Carbon Resonances Research Articles

Exploring Novel Quinoline-1,3,4-Oxadiazole Derivatives for Alzheimer's Disease: Their Design, Synthesis, and In-Vitro and In-Silico Investigations.

Alzheimer's Disease (AD) is a complicated and advanced neurodegenerative condition accompanied by gradual cholinergic neuronal death and higher levels of monoamine oxidase-B (MAO-B) enzyme. In this study, a series of novel hybrid compounds combining 1,3,4-oxadiazole and quinoline moieties were synthesized and evaluated for their potential as inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and MAO enzymes. The chemical structures of the synthesized compounds were confirmed using various analytical techniques, such as mass spectrometry, infrared spectroscopy (IR), proton nuclear magnetic resonance (1H-NMR), and carbon and nuclear magnetic resonance (13C-NMR). The final products were evaluated for anticholinesterase potential by applying modified Ellman's spectrometric method, whereas a fluorometric method was used to assess MAO inhibition properties. In-silico studies using molecular docking and molecular dynamics simulation (MDS) methods has been also conducted. Among the synthesized compounds, 5a, 5c, and 6a demonstrated substantial activity against AChE, with IC50 values of 0.033 μM, 0.096 μM, and 0.177 μM, respectively. A molecular docking study was performed to elucidate the binding modes and establish the structure-activity relationship (SAR) of the most active compounds (5a, 5c, and 6a). Molecular dynamics simulation (MDS) of the most potent compound, 5a, was also conducted to examine the stability of the interactions with the receptor. Moreover, the physicochemical properties of the active products were also studied. Overall, this research contributes to the development of 1,3,4-oxadiazole- quinoline hybrids as potential AChE inhibitors for the treatment of Alzheimer's disease.

Computational NMR Study of Benzothienoquinoline Heterohelicenes.

Early NMR studies of several heterohelicenes containing an annular nitrogen atom and a thiophene ring in their structure suggested the possibility of the lengthening of the carbon-carbon bonds in the interior of the helical turn of the molecule based on the progressive upfield shift of 13C resonances toward the center of the helical turn. We now report a comprehensive analysis of the optimized geometry and a comparison of the calculated vs. observed 1H and 13C NMR chemical shifts of nineteen representative benzothienoquinoline heterohelicenes. As was initially hypothesized on the basis of the progressive upfield shift of carbon resonances toward the center of the interior helical turn, the present computational study has demonstrated that carbon-carbon bonds indeed have more sp3 character and are longer than normal sp2 bonds to accommodate the helical twist of the molecule, as expected.

Inherent resonance of carbon and graphene-based nanocomposite coupled single-span arch beams

In recent decades, there has been a significant rise in the utilization of composite materials for various engineering applications. These advanced materials offer the potential to improve the mechanical properties and vibration characteristics of structural components. This particular study is dedicated to enhancing the vibration performance of coupled curved-curved beams that feature a linear elastic mid-layer, achieved through the incorporation of carbon nanotubes (CNTs), graphene nanoplates (GNPs), and graphene oxide powder (GOPs). The governing equations of the system are solved using the generalized differential quadrature (GDQ) method. While previous research primarily focused on the use of CNTs to enhance the vibration behavior of coupled-curved beams, this study delves into the utilization of multiple nanofillers for this purpose. An essential aspect of modeling composite materials lies in determining their equivalent mechanical properties. This research undertakes a comparison between the rule of mixture (RoM) and Halpin-Tsai methods for calculating these properties, revealing that frequencies derived from the RoM method are higher than those obtained through the Halpin-Tsai approach. Additionally, the study highlights that systems incorporating GNPs demonstrate higher frequencies at lower nanofiller volumes, with CNTs and GOPs following in ranking. However, this hierarchy shifts at higher nanofiller volumes. The arrangement of nanofillers within the system is influenced by its boundary conditions, with the curvature of the bottom beam playing a significant role in affecting vibration behavior. Increasing the radius of the bottom beam (R2) leads to higher system frequencies, which subsequently decrease with higher R2 values.

A Thiourea Derivative of 2-[(1R)-1-Aminoethyl]phenol as a Chiral Sensor for the Determination of the Absolute Configuration of N-3,5-Dinitrobenzoyl Derivatives of Amino Acids.

