Novel Microwave-Assisted Synthesis of COFs: 2020-2022.

Covalent organic frameworks (COFs) have emerged as a new type of crystalline porous polymers of great interest. However, their preparation requires long reaction times. Microwave-assisted synthesis (MAS) offers an interesting approach to increasing the reaction rate of chemical processes. Thus, microwaves can be a key tool for the fast and scalable synthesis of COFs. Since our previous review on the topic, the preparation of COFs with microwaves has been evolving. Herein, we present a compilation of COFs studies and experiments published in the last three years on the synthesis of COFs using microwave-assisted synthesis as a source of energy. The articles include imine, triazine, and other 2D COFs synthesized using MAS. The 3D COFs have also been compiled. The chemical structure of the monomers and the COFs and their main parameters of synthesis and application are summarized for each article.

Batch and Flow Synthesis of CeO2 Nanomaterials Using Solid-State Microwave Generators.

Microwave-assisted synthesis in combination with flow synthesis offers an interesting approach to develop faster and more sustainable procedures for the preparation of homogeneous nanomaterials. Recently, solid-state generators of microwaves appeared as a tool with improved control over power and frequency. Cerium oxide, despite its excellent catalytic activity, has not been prepared before using solid-state generators or microwave-assisted flow chemistry. We report a procedure for the preparation of nanoparticulated CeO2 (around 4 nm) under 2.45 GHz microwaves in only 30 s. The materials are further calcined at 800 °C to increase particle size, with a better defined particle size and crystallinity. The procedure was tested in batch at pH 11 and 12 and diverse potencies, and the products were characterized by TEM, XRD, DLS, and N2 adsorption-desorption isotherms. The materials were similar at the diverse pH values and potencies. XRD confirms the crystallinity of the CeO2 material with a fluorite-like structure. They are composed of particles around 40 nm that aggregate as structures of around 100 nm. The procedure was successfully adapted to flow synthesis, obtaining materials with structure and properties equivalent to batch synthesis. The batch and flow materials offer peroxidase properties, opening the door for their use as ROS scavengers.

In situ growth of metal-organic framework HKUST-1 in an organic polymer as sorbent for nitrated and oxygenated polycyclic aromatic hydrocarbon in environmental water samples prior to quantitation by HPLC-UV.

An in situ preparation of metal-organic framework (HKUST-1) on the surface of an organic polymer is reported. The hybrid material was evaluated as sorbent for solid-phase extraction (SPE) of oxygenated and nitrated polycyclic aromatic hydrocarbons (PAHs). The growth of HKUST-1 on MAA-based polymer was accomplished using a layer-by-layer assembly strategy. The HKUST-1-polymer was characterized using powder X-ray diffraction and scanning electron microscopy to demonstrate the incorporation of MOF crystals onto the polymer surface. The MOF (nano)crystals were characterized using high-resolution transmission electron microscopy and high-angle annular-dark-field scanning transmission electron microscopy. The water-stable MOF-polymer was evaluated as SPE sorbent, and several variables that can influence the extraction recoveries of PAH derivatives were investigated. Under the selected conditions, the detection limits varied between 4 and 21 ng·L-1, and the precision (relative standard deviation) was below 12%. The recovery values for spiked solutions ranged from 95 to 104%, and the enrichment factor achieved was close to 1000-fold using a high sample volume (100 mL) and very low desorption volume (100 µL). The SPE enrichment combined with HPLC and DAD detector was successfully applied to the extraction and determination of polycyclic hydrocarbons in environmental water samples. Graphical abstract A layer-by-layer synthesis of HKUST-1 onto polymer surface was performed and applied to isolation of PAH derivatives in environmental water samples.

A poly(glycidyl-co-ethylene dimethacrylate) nanohybrid modified with ß-cyclodextrin as a sorbent for solid-phase extraction of phenolic compounds.

