Radical-Smiles Rearrangement by a Vitamin B2-Derived Photocatalyst in Water.

Herein, we report a catalytic radical-Smiles rearrangement system of arene migration from ether to carboxylic acid with riboflavin tetraacetate (RFT), a readily available ester of natural vitamin B2, as the photocatalyst and water as a green solvent, being free of external oxidant, base, metal, inert gas protection, and lengthy reaction time. Not only the known substituted 2-phenyloxybenzoic acids substrates but also a group of naphthalene- and heterocycle-based analogues was converted to the corresponding aryl salicylates for the first time. Mechanistic studies, especially a couple of kinetic isotope effect (KIE) experiments, suggested a sequential electron transfer-proton transfer processes enabled by the bifunctional flavin photocatalyst.

C-N cleavage of secondary amide to access primary amide by a Co(II)/Oxone oxidation system.

Cleavage of the C-N bond of a secondary amide could provide alternative access to primary amides; however, this strategy remains challenging due to oxidation resistance of the amide. Herein, we employed the cobalt(II)/Oxone catalytic system, one of the advanced oxidation processes (AOPs), to make it available to break the strong C-N bond of various secondary (sulfon)amides, especially those bearing electron-poor or ortho-substituted N-arenes, en route to desirable primary (sulfon)amides. Control experiments showed that it was probably not the generally-considered persulfate anion radical in the cobalt/peroxymonosulfate (Co/PMS) system but the proposed high-valent cobalt-oxo intermediate that should be the major active species for the initial N-H oxidation of N-aryl amides. In the case of N-alkylated secondary amides, the α-C-H bond, rather than the N-H bond, should be oxidized first by both the reactive radicals and high-valent cobalt-oxo species. This work not only establishes an efficient method for removing the N-substituents of secondary amides at low cost, with readily available and eco-friendly reagents, but also demonstrates further synthetic application and provides more insight into intermediates for metal-based AOPs in environmental remediation.

Alkyne Oxidation by a Vitamin B2-Based Photocatalytic System with Both H2O and O2 as the Oxygen Source.

The employment of readily available photocatalysts and green oxygen atom sources is recognized as a promising strategy to develop sustainable catalysis for oxidation reactions. We herein reported a sacrificial reagent-free system consisting of riboflavin tetraacetate (RFT), an ester of natural vitamin B2 as the photocatalyst, and Sc(OTf)3 and NaCl as the cocatalysts for alkyne oxidation under blue light or even sunlight irradiation to produce 1,2-diketone in which the oxygen atoms were from both water and molecular oxygen, respectively. A major Cl-/Cl• cycle was proposed to be involved and achieved by the excited [RFT-2Sc3+]* complex via single electron transfer for the first time, distinguished from the OCl- active species by a two-electron process in previous flavin-halide photo-oxidation systems.

Visible-light-induced aerobic epoxidation with vitamin B2-based photocatalyst.

Herein we described the catalytic epoxidation of α,ß-enone, with peroxide in situ generated, via a predominant single electron transfer and a minor energy transfer pathway. We use inexpensive natural vitamin B2 (riboflavin, RF) or its simple ester (riboflavin tetraacetate, RFT) as the photocatalysts, commonly used 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) as both the electron source and organic base, and ambient air as the terminal oxidant, under visible-light irradiation and room temperature.

Polyelectrolyte-Functionalized NanoMOFs for Highly Efficient Aqueous Lubrication and Sustained Drug Release.