In the exploration of chiral solvating agents (CSAs) for nuclear magnetic resonance (NMR) spectroscopy designed for the chiral analysis of amino acid derivatives, notable advancements have been made with thiourea-CSAs. 1-TU, derived from 2-[(1R)-1-aminoethyl]phenol and benzoyl isothiocyanate, is effective in the enantiodifferentiation of N-3,5-dinitrobenzoyl (N-DNB) amino acids. In order to broaden the application of 1-TU for configurational assignment, enantiomerically enriched N-DNB amino acids were analyzed via NMR. A robust correlation was established between the relative position of specific 1H and 13C NMR resonances of the enantiomers in the presence of 1-TU. 1,4-Diazabicyclo[2.2.2]octane (DABCO) was selected for the complete solubilization of amino acid substrates. Notably, the para and ortho protons of the N-DNB moiety displayed higher frequency shifts for the (R)-enantiomers as opposed to the (S)-enantiomers. This trend was consistently observed in the 13C NMR spectra for quaternary carbons bonded to NO2 groups. Conversely, an inverse correlation was noted for quaternary carbon resonances of the carboxyl moiety, amide carbonyl, and methine carbon at the chiral center. This observed trend aligns with the interaction mechanism previously reported for the same chiral auxiliary. The configurational correlation can be effectively exploited under conditions of high dilution or, significantly, under sub-stoichiometric conditions.

Boosted antibacterial efficacy: Di and triorganotin complexes via 2-[(2,3-dimethylphenyl)amino]benzoic acid

Using appropriate organotin chloride salts and a ligand called 2-[(2,3-dimethylphenyl) amino] benzoic acid (DMPAB), a condensation procedure produced novel complexes such as triphenyltin, dimethyl, diphenyl, and dibutyl-tin. For difficult identification, a variety of analytical methods were used, including elemental analysis, carbon and proton magnetic resonance, and infrared spectra. The agar ditch method was used to assess the antibacterial effectiveness against Staphylococcus aureus and Escherichia coli. When compared to the molecule generated from the ligand, the complexes showed more inhibitory action. Among the complexes tested, the dimethyltin carboxylate complex showed the strongest antibacterial action against Staphylococcus aureus and Escherichia coli.
 KEY WORDS: Complexes, Antibacterial properties, Condensation process, Agar Ditch, Staphylococcus aureus and Escherichia coli
 Bull. Chem. Soc. Ethiop. 2024, 38(3), 647-655. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i3.8

Structurally diverse analgesic diterpenoids from the flowers of Rhododendron molle

Thirteen diterpenoids (1–13), classified into four structurally diverse carbon skeletons, including 1,5-seco-kalmane (1 and 6), grayanane (2–11), kalmane (12), and rhodomollane (13), were isolated from the flowers extract of Rhododendron molle. Among them, rhodomollinols A − E (1–5) were five new diterpenoids and their structures were elucidated by extensive spectroscopic methods including HRESIMS, UV, IR, 1D and 2D NMR, as well as quantum ECD calculations. Rhodomollinol A (1) is the first representative of a 6-deoxy-1,5-seco-kalmane diterpenoid. The abnormal NMR phenomenon of the presence of only 9 carbon resonances instead of 20 carbons in the 13C NMR spectrum of 1 was observed and elucidated by the quantum NMR calculations. All diterpenoids 1–13 showed significant analgesic activities in an acetic acid-induced writhing model. It's the first time to report the analgesic activity of a rhodomollane-type diterpenoid. At a dose of 1.0 mg/kg, diterpenoids 1–3, 6, 8, 9, and 12 reduced the writhe numbers with inhibition rates over 50%, and 9 exhibited stronger analgesic activity with a writhe inhibition rate of 89.7% than that of the positive control morphine. Importantly, even at the lowest dose of 0.04 mg/kg, rhodomollinols A (1) and B (2), rhodomollein X (7), and 2-O-methylrhodojaponin VI (9) still showed more potent analgesic effects than morphine with the writhe inhibition rates of 51.8%, 48.0%, 61.7%, and 60.0%, respectively. A preliminary structure-activity relationship might provide some clues to design potential analgesics on the basis of structurally diverse Ericaceae diterpenoids.