A hybrid material made of ß-cyclodextrin anchored to a polymeric network is described and evaluated as a sorbent for solid-phase extraction of phenolic compounds (phenol, cresol isomers, 2-methoxy-4-vinylphenol, 4-ethylphenol, 4-vinylphenol, 4-ethylguaiacol, guaiacol, and eugenol). The polymeric backbone of the sorbent consists of a poly(glycidyl-co-ethylene dimethacrylate) network, whose surface has been modified with ß-cyclodextrin by a click-chemistry based procedure. The resulting material has been characterized by different techniques, and it has shown to be viable as a sorbent for its use in extraction cartridges. In this way, a method for the determination of the above analytes in tea has been validated. Under optimum conditions, the method has good repeatability, with coefficients of variation between 0.6 and 7.2%. In addition, recoveries from spiked samples at the level of 50 µg L-1 are between 57 and 101%. The method has been then applied to the determination of phenolic compounds in the drinkable portion of infusions made from tea bags. The quantification has been carried out by using gas chromatography coupled to a mass spectrometry detector. Following their elution from the sorbent with a mixture of acetonitrile and methanol, the limits of quantification reached are between 4.6 and 400 µg L-1. Results have been compared with those obtained with a reference method by using the paired t-test for comparing individual differences. The solid phase is reusable, and no cyclodextrin is lost during extraction due to its covalent anchoring to the polymeric support. Graphical abstract Schematic representation of the structure and characterization of the hybrid material made of ß-cyclodextrin anchored to a polymeric network. The material is described and evaluated as a sorbent for the solid-phase extraction of phenolic compounds.

Extraction of aflatoxins by using mesoporous silica (type UVM-7), and their quantitation by HPLC-MS.

A solid-phase extraction procedure has been developed by using a sorbent derived from UVM-7 mesoporous silica. The sorbent was applied to the extraction of aflatoxins B1, B2, G1 and G2 from tea samples followed by HPLC with mass spectrometric detection. The sorbent was characterized by transmission electron microscopy, nuclear magnetic resonance, X-ray diffraction and nitrogen adsorption-desorption. UVM-7 is found to be the best solid phase. The amount of solid-phase, type and volume of eluent, pH value and ionic strength and breakthrough volume were optimized. Following the recommended procedure, recoveries between 96.0 and 98.2% were achieved, with RSD values of <5.1%, and the limits of detection are in the range from 0.14 to 0.7 µg·kg-1. The material is reusable. The method was applied to the analysis of real tea samples. A low matrix effect is found, and recoveries are >88%. The results were compared with those obtained by immunoaffinity columns as a reference method. Only low concentrations of aflatoxin G2 were found in some samples, and results obtained with both methods are shown to be statistically sound and comparable. Graphical abstractSchematic representation of a mesoporous silica sorbent (type UVM-7) for the extraction of aflatoxins (AF) from tea by solid-phase extraction (SPE), and its determination by liquid chromatography. The morphology of the material allows to retain the analytes very well.

Not always what closes best opens better: mesoporous nanoparticles capped with organic gates.

Four types of calcined MCM-41 silica nanoparticles, loaded with dyes and capped with different gating ensembles are prepared and characterized. N1 and N2 nanoparticles are loaded with rhodamine 6G and capped with bulky poly(ethylene glycol) derivatives bearing ester groups (1 and 2). N3-N4 nanoparticles are loaded with sulforhodamine B and capped with self-immolative derivatives bearing ester moieties. In the absence of esterase enzyme negligible cargo release from N1, N3 and N4 nanoparticles is observed whereas a remarkable release for N2 is obtained most likely due to the formation of an irregular coating on the outer surface of the nanoparticles. In contrast, a marked delivery is found in N1, N3, and N4 in the presence of esterase enzyme. The delivery rate is related to the hydrophilic/hydrophobic character of the coating shell. The use of hydrophilic poly(ethylene glycol) derivatives as gating ensembles on N1 and N2 enables an easy access of esterase to the ester moieties with subsequent fast cargo release. On the other hand, the presence of a hydrophobic monolayer on N3 and N4 partially hinders esterase enzyme access to the ester groups and the rate of cargo release was decreased.

Solid-phase extraction of phospholipids using mesoporous silica nanoparticles: application to human milk samples.