This study demonstrates the hybridization of polyelectrolyte brushes with anti-inflammatory drug-loaded nanoMOFs that can achieve highly efficient aqueous lubrication and sustained drug release for the synergistic therapy of osteoarthritis (OA). Poly(3-sulfopropyl methacrylate potassium salt) (PSPMK) brushes are grown on the surface of the UiO-66-NH2 via one-pot grafting polymerization, which served as a general surface modification method of NH2 -MOFs to grow the polymer brushes. The growth of the PSPMK brushes greatly enhance the stability, dispersity, and swollen property of the AS-UiO-66-NH2@PSPMK in aqueous media. Using as lubricating additives, the UiO-66-NH2 @PSPMK achieves not only reductions in both coefficient of friction and wear volume over 70% and 99% but also supports high load-carrying capacity and long-term durability. The PSPMK brushes can be served as an universal interfacial modification soft layer that can significantly improve the aqueous lubricating performance of other types of NH2 -MOFs. After encapsulating the anti-inflammatory aspirin (AS), the AS-UiO-66-NH2 @PSPMK shows both sustained drug release and good biocompatibility toward the human normal chondrocytes. This work establishes anti-inflammatory drug-loaded UiO-66-NH2 @PSPMK as a potential multifunctional joint lubricant for OA treatment.

Construction of Core-Shell NanoMOFs@microgel for Aqueous Lubrication and Thermal-Responsive Drug Release.

The construction of porous nanocarriers with good lubricating performance and stimuli-responsive drug release is significant for the synergetic therapy of osteoarthritis (OA). Although metal-organic framework nanoparticles (nanoMOFs) as carriers can support drug delivery, achieving the synergy of aqueous lubrication and stimuli-responsive drug release is challenging. In this work, a core-shell nanoMOFs@poly(N-isopropylacrylamide) (PNIPAm) microgel hybrid via one-pot soap-free emulsion polymerization is developed. Programmable growth of the PNIPAm microgel layer on the surface of nanoMOFs is achieved by tuning the concentration of the monomer and the crosslinker in the reaction. Reversible swelling-collapsing behaviors of the hybrid are realized by tuning the temperature below and above the lower critical solution temperature. When used as water lubrication additives, the hybrid enables reductions in both the coefficient of friction and wear volume. In vitro thermal-responsive drug release is demonstrated on the diclofenac sodium-loaded hybrid by controlling the swelling and collapsing states of the PNIPAm nanolayer. Moreover, the good biocompatibility of the hybrid is verified by culturing toward HeLa and BEAS-2B cells. These results establish a nanoMOFs@microgel hybrid that can achieve friction and wear reduction and thermal-responsive drug release.

Cerium Ammonium Nitrate-Mediated Access to Biaryl Lactones: Substrate Scopes and Mechanism Studies.

Herein we described an access to biaryl lactones from ortho-aryl benzoic acids via intramolecular O-H/C-H oxidative coupling with the commonly used cerium ammonium nitrate (CAN) as the one-electron oxidant under a thermal condition. The radical interrupting experiment suggested a radical process, while the kinetic isotope effect (KIE) showed that the C-H cleavage likely was not involved in the rate-determining step. Competitive reactions, especially the strikingly different ρ values of Hammett equations, indicated that the reaction rate was more sensitive to the electronic properties on the aryl moiety rather than the carboxylic moiety, which corresponded to the first single electron transfer (SET) step. In addition, the quite negative ρ values (-4.7) of the aryl moiety unveiled the remarkable electrophilic nature of the second intramolecular radical addition process, which was also consistent with product yields and regioselectivity. Moreover, control experiments disclosed that the single electron in the third step was also transferred to CeIV instead of molecular oxygen. Besides, the possible role of co-solvents trifluoroethanol (TFE) and its influences on the CeIV species were discussed. This work elucidated the possible mechanism by proposing the step that had more effects on the total reaction rate and the species that was responsible for the last single electron transfer.

Catalyst-Free and Transition-Metal-Free Approach to 1,2-Diketones via Aerobic Alkyne Oxidation.

A catalyst-free and transition-metal-free method for the synthesis of 1,2-diketones from aerobic alkyne oxidation was reported. The oxidation of various internal alkynes, especially more challenging aryl-alkyl acetylenes, proceeded smoothly with inexpensive, easily handled, and commercially available potassium persulfate and an ambient air balloon, achieving the corresponding 1,2-diketones with up to 85% yields. Meanwhile, mechanistic studies indicated a radical process, and the two oxygen atoms in the 1,2-diketons were most likely from persulfate salts and molecular oxygen, respectively, rather than water.

