low molecular weight heparins (LMWHs). We here present the facile synthesis of four porous multicationic dynamic covalent polymers (DCPs) from the condensation of tritopic aldehyde and acylhydrazine precursors. We show that, as new water-soluble polymeric antidotes, the new DCPs can effectively include both UFH and LMWHs and thus reverse their anticoagulating activity, which is confirmed by the activated partial thromboplastin time and thromboelastographic assays as well as mouse tail transection assay (bleeding model). The neutralization activities of two of the DCPs were found to be overall superior to that of protamine and have wider concentration windows and good biocompatibility. This pore-inclusion neutralization strategy paves the way for the development of water-soluble polymers as universal heparin binding agents.

Phase I-III clinical studies show that aldoxorubicin (AlDox), a prodrug of doxorubicin (Dox), displays reduced cardiotoxicity compared to Dox, but does not demonstrate an overall survival benefit in patients. Here we report that three-dimensional supramolecular organic frameworks (SOFs) can conjugate AlDox through quantitative thiol-maleimide addition to afford two polymeric prodrugs of Dox. The previously established ability of SOFs in overcoming the multidrug resistance of tumor cells is utilized to achieve efficient intracellular delivery of the conjugated AlDox, which releases Dox as an active agent through acid-responsive hydrolysis of the hydrazone bond of AlDox within tumor cells.

A water-soluble porous supramolecular polymer is assembled through a CB[8]-based 2 + 2 host–guest binding motif, which can greatly increase the efficiency of photocatalysis.

Self-assembled nanoparticles based on supramolecular-organic frameworks and temoporfin demonstrate improved photo cytotoxicity in vitro and anti-tumor efficacy in vivo due to a reduced aggregation-induced quenching effect.

Broad-spectrum agents for the reversal of residual curarization induced by neuromuscular blocking agents are of great significance. Here, we report a highly water-soluble cucurbit[8]uril (CB[8]) derivative as a broad-spectrum neuromuscular block reversal agent induced by both benzylisquinolinium and aminosteroid neuromuscular block agents by the supramolecular sequestration strategy. The UV/Vis competition titration assays suggest the high binding affinity of the CB[8] derivative toward both benzylisquinolinium-type cisatracurium besylate and aminosteroid-type rocuronium, vecuronium, and pancuronium, at the level of 10

Thouless pump with quantized transports is topologically robust against small perturbations and disorders, while breaks down under sufficiently strong disorders. Here we propose counter-intuitive topological pumps induced by disorders in noninteracting and interacting systems. We first show an extrinsic topological pump driven by the on-site quasiperiodic potential for a two-loop sequence, where the disorder inequivalently suppresses the topology of two pump loops. Moreover, we reveal an intrinsic topological pump induced by the hopping quasiperiodic disorder from a trivial single-loop pump in the clean limit, dubbed the topological Anderson-Thouless pump (TATP) as a dynamical analogue of topological Anderson insulators. We demonstrate that the mechanism of the TATP is the disorder-induced shift of gapless critical points and the TATP can even exhibit in the dynamic disorder and interacting cases. Finally, we extend the TATP to higher-order topological systems with disorder-induced quantized corner transports. Our proposed TATPs present new members of the topological pump family and could be realized with ultracold atoms or photonic waveguides., Comment: 13 pages, 13 figures (including supplemental materials)

Topological vacua are a family of degenerate ground states of Yang-Mills fields with zero field strength but nontrivial topological structures. They play a fundamental role in particle physics and quantum field theory, but have not yet been experimentally observed. Here we report the first theoretical proposal and experimental realization of synthetic topological vacua with a cloud of atomic Bose-Einstein condensates. Our setup provides a promising platform to demonstrate the fundamental concept that a vacuum, rather than being empty, has rich spatial structures. The Hamiltonian for the vacuum of topological number n = 1 is synthesized and the related Hopf index is measured. The vacuum of topological number n = 2 is also realized, and we find that vacua with different topological numbers have distinctive spin textures and Hopf links. Our work opens up opportunities for exploring topological vacua and related long-sought-after instantons in tabletop experiments.