In this study, mesoporous silica materials (MSMs) with bimodal pore systems (namely, UVM-7), MCM-41 silica, and a commercial silica-based material were evaluated as solid-phase extraction (SPE) sorbents for the isolation of phospholipids (PLs) using phosphatidylcholine as a test compound. Morphological characterization (including TEM, surface, and size pore measurements) of these materials was carried out. The mechanism of interaction of the target analyte with the MSMs was also studied. With regard to the SPE process, several experimental parameters that affect the extraction performance (e.g., loading and elution solvent, breakthrough volume, loading capacity, and reusability) were investigated. The recommended protocol was applied to the extraction of PLs in human milk fat samples. The extracted PLs were then determined by hydrophilic interaction liquid chromatography (HILIC) using evaporative light scattering detection (ELSD). This work reports the first application of silica-based mesoporous materials to preconcentrate PLs in these complex matrices. Graphical abstract ᅟ.

Fluorogenic Sensing of Carcinogenic Bisphenol A using Aptamer-Capped Mesoporous Silica Nanoparticles.

Mesoporous silica nanoparticles loaded with rhodamine B and capped with a bisphenol A aptamer were used for the selective and sensitive detection of this lethal chemical. The pores of the nanoparticles are selectively opened in the presence of bisphenol A (through its selective coordination with the aptamer) with subsequent rhodamine B delivery. With this capped material a limit of detection as low as 3.5 µm of bisphenol A was measured.

Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells.

We describe herein a Toll-like receptor 3 (TLR3) targeting delivery system based on mesoporous silica nanoparticles capped with the synthetic double stranded RNA polyinosinic-polycytidylic acid (poly(I:C)) for controlled cargo delivery in SK-BR-3 breast carcinoma cells. Our results show that poly(I:C)-conjugated nanoparticles efficiently targeted breast cancer cells due to dsRNA-TLR3 interaction. Such interaction also triggered apoptotic pathways in SK-BR-3, significantly decreasing cells viability. Poly(I:C) cytotoxic effect in breast carcinoma cells was enhanced by loading nanoparticles' mesopores with the anthracyclinic antibiotic doxorubicin, a commonly used chemotherapeutic agent.

Caspase 3 Targeted Cargo Delivery in Apoptotic Cells Using Capped Mesoporous Silica Nanoparticles.

Excessive apoptotic cell death is at the origin of several pathologies, such as degenerative disorders, stroke or ischemia-reperfusion damage. In this context, strategies to improve inhibition of apoptosis and other types of cell death are of interest and may represent a pharmacological opportunity for the treatment of cell-death-related disorders. In this scenario new peptide-containing delivery systems (solids S1 -P1 and S1 -P2 ) are described based on mesoporous silica nanoparticles (MSNs) loaded with a dye and capped with the KKGDEVDKKARDEVDK (P1 ) peptide that contains two repeats of the DEVD target sequence that are selectively hydrolyzed by caspase 3 (C3). This enzyme plays a central role in the execution-phase of apoptosis. HeLa cells electroporated with S1 -P1 are able to deliver the cargo in the presence of staurosporin (STS), which induces apoptosis with the consequent activation of the cytoplasmic C3 enzyme. Moreover, the nanoparticles S1 -P2 , containing both a cell-penetrating TAT peptide and P1 also entered in HeLa cells and delivered the cargo preferentially in cells treated with the apoptosis inducer cisplatin.

Gated mesoporous silica nanoparticles for the controlled delivery of drugs in cancer cells.

In recent years, mesoporous silica nanoparticles (MSNs) have been used as effective supports for the development of controlled-release nanodevices that are able to act as multifunctional delivery platforms for the encapsulation of therapeutic agents, enhancing their bioavailability and overcoming common issues such as poor water solubility and poor stability of some drugs. In particular, redox-responsive delivery systems have attracted the attention of scientists because of the intracellular reductive environment related to a high concentration of glutathione (GSH). In this context, we describe herein the development of a GSH-responsive delivery system based on poly(ethylene glycol)- (PEG-) capped MSNs that are able to deliver safranin O and doxorubicin in a controlled manner. The results showed that the PEG-capped systems designed in this work can be maintained closed at low GSH concentrations, yet the cargo can be delivered when the concentration of GSH is increased. Moreover, the efficacy of the PEG-capped system in delivering the cytotoxic agent doxorubicin in cells was also demonstrated.

Cathepsin-B induced controlled release from peptide-capped mesoporous silica nanoparticles.