Vortex-assisted microextraction of melamine from milk samples using green short chain ionic liquid solvents coupled with high performance liquid chromatography determination

Melamine is added illegally to milk and dairy products to increase the amount of apparent protein. This organic nitrogen rich chemical compound has been of great challenge in food safety based on its adverse effect on health. Therefore, the extraction and determination of melamine from milk is necessary. Recently, ionic liquid (ILs) as solvent usage has been noticeable for low melting point, low toxicity, high thermal stability, and high extraction capabilities in a wide range of separation processes. ILs are introduced as organic–inorganic salts and green solvents in microextraction preparation. Therefore, in this study, three ionic liquids ([C6mim][NTF2], [C4mim][NTF2] and [C2mim][NTF2] ILs) were prepared and employed as an extraction solvent in dispersive liquid–liquid microextraction (DLLME) of melamine from milk samples followed by HPLC-UV. The selected ILs were designed using three types of alkyl-imidazolium (as the short organic cations) and bis (tri fluoro methyl sulfonyl) imide as anion and characterized by ATR-FTIR spectra, carbon, and hydrogen Nuclear Magnetic Resonance spectroscopy (H&C-NMR) and energy-dispersive X-ray spectroscopy (EDX). These techniques confirmed the formation of functional groups, the structure of hydrogen and carbon atoms, and various elements of ionic bond between imidazolium and bis (tri fluoro methyl sulfonyl) imide. In the next step, the effect of significant parameters, including type and volume of ILs, adsorption time, pH of the sample solution, and sample volume, were optimized. Under the optimal conditions, the limits of detection (LOD), limits of quantification (LOQ), and linearity range were obtained 63.64 µg kg−1, 210.03 µg kg−1, and 210.03–1000 µg kg−1, respectively, for as prepared [C6mim][NTF2] as the best ILs. Notably, the achieved LOQ was lower than the maximum residue level (MRL) for the melamine residue in dairy products. Eventually, the proposed method was applied to detect melamine in milk samples, and the relative recoveries were examined as 79.6–105.0 %.

Design, Synthesis, Molecular Docking, ADMET, and Biological Studies of Some Novel 1,2,3-Triazole Linked Tetrazoles as Anticancer Agents.

1,2,3-Triazole-tetrazoles have received substantial attention because of their unique bioisosteric properties and an extraordinarily broad spectrum of biological activity, making them interesting for the drug design, and synthesis of a delightful class of widely investigated heterocyclic compounds. To address major health concerns, it is consequently important to devote ongoing effort to the identification and development of New Chemical Entities (NCEs) as possible anticancer medicines. We began our initial investigation of the reaction between 5-(azidomethyl)-1H-pyrrolo[ 2,3-b]pyridine and 1-phenyl substituted-5-(prop-2-yn-1-ylthio)-1 H-tetrazole under click chemistry to give the corresponding triazole precursors and screened for their cytotoxicity reported by variations in therapeutic actions of the parent molecule. All of the prepared scaffolds were characterized by proton, carbon resonance spectroscopy, IR, and mass spectral techniques. When tested for in vitro antitumor activity the prepared compounds 7e, 7h had a significant anticancer activity against human adenocarcinoma Hs766T cell line with IC50 = 5.33, 4.92 μg/mL and Hs460 cell line with IC50 = 4.82, 6.15 μg/mL respectively. Final scaffolds 7f, 7h, and 7j acquire the highest potential drug binding scores ΔG = -10.42, -8.80, -9.37 Kcal/, with amino acids residues Ala A:11 (2.195 A˚), Asp A:119 (1.991 A˚), Thr A:58 (1.890 A˚), Lys A:16 (1.253 A˚), Asp A:38 (2.013 A˚), Lys A:117 (2.046 A˚) respectively and process Lipinski's rule of five as good agents for oral bioavailability. The molecular framework for the synthesis of novel Aza indole 1,2,3-triazole scaffolds coupled to tetrazole core was discovered in our study and evaluated for their anticancer activity.