Biomimetic synthesis of a novel O2-regeneration nanosystem for enhanced starvation/chemo-therapy.

Glucose oxidase-mediated starvation therapy that effectively cuts off energy supply holds great promise in cancer treatment. However, high glutathione (GSH) contents and anoxic conditions severely reduce therapy efficiency and cannot fully kill cancer cells. Herein, to resolve the above problem, this study constructed a biomimetic nanosystem based on nanreproo-MnO2with porous craspedia globose-like structure and high specific surface area, and it was further modified with dopamine and folic acid to guarantee good biocompatibility and selectivity toward cancer cells. This nanosystem responsively degraded and reacted with GSH and acid to regenerate O2, which significantly increased intracellular O2levels, accelerated glucose consumption, and improved starvation therapy efficiency. Moreover, anticancer drug of camptothecin was further loaded, and notably enhanced cancer growth inhibition was obtained at very low drug concentrations. Most importantly, this novel therapy could unprecedentedly inhibit cancer cell migration to a very low ratio of 19%, and detailed cell apoptosis analyses revealed late stage apoptosis contributed most to the good therapeutic effect. This work reported a new train of thought to improve starvation therapy in biomedicine, and provided a new strategy to design targeted nanocarrier to delivery mixed drugs to overcome the restriction of starvation therapy and develop new therapy patterns.

Functionalized Ultrasmall Fluorinated Graphene with High NIR Absorbance for Controlled Delivery of Mixed Anticancer Drugs.

Fluorinated graphene (FG) possess distinctively novel properties different from graphene and is suitable for many biomedical applications. However, the hydrophobic nature and inert properties of FG limit its further application as a biological material. Here we show the preparation of nano-sized FG (ca. 60 nm) that exhibits high NIR absorbance for photothermal therapy. In order to make it stable in physiological solutions, the FG is enriched with oxygen and followed by covalent binding with chitosan as a novel pH-responsive nanocarrier. Furthermore, controlled loading of two anticancer drugs, doxorubicin (DOX) and camptothecin (CPT) has been realized and the functionalized ultrasmall FG shows remarkably high cytotoxicity toward Hela cancer cells compared to that loaded with either CPT or DOX only. This work established nano-sized FG as a novel photothermal agent due to its small size and can be used a stimulus-responsive nanocarrier for mixed drug delivery and combined therapy.

A versatile ratiometric nanosensing approach for sensitive and accurate detection of Hg2+ and biological thiols based on new fluorescent carbon quantum dots.

Herein, we first reported a facile synthesis method for fabrication of highly photoluminescent carbon quantum dots (CQDs) using sodium alginate as the carbon source and histidine as both the nitrogen source and functional monomer by one-pot hydrothermal synthesis. The as-prepared CQDs gave a high quantum yield of 32%. By employing the new CQDs and rhodamine B (RhB), we demonstrated a simple, facile, sensitive, and accurate ratiometric sensor for detection of Hg2+ and biological thiols. The photoluminescence of CQDs in the ratiometric sensor can be selectively and intensively suppressed by Hg2+ due to strong electrostatic interaction between the surface functional groups of the CQDs and Hg2+. When glutathione (GSH) was introduced into the "Turn Off" CQDs-RhB-Hg2+ sensing system, the fluorescence of the CQDs can be recovered rapidly due to the stronger affinity between thiol and Hg2+, while the fluorescence of the RhB remained constant in this sensing process. Based on the above principle, the ratiometric strategy for detecting Hg2+ and GSH can be achieved readily, and gives satisfactory limit of detections (LODs) of 30 and 20 nM for Hg2+ and GSH, respectively. The dual-emission fluorescent CQDs-RhB sensor does not need the complicated molecular design and the synthesis of dual-emission fluorophores. Meanwhile, the feasibility of the proposed method for analysis of water samples, food samples, and biological samples (plasma from mice oxidative stress study) was investigated. The developed ratiometric nanosensor is proven to be facile, with less sample consumption, rapid, lost cost, highly sensitive, and very selective for Hg2+ and biological thiol detection, which offers a new approach for environmental, food, and biological analysis. Graphical abstract Ratiometric nanosensing approach detection of Hg2+ and biological thiols.

