Microwave-assisted Protocol Research Articles

Structure Matters: Tailored Graphitization of Carbon Dots Enhances Photocatalytic Performance.

The chemical structure and photoredox properties of carbon dots (CDs) are not yet fully understood. However, it has been reported that, by carefully choosing the starting materials and tuning their synthesis conditions, it is possible to obtain CDs with different chemical structures and therefore different photocatalytic performance. For this work, a family of different CDs was synthesized in Milli-Q water via a microwave-assisted protocol, using citric acid and urea as precursors. The syntheses were carried out at different times and temperatures to assess the impact of the synthetic parameters on the photocatalytic properties of the final materials. After extensive and accurate purification, the photocatalytic abilities of a selected subset of CDs were tested by performing a photocatalyzed atom transfer radical addition reaction. Among the tested CDs, the best performing ones were found to be those synthesized at the highest temperature, which were the most graphitic. A number of different characterization techniques were then used to evaluate the degree of graphitization of CDs and to elucidate the origin of their different photocatalytic performance.

Microwave-assisted protocol towards synthesis of heterocyclic molecules: a comparative analysis with conventional synthetic methodologies (years 2019–2023): a review

Microwave-assisted protocol towards synthesis of heterocyclic molecules: a comparative analysis with conventional synthetic methodologies (years 2019–2023): a review

Orange fruit peels from PDO varieties of Ribera (Sicily, Italy): An insight into the chemistry and bioactivity of volatile and non-volatile secondary metabolites extracted using a microwave-assisted method

Peels of Washington Navel (WAS), Navelina (NAV), and Vaniglia Apireno (VAN) orange fruits from Ribera (Sicily, Italy) represent abundant by-products of the Italian agro-food sector. In this work, volatile (VE) and non-volatile (NVE) extracts were obtained from fresh peels using a microwave-assisted protocol, and were characterized for their content in secondary metabolites and bioactivity. VEs exerted antibacterial activity against different pathogens, and were toxic on Caco2 cells. Their main component was limonene (>85 %). NVEs inhibited tyrosinase, amylase, and glucosidase in vitro, and exerted significant antioxidant effects on THP-1 XBlue cells. They showed also anti-inflammatory properties, by decreasing NF-κB activity in LPS-stimulated cells. Putative molecular effectors were highlighted by multivariate correlation analysis. Overall, NVEs may represent novel sustainable nutraceutical ingredients with anti-inflammatory and metabolic properties, and can be obtained by using eco-sustainable approaches. Our results will encourage the reuse of by-products of the orange processing chain and will contribute to increase its circularity in the future.

6-Aryl-4-cycloamino-1,3,5-triazine-2-amines: synthesis, antileukemic activity, and 3D-QSAR modelling.

Despite significant progress in immunotherapy and chimeric antigen receptor T cell therapy of leukemia, chemotherapy is the major treatment option for the disease. Therefore, the development of potent and safe drugs for standard and targeted chemotherapy of leukemia remains an important task for medicinal chemists. A library of 94 diverse 6-aryl-4-cycloamino-1,3,5-triazine-2-amines was prepared using a one-pot microwave-assisted protocol, which involves a three-component reaction of cyanoguanidine, aromatic aldehydes and cyclic amines, and subsequent dehydrogenative aromatization of the dihydrotriazine intermediates in the presence of alkali. The cytotoxic properties of prepared compounds were evaluated against the leukemic Jurkat T cell line and the selectivity of the 24 most active compounds was also assessed using a normal fibroblast MRC-5 cell line, indicating selective antiproliferative activity against leukemic cells. The structure-activity relationship was analysed, and the prepared 3D-QSAR model was found to predict the antileukemic activity of the compounds with reasonable accuracy. In the cell morphology study, both apoptosis and necrosis features were observed in Jurkat T cells after treatment with the most active compound.

Modular and Computational Access to Innocuous Multistep Metal-Free Synthesis of 1,3,4-Oxadiazoles as Enzyme Inhibitors.

