Synthesis strategies of covalent organic frameworks: An overview from nonconventional heating methods and reaction media

Covalent organic frameworks(COFs), as an emerging class of porous crystalline materials constructed by covalent links between the building monomers, have gained tremendous attention. Over the past 15 years, COFs have made rapid progress and substantial development in the chemistry and materials fields. However, the synthesis of COFs has been dominated by solvothermal methods for a long time and it usually involves high temperature, high pressure and toxic organic solvents, which created many challenges for environmental considerations. Recently,the exploration of new approaches for facile fabrication of COFs has aroused extensive interest. Hence, in this review, we comprehensively describe the synthetic strategies of COFs from the aspects of nonconventional heating methods and reaction media. In addition, the advantages,limitations and properties of the preparation methods are compared. Finally, we outline the main challenges and development prospects of the synthesis of COFs in the future and propose some possible solutions.

Copper coordination-driven self-assembly and encapsulation of PCR reagents

Polymerase chain reactions(PCR)are a very important tool for use in cloning,nucleic acid sequencing and diagnostic testing.The storage conditions of PCR reagents are limited to freezing and a lot of mixing steps are needed.In this paper,we report using metal ions to form coordination nanomaterials with the intrinsic components of the PCR reagents including dNTP,DNA primers and DNA polymerase as an integrated PCR reaction system.To complete PCR reactions,users need only to dissolve the coordination nanomaterials with a buffer and add template DNA.A few transition metal ions were screened and Cu^(2+)was found to be the most effective metal ion for this purpose.Then the encapsulation efficiency of PCR reagents was measured,which can reach close to 100%for the primers and DNA polymerase,but only 10%for dNTP because dNTP was excess.Further study also exhibited this integrated PCR reaction system can be used for DNA detection with a similar detection limit to the normal PCR,and showed good stability of encapsulated PCR nanomaterial after storage for a week.

Capture-SELEX for Chloramphenicol Binding Aptamers for Labeled and Label-Free Fluorescence Sensing

Chloramphenicol(CAP)is a potent antibiotic.Due to its side effects,CAP is currently banned in most countries,but it is still found in many food products and in the environment.Developing aptamer-based biosensors for the detection of CAP has interested many researchers.While both RNA and DNA aptamers were previously reported for CAP,they were all obtained by immobilization of the CAP base,which omitted the two chlorine atoms.In this work,DNA aptamers were selected using the libraryimmobilized method and free unmodified CAP.Three families of aptamers were obtained,and the best one named CAP1 showed a dissociation constant(K_(d))of 9.8μM using isothermal titration calorimetry(ITC).A fluorescent strand-displacement sensor showed a limit of detection(LOD)of 14μM CAP.Thioflavin T(ThT)staining allowed label-free detection of CAP with a LOD of 1μM in buffer,1.8μM in Lake Ontario water,and 3.6μM in a wastewater sample.Comparisons were made with previously reported aptamers,and ITC failed to show binding of a previously reported 80-mer aptamer.Due to the small size and well-defined secondary structures of CAP1,this aptamer will find analytical applications for environmental and food monitoring.

Robust magnetic laccase-mimicking nanozyme for oxidizing o-phenylenediamine and removing phenolic pollutants

In this study, we report a novel magnetic biomimetic nanozyme(Fe3O4@Cu/GMP(guanosine5′-monophosphate)) with high laccase-like activity, which could oxidize toxic ophenylenediamine(OPD) and remove phenolic compounds.The magnetic laccase-like nanozyme was readily obtained via complexed Cu2+and GMP that grew on the surface of magnetic Fe3O4 nanoparticles.The prepared Fe3O4@Cu/GMP catalyst could be magnetically recycled for at least five cycles while still retaining above 70% activity.As a laccase mimic,Fe3O4@Cu/GMP had more activity and robust stability than natural laccase for the oxidization of OPD.Fe3O4@Cu/GMP retained about 90% residual activity at 90℃ and showed little change at pH 3–9, and the nanozyme kept its excellent activity after long-term storage.Meanwhile, Fe3O4@Cu/GMP had better activity for removing phenolic compounds, and the removal of naphthol was more than 95%.Consequently, the proposed Fe3O4@Cu/GMP nanozyme shows potential for use as a robust catalyst for applications in environmental remediation.