Key factors controlling oil contents in different lithofacies shales from the Funing Formation, Subei Basin: Evidence from scanning electron microscopy

Lacustrine shales with complex mineral compositions and rock formations are associated with different lithofacies, and shale oil contents vary significantly depending on the lithofacies. This study examines lacustrine shales from the Funing Formation, Gaoyou Sag, Subei Basin using scanning electron microscopy, total organic carbon (TOC), Rock-Eval pyrolysis, X-ray diffraction, thin section, and nuclear magnetic resonance T1–T2 to determine the key factors controlling oil content in different shale lithofacies. Shale lithofacies were determined based on the mineral composition, rock structure, and organic matter content. The micro-distributions of shale oil in different lithofacies were disclosed. The results show that the studied shales in Gaoyou Sag are primarily divided into massive felsic-rich, stratified felsic-rich, laminated felsic-rich, laminated felsic, laminated calcareous-rich, and laminated calcareous shales. Massive felsic-rich shales have the largest TOC, S1, and free oil contents associated with organic-rich shales. Stratified felsic-rich shales have the larger TOC, S1, and free oil contents, followed by the laminated felsic-rich and felsic shales. However, laminated calcareous-rich shales are characterized by larger TOC but lower S1 and free oil contents, whereas laminated calcareous shales have the lowest organic matter and oil contents. Shale oil content is mainly affected by the organic matter content and the development of reservoir space. Massive felsic-rich shales are characterized by almost all pores saturated with oil. The oil contents in stratified felsic-rich, laminated felsic-rich, laminated felsic, and laminated calcareous-rich shales are primarily affected by the development of reservoir spaces, followed by organic matter abundance. However, laminated calcareous shales are the opposite. Interparticle pores at the edge of granules are the most developed pores, whereas interparticle pores associated with quartz are generally saturated with oil, followed by those related to calcite or dolomite. Intraparticle pores in clay minerals are usually free of oil. Moreover, shale oil primarily occurs in large interparticle pores. The organic-rich massive felsic-rich and organic-bearing laminated felsic-rich shales are favorable for shale oil enrichment, and organic-bearing laminated felsic-rich shales with larger pores and interlayer micro-fractures may be the optimal lithofacies for shale oil. This study provides insight into the micro-distribution of shale oil in different lithofacies, which will guide shale oil development in the Gaoyou Sag, Subei Basin.

1H, 13C and 15N backbone and sidechain assignment of the Burkholderia mallei acyl carrier protein.

Acyl carrier proteins (ACPs) are universally conserved proteins amongst different species and are involved in fatty acid synthesis. Bacteria utilize ACPs as acyl carriers and donors for the synthesis of products such as endotoxins or acyl homoserine lactones (AHLs), which are used in quorum sensing mechanisms. In this study, wehave expressed isotopically labeled holo-ACP from Burkholderia mallei in Escherichia coli to assign 100% of non-proline backbone amide (HN) resonances, 95.5% of aliphatic carbon resonances and 98.6% of aliphatic hydrogen sidechain resonances.

Application of Band-Selective HSQC NMR in Species Discrimination and Adulteration Identification of Panax Linn.

The quality of Panax Linn products available in the market is threatened by adulteration with different Panax species, such as Panax quinquefolium (PQ), Panax ginseng (PG), and Panax notoginseng (PN). In this paper, we established a 2D band-selective heteronuclear single quantum coherence (bs-HSQC) NMR method to discriminate species and detect adulteration of Panax Linn. The method involves selective excitation of the anomeric carbon resonance region of saponins and non-uniform sampling (NUS) to obtain high-resolution spectra in less than 10 min. The combined strategy overcomes the signal overlap limitation in 1H NMR and the long acquisition time in traditional HSQC. The present results showed that twelve well-separated resonance peaks can be assigned in the bs-HSQC spectra, which are of high resolution, good repeatability, and precision. Notably, the identification accuracy of species was found to be 100% for all tests conducted in the present study. Furthermore, in combination with multivariate statistical methods, the proposed method can effectively determine the composition proportion of adulterants (from 10% to 90%). Based on the PLS-DA models, the identification accuracy was greater than 80% when composition proportion of adulterants was 10%. Thus, the proposed method may provide a fast, practical, and effective analysis technique for food quality control or authenticity identification.