New capped silica mesoporous nanoparticles for intracellular controlled cargo release within cathepsin B expressing cells are described. Nanometric mesoporous MCM-41 supports loaded with safranin O (S1-P) or doxorubicin (S2-P) containing a molecular gate based on a cathepsin B target peptidic sequence were synthesized. Solids were designed to show "zero delivery" and to display cargo release in the presence of cathepsin B enzyme, which selectively hydrolyzed in vitro the capping peptide sequence. Controlled delivery in HeLa, MEFs WT, and MEFs lacking cathepsin B cell lines were also tested. Release of safranin O and doxorubicin in these cells took place when cathepsin B was active or present. Cells treated with S2-P showed a fall in cell viability due to nanoparticles internalization, cathepsin B hydrolysis of the capping peptide, and cytotoxic agent delivery, proving the possible use of these nanodevices as new therapeutic tools for cancer treatment.

Enzyme-responsive intracellular-controlled release using silica mesoporous nanoparticles capped with ε-poly-L-lysine.

The synthesis and characterization of two new capped silica mesoporous nanoparticles for controlled delivery purposes are described. Capped hybrid systems consist of MCM-41 nanoparticles functionalized on the outer surface with polymer ε-poly-L-lysine by two different anchoring strategies. In both cases, nanoparticles were loaded with model dye molecule [Ru(bipy)3](2+). An anchoring strategy involved the random formation of urea bonds by the treatment of propyl isocyanate-functionalized MCM-41 nanoparticles with the lysine amino groups located on the ε-poly-L-lysine backbone (solid Ru-rLys-S1). The second strategy involved a specific attachment through the carboxyl terminus of the polypeptide with azidopropyl-functionalized MCM-41 nanoparticles (solid Ru-tLys-S1). Once synthesized, both nanoparticles showed a nearly zero cargo release in water due to the coverage of the nanoparticle surface by polymer ε-poly-L-lysine. In contrast, a remarkable payload delivery was observed in the presence of proteases due to the hydrolysis of the polymer's amide bonds. Once chemically characterized, studies of the viability and the lysosomal enzyme-controlled release of the dye in intracellular media were carried out. Finally, the possibility of using these materials as drug-delivery systems was tested by preparing the corresponding ε-poly-L-lysine capped mesoporous silica nanoparticles loaded with cytotoxic drug camptothecin (CPT), CPT-rLys-S1 and CPT-tLys-S1. Cellular uptake and cell-death induction were studied. The efficiency of both nanoparticles as new potential platforms for cancer treatment was demonstrated.

Chromo-fluorogenic detection of nitroaromatic explosives by using silica mesoporous supports gated with tetrathiafulvalene derivatives.

Three new hybrid gated mesoporous materials (SN3 -1, SNH2 -2, and SN3 -3) loaded with the dye [Ru(bipy)3 ](2+) (bipy=bipyridine) and capped with different tetrathiafulvalene (TTF) derivatives (having different sizes and shapes and incorporating different numbers of sulfur atoms) have been prepared. The materials SN3 -1 and SN3 -3 are functionalized on their external surfaces with the TTF derivatives 1 and 3, respectively, which were attached by employing the "click" chemistry reaction, whereas SNH2 -2 incorporates the TTF derivative 2, which was anchored to the solid through an amidation reaction. The final gated materials have been characterized by standard techniques. Suspensions of these solids in acetonitrile showed "zero release", most likely because of the formation of dense TTF networks around the pore outlets. The release of the entrapped [Ru(bipy)3 ](2+) dye from SN3 -1, SNH2 -2, and SN3 -3 was studied in the presence of selected explosives (Tetryl, TNT, TNB, DNT, RDX, PETN, PA, and TATP). SNH2 -2 showed a fairly selective response to Tetryl, whereas for SN3 -1 and SN3 -3 dye release was found to occur with Tetryl, TNT, and TNB. The uncapping process in the three materials can be ascribed to the formation of charge-transfer complexes between the electron-donating TTF units and the electron-accepting nitroaromatic explosives. Finally, solids SNH2 -2 and SN3 -1 have been tested for Tetryl detection in soil with good results, pointing toward a possible use of these or similar hybrid capped materials as probes for the selective chromo-fluorogenic detection of nitroaromatic explosives.