Effective mass in the Dirac equation model is generally applied to condensed-matter systems for describing the state of electrons and determining the topological character. In these systems, the si...

We investigate the topology and localization of one-dimensional Hermitian and non-Hermitian Su-Schrieffer-Heeger chains with quasiperiodic hopping modulations. In the Hermitian case, phase diagrams are obtained by numerically and analytically calculating various topological and localization characters. We show the presence of topological extended, intermediate, and localized phases due to the coexistence of independent topological and localization phase transitions driven by the quasiperiodic disorder. Unlike the gapless and localized TAI phase in one-dimensional random disordered systems, we uncover three types of quasiperiodic-disorder-induced gapped topological Anderson insulators (TAIs) with extended, intermediate (with mobility edges), and localized bulk states in this chiral chain. Moreover, we study the non-Hermitian effects on the TAIs by considering two kinds of non-Hermiticities from the non-conjugate complex hopping phase and asymmetric hopping strength, respectively. We demonstrate that three types of TAIs preserve under the non-Hermitian perturbations with some unique localization and topological properties, such as the non-Hermitian real-complex and localization transitions and their topological nature. Our work demonstrates that the disorder-induced TAIs in Hermitian and non-Hermitian quasiperiodic systems are not tied to Anderson transitions and have various localization properties., 12 pages, 7 figures

Two metal porous organic polymers (POPs) that contain the [Ru(bpy)

Selective preparation of two-dimensional polymers (2DPs) and supramolecular polymers (2DSPs) with defined thickness is crucially important for controlling and maximizing their functions, yet it has remained as a synthetic challenge. In the past decade, several approaches have been developed to allow selective preparation of discrete monolayer 2DPs and 2DSPs. Recently, crystal exfoliation and self-assembly strategies have been employed to successfully prepare bilayer 2DP and 2DSP, which represent the first step towards the controlled "growth" of 2D polymers from the thinnest monolayers to thicker few-layers along the third dimension. This Concept review discusses the concept of accurate synthesis of 2D polymers with defined layers. Advances in this research area will pave the way to rational synthetic strategies for 2D polymers with controlled thickness.

Supramolecular sequestration and reversal of neuromuscular block (NMB) have great clinical applications. Water-soluble flexible organic frameworks (FOFs) cross-linked by disulfide bonds are designed and prepared. Different linker lengths are introduced to FOFs to give them varied pore sizes. FOFs are anionic nanoscale polymers and capable of encapsulating cationic neuromuscular blocking agents (NMBAs), including rocuronium (Roc), vecuronium (Vec), pancuronium (Panc) and cisatracurium (Cis). A host-guest study confirms that FOFs bind NMBAs in water. The multivalency interaction between FOFs and NMBAs is able to sequester NMBAs, and prevent them from escaping. These FOFs are non-toxic and biocompatible. Animal studies show that FOFs are effective for the reversal of NMB induced by Roc, Vec and Cis, which shorten the time to a train-of-four ratio of 0.9 by 2.6, 3.8 and 5.7-fold compared to a placebo, respectively.

Two organic cages have been prepared in situ in water through the 2 + 3 hydrazone coupling of two pyridinium-derived trialdehydes and oxalohydrazide. The highly water-soluble cages encapsulate and solubilize linear neutral molecules. Such encapsulation has been applied for the promotion of both two- or three-component hydrazone condensation in water. For two-component reactions, the yields of the resulting monohydrazones are increased from 5-10 to 90-96%. For three-component reactions of hydrazinecarbohydrazide with 11 aromatic aldehydes, in the presence of the organic cages, the bihydrazone products can be produced in 88-96% yields. In contrast, without the promotion of the organic cages, 9 of the reactions do not afford the corresponding dihydrazone product.