“On Water” Effect for Green Click Reaction: Spontaneous Polymerization of Activated Alkyne with “Inert” Aromatic Amine in Aqueous Media

“On Water” Effect for Green Click Reaction: Spontaneous Polymerization of Activated Alkyne with “Inert” Aromatic Amine in Aqueous Media

Exploration of Cytotoxic Potential of Longifolene/Junipene Isolated from Chrysopogon zizanioides

Since ancient times, Chrysopogon zizanioides has been utilized as a traditional medicinal plant for the treatment of numerous ailments, but neither its plant extract form nor its phytoconstituents have been fully explored. With this in mind, the present research was designed to isolate and structurally characterize one of its chemical constituents and evaluate its cytotoxic potential. Therefore, an ethanolic extract of roots was prepared and subjected to column chromatography using solvents of varying polarities. The obtained pure compound was characterized using various chromatographic and spectroscopic techniques such as high-performance liquid chromatography (HPLC), carbon and proton nuclear magnetic resonance (NMR), and liquid chromatography–mass spectroscopy (LC-MS) and identified as longifolene. This compound was evaluated for its cytotoxic potential using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on the prostate (DU-145), oral (SCC-29B) cancer cell line and normal kidney cell line (Vero cells), taking doxorubicin as a standard drug. The obtained outcomes revealed that longifolene possesses cytotoxic potential against both prostate (IC50 = 78.64 µg/mL) as well as oral (IC50 = 88.92 µg/mL) cancer cell lines with the least toxicity in healthy Vero cells (IC50 = 246.3 µg/mL) when compared to doxorubicin. Hence, this primary exploratory study of longifolene exhibited its cytotoxic potency along with wide safety margins in healthy cell lines, giving an idea that the compounds possess some ability to differentiate between cancerous cells and healthy cells.

Zinc-dithiocarbimates for the control of Hemileia vastatrix: a versatile alternative.

The purpose of this work was to investigate the potential use of zinc-dithiocarbimate salts to control Hemileia vastatrix, the causal agent of the coffee leaf rust disease, and to evaluate their toxicity towards Apis mellifera, one of the most important coffee plant pollinators. Zinc-dithiocarbimate salts were prepared and fully characterized by infrared, proton (1 H) and carbon-13 (13 C) nuclear magnetic resonance and elemental analyses of carbon (C), hydrogen (H), nitrogen (N) and zinc (Zn). X-ray diffraction technique studies confirmed the proposed structures. The salts inhibited the germination of H. vastatrix spores in vitro, with a 50% inhibitory concentration (IC50 ) from 12 to 18 μmol.L-1 and a 90% inhibitory concentration (IC90 ) from 23 to 26 μmol.L-1 . Zinc-dithiocarbimate salts with the best in vitro results were selected for in vivo experiments with Coffea arabica var Caturra and with the pollinator A. mellifera. The results were similar to those of Mancozeb, a broad-spectrum contact fungicide, with a good control of the disease and low toxicity to the honeybee. The zinc-dithiocarbimate complex salts have potential to control coffee leaf rust, with low toxicity to the pollinator insect. © 2022 Society of Chemical Industry.

Binding methane to a metal centre.

The σ-alkane complexes of transition metals, which contain an essentially intact alkane molecule weakly bound to the metal, have been well established as crucial intermediates in the activation of the strong C-H σ-bonds found in alkanes. Methane, the simplest alkane, binds even more weakly than larger alkanes. Here we report an example of a long-lived methane complex formed by directly binding methane as an incoming ligand to a reactive organometallic complex. Photo-ejection of carbon monoxide from a cationic osmium-carbonyl complex dissolved in an inert hydrofluorocarbon solvent saturated with methane at -90 °C affords an osmium(II) complex, [η5-CpOs(CO)2(CH4)]+, containing methane bound to the metal centre. Nuclear magnetic resonance (NMR) spectroscopy confirms the identity of the σ-methane complex and shows that the four protons of the metal-bound methane are in rapid exchange with each other. The methane ligand has a characteristically shielded 1H NMR resonance (δ -2.16), and the highly shielded carbon resonance (δ -56.3) shows coupling to the four attached protons (1JC-H = 127 Hz). The methane complex has an effective half-life of about 13 hours at -90 °C.

