Synthesis and evaluation of new phosphonated δ-lactam and glutarimide derivatives as angiotensin converting enzyme inhibitors

An efficient synthesis of new γ,δ-insaturated δ-lactam and glutarimide derivatives bearing a phosphonomethyl group from a common allylphosphonate precursor is described. Our approach is based on a two-step procedure involving the preparation of phosphonated-1,5-ketoester and −1,5-diester followed by an amidation–heterocyclization sequence. The first step proceeds via Michael's addition of ethyl acetoacetate and diethyl malonate on an allylphosphonate starting material. The second step consists of a base-promoted intramolecular amidation-cyclization sequence with primary amines, which accounts for the construction of δ-lactams and glutarimide skeletons. We performed the evaluation of angiotensin I-converting enzyme (ACE) inhibition using an in vitro enzyme assay on six new compounds. Five compounds showed potent ACE inhibitory activity, with IC₅₀ values ranging from 0.02 to 0.27 mg/ml. Compared with Captopril, used as a reference drug, two new glutarimide derivatives exhibited higher efficiency ACE inhibition activity.     

The Ambident Reactivity of 2,4,6‐Tris(trifluoromethanesulfonyl)anisole in Methanol: Using the SO2CF3 Group as a Tool to Reach the Superelectrophilic Dimension in σ‐Complexation Processes

The kinetics of σ complexation of 2,4,6‐tris(trifluoromethanesulfonyl)anisole ( 7 d ) have been investigated over a large pH range of 2–13.70 at T=20 °C in methanol. Two competitive processes associated with the initial addition of MeO^? at the unsubstituted 3‐position of 7 d to give a 1,3‐dimethoxy adduct ( 9 d ‐Me) and a subsequent and slow conversion of this species into a 1,1‐dimethoxy isomer ( 8 d ‐Me) have been identified. Both adducts 8 d ‐Me and 9 d ‐Me are 10⁵–10⁶ times more stable than the related adducts 8 a ‐Me and 9 a ‐Me of 2,4,6‐trinitroanisole ( 7 a ), a conventional reference aromatic electrophile in Meisenheimer complex chemistry. The high stability of 8 d ‐Me and 9 d ‐Me is shown to derive from greater rates of formation and lower rates of decomposition than previously determined for 8 a ‐Me and 9 a ‐Me, thereby emphasising the especially high activation of a benzene ring by SO₂CF₃ group(s). Analysis of the collected rate and equilibrium data for σ complexation in the anisole series 2,4,6‐tris(SO₂CF₃)‐, 2,6‐bis(SO₂CF₃)‐4‐nitro‐, 4‐SO₂CF₃‐2,6‐dinitro‐ and 2,4,6‐trinitro‐ supports the idea that the especially high capacity of resonance stabilisation of the negative charge of the adducts through an F_π‐type (as defined in ref. 49 ) polarisation effect is a major factor that accounts for the strong activation provided by SO₂CF₃ groups. A most significant result is the finding that the 1,1‐dimethoxy adduct 8 d ‐Me is by far the most stable benzene σ adduct so far reported. With a p value of 7.32, this adduct is formed exclusively through methanol addition up to pH≈10. This is consistent with the location of 7 d in the superelectrophilic region defined by p ≤9.5–10.5. For comparison, the solvent contribution is negligible in the formation of the 1,3‐isomer 9 d ‐Me, the p (10.59) of which is situated on the upper limit of the boundary. Taking advantage of the simple relationship linking pK_a values for σ complexation in methanol and water, a ranking of the triflone 7 d on the general thermodynamic scale constructed for Meisenheimer electrophiles in water is informative. An approximate calibration on the electrophilicity scale kinetically derived by Mayr et al. has also been made.     