Development of a facile and sensitive HPLC-FLD method via fluorescence labeling for triterpenic acid bioavailability investigation.

Triterpenic acids are widely distributed in many fruits and are known for their medicinal benefits. The study of bioavailability has been an important task for a better understanding of the triterpenic acids. Although many methods based on fluorescence labeling for triterpenic acid determination have been established, these reported methods needed anhydrous conditions, which are not suitable for the convenient study of triterpenic acid bioavailability. Inspired by that, a versatile method, which overcomes the difficulty of the reported methods, has been first developed in this study. The novel method using 2-[12-benzo[b]acridin-5- (12H)-yl]-acetohydrazide (BAAH) as the fluorescence labeling reagent coupled with high-performance liquid chromatography with fluorescence detection was first developed for the study of triterpenic acid bioavailability. Furthermore, the labeling conditions have been optimized in order to achieve the best fluorescence labeling yield. Under the optimal conditions, the quantitative linear range of analytes was 2-1000 ng mL-1 , and the correlation coefficients were >0.9998. The detection limits for all triterpenic acid derivatives were achieved within the range of 0.28-0.29 ng mL-1 . The proposed method was successfully applied to the study of triterpenic acid bioavailability with excellent applicability and good reproducibility.

Facile and Sensitive Fluorescence Sensing of Alkaline Phosphatase Activity with Photoluminescent Carbon Dots Based on Inner Filter Effect.

A simple and sensitive fluorescent assay for detecting alkaline phosphatase (ALP) based on the inner filter effect (IFE) has been proven, which is conceptually different from the previously reported ALP fluorescent assays. In this sensing platform, N-doped carbon dots (CDs) with a high quantum yield of 49% were prepared by one-pot synthesis and were directly used as a fluorophore in IFE. p-Nitrophenylphosphate (PNPP) was employed to act as an ALP substrate, and its enzyme catalytic product (p-nitrophenol (PNP)) was capable of functioning as a powerful absorber in IFE to influence the excitation of fluorophore (CDs). When in the presence of ALP, PNPP was transformed into PNP and induced the absorption band transition from 310 to 405 nm, which resulted in the complementary overlap between the absorption of PNP and the excitation of CDs. Because of the competitive absorption, the excitation of CDs was significantly weakened, resulting in the quenching of CDs. The present IFE-based sensing strategy showed a good linear relationship from 0.01 to 25 U/L (R(2) = 0.996) and provided an exciting detection limit of 0.001 U/L (signal-to-noise ratio of 3). The proposed sensing approach was successfully applied to ALP sensing in serum samples, ALP inhibitor investigation and phosphatase cell imaging. The presented IFE-based CDs fluorescence sensing strategy gives new insight on the development of the facile and sensitive optical probe for enzyme activity assay because the surface modification or the linking between the receptor and the fluorophore is no longer required.

Photothermal COFs with donor-acceptor structure for friction reduction and antiwear.

For the first time, a novel donor-acceptor structured COF with excellent photothermal conversion and mono-dispersity in various oils without any further modification is reported; it realized responsive friction reduction, excellent antiwear and long-time lubrication.

A biomimetic lubricating nanosystem for synergistic therapy of osteoarthritis.