Recent progress in nanomaterial-enhanced fluorescence polarization/anisotropy sensors

As a promising signaling transduction approach, fluorescence polarization(FP)/fluorescence anisotropy(FA), provides a powerful quantitative tool for the rotational motion of fluorescently labeled molecules in chemical or biological homogeneous systems. Unlike fluorescence intensity, FP/FA is almost independent the concentration or quantum of fluorophores, but they are highly dependent on the size or molecular weight of the molecules or materials attached to fluorophores. Recently, significant progress in FP/FA was made, due to the introduction of some nanomaterials as FP/FA enhancers. The detection sensitivity is thus greatly improved by using nanomaterials as FP/FA enhancers, and nanomaterial-based FP/FA is currently used successfully in immunoassay, and analysis of protein, nucleic acid, small molecule and metal ion.Nanomaterial-based FP/FA provides a new kind of strategy to design fluorescent sensors and establishes innovative analytical methods. In this review, we summarize the scientific publications in the field of FP/FA sensor in recent five years, and first introduce the recent progress of FP/FA sensor based on nanomaterial. Subsequently, the various analytical applications of FP/FA based on nanomaterial are discussed. Finally, we provide perspectives on the current challenges and future prospects in this promising field.

Graphene oxide as a photocatalytic nuclease mimicking nanozyme for DNA cleavage

Developing nanomaterial-based enzyme mimics for DNA cleavage is an interesting challenge and it has many potential applications.Single-layered graphene oxide(GO)is an excellent platform for DNA adsorption.In addition,GO has been employed for photosensitized generation of reactive oxygen species(ROS).Herein,we demonstrate that GO sheets could cleave DNA as anuclease mimicking nanozyme in the presence of UV or blue light.For various DNA sequences and lengths,well-defined product bands were observed along with photobleaching of the fluorophore label on the DNA.Different from previously reported GO cleavage of DNA,our method did not require metal ions such as Cu^2+.Fluorescence spectroscopy suggested a high adsorption affinity between GO and DNA.For comparison,although zero-dimensional fluorescent carbon dots(C-dots)had higher photosensitivity ir terms of producing ROS,their cleavage activity was much lower and only smeared cleavage products were observed,indicatingthat the ROS acted on the DNA in solution.Based on the results,GO behaved like a classic heterogeneous catalyst following substrate adsorption,reaction,and product desorption steps.This simple strategy may help in the design of new nanozymes by introducing light.

Gold nanoparticles as dehydrogenase mimicking nanozymes for estradiol degradation

Nanozyme catalysis has been mainly focused on a few chromogenic and fluorogenic substrates, while environmentally and biologically important compounds need to be tested to advance the field. In this work, we studied oxidation of estradiol(E2) in the presence of various nanomaterials including gold nanoparticles(AuNPs), nanoceria(CeO2), Fe3O4, Fe2O3, MnO2 and Mn2O3, and found that AuNPs had a dehydrogenase-mimicking activity to convert E2 to estrone(E1). This conversion was monitored using HPLC. The reaction was faster at higher pH and reached saturation at pH 8. Smaller AuNPs had a higher catalytic efficiency and 5 nm AuNPs were 4.8-fold faster than 13 nm at the same total surface area. Finally,we tried 17α-ethinylestradiol(EE2) as a substrate and found that 5 nm AuNPs can catalyze EE2 oxidation in the presence of H2O2. This work indicated that some nanomaterials can affect environmentally important hormones via oxidation reactions, and this study has expanded the scope of substrate of nanozymes.