An array of 1,3,4-oxadiazole hybrids, 7a-s, structurally intriguing cores with potential in natural product synthesis and drug discovery, have been synthesized using innovative comparable conventional and microwave-assisted protocols. The synthesis was performed by the reaction of secondary amine-based acetamides, 6a-s, as the electrophile and piperidine-based oxadiazoles as the nucleophile, 3, under the metal-free reaction conditions. High yield in minimum time with highest purity was obtained by the microwave-irradiated method instead of the conventional one. The structural elucidations were made through infrared, 1H NMR, 13C NMR, and elemental analysis studies. The whole array of synthesized compounds, 7a-s, was evaluated for their potential against α-glucosidase and butyryl cholinesterase (BChE) enzymes. Natural bond orbital and structural optimizations were made by using the B3LYP method and the basis set of 6-311++G(d,p). Frontier molecular orbitals and molecular electrostatic potential were calculated at the same level of selected compounds as potential candidates against BChE and α-glucosidase enzymes utilizing the time-dependent density functional theory. Fifteen compounds out of 19 were observed to be active against α-glucosidase enzyme in comparison with acarbose as the reference standard and 7 against the BChE enzyme compared to eserine as the reference standard. The highest potential of compound 7j against BChE is well correlated by the higher binding interaction with target protein as -10.2, calculated by docking studies. The recruited compounds against both enzymes could be the best anti-enzymatic drugs and part of drugs discovery programs after further analysis.

Sustainable Synthesis, Antiproliferative and Acetylcholinesterase Inhibition of 1,4- and 1,2-Naphthoquinone Derivatives.

This work describes the design, sustainable synthesis, evaluation of electrochemical and biological properties against HepG2 cell lines, and AChE enzymes of different substituted derivatives of 1,4- and 1,2-naphthoquinones (NQ). A microwave-assisted protocol was optimized with success for the synthesis of the 2-substituted-1,4-NQ series and extended to the 4-substituted-1,2-NQ family, providing an alternative and more sustainable approach to the synthesis of naphthoquinones. The electrochemical properties were studied by cyclic voltammetry, and the redox potentials related to the molecular structural characteristics and the biological properties. Compounds were tested for their potential anti-cancer activity against a hepatocellular carcinoma cell line, HepG2, using MTT assay, and 1,2-NQ derivatives were found to be more active than their 1,4-NQ homologues (3a-f), with the highest cytotoxic potential found for compound 4a (EC50 = 3 μM). The same trend was found for the inhibitory action against acetylcholinesterase, with 1,2-NQ derivatives showing higher inhibition50µM than their 1,4-NQ homologues, with 4h being the most potent compound (Inhibition50µM = 85%). Docking studies were performed for the 1,2-NQ derivatives with the highest inhibitions, showing dual binding interactions with both CAS and PAS sites, while the less active 1,4-NQ derivatives showed interactions with PAS and the mid-gorge region.

Microwave-assisted Cu(i)-catalyzed one-pot tandem synthesis of pyridoimidazole-fused quinolines as new antimycobacterial agents: DFT and ESI-HRMS study

One-pot tandem synthesis of diverse pyrido[2′,1′:2,3]imidazo[4,5-c]quinolines as new antimycobacterial agents through a Cu(i)-catalyzed microwave-assisted protocol.

Development of Fluorinated Peptoid-Based Histone Deacetylase (HDAC) Inhibitors for Therapy-Resistant Acute Leukemia.

Using a microwave-assisted protocol, we synthesized 16 peptoid-capped HDAC inhibitors (HDACi) with fluorinated linkers and identified two hit compounds. In biochemical and cellular assays, 10h stood out as a potent unselective HDACi with remarkable cytotoxic potential against different therapy-resistant leukemia cell lines. 10h demonstrated prominent antileukemic activity with low cytotoxic activity toward healthy cells. Moreover, 10h exhibited synergistic interactions with the DNA methyltransferase inhibitor decitabine in AML cell lines. The comparison of crystal structures of HDAC6 complexes with 10h and its nonfluorinated counterpart revealed a similar occupation of the L1 loop pocket but slight differences in zinc coordination. The substitution pattern of the acyl residue turned out to be crucial in terms of isoform selectivity. The introduction of an isopropyl group onto the phenyl ring provided the highly HDAC6-selective inhibitor 10p, which demonstrated moderate synergy with decitabine and exceeded the HDAC6 selectivity of tubastatin A.

Fe3O4-carbon spheres core–shell supported palladium nanoparticles: A robust and recyclable catalyst for suzuki coupling reaction

Suzuki-Miyaura (S-M) is regarded the most powerful way for synthesis biaryls, triaryls, or incorporating of substituted aryl moieties in organic preparation by the cross-coupling of aryl boronic acid with aryl halides using the Pd catalyst. This work reports the combining of the hydrothermal and microwave-assisted protocol to convert the glucose to magnetic carbon spheres (Fe3O4-CSPs) decorated with Pd nanoparticles (NPs) as the catalyst for Suzuki-Miyaura cross-coupling reactions. The physicochemical properties in the produced composite were examined using FESEM, HRTEM, nitrogen isotherms, Raman spectroscopy, FTIR, XPS, and XRD. The as-fabricated composite Pd/Fe3O4-CSPs is mostly spherical with a core–shell structure and possesses a great surface area of 253.2 m2·g−1. Its catalytic performance demonstrates that the composite has excellent stability and high tolerance Suzuki-Miyaura cross-coupling reactions in 30 min at 80 °C. Both activated and deactivated aryl halides provided excellent yield. The as-fabricated catalyst was recycled for up to four catalytic cycles without a substantial decline in performance. Moreover, this research offers a facile roadmap for synthesizing Pd/Fe3O4-CSPs composites and promoting the practical implementation of Pd/Fe3O4-CSPs catalysts for organic transformation processes.