Synthesis of novel aminoquinolines with potential leishmanicidal and antimalarial biological activity / Síntese de novas aminoquinolinas com potencial actividade biológica leishmanicida e antimalárica

Leishmaniasis is a disease transmitted by different parasite species of the genus Leishmania, while malaria, by protozoa of the genus Plasmodium sp. These diseases affect tropical and subtropical regions, where about half of the world's population live. However, leishmaniasis and malaria are considered neglected diseases because these regions are poor, and consequently have precarious essential sanitation networks. In response to the lack of vaccines and effective medical measures, some natural and synthetic medicines are used as forms of treatment, such as quinoline derivatives necessary to treat malaria. Even so, the parasites have shown resistance to forms of treatment, which makes needed the constant development of new drugs with potential against them. Quinoline derivatives, chloroquine analogues, have potential activity for the diseases of interest, while anilines are molecules used in nucleophilic reactions on different substrates. Therefore, the work consisted of exploring the synthesis between these two compounds through subsequent reactions involving the formation of intermediates that resulted in the products of interest. Twelve novel derivatives with potential leishmanicidal and antimalarial biological activity were synthesized. The molecules produced were purified and rightly characterized by several methods, such as mass spectrometry, infrared spectroscopy, and Nuclear Magnetic Resonance of Carbon (13C) and Hydrogen (1H). Also, were obtained the melting points of the synthesized molecules. Finally, all products were sent for biological tests against the parasites, getting highly effective results for the protozoa responsible for leishmaniasis.

Experimentally probing the chiral recognition mechanism of 1,1′-bi-2-naphthol on a nitrogen enriched chiral metal-organic framework

In this article, a micropore CMOF structure with abundant nitrogen species, D-His-ZIF-L (DHZL), was synthesized in water according to the reference with a modification. The performance of DHZL was verified by enantioselective capture of S-1,1′-bi-2-naphthol (S-BINOL), with an enantiomeric excess (ee) value of 60.5% under optimal conditions. To experimentally elucidate the chiral recognition mechanism, the chemical shifts of carbon and nitrogen signals were investigated on the basis of CP MAS NMR spectroscopy by using DHZL (200 mg) with R/S-BINOL of 750 μg mL−1 in CH3CN at room temperature, in which DHZL acts as the chiral shift reagent. The peaks corresponding to the chiral carbon and one imidazole ring carbon resonances in the D-histidine moiety of DHZL exhibit obvious upfield and downfield shifts in the presence of S-BINOL, respectively, indicating that the the strong hydrogen bonding and π-π interactions existed. Clear nitrogen splitting further indicates the hydrogen-bond interaction site between the hydroxyl of the optical S-isomer and the amino of D-histidine in the chiral framework. In addition, the positive shift in the N 1 s peak of DHZL by X-ray photoelectron spectroscopy (XPS) analysis was also proved the described observations when loaded with S-BINOL in contrast with R-one. Furthermore, a control experiment was performed to identify the essential features of the chiral microenvironment in DHZL. Based on these results above, the chiral recognition mechanism was experimentally determined.

Elucidation of substituent distribution states for carboxymethyl chitosan by detailed NMR analysis

A series of carboxymethyl chitosan (CMCh) samples with a wide degree of substitution (0.65–2.03) was prepared by multi-step carboxymethylation of chitosan using a 2-propanol/aqueous sodium hydroxide solution mixture as the solvent and monochloroacetic acid as the etherification reagent. Two-dimensional NMR correlation maps of the direct and long-range coupled 1H and 13C spin pairs of the CMCh samples allowed complete assignment of the 1H and 13C chemical shifts of eight anhydroglucosamine units (AGUs) comprising CMCh chains, namely un-, 2-mono-, 3-mono-, 6-mono-, 2,3-di-, 2,6-di-, 3,6-di-, and 2,3,6-tri-substituted AGUs. Line-shape analysis of the anomeric carbon resonance in the quantitative 13C NMR spectra determined the mole fractions of these AGUs. Plots of the mole fractions against the change in the degree of substitution clarified the detailed substitution state at the 2-amino and 3-/6‑hydroxyl groups of chitosan and the transition of the monomer fractions during the change from the unsubstituted to the fully substituted state. Therefore, the method estimating the mole fractions of the eight AGUs in CMCh is expected to be an effective and powerful tool for elucidating functionalities from a structural perspective.