KCo(H2O)2BP2O8·0.48H2O and K0.17Ca0.42Co(H2O)2BP2O8·H2O: two cobalt borophosphates with helical ribbons and disordered (K,Ca)/H2O schemes

The two title compounds, potassium diaquacobalt(II) borodiphosphate 0.48‐hydrate and potassium–calcium(0.172/0.418) diaquacobalt(II) borodiphosphate monohydrate, were synthesized hydrothermally. They are new members of the borophosphate family characterized by _∞[BP₂O₈]³⁻ helices running along [001] and constructed of boron (Wyckoff position 6b, twofold axis) and phosphorus tetrahedra. The [CoBP₂O₈]⁻ anionic frameworks in the two materials are structurally similar and result from a connection in the ab plane between the CoO₄(H₂O)₂ coordination octahedra (6b position) and the helical ribbons. Nevertheless, the two structures differ in the disorder schemes of the K,Ca and H₂O species. The alkali cations in the structure of the pure potassium compound are disordered over three independent positions, one of them located on a 6b site. Its framework is characterized by double occupation of the tunnels by water molecules located on twofold rotation axes (6b) and a fraction of alkali cations; its cell parameters, compared with those for the mixed K,Ca compound, show abnormal changes, presumably due to the disorder. For the K,Ca compound, the K and Ca cations are on twofold axes (6b) and the channels are occupied only by disordered solvent water molecules. This shows that it is possible, due to the flexibility of the helices, to replace the alkali and alkaline earth cations while retaining the crystal framework.     

Evaluation of antileishmanial, cytotoxic and antioxidant activities of essential oils extracted from plants issued from the leishmaniasis-endemic region of Sned (Tunisia)

In this study, we tested 10 essential oils (EOs) extracted from 10 plants issued from Sned region (Tunisia) to evaluate both their leishmanicidal effects against Leishmania major and L. infantum, and their cytotoxicity against murine macrophage cell line RAW 264.7 (ATCC, TIB-71). The antioxidant activity was also monitored by the DDPH method, while the chemical composition of active EO was assessed by GC-MS analysis. The results showed that the EOs obtained from Thymus hirtus sp. algeriensis (rich on monoterpenoids, especially linalool at 17.62% and camphor at 13.82%) is significantly active against both L. major and L. infantum, whereas Ruta chalepensis EO (rich on 2-undecanone at 84.28%) is only active against L. infantum. Both oil extracts showed low cytotoxicity towards murine macrophages. The characteristic ratios (IC?? Raw264.7 cells/IC?? L. infantum and IC?? Raw264.7 cells/IC?? L. major) were, respectively, 2.7 and 1.57 for T. hirtus sp. algeriensis, and 1.34 and 0.19 for R. chalepensis. However, when measuring the antioxidant effects (DDPH method), the two latter EOs presented a moderate 2,2-diphenyl-2-picrylhydrazyl hydrate scavenging effects compared to EOs from Eucaliptus globulus, Pinus halepensis, Pituranthos tortuosus, Rosmarinus officinalis, Tetraclinis articulata or to BHT.     

Application of phenolic compounds as natural dye extracted from date-pits: dyeing studies of modified acrylic fibres

This research work involves the dyeing of acrylic fabric with natural dye extracted from date pits powders using Soxhlet extraction process. The effect of dye bath pH, salt concentration, dyeing time and temperature were studied. The optimal dyeing conditions where pH 4, 0 g/L salt, 60 min, and 80 °C. The COD and the BOD5 of the residual dye bath were measured and it was shown from the registered values that the residual dye bath presents an acceptable rate of organic discharge.     

Forming architectured paper by printing a starch patterned grid: a new low-cost approach for lightweighting packaging

To meet the environmental challenges, the use of plastic packaging must be drastically reduced. Paper-based solutions may be a credible alternative provided that their production cost is reduced. One way may be to improve the paper stiffness to weight ratio. In this work, a simple and low-cost approach is proposed, which consists in printing a patterned grid of starch at the paper surface by using a widespread printing process. With only a small quantity of starch (7 g/m²), the bending stiffness of a packaging paper of 60 g/m² was multiplied by more than a factor three. This improvement originates from the permanent 3D shape the paper unexpectedly took after printing. The printed lines formed “valleys” whereas the unprinted zones were raised, forming “mountains”. Drying shrinkage of the starch is assumed to play a major role, in particular by inducing local buckling of the unprinted zones. In addition, the resulting 3D shape could be interestingly tuned by adjusting the grid pattern. Even if a better understanding is necessary to be able to well control the phenomena, this approach appears relevant to form “architectured” papers with improved bending resistance to weight ratio.