Self-assembled manganese phthalocyanine nanoparticles with enhanced peroxidase-like activity for anti-tumor therapy

The use of functional nanoparticles as peroxidase-like(POD-like)catalyst has recently become a focus of research in cancer therapy.Phthalocyanine is a macrocyclic conjugated metal ligand,which is expected to achieve a high POD-like catalytic activity,generating free radicals and inhibiting the proliferation of cancer cells.In this paper,we synthesized phthalocyanine nanocrystals with different structures through noncovalent self-assembly confined within micro-emulsion droplets,and manganese phthalocyanine(MnPc)possessing a metal–N–C active center was used as the building block.These nano-assemblies exhibit shape-dependent POD-like catalytic activities,because the emulsifier and MnPc co-mixed assembly reduced the close packing between MnPc molecules and exposed more active sites.The assembly had a water-dispersed nanostructure,which is conducive to accumulation at tumor sites through the enhanced permeability and retention effect(EPR).Because of a highly efficient microenvironmental response,the assembly showed higher catalytic activity only emerged under the acidic tumor-like microenvironment,but caused less damage to normal tissues in biomedical applications.In vivo and in vitro catalytic therapy tests showed excellent anti-tumor effects.This work explored a new way for the application of metal–organic macromolecules such as MnPc as nanozymes for catalytic tumor therapy.

Nucleobase,nucleoside,nucleotide,and oligonucleotide coordinated metal ions for sensing and biomedicine applications

Metal ions play critical roles in chemical,biological,and environmental processes.Various biomolecules have the ability to coordinate with metal ions and form various materials.Nucleobases,nucleosides,and nucleotides,as the essential components of DNA,have emerged as a useful building block for the construction of functional nanomaterials.In recent years,DNA oligonucleotides have also been used for this purpose.We herein review the strategies for the synthesis of soft nanomaterials through the assembly of nucleotides(or DNA)and metal ions to yield various nanoparticles,fibers,and hydrogels.Such coordination methods are simple to operate and can be carried out under ambient conditions.The luminescent,catalytic,and molecular recognition properties of these coordination materials are described with representative recent examples.Their applications ranging from biosensing,enzyme encapsulation,catalysis,templated shell growth to cancer therapy are highlighted.Finally,challenges of this field and future perspectives are discussed.

Nucleic acids analysis

Nucleic acids are natural biopolymers of nucleotides that store, encode, transmit and express genetic information, which play central roles in diverse cellular events and diseases in living things. The analysis of nucleic acids and nucleic acids-based analysis have been widely applied in biological studies, clinical diagnosis, environmental analysis, food safety and forensic analysis.During the past decades, the field of nucleic acids analysis has been rapidly advancing with many technological breakthroughs.In this review, we focus on the methods developed for analyzing nucleic acids, nucleic acids-based analysis, device for nucleic acids analysis, and applications of nucleic acids analysis. The representative strategies for the development of new nucleic acids analysis in this field are summarized, and key advantages and possible limitations are discussed. Finally, a brief perspective on existing challenges and further research development is provided.

Robust Colorimetric Detection of Cu^(2+) by Excessed Nucleotide Coordinated Nanozymes

Many sensors for Cu^(2+)rely on the catalytic activity of Cu^(2+)to produce a color change,but these colorimetric sensors often suffer from poor selectivity and are susceptible to interference.In this work,we found that Cu^(2+)-catalyzed TMB oxidation can be significantly improved with excessed nucleotides and nucleosides.Especially,with oversaturated guanosine 5′-monophos-phate(GMP)to form a coordination nanozyme,the catalytic efficiency was greatly accelerated.It can be attributed to the specific binding between the electron-rich oxygen and nitrogen atoms of guanine with Cu^(2+).A sensitive and selective strategy for Cu^(2+)sensing was proposed.Owing to the presence of excessed GMP,it ensures robust activity and less susceptibility to interference.This allowed us to test the sensor in complex samples such as the seawater.This work strongly suggests that by supplying excessed ligands,far exceeding the binding stoichiometry,we may produce more robust sensing systems.

Coordination Nanoparticles Formed by Fluorescent 2-Aminopurine and Au^(3+): Stability and Nanozyme Activities

Nucleobase-metal coordination polymers(CPs)have been the target of much recent research owing their interesting properties and ease of preparation.Natural nucleobases are nonfluorescent,and 2-aminopurine(2AP)is a strongly fluorescent analog of adenine.In this work,we compared the CPs formed by adenine,2AP and adenosine with various metals.Only Au3+produced CP nanoparticles with both adenine and 2AP.Both products were similar in terms of size,suggesting that the position of the exocyclic amine is unimportant for coordination with gold.Since 2AP is fluorescent,the dissolution of the nanoparticles in the presence of various chemicals including KCN,GSH,iodide,bromide and chloride,was studied and compared to fluorescent adenosine-Au nanoparticles.It appears that the 2AP CP was more robust than the adenosine one since even chloride can quench the fluorescence of the adenosine/Au complex.Finally,the adenine and 2AP nanoparticles exhibited weak oxidase-like activity for oxidation of TMB possibly by the Au3+exposed on the surface.