Failure of articular cartilage lubrication and inflammation are the main causes of osteoarthritis (OA), and integrated treatment realizing joint lubrication and anti-inflammation is becoming the most effective treat model. Inspired by low friction of human synovial fluid and adhesive chemical effect of mussels, our work reports a biomimetic lubricating system that realizes long-time lubrication, photothermal responsiveness and anti-inflammation property. To build the system, a dopamine-mediated strategy is developed to controllably graft hyaluronic acid on the surface of metal organic framework. The design constructs a biomimetic core-shell structure that has good dispersity and stability in water with a high drug loading ratio of 99%. Temperature of the solution rapidly increases to 55 °C under near-infrared light, and the hard-soft lubricating system well adheres to wear surfaces, and greatly reduces frictional coefficient by 75% for more than 7200 times without failure. Cell experiments show that the nanosystem enters cells by endocytosis, and releases medication in a sustained manner. The anti-inflammatory outcomes validate that the nanosystem prevents the progression of OA by down-regulating catabolic proteases and pain-related genes and up-regulating genes that are anabolic in cartilage. The study provides a bioinspired strategy to employ metal organic framework with controlled surface and structure for friction reduction and anti-inflammation, and develops a new concept of OA synergistic therapy model for practical applications.

A Biomimetic Lubricating Nanosystem with Responsive Drug Release for Osteoarthritis Synergistic Therapy.

Osteoarthritis (OA) is associated with lubrication failure of articular cartilage and severe inflammatory response of joint capsule. Synergistic therapy combining joint lubrication and anti-inflammation emerges as a novel treatment of OA. In this study, bioinspired by ultralow friction of natural articular synovial fluid and mussel adhesion chemistry, a biomimetic nanosystem with dual functions of enhanced lubrication and stimuli-responsive drug release is developed. A dopamine mediated strategy realizes one step biomimetic grafting of hyaluronic acid (HA) on fluorinated graphene. The polymer modified sheets exhibit highly efficient near-infrared absorption, and show steady lubrication with a long time under various working conditions, in which the coefficient of friction is reduced by 75% compared to H2 O. Diclofenac sodium (DS) with a high loading capacity of 29.2% is controllably loaded, and responsive and sustained drug release is adjusted by near-infrared light. Cell experiments reveal that the lubricating nanosystem is taken up by endocytosis, and anti-inflammation results confirm that the nanosystem inhibits osteoarthritis deterioration by upregulating cartilage anabolic gene and downregulating catabolic proteases and pain-related gene. This work proposes a promising biomimetic approach to integrate polymer modified fluorinated graphene as a dual-functional nanosystem for effective synergistic therapy of OA.

Dual-functional MOFs-based hybrid microgel advances aqueous lubrication and anti-inflammation.

This paper demonstrates the hybridization of copolymer microgel with drug-loaded metal-organic frameworks nanoparticles that can achieve excellent aqueous lubricating performance and anti-inflammatory effect for synergistic treatment of osteoarthritis (OA). Poly(ethylene glycol)-graft-poly(N-isopropylacrylamide) (PEG-g-PNIPAm) microgel layer is grown on the MIL-101(Cr) surface via one-pot soap-free emulsion polymerization method. The lower critical solution temperature of the MIL-101(Cr)@PEG-g-PNIPAm hybrid is raised significantly by incorporating PEG chains into the PNIPAm microgel matrix, which greatly enhances the high-temperature aqueous dispersion stability. The hybrid microgel demonstrated reversibly thermo-sensitive swelling-collapsing behavior to modulate the optical properties and hydrodynamic size. Using as aqueous lubricating additives, the hybrid reduces over 64% and 97% in friction coefficient and wear volume. Also, the hybrid supports desirable temperature-controlled lubrication modulation due to their reversible thermo-responsive behavior, which is benefit to joint lubrication of OA. After encapsulating anti-inflammatory diclofenac sodium (DS), the DS-MIL-101(Cr)@PEG-g-PNIPAm shows thermo-responsive drug release in aqueous media, which can improve the drug-delivery efficiency. By co-culturing the DS-loaded hybrid with human normal chondrocytes, we demonstrate good biocompatibility and anti-inflammatory effect on the chondrocytes with inflammation by regulating the expression of OA-related genes and proteins. Our work establishes multifunctional MOFs-based hybrid microgel systems for advanced colloids modulation and biomedical application.