Five water-soluble flexible organic frameworks have been synthesized from a pyridinium-derived tetracationic tetraaldehyde and five diacylhydrazines (1 : 2) through the quantitative formation of a hydrazone bond in water at ambient temperature. Dynamic light scattering experiments reveal that the homogeneous frameworks display hydrodynamic diameters ranging from 68 nm to 167 nm, which can be tuned by changing the concentration of the components. Molecular modelling shows that, when adopting an ideal, extended conformation, the frameworks form an aperture of 4 nm diameter. The new flexible frameworks are generally of low cytotoxicity. Fluorescence imaging and flow cytometric analysis demonstrate that the new flexible porous frameworks can quickly include single and double stranded DNA of 21 nucleotides and deliver the included DNA into both normal and cancer cells, with the percentage of delivered cells reaching up to 99.5%.

A series of peptide-appended bisresorcinarenes were synthesized, which adopted tubular conformation induced by intramolecular hydrogen bonds. The derivatives formed unimolecular artificial transmembrane channels in lipid bilayers to enable selective transport of monovalent cations. Importantly, the channels exhibited reversible ligand-gating behavior in response to alkyl amine and Cu2+.

A series of glycoside-peptide conjugates were prepared by engineering at the N-terminus of the natural peptide gramicidin A. The conjugate containing galactose moiety formed a unimolecular transmembrane channel and mediated ion transport to induce apoptosis of cancer cells. More importantly, it exhibited liver cancer cell-targeting behavior due to the galactose-asialoglycoprotein receptor recognition.

Pyrrole and porphyrin-derived nanoparticles have great potential use in bioimaging and therapy because of their unique magnetic, optical, and other photophysical properties, whereas the poor solubility in aqueous solution is one of the drawbacks of current photosensitizers for their photodynamic therapy (PDT) applications. Here, we developed a kind of water-soluble porphyrin-based nanoparticles that are coassembled mainly by the electrostatic interaction of anionic porphyrins and cationic tetraphenylmethane derivative. No aggregation-caused quenching (ACQ) was detected for these nanoparticles. In addition, the simple porphyrin transformation into nanoparticles improved their ability to generate reactive oxygen species singlet oxygen (

The complete geometry of quantum states in parameter space is characterized by the quantum geometric tensor, which contains the quantum metric and Berry curvature as the real and imaginary parts, respectively. When the quantum states are degenerate, the quantum metric and Berry curvature take non-Abelian forms. The non-Abelian (Abelian) Berry curvature and Abelian quantum metric have been experimentally measured. However, an experimentally feasible scheme to extract all the components of the non-Abelian quantum metric tensor is still lacking. Here we propose a generic protocol to directly extract the non-Abelian quantum metric tensor in arbitrary degenerate quantum states in any dimensional parameter space, based on measuring the transition probabilities after parameter quenches. Furthermore, we show that the non-Abelian quantum metric can be measured to obtain the real Chern number of a generalized Dirac monopole and the second Chern number of a Yang monopole, which can be simulated in three and five-dimensional parameter space of artificial quantum systems, respectively. We also demonstrate the feasibility of our quench scheme for these two applications with numerical simulations., 10 pages, 5 figures

A water-soluble flexible organic framework FOF-hz of low cytotoxicity has been synthesized from a pyridinium-derived tetracationic tetraaldehyde and a citric acid-derived tritopic acylhydrazine (1:...

A covalently bonded three-dimensional [Ru(bpy)3]2+-cored metallosupramolecular polymer (MSP-CB[8]-c) has been prepared from a noncovalently bonded metallosupramolecular polymer (MSP-CB[8]-nc) throu...

Two metal porous organic polymers (POPs) that contain the [Ru(bpy)3]2+ cores are prepared via one-pot Suzuki–Miyaura coupling reactions. Both Ru-POPs are thermally stable at up to 340 °C in air and...