     

Application of anthocyanins as natural dye extracted from Brassica oleracea L. var. capitata f. rubra: dyeing studies of wool and silk fibres

Brassica oleracea L. var. capitata f. rubra (Red Cabbage) dye is composed mainly of natural pigment called anthocyanins used as a natural colourant. Wool and silk fibres were dyed with the aqueous extract obtained from red cabbage. The dyeing process was investigated and the combined effects of dyeing conditions on the colour yield parameter (K/S) were studied. Resulted fastness to wash, rubbing and light of the dyed fabrics were evaluated. Chemical Oxygen Demand (COD) and Biological Oxygen Demand (BOD₅₎ of the residual effluent were measured. Best dyeing conditions were found to be: 50 g/100 mL, pH 2, 60 min and 100 °C, respectively, for the red cabbage weight, pH, dyeing duration and temperature. Good fastnesses properties were found in both cases: for wool and silk fabrics. It was found also that the calculated biodegradability ratio (COD/BOD₅) of the residual bath of dyeing wool and silk with red cabbage extract are lower than 1.5 which means that these baths are biodegradable.     

New Synthetic Route for Reaching Higher Phase Stabilization in LAMOX-Based Electrolyte for Solid Oxide Fuel Cells

S-substituted La₂Mo₂O₉ were synthesized by a solid-state procedure employing ammonium sulfate (NH₄)₂SO₄ as a sulfur source. The synthesized powders were examined using X-ray diffraction (XRD), thermogravimetric analysis (TGA), infrared, and Raman spectroscopies. The results divulged that the stabilization of the β-La₂Mo₂O₉ polymorph occurred in the interval of sulfur composition 0.1≤y≤0.6. This substitution generates a linear dwindling of the unit cell volume. The decomposition of all substituted samples started above 900 °C with a total weight loss linearly dependent on the sulfur content. Electrical studies confirmed that substituting S⁶⁺ for Mo⁶⁺ suppresses the phase transition of La₂Mo₂O₉ and stabilizes the cubic polymorph down to ambient temperature. It was also remarkable that this substitution caused a decrease in the conductivity, and unfortunately, none of the tested compositions allowed exceeding the conductivity of La₂Mo₂O₉. Infrared and Raman spectra confirmed the presence of the characteristic peaks of sulfates and molybdates groups.     

Synthesis, crystal structure and charge distribution of Na7As11O31: An oxygen-deficient layered sodium arsenate

A new sodium arsenate with layer structure has been synthesized and its crystal structure solved and refined by single-crystal X-ray diffraction. The crystal is trigonal, space group , a=11.199(3) Å, c=5.411(2) Å, V=587.80(3) Å³, Z=1; the refinement converged to R=0.0282 and wR=0.0751 for 590 reflections with (I)>2sigma(I). The structural model gives the formula Na₇As₁₁O₃₂, which would be non-neutral; besides, the structural model is not validated by the charge distribution (CD) analysis, which gives an unsatisfactory agreement on the computed charges of the cations. The CD analysis suggest incomplete (5/6) occupation of the O5 site, which leads to the deficiency of an oxygen atom per unit cell and to formula Na₇As₁₁O₃₁: this new structural model corresponds to a neutral compound, is validated by the CD analysis, and results in better displacement parameters for O5 than its non neutral counterpart. The (001) anionic layers are built up from corner and edge sharing of As1 and As2 distorted octahedra and As3 distorted tetrahedra, the sodium cations playing the role of interlayer cations. The effects of the oxygen deficiency on the crystal structure are discussed.     

Synthesis,spectroscopic and structural studies of 2,2,2-trifluoroethyl phosphorodiamidate complexes with tin(IV) chloride

The two octahedral complexes SnCl₄ · 2(O)P(NR₂)₂OCH₂CF₃ (R = Me (1) or Et (2)) have been prepared from SnCl₄ and the ligands (R₂N)₂P(O)OCH₂CF₃ in chloroform solution. Both adducts have been characterised by (³¹P and ¹¹⁹Sn) NMR, IR spectroscopy and elemental analysis. The NMR data show that the complexes exist as mixtures of cis and trans isomers in solution with the latter isomer being the predominant species. The structure of 1 has been determined by X-ray crystallography. Accordingly, the structure is centrosymmetric and the two ligands are bound trans to each other in the octahedral tin complex. DFT/B3LYP calculations show that trans configuration does indeed lead to the lowest energy species. Comparison of the structural, NMR and theoretical data of both complexes with those related to SnCl₄ · 2L (L = (Me₂N)₃P(O) and (Me₂N)₂P(O)F) further supports the important effects of the nature of the substituents in the ligand on the stereochemistry of the complex formed.