Towards chemical communication between gated nanoparticles.

The design of comparatively simple and modularly configurable artificial systems able to communicate through the exchange of chemical messengers is, to the best of our knowledge, an unexplored field. As a proof-of-concept, we present here a family of nanoparticles that have been designed to communicate with one another in a hierarchical manner. The concept involves the use of capped mesoporous silica supports in which the messenger delivered by a first type of gated nanoparticle is used to open a second type of nanoparticle, which delivers another messenger that opens a third group of gated nanoobjects. We believe that the conceptual idea that nanodevices can be designed to communicate with one another may result in novel applications and will boost further advances towards cooperative systems with complex behavior as a result of the communication between simple abiotic individual components.

Graphene oxide as inhibitor on the hydrolysis of fats under simulated in vitro duodenal conditions.

Obesity is a global pandemic, thus novel developments that reduce the absorption of fats is of interest. We have evaluated the effect of graphene oxide (GO) on the lipase catalyzed hydrolysis of fats (tributyrin, sunflower and olive oil) under simulated duodenal conditions. Results indicate that the presence of GO in the digestion mixture can inhibit lipase activity up to a 90% of the initial reaction rate, and this inhibition lasts even during 2 h of digestion. The inhibition mechanism seems non competitive and could be opposite to the effect of bile salts, although the direct interaction between GO and the enzyme cannot be discarded. The inhibition is found also in alimentary fats suggesting that GO could be a strong inhibitor for fat hydrolysis.

Selective, sensitive, and rapid analysis with lateral-flow assays based on antibody-gated dye-delivery systems: the example of triacetone triperoxide.

Set them free: Brightly fluorescent indicators that are loaded into mesoporous silica nanoparticle carriers, capped with bulky antibodies, are released into the lateral flow of a test strip upon analyte arrival. Integration of the system into a rapid, simple flow test with fluorescence readout is applied for the selective and sensitive determination of the presence of triacetone triperoxide (TATP) as a prototype small-molecule analyte (see figure).

Enzyme-responsive silica mesoporous supports capped with azopyridinium salts for controlled delivery applications.

The preparation of a new capped silica mesoporous material, Rh-Azo-S, for on-command delivery applications in the presence of target enzymes is described. The material consists of nanometric mesoporous MCM-41-like supports loaded with Rhodamine B and capped with an azopyridine derivative. The material was designed to show "zero delivery" and to display a cargo release in the presence of reductases and esterases, which are usually present in the colon, mainly due to intestinal microflora. The opening and cargo release of Rh-Azo-S in vitro studies were assessed and seen to occur in the presence of these enzymes, whereas no delivery was noted in the presence of pepsine. Moreover, Rh-Azo-S nanoparticles were used to study controlled Rhodamine B dye delivery in intracellular media. HeLa cells were employed for testing the "non"-toxicity of nanoparticles. Moreover, delivery of the dye in these cells, through internalization and enzyme-mediated gate opening, was confirmed by confocal microscopy. Furthermore, the nanoparticles capped with the Azo group and loaded with a cytotoxic camptothecin (CPT) were also prepared (solid CPT-Azo-S) and used as delivery nanodevices in HeLa cells. When this solid was employed, the cell viability decreased significantly due to internalization of the nanoparticles and delivery of the cytotoxic agent.

Enhanced efficacy and broadening of antibacterial action of drugs via the use of capped mesoporous nanoparticles.

Bug busters: A novel nanodevice consisting of mesoporous nanoparticles loaded with vancomycin and capped with ε-poly-L-lysine (ε-PL) was prepared and its interaction with different Gram-negative bacteria studied. A remarkable improvement in the efficacy of the antimicrobial drug ε-PL and a broadening of the antimicrobial spectrum of vancomycin is demonstrated.

Selective and sensitive chromofluorogenic detection of the sulfite anion in water using hydrophobic hybrid organic-inorganic silica nanoparticles.

In water and wine: Chromofluorogenic detection of the sulfite anion in pure water was accomplished by using a new hybrid organic-inorganic material that contained a probe entrapped in hydrophobic biomimetic cavities. This material was used for the detection of sulfite in red wine.