Formation of dioxospiroindene[1,3]thiazine and thioxoindeno[2,1-<Emphasis Type="Italic">d</Emphasis>]imidazolone derivatives from alkenylidene-hydrazinecarbothioamides

The reaction of (substituted) alkenylidene-hydrazinecarbothioamides with 2-(1,3-dioxo-2,3-dihydro-1H-inden-2-ylidene)propanedinitrile led to the formation of 1,3-dioxospiroindene[1,3]-thiazine and thioxoindeno[2,1-d]imidazolone derivatives in modest yields. In addition, 1,3-dihydroxyindan-2-ylidenepropanedinitrile was found. Explanations of these conversions involving nucleophilic reactions and condensations are presented.     

Quantitative determination of oxybutynin hydrochloride by spectrophotometry, chemometry and HPTLC in presence of its degradation product and additives in different pharmaceutical dosage forms

Simple, accurate, sensitive and validated UV spectrophotometric, chemometric and HPTLC-densitometric methods were developed for determination of oxybutynin hydrochloride (OX) in presence of its degradation product and additives in its pharmaceutical formulations. Method A is the first derivative of ratio spectra (DD¹) which allows the determination of OX in presence of its degradate in pure form and tablets by measuring the peaks amplitude at 216 nm. Method B and C are principal component regression (PCR) and partial least-squares (PLS) for determination of OX in presence of its degradate in pure form, tablets and syrup. While, the developed high performance thin layer chromatography HPTLC-densitometric method was based on the separation of OX from its degradation product, methylparaben and propylparaben followed by densitometric measurement at 220 nm which allows the determination of OX in pure form, tablets and syrup. The separation was achieved using HPTLC silica gel F₂₅₄ plates and chloroform:methanol:ammonia solution:triethylamine (100:3:0.5:0.2, v/v/v/v) as the developing system. The accuracy, precision and linearity ranges of the developed methods were determined. The results obtained were statistically compared with each other and to that of a reported HPLC method, and there was no significant difference between the proposed methods and the reported method regarding both accuracy and precision.     

Synthesis and thermal characterization of new ternary chelates of piroxicam and tenoxicam with glycine and DL-phenylalanine and some transition metals

The ternary chelates of piroxicam (Pir) and tenoxicam (Ten) with Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) in the presence of various amino acids such as glycine (Gly) or dl-phenylalanine (PhA) were prepared and characterized with different physicochemical methods. IR spectra confirm that Pir and Ten behave as a neutral bidentate ligand coordinated to the metal ions via the pyridine-N and carbonyl group of the amide moiety. Gly molecule acted as a uninegatively monodentate ligand and coordinate to the metal ions through its deprotonated carboxylic group. In addition, PhA acted as a uninegatively bidentate ligand and coordinate to the metal ions through its deprotonated carboxylic and amino groups. The solid reflectance spectra and magnetic moment measurements confirm that all the chelates have octahedral geometrical structures while Cu(II)- and Zn(II)-ternary chelates with PhA have square planar geometrical structures. Thermal behaviour of the complexes is extensively studied using TG and DTA techniques. TG results show that water molecules (hydrated and coordinated) and anions are removed in the first and second steps while Gly, PhA, Pir and Ten are decomposed in the next and subsequent steps. The pyrolyses of the chelates into different gases are observed in the DTA curves as exo- or endothermic peaks. Also, phase transition states are observed in some chelates. Different thermodynamic parameters are calculated using Coats-Redfern method and the results are interpreted.     

Enhancing gas adsorption and separation capacity through ligand functionalization of microporous metal-organic framework structures

Hydroxyl- and amino- functionalized [Zn(BDC)(TED)(0.5)]·2DMF·0.2H(2)O leads to two new structures, [Zn(BDC-OH)(TED)(0.5)]·1.5DMF·0.3H(2)O and [Zn(BDC-NH(2))(TED)(0.5)]·xDMF·yH(2)O (BDC=terephthalic acid, TED=triethylenediamine, BDC-OH=2-hydroxylterephthalic acid, BDC-NH(2)=2-aminoterephthalic acid). Single-crystal X-ray diffraction and powder X-ray diffraction studies confirmed that the structures of both functionalized compounds are very similar to that of their parent structure. Compound [Zn(BDC)(TED)(0.5)]·2DMF·0.2H(2)O can be considered a 3D porous structure with three interlacing 1D channels, whereas both [Zn(BDC-OH)(TED)(0.5)]·1.5DMF·0.3H(2)O and [Zn(BDC-NH(2))(TED)(0.5)]·xDMF·yH(2)O contain only 1D open channels as a result of functionalization of the BDC ligand by the OH and NH(2) groups. A notable decrease in surface area and pore size is thus observed in both compounds. Consequently, [Zn(BDC)(TED)(0.5)]·2DMF·0.2H(2)O takes up the highest amount of H(2) at low temperatures. Interestingly, however, both [Zn(BDC-OH)(TED)(0.5)]·1.5DMF·0.3H(2)O and [Zn(BDC-NH(2))(TED)(0.5)]·xDMF·yH(2)O show significant enhancement in CO(2) uptake at room temperature, suggesting that the strong interactions between CO(2) and the functionalized ligands, indicating that surface chemistry, rather than porosity, plays a more important role in CO(2) adsorption. A comparison of single-component CO(2), CH(4), CO, N(2), and O(2) adsorption isotherms demonstrates that the adsorption selectivity of CO(2) over other small gases is considerably enhanced through functionalization of the frameworks. Infrared absorption spectroscopic measurements and theoretical calculations are also carried out to assess the effect of functional groups on CO(2) and H(2) adsorption potentials.     