Microwave-Assisted Copper(II)-Catalyzed Cascade Cyclization of 2-Propargylamino/Oxy-Arylaldehydes and O-Phenylenediamines: Access to Densely Functionalized Benzo[f]Imidazo[1,2-d][1,4]Oxazepines and Benzo[f]Imidazo[1,2-d][1,4]Diazepines.

A highly efficient microwave-assisted copper(II)-catalyzed cyclization cascade was established starting from readily accessible O/N-propargylated 2-hydroxy or 2-aminobenzaldehydes and o-phenylenediamines to synthesize densely functionalized imidazo[1,2-d][1,4]oxazepines and imidazo[1,2-d][1,4]diazepines in high yields (up to 93%). This one-pot two-step process was found to be highly atom economical (-H2O, -H2) and operationally simple and enabled the generation of two new heterocycle rings (seven- and five-membered) and three new C-N bonds in a single synthetic operation. These reactions well tolerated a variety of substituents including electron-donating and electron-withdrawing groups and furnished the desired fused heterocycles in high yields under microwave irradiation in a very short reaction time. The mechanism of the established protocol involves sequential imine formation-intramolecular cyclization-air oxidation followed by 7-exo-dig cyclization steps. A comparative study between the microwave-assisted approach and conventional heating was also performed to demonstrate the advantages of the microwave-assisted protocol in terms of high yield and shorter reaction time.

Green Process for the Synthesis of 3-Amino-2-methyl-quinazolin-4(3H)-one Synthones and Amides Thereof:DNA Photo-Disruptive and Molecular Docking Studies

Eleven 3-amino-2-methyl-quinazolin-4(3H)-ones have been synthesized, in good to excellent yields, via their corresponding benzoxazinones using an efficient tandem microwave-assisted green process. Representative acetamides have been thermally derived from their functional free 3-amino group, whereas for the synthesis of various arylamides, a novel green microwave-assisted protocol has been developed, which involved the attack of hydrazides on benzoxazinones. Eight out of the eleven 3-amino-2-methyl-quinazolin-4(3H)-ones were found photo-active towards plasmid DNA under UVB, and four under UVA irradiation. Amongst all acetamides, only the 6-nitro derivative retained activity both under UVB and UVA irradiation, whereas the 6-bromo-substituted one was active only under UVB. 3-arylamido-6-bromo derivatives exhibited dramatically decreased photo-activity; however, all 3-arylamido-6-nitro compounds developed extraordinary activity, even at concentrations as low as 1μM, which was enhanced compared to their parent 3-amino-2-methyl-6-nitro-quinazolinone. Molecular docking studies were indicative of satisfactory binding to DNA and correlated to the presented photo-activity. Since quinazolinones are known “privileged” pharmacophores for anticancer and antimicrobial activities, the present study gives information on turning “on” and “off” photosensitization on various derivatives which are often used as synthones for drug development, when chromophores and auxochromes are incorporated or being functionalized. Thus, certain compounds may lead to the development of novel photo-chemo or photodynamic therapeutics.

Efficient microwave-assisted selective alkaline hydrolysis of diversely substituted phosphonate esters

A simple and rapid microwave-assisted protocol for the selective alkaline hydrolysis of phosphonate diesters has been developed to access phosphonic acid monoesters, which are otherwise difficult to obtain by conventional approaches.

New preparation protocols for coumarin-thiosemicarbazone hybrids: Solid state characterization, and in silico/NMR studies of the Z/E isomerization equilibria in solution