Nucleotide coordination with 14 lanthanides studied by isothermal titration calorimetry

With their hydrolytic, optical and magnetic properties, nucleic acids, In addition, nucleotide-coordinated LnTM anthanide ions （Ln3＋） are versatile probes for ons form useful oanoparticles. However, the thermodynamic basis of their interaction is still lacking. In this work, isothermal titration calorimetry （ITC） is used to study the binding between nuc]eotides and 14 different Ln3＋ ions. Ln3＋ interacts mainly with the phosphate of cytidine and thymidine monophosphate （CMP and TMP）, while the nucleobases in adenosine and guanosine monophosphate （AMP and GMP） are also involved. Phosphate binding is fully entropy driven since the reactions absorb heat. Nucleosides alone do not bind Ln3＋ and the purines need the phosphate for chelation. With increasing atomic number of Ln3＋, tile binding reaction with GMP goes from exothermic to endothermic. The entropy contribution starts to increase from Gd3＋, explaining the ＇gadolinium break＇ observed in many Ln3＋-mediated RNA cleavage reactions. This study provides fundamental insights into the Ln3＋/nucleotide interactions, and it is useful for understanding related biosensors, nanomaterials, catalysts, and for lanthanide separation.

Nanomaterials for analytical chemistry

Over the last few decades, nanomaterials have been playing increasingly important roles in developing analytical biosensors. With a large specific surface area, nanomaterials offer various surfaces for immobilization of biological probes. In addition, taking advantage of their magnetic, catalytic and various optical properties such as fluorescence emission and quenching, light absorption and scattering, Raman enhancement, localized surface plasmon resonance, versatile signaling and signal amplification methods can be realized.

Cryptosporidium parvum oocyst directed assembly of gold nanoparticles and graphene oxide

Understanding the interactions between inorganic nanomaterials and biological species is an important topic for surface and environmental chemistry. In this work, we systematically studied the oocysts of Cryptosporidium pa r v u m as a model protozoan parasite and its interaction with gold nanoparticles (AuNPs) and graphene oxide (GO). The as-prepared citrate-capped AuNPs adsorb strongly on the oocysts leading to a vivid color change. The adsorption of the AuNPs was confirmed by transmission electron microscopy. Heat treatment fully inhibited the color change, indicating a large change of surface chemistry of the oocysts that can be probed by the AuNPs. Adding proteases such as trypsin and proteinase K partially inhibited the color change. DNA-capped AuNPs, on the other hand, could not be adsorbed by the oocysts. GO was found to wrap around the oocysts forming a conformal shell reflecting the shape of the oocysts. Both citratecapped AuNPs and GO compromised the membrane integrity of the oocysts as indicated by the propidium iodide staining experiment, and they may be potentially used for inactivating the oocysts. This is the first example of using nanomaterials to probe the surface of the oocysts, and it suggests the possibility of using such organisms to template the assembly of nanomaterials.

Signaling Kinetics of DNA and Aptamer Biosensors Revealing Graphene Oxide Surface Heterogeneity

Adsorption of fluorescently labeled DNA and aptamer probes to graphene oxide(GO)has been one of the most popular methods for developing biosensors.In the presence of target analytes,the quenched fluorescence would recover.In this work,we followed the kinetics of the reactions and found that the fluorescence would eventually drop after an initial increase,and this was attributed to the re-adsorption of the desorbed probe DNA molecules.Both a DNA probe and an aptamer for adenosine were used.This re-adsorption was attributed to the surface heterogeneity of GO,and the DNA probes desorbed from relatively weaker binding sites were re-adsorbed on the stronger binding sites.This re-adsorption can be avoided by extensive washing the samples,and also by blocking the GO surface or by heating.This fundamental understanding is important for achieving a stable signal of such biosensors.