Template-assisted hydrogelation of a dynamic covalent polyviologen-based supramolecular architecture via donor-acceptor interactions

A novel polyviologen-based molecular architecture was developed via the step-growth polymerization of a hydroxyl-substituted aryl dihydrazide with a water soluble viologen-dialdehyde in water under acidic conditions. When polymerized in the presence of π-electron rich aromatic templates, the reaction mixture underwent hydrogelation. The templates were found to facilitate monomer-monomer as well as monomer-polymer preorganization during polymerization via donor-acceptor charge transfer interactions. Following polymerization, the templates effectively served as post-synthetic non-covalent cross linkers connecting the hydrogel network. The chemical structures of the polymers and molecular recognition between the reacting species were investigated in solution using ¹H NMR, while donor-acceptor charge transfer interactions were investigated using UV-vis absorption spectroscopy. We also report the hydrochromic behavior of the templated and non-templated polymers. The surface morphology of the polymers was characterized using scanning electron microscopy, which revealed the formation of sheet-like structures. The new hydrogels developed in this work represents an interesting example of materials comprised of reversible dynamic covalent bonds and reversible non-covalent crosslinking interactions occurring between the electron-rich aryl templates and the electron-deficient bipyridinium units.     

Copper(ii) ketimides in sp3 C–H amination

Commercially available benzophenone imine (HN CPh₂) reacts with β-diketiminato copper(ii) tert-butoxide complexes [Cu^II]–O^tBu to form isolable copper(ii) ketimides [Cu^II]–N CPh₂. Structural characterization of the three coordinate copper(ii) ketimide [Me₃NN]Cu–N CPh₂ reveals a short Cu-N_ketimide distance (1.700(2) Å) with a nearly linear Cu–N–C linkage (178.9(2)°). Copper(ii) ketimides [Cu^II]–N CPh₂ readily capture alkyl radicals R˙ (PhCH(˙)Me and Cy˙) to form the corresponding R–N CPh₂ products in a process that competes with N–N coupling of copper(ii) ketimides [Cu^II]–N CPh₂ to form the azine Ph₂C N–N CPh₂. Copper(ii) ketimides [Cu^II]–N CAr₂ serve as intermediates in catalytic sp³ C–H amination of substrates R–H with ketimines HN CAr₂ and ^tBuOO^tBu as oxidant to form N-alkyl ketimines R–N CAr₂. This protocol enables the use of unactivated sp³ C–H bonds to give R–N CAr₂ products easily converted to primary amines R–NH₂via simple acidic deprotection.

Commercially available benzophenone imine (HN CPh₂) reacts with β-diketiminato copper(ii) tert-butoxide complexes [Cu^II]–O^tBu to form isolable copper(ii) ketimides [Cu^II]–N CPh₂ that serve as intermediates in catalytic sp³ C−H amination via radical relay.     

Identification of a Sesquiterpene Lactone from Arctium lappa Leaves with Antioxidant Activity in Primary Human Muscle Cells

Many pathologies affecting muscles (muscular dystrophies, sarcopenia, cachexia, renal insufficiency, obesity, diabetes type 2, etc.) are now clearly linked to mechanisms involving oxidative stress. In this context, there is a growing interest in exploring plants to find new natural antioxidants to prevent the appearance and the development of these muscle disorders. In this study, we investigated the antioxidant properties of Arctium lappa leaves in a model of primary human muscle cells exposed to H₂O₂ oxidative stress. We identified using bioassay-guided purification, onopordopicrin, a sesquiterpene lactone as the main molecule responsible for the antioxidant activity of A. lappa leaf extract. According to our findings, onopordopicrin inhibited the H₂O₂-mediated loss of muscle cell viability, by limiting the production of free radicals and abolishing DNA cellular damages. Moreover, we showed that onopordopicrin promoted the expression of the nuclear factor-erythroid-2-related factor 2 (Nrf2) downstream target protein heme oxygenase-1 (HO-1) in muscle cells. By using siRNA, we demonstrated that the inhibition of the expression of Nrf2 reduced the protective effect of onopordopicrin, indicating that the activation of the Nrf2/HO-1 signaling pathway mediates the antioxidant effect of onopordopicrin in primary human muscle cells. Therefore, our results suggest that onopordopicrin may be a potential therapeutic molecule to fight against oxidative stress in pathological specific muscle disorders.     

Novel Spectrophotometric Method for Determination of Macro-paracetamol via Reaction with Bromine

The reaction between Br2 and paracetamol(p-AAP) leads to the formation of a coloured product, which can be used for spectrophotometric determination of the p-AAP content in its pure form and in different pharmaceutical preparations with p-AAP. The stoichiometric composition of the reaction was found to be n(p-AAP)∶n(bromine)=1∶3. The effects of pH and time on the spectra of p-AAP-bromine redox reaction product were studied. The interference of different additives on the measured spectra of the obtained product was also studied. The results obtained by the present method were compared with those obtained by the standard method. The F- and t- test values were calculated for both of the applied procedures and they met a confidence level of 99%. The proposed procedure actually needs no separation of these drugs from their sources before analysis and was unaffected by interference of other phenolic compounds. The proposed method is simpler and faster than the repoeted ones.