In this work, two improved experimental protocols for the preparation of eight coumarin-thiosemicarbazone hybrids are described. The novel methodologies, based on the use of a microwave-assisted protocol (MW) or a sealed vessel conventionally heated reactor (SVR) are faster, more efficient and render higher yields (average increase in yield = 11% and 16%, respectively). For the solid state characterization, infrared spectra of the obtained compounds were analyzed with the aid of computational tools for signal assignation. In addition, a new crystal structure for the E isomer of compound 2d was obtained and a thorough analysis of the intra and intermolecular interactions was performed by Hirshfeld surface analysis. On the other hand, the hybrids were characterized in DMSO-d6 solution by 1H and 13C NMR experiments. All of them showed a set of minor signals neither ascribable to the products nor described in the literature. Variable temperature 1H NMR experiments revealed that a single interconversion equilibrium was operative in the solution, having thermodynamic parameters compatible to those predicted for a Z/E isomerization process by a DFT model. The most stable configuration (E) was further confirmed by DFT, calculating the 13C NMR chemical shifts for both configurations. The computational model shows that the E configuration is stabilized through the formation of a non-conventional C-H···O=C intramolecular H-bond between the methyl and carbonyl groups, adopting a conformation less sterically strained. These findings allow to gain insights into the E/Z isomerization equilibria displayed by thiosemicarbazones in solution, a phenomenon usually under described in literature, which seems to be promoted by a balance between weak intramolecular interactions that modulate the relative isomeric stability in solution.

Protocol Comparison for Organic Residue Analyses from Waterproofing Materials and Shards of Roman Archaeological Amphorae

With the aim of addressing the impact of extractive protocols in molecular characterization of ceramic content, sixteen archaeological shards and waterproofing coatings of Roman amphorae were studied to compare the extractive capacities of protocols prevalently mentioned in wine amphorae analysis. A microwave-assisted protocol is developed in order to esterify grape-derivative markers from archaeological pitch and shard. Gas chromatography-mass spectrometry is used to highlight the great capacities of a two-step protocol that combines organic extraction with BF3-etherate complex butylation applied on archaeological shards. Instead, simultaneous alkaline fusion and direct-resin acid-catalyzed butylation are favored for the characterization of waterproofing material. The identification of tartaric acid, together with succinic, fumaric pyruvic and syringic acids provide valuable insights on the archaeological grape-derivative content, possibly wine. Diterpenic markers highlighted Pinus pitch and wood tar, originally used to waterproof the amphorae. Since markers are reliable tools in organic residue analyses, protocols exhibiting high extractive capacities are favored to avoid false conclusions drawn through the absence of markers.

Synthesis of Catechol Derived Rosamine Dyes and Their Reactivity toward Biogenic Amines.

Functional organic dyes play a key role in many fields, namely in biotechnology and medical diagnosis. Herein, we report two novel 2,3- and 3,4-dihydroxyphenyl substituted rosamines (3 and 4, respectively) that were successfully synthesized through a microwave-assisted protocol. The best reaction yields were obtained for rosamine 4, which also showed the most interesting photophysical properties, specially toward biogenic amines (BAs). Several amines including n- and t-butylamine, cadaverine, and putrescine cause spectral changes of 4, in UV–Vis and fluorescence spectra, which are indicative of their potential application as an effective tool to detect amines in acetonitrile solutions. In the gas phase, the probe response is more expressive for spermine and putrescine. Additionally, we found that methanolic solutions of rosamine 4 and n-butylamine undergo a pink to yellow color change over time, which has been attributed to the formation of a new compound. The latter was isolated and identified as 5 (9−aminopyronin), whose solutions exhibit a remarkable increase in fluorescence intensity together with a shift toward more energetic wavelengths. Other 9-aminopyronins 6a, 6b, 7a, and 7b were obtained from methanolic solutions of 4 with putrescine and cadaverine, demonstrating the potential of this new xanthene entity to react with primary amines.

CdSe-ZnO Core–Shell Quantum Dots for Protein Detection: A Potential Sensing Platform

A highly sensitive biosensing platform comprised of CdSe-ZnO core–shell nanostructures for targeted applications in protein detection is demonstrated. This innovative technique uses a microwave-assisted thermal decomposition method to produce a rapid, less hazardous, and user-friendly procedure to synthesize a semiconductor core surrounded by nanometer-thick metal oxide shells. The benefit of using a metal oxide shell includes mitigating the toxicity of the CdSe core, thus increasing its biocompatibility and minimizing its photochemical corrosion and oxidation. We present a simple one-pot microwave-assisted protocol for the formation of CdSe-ZnO core–shell quantum dots (QDs). These QDs optimize the recognition limit of bovine serum albumin (BSA) protein through a spectral signal at a considerably low concentration (2.5 × 10−6 M), thus demonstrating its potential to become a highly effective surface-plasmon-enhanced Raman spectroscopy (SERS)-like sensing platform. We report a QD material that can mimic a strong SERS-like behavior due to charge transfer affecting the local electric field.