Aqueous electrochemical conversion of CO2 with renewable energy is a sustainable pathway to produce carbon-neutral fuels and address the growing crisis of global warming. A key challenge in the field of electrochemical CO2 reduction (CO2R) is the design of catalytic materials featuring high product selectivity, stability, and a composition of earth-abundant elements. In this work, we demonstrate anion exchange as a promising strategy to achieve synergistic catalysis via secondary coordination sphere interactions between the catalyst and the support. We encapsulate an anionic cobalt porphyrin-based electrocatalyst, with a single-molecule dispersion, into a cationic porous polymer skeleton, and construct a class of electrocatalysts to convert CO2 to CO with remarkable activity, selectivity and durability. Detailed examination of CO2R revealed selectivity for CO production in excess of 83% and stability over 7 hours with a per-site turnover frequency of 1.4 s−1. In situ spectroelectrochemical measurements using surface-enhanced infrared absorption spectroscopy (SEIRAS) provided insights into the capability of the cationic polymer framework to control the interactions of intermediates with groups in close proximity via modifying the secondary coordination sphere interactions around the active sites. Our findings highlight the importance of a rationally designed electrocatalyst/solid support interface and offer a paradigm to integrate catalytically active components and develop efficient electrocatalytic systems via marrying the catalyst and support, and creating synergy.

Two rigid porous organic polymers (Ir-POP-1 and Ir-POP-2) were prepared from the coupling reactions of tetraphenylmethane tetraborate and two [Ir(ppy)2(dtbbpy)]+-based bitopic linkers and applied as heterogeneous visible-light photocatalysts for organic transformations. Ir-POP-2 was found to exhibit high catalytic activity for a wide range of organic reactions, which include Smiles–Truce rearrangement of alkyliodides, desulfurative conjugate addition to Michael acceptors, and aerobic oxidations of sulfides and arylboronic acids. For all the transformations, Ir-POP-2 could achieve heterogeneous photocatalytic efficiency that rivals that of the homogeneous prototype iridium complexes. This remarkably high photocatalytic performance has been attributed to the large pore size of the conjugated backbone. The new heterogeneous photocatalyst was also highly stable to achieve good recyclability for all the studied reactions and could be reused eight to nineteen times.

Covalent organic frameworks (COFs) are emerging porous polymers that have 2D or 3D long-range ordering. Currently available COFs are typically insoluble or decompose upon dissolution, which remarkably restricts their practical implementations. For 3D COFs, the achievement of noninterpenetration, which maximizes their porosity-derived applications, also remains a challenge synthetically. Here, we report the synthesis of the first highly water-soluble 3D COF (sCOF-101) from irreversible polymerization of a preorganized supramolecular organic framework through cucurbit[8]uril (CB[8])-controlled [2 + 2] photodimerization. Synchrotron X-ray scattering and diffraction analyses confirm that sCOF-101 exhibits porosity periodicity, with a channel diameter of 2.3 nm, in both water and the solid state and retains the periodicity under both strongly acidic and basic conditions. As an ordered 3D polymer, sCOF-101 can enrich [Ru(bpy)3]2+ photosensitizers and redox-active polyoxometalates in water, which leads to remark...

Porous organic polymers (POPs) have attracted increasing attention and emerged as a new research area in polymer chemistry. During the past decade, the intense desirability for application in aqueous scenarios has spawned the development of a specific class of POPs

Despite that photodynamic therapy (PDT) has been applied for the treatment of cancer and skin diseases for more than two decades, all clinically used photodynamic agents (PDAs) suffer the drawback of skin phototoxicity of PDAs, which requires patients to avoid exposure to natural light for weeks after treatment, but has so far lacked effective suppression methods. Here, we report that three-dimensional diamondoid supramolecular organic frameworks (SOFs), that possess well-defined 2.1-nm porosity, can be used to suppress the skin phototoxicity of Photofrin, HiPorfin and Talaporfin, three porphyrin-based PDAs which clinically receive the most wide applications by injecting SOF after PDT, via an adsorption and retention mechanism. Fluorescence and dynamic light scattering experiments confirm that the SOFs have strong interaction with PDAs, and can adsorb PDAs at a micromolar concentration, whereas dialysis experiments support that the adsorption leads to an important retention effect. In vitro and in vivo experiments reveal that SOFs have high biocompatibility. Studies with healthy and tumor-bearing mouse models demonstrate that, when the PDAs are administrated at a dose comparable with the clinical one, SOF can remarkably suppress sunlight-induced skin phototoxicity, whereas the PDT efficacy of mice treated with SOF post-PDT is maintained. This work provides an efficient strategy for the improvement of the safety of clinically used PDAs.