A snowboard-inspired lubricating nanosystem with responsive drug release for osteoarthritis therapy.

Most of present works of osteoarthritis (OA) therapy are focusing on reducing friction and improving drug loading capacity, while little attention is paid to realizing long-time lubrication and on-demand drug release. In this study, inspired by snowboards with good solid-liquid interface lubrication, a fluorinated graphene based nanosystem with dual functions of long-time lubrication and thermal-responsive drug release was constructed for OA synergetic therapy. An aminated polyethylene glycol bridging strategy was developed to enable covalent grafting of hyaluronic acid on fluorinated graphene. This design not only greatly increased the nanosystem's biocompatibility, but also reduced the coefficient of friction (COF) by 83.3 % compared to H2O. The nanosystem showed long-time and steady aqueous lubrication behavior even after more than 24,000 times of friction tests, and a low COF of 0.13 was obtained with over 90% wear volume reduction. Diclofenac sodium was controllably loaded and sustained drug release was tuned by near-infrared light. Moreover, anti-inflammation results showed that the nanosystem had good protective effect on inhibiting OA deterioration, which could up-regulate cartilage anabolic genes of Col2α and aggrecan while down-regulating catabolic proteases genes of TAC1 and MMP1. This work constructs a novel dual-functional nanosystem that realizes friction and wear reduction with long lubrication life, and shows thermal-responsive on-demand drug release with good synergistic therapeutic effect of OA.

Controlled Growing of Graphdiyne Film for Friction Reduction and Antiwear.

Like the multilayered graphene which is the most widely used solid lubricant, graphdiyne (GDY) as a 2D material holds potential similar prospects but has been rarely researched so far. One reason is that growing a GDY film in a controllable manner on diverse material surfaces remains a great challenge. To address the issue, a catalytic pregrowth and solution polymerization method is developed to synthesize a GDY film on various substrates. It allows fine control over film structure and thickness. A macroscopic ultralow friction coefficient of 0.08 is obtained, and a relatively long life of more than 5 h under a high load of 1378 MPa is achieved. Molecular dynamics simulations together with the surface analysis demonstrate that the increased deformation degree and weakened relative motion between GDY layers contribute to the low friction. Especially, different from graphene, the friction of GDY exhibits a double increase and decrease in one period of λ ≈ 8-9 Å, and it is roughly equal to the distance between two adjacent alkyne bonds in the x direction, indicating GDY's structure and lattice play an important role in reducing friction.

Enzyme coordination conferring stable monodispersity of diverse metal-organic frameworks for photothermal/starvation therapy.

The agglomeration of metal-organic frameworks (MOFs) has long been a problem, and achieving stable monodispersity in water remains a great challenge. This paper reports a universal strategy that functionalizes MOFs by using an endogenous bioenzyme namely glucose oxidase (GOx), to achieve stable water monodispersity, and integrates it as a highly efficient nanoplatform for cancer synergistic therapy. Phenolic hydroxyl groups in GOx chain confers robust coordination interactions with MOFs, which not only endows stable monodispersion in water, but also provides many reactive sites for further modification. Silver nanoparticles are uniformly deposited onto MOFs@GOx to achieve high conversion efficiency from near-infrared light to heat, resulting in an effective starvation and photothermal synergistic therapy model. In vitro and in vivo experiments confirm excellent therapeutic effect at very low doses without using any chemotherapeutics. In addition, the nanoplatform generates large amounts of reactive oxygen species, induces heavy cell apoptosis, and demonstrates the first experimental example to effectively inhibit cancer migration. Our universal strategy enables stable monodispersity of various MOFs via GOx functionalization and establishes a non-invasive platform for efficient cancer synergistic therapy.