Catalytic wet hydrogen peroxide oxidation of isoeugenol to vanillin using microwave-assisted synthesized metal loaded catalysts

• Supported metal nanoparticles (Cu, W, Mo) on a silica matrix using a one-pot microwave-assisted protocol. • Catalytic activity evaluated in the oxidation of isoeugenol into vanillin. • Moderate conversions, up to 50–60 % (for Cu-MINT). • Acceptable selectivities towards vanillin production (22–45 %). • High catalyst stability (imperceptible decrease of activity after the fourth use). Supported metal nanoparticles (Cu, W, Mo among others) have been stabilized on a silica matrix following an efficient and sustainable one-pot microwave-assisted protocol. The materials synthesized were characterized, mainly, by nitrogen adsorption desorption measurements, X-ray diffraction (XRD), scanning electron microscopy/energy dispersive X-ray analysis (SEM/EDS). The materials exhibited large surface area and pore size in the mesopore range. The incorporation of metal particles in the silica matrix was also confirmed with particle size in a wide range between 2 and 52 nm. The catalytic activity of the resulting materials was evaluated in the catalytic wet oxidation of isoeugenol into vanillin using hydrogen peroxide as oxidant. The catalysts shown moderate conversions, up to 50–60 % for Cu-MINT with acceptable selectivity towards vanillin production (22–45 %), obtaining dimers as main side products. The stability of the catalysts was investigated as well, obtaining an imperceptible decrease after the fourth use.

Design, Synthesis, and Biological Evaluation of a Series of 5- and 7-Hydroxycoumarin Derivatives as 5-HT1A Serotonin Receptor Antagonists.

We have designed and synthesized a series of 60 new 5- and 7-hydroxycoumarin derivatives bearing the piperazine moiety with the expected binding to 5-HT1A and 5-HT2A receptors. Molecular docking of all investigated compounds revealed subnanomolar estimates of 5-HT1AR Ki for three ligands and 5-HT2AR Ki for one ligand as well as numerous low nanomolar estimates of Ki for both receptors. Intrigued by these results we synthesized all 60 new derivatives using microwave-assisted protocols. We show that three new compounds show a relatively high antagonistic activity against the 5HT1A receptor, although lower than the reference compound WAY-100635. These compounds also showed relatively low binding affinities to the 5-HT2A receptor. We also provide a detailed structure–activity analysis of this series of compounds and compare it with previously obtained results for an exhaustive series of coumarin derivatives.

Development of poly(1-vinylimidazole)-chitosan composite sorbent under microwave irradiation for enhanced uptake of Cd(II) ions from aqueous media

A chitosan-based composite named poly(1-vinylimidazole)-chitosan (PVI-CS) was fabricated employing a microwave-assisted protocol to be used as a novel composite for CdII contaminated water. The prepared PVI-CS composite was evaluated using SEM-coupled EDX, FTIR and zeta potential analyses. Under certain experimental conditions of the batch process, the binding behavior of PVI-CS sorbent against CdII ions was investigated. Results demonstrate that the optimized experimental conditions for CdII ions removal by PVI-CS composite sorbent were to be pH 7.2, the PVI-CS dose 2.5 g/L and the CdII concentration 25 mg/L at 30 °C. The Langmuir qmax of the PVI-CS turned out to be 204.92 mg/g for CdII ions. The kinetics analysis revealed that the process was best-fitted for pseudo-first-order kinetics with R2 > 0.999. The CdII ions removal efficiency of PVI-CS sorbent remained satisfactory even after five cycles, which establish that PVI-CS is a sustainability composite for an effective water purification system.

Enhanced photocatalytic conversion of NOx with satisfactory selectivity of 3D-2D Bi4O5Br2-GO hierarchical structures via a facile microwave-assisted preparation

A novel series of 3D-2D Bi4O5Br2-GO hierarchical composites were fabricated via a facile and efficient microwave-assisted protocol and were systematically characterized by various analyses. In composites, both components of 3D hierarchical Bi4O5Br2 and 2D graphite-phased graphene oxide (GO) were verified in heterojunction structures by Raman, UV–Vis DRS, TEM, and elemental mapping spectra. Under visible light irradiation, the photocatalytic NOx removal by composites was obviously enhanced with satisfactory selectivity, though removal of NO was remained almost unchanged. Particularly, the best catalog Bi4O5Br2-GO1.6 possessed outstanding conversion rate for NOx increased by 18% and selectivity for nitrite and nitrate declined by 32% comparing to pure Bi4O5Br2, which was mainly relevant to enhanced visible-light harvesting, strengthened spatial separation of photoinduced charge carries, proper phase composition, and harmony of 3D-2D morphology. Moreover, these stable composites could be reused for several times without obvious activity loss. Basing upon entrapping experiments and analytical results, a plausible photocatalysis mechanism was eventually proposed.