The topological Anderson and Mott insulators are two phases that have so far been separately and widely explored beyond topological band insulators. Here we combine the two seemingly different topological phases into a system of spin-1/2 interacting fermionic atoms in a disordered optical lattice. We find that the topological Anderson and Mott insulators in the noninteracting and clean limits can be adiabatically connected without gap closing in the phase diagram of our model. Lying between the two phases, we uncover a disordered correlated topological insulator, which is induced from a trivial band insulator by the combination of disorder and interaction, as the generalization of topological Anderson insulators to the many-body interacting regime. The phase diagram is determined by computing various topological properties and confirmed by unsupervised and automated machine learning. We develop an approach to provide a unified and clear description of topological phase transitions driven by interaction and disorder. The topological phases can be detected from disorder/interaction induced edge excitations and charge pumping in optical lattices., Comment: 6+9 pages, 4+9 figures

Ru(bpy)3]2+-cored supramolecular organic framework SMOF-1, assembled from a [Ru(bpy)3]2+-derived hexaarmed molecule and cucurbit[8]uril, has been demonstrated to heterogeneously catalyze visible light-induced reduction of phenyl, benzyl, 2-phenylethyl and 3-phenylpropyl azides in acetonitrile to produce the corresponding amines in good to high yields. For the last two kinds of azides that bear a CO2Me group at the para-position of the benzene ring, cascade reactions take place to generate the corresponding lactams in high yields. Compared with homogeneous control [Ru(bpy)3]Cl2, SMOF-1 exhibits remarkably increased photocatalysis activity as a result of synergistic effect of the [Ru(bpy)3]2+ units that form cubic cages to host the azide molecules and related intermediates. Moreover, SMOF-1 displays high recyclability and considerable photocatalysis activity after 3 to 12 runs.

The crystal structures of three intramolecularly hydrogen bonded rigid aromatic amide derivatives, which all bear one iodine atom at one end as the donor and one pyridine unit at the other end as the acceptor, have been described to reveal the utility of halogen bonding in inducing the formation of supramolecular macrocycles. All the three compounds formed intermolecular I⋯N halogen bonding. For short compound 1, halogen bonding induced the formation of an extended supramolecular array. For longer folded compounds 2 and 3, halogen bonding could hold two molecules to form supramolecular macrocycles even by adopting a highly distorted, energetically less favorable conformation (for 3). Depending on the solvent for the growth of crystals, compound 3 could also gave rise to a halogen bonded supramolecular double helix.

Two hydrogen-bonded 3-mer arylamide foldamers 1 and 2, which bear two pyridine or iodobenzene subunits at the ends, have been designed and prepared. Compound 1 co-assembles with 1,4-diiodotetrafluorobenzene (3) to form 2 + 2 macrocycles through four (py)N⋯I halogen bonds, whereas compound 2 dimerizes into a macrocycle through two CO⋯I hydrogen bonds. Macrocycles formed by 1 and 3 stack to produce a supramolecular tube, with two neighboring macrocycles encapsulating one molecule of 3 through two CO⋯I halogen bonds. Through such a cross-layer connection, formally the two molecules also give rise to a new halogen-bonded supramolecular helix, and further stack alternately to afford a double helix. In contrast, the mixture of 1 and fumaric acid (5) did not produce a similar encapsulation-derived helix, even though they also formed a halogen-bonded 2 + 2 supramolecular macrocycle.

The cooperative electrostatic attraction and π-π aromatic stacking interactions between tetrahedral tetrapyridinium TP and three tetraanionic tetraphenylethylene derivatives TPE-1∼3 led to the formation of a new kind of supramolecular polymer networks in water, which have been confirmed by 1H NMR, fluorescence, isothermal titration calorimetric (ITC) and dynamic light scattering (DLS) experiments. ITC studies show that the contributions of enthalpy and entropy were comparable, reflecting the importance of hydrophobicity in driving the intermolecular aromatic stacking. DLS experiments indicate that the linear supramolecular polymers formed by these tetratopic monomers further aggregated into networks of 102-nm size.