Adsorption of Selenite and Selenate by Metal Oxides Studied with Fluorescent DNA Probes for Analytical Application

Selenium is a required micronutrient at low concentrations,while it becomes toxic at high concentrations.Inorganic selenium exists mainly as SeO32-(selenite or Se(IV))and SeO42-(selenate or Se(VI)).Currently,few biosensors can effectively measure these selenium species in water.In this work,we study the adsorption of selenite/selenate by various metal oxide nanoparticles including CeO2,CoO,Cr2O3,Fe2O3,Fe3O4,In2O3,Mn2O3,NiO,TiO2,and ZnO.Fluorescently-labeled DNA molecules are used as probes and first adsorbed on these oxides,resulting in quenched fluorescence.Upon addition of selenite,the DNA probes are displaced from the surface with fluorescence recovered for six out of the ten oxides,while the response to selenate was much lower in all the cases.The signaling is optimal below 400 mM NaCl at near neutral pH when Fe3O4 nanoparticles were used.Quantitative studies were performed on three oxides with detection limits for selenite being 0.3 lM(CeO2),2.0 lM(Fe3O4),and 3.0 lM(Fe2O3),respectively.The system,however,is also responsive to a few other anions such as phosphate and arsenate.Therefore,it can be used as a method for analyzing selenium species when the system is known to be free of such competing anions.This study represents the first effort of designing selenite sensors using DNA as probes,and it may stimulate related work for this important analyte.

Special Topic: Nanozyme-Based Analysis and Testing

Developing stable and cost-effective sensors and biosensors is one of the main goals of analytical chemists.Many biosensors rely on enzymes either for recognition of target analytes such as using glucose oxidase for detecting glucose,or for signal generation such as using horse radish peroxidase(HRP)in immunoassays.While these protein-based enzymes are highly efficient,they are susceptible to denaturation and some enzymes are quite costly.Using nanomaterials to mimic enzyme activities has attracted growing interest over the last 10 years or so.Many common metal oxides,metals,and carbon-based nanomaterials have oxidase,peroxidase and catalase like activities,and nanozyme was coined for describing them.

An Activatable Nanoenzyme Reactor for Coenhanced Chemodynamic and Starving Therapy Against Tumor Hypoxia and Antioxidant Defense System

It is critical to improve the efficiency of cancer therapy with minimized side effects.Chemodynamic therapy(CDT)is a tumor therapeutic strategy designed to generate abundant reactive oxygen species(ROS)at tumor sites through a Fenton or Fenton-like reaction.Recently,this developing scheme has demonstrated an incredible promise for tumor therapy.The process involved could induce cell death without the input of external energy,and this could only occur via the conversion of hydrogen peroxide(H_(2)O_(2))to hydroxyl radicals(·OH).Although Fenton or Fenton-like reactions are being exploited for CDT,along with an application of oxidation reactions to supplement H_(2)O_(2),it has been proven that in cancer cells,the high levels of the existing antioxidants could suppress CDT via·OH depletion,and,unfortunately,tumor hypoxia also inhibits the oxidation reactions.Herein,the authors aimed to fabricate an activatable nanoenzyme reactor(NER)to solve this challenge.Fluorescent reporters(FRs)and bioenzyme glucose oxidase(GOX)were coassembled on nanozyme MnO_(2) nanosheets,which was enwrapped by the tumor-targeting material,hyaluronic acid(HA).NER was internalized explicitly by cancer cells through ligand/receptor recognitionmediated endocytosis,followed by intracellular hyaluronidase(HAase)-dependent activation.As a result,the oxygen level was improved,and the antioxidants were depleted,leading to the promotion of glucose consumption and an increase in·OH level.Thus,the NER exhibited multiple effects to induce coenhanced,chemodynamic and starving therapy against tumor hypoxia and antioxidant defense system to achieve a favorable targeted tumor therapeutic,via these rigorously highly effective,and targeted biochemical reactions both in an in vitro cultured cancer cells systemor in an in vivo mice tumor model.