A hepatic sinusoids-based microtube reactor for (Z)-5-(4-hydroxybenzylidene)thiazolidine-2,4-dione intermediate drug synthesis

Microreactor technology is considered a breakthrough technology that can replace regular reactors systems as microreactors deliver proper mixing and reaction performance which satisfy both industry and research demands. This drives researchers to develop several microreactor systems with improved characteristics for plenty of applications, including medicine and pharmaceutical applications. In the present study, a microtube reactor system is constructed to produce (Z)-5-(4-hydroxybenzylidene)thiazolidine-2,4-dione intermediate drug with a hepatic sinusoids-based micromixer used as the part responsible of mixing the reactants in early stages. (Z)-5-(4-hydroxybenzylidene)thiazolidine-2,4-dione is an intermediate drug that belongs to glitazones. A batch reactor system is also constructed for the purpose of comparison. Thiazolidine-2,4-dione (TZD) and p-hydroxybenzaldehyde are used as the main reactants while two compounds are used as catalysts; diethylamine and piperdine. Effects of different parameters such as initial reactants concentration, catalyst concentration, and flow rate and residence time on the product yield and the pressure drop across the micromixer are investigated. Analysis of the collected samples is done using different characterization methods such as High Pressure Liquid Chromatography, Thermogravimetric/Differential Thermal Analysis, X-ray diffraction spectroscopy, Fourier Transform Infrared spectroscopy, and carbon and proton Nuclear magnetic resonance spectra. The microtube reactor system has proven to be more efficient than the batch system. The maximum yield obtained from the microtube reactor system is 97% with a residence time of only 22 min using diethylamine as a catalyst compared with 92% obtained from the batch system using piperdine as a catalyst after 12 hr run. The yield obtained from the microtube reactor system spans from 77% to 97% using diethylamine as a catalyst and from 56% to 84% using piperdine as a catalyst while the pressure drop across the micromixer ranges from 0.9 to 12 kPa.

Densities, heat capacities, viscosities, 1H- and 13C-NMR spectra, and solvatochromic parameters of binary mixtures of 1,3-dimethyl-1,3-diazinan-2-one (DMPU) and water

The compound 1,3-dimethyl-1,3-diazinan-2-one (N,N’-dimethylpropyleneurea, DMPU) is a dipolar aprotic solvent with very strong electron-donating abilities but which is much less toxic and less carcinogenic than similar solvents such as the widely used HMPA (hexamethylphosphorictriamide). This paper reports densities and viscosities of the binary mixtures of (DMPU + water) in the temperature range (293.15 to 353.15) K at 5 K intervals, over the whole composition range. Isobaric heat capacities of these mixtures were measured by flow calorimetry at 298.15 K. The 1H- and 13C-NMR spectra as well as the solvatochromic parameters (polarizability, π*, hydrogen-bond acceptor basicity, β, and hydrogen-bond donor acidity, α) of the mixtures were also determined. The densities and viscosities were sensitive to traces of water in the organic-rich region while the heat capacities were not. Excess molar volumes were strongly negative, showing an extremum at mole fraction xDMPU ≈ 0.40. The variation of viscosity with mixture composition was similar to the density with a sharp maximum at xDMPU ≈ 0.35. Apparent molar volumes, Vϕ, of the mixtures show that the water-DMPU interactions have a larger effect on Vϕ of water than on DMPU. While the standard isobaric molar heat capacity of DMPU in water is much higher than that of DMPU itself, the corresponding value for water in DMPU was not much influenced by the presence of DMPU. The 1H-NMR spectra show that the chemical shift of the water protons is more influenced by mixture composition than those of the DMPU protons. A de-shielding of the DMPU carbonyl carbon resonance was observed in the 13C-NMR spectra at low xDMPU, indicative of H-bonding between the water protons and the non-bonding electrons of the carbonyl oxygen.