Synthesis of aryl-substituted or aryl-fused N-hydroxyethyl and N-hydroxymethypyrazole derivatives as potential ligands for the estrogen receptor

A new series of N-hydroxyethylpyrazole (12a–f) and N-hydroxymethylpyrazole derivatives (15a–f) were designed for their estrogenic activities, having a 11.0 ± 0.5 Å distance between their two hydroxyl groups, aliphatic–OH and phenolic–OH similar to 17β-estradiol (E2) as an endogenous hormone. To synthesize the title compounds, the key intermediate 1,3-dicarbonyl derivatives (2 and 8), were treated with hydrazine hydrate to produce the pyrazole ring 5 and 9. Further hydroxyalkylation of the latter produced the title pyrazoles. The position of hydroxyethyl or hydroxymethyl substituents in the products was determined through 2D NOE NMR spectroscopy.     

Phytochemical Study of the Rhizome of Pinellia ternata and Quantification of Phenylpropanoids in Commercial Pinellia Tuber by RP-LC

Four phenylpropanoids, (E)-p-coumaryl alcohol (1), 3,4-dihydroxycinnamyl alcohol (2), sachaliside 1 (3), and coniferin (4) have been isolated from the rhizome of Pinellia ternata. Their structures were elucidated by spectroscopic methods. Compounds 1–3 were isolated from the genus Pinellia for the first time. Compound 4 was isolated from this plant for the first time. A rapid, sensitive, and accurate reversed-phase high-performance liquid chromatographic method with UV detection at 260 nm was established for simultaneous separation and determination of the four phenylpropanoids in nineteen batches of dried rhizomes of P. ternata. Compounds were separated on a 250 × 4.6 mm C₁₈ column with methanol–acetonitrile–water–phosphoric acid, 20:5:75:0.3, as mobile phase. The amounts of 1–4 in the rhizome of P. ternata could be easily determined within 30 min. The linear calibration ranges for 1–4 were 0.05–137.50, 0.66–1050.00, 0.06–30.00, and 0.05–67.50 μg mL^?1, respectively. Recovery of 1–4 was 97.43–103.73%, with RSD from 0.12 to 1.62%. Limits of quantification for 1–4 were 50, 660, 60, and 50 ng mL^?1, respectively. The method was successfully used for phytochemical analysis of phenylpropanoids from the rhizome of P. ternata.     

Synthesis and thermal behavior study of complexes of the type [Pd(μ-X)(4-eb-p-phen)]2 (X = Cl,Br, I,N3, NCO,SCN) and 4-eb-p-phen [bis(4-ethylbenzyl)p-phenylenediimine]

The Schiff base bis(4-ethylbenzyl) p-phenylenediimine, 4-eb-p-phen (1), and six new dimeric Pd(II) complexes of the type [Pd(μ-X)(4-eb-p-phen)]₂ {X = Cl (2), Br (3), I (4), N₃ (5), NCO (6), SCN (7)} have been synthesized and characterized by elemental analysis, IR spectroscopy, and ¹H and ¹³C{¹H}-NMR experiments. The thermal behavior of the complexes 2–7 has been investigated by means of thermogravimetry and differential thermal analysis. From the final decomposition temperatures, the thermal stability of the complexes can be ordered in the following sequence: 3 > 4 > 7 > 2 ≈ 5 > 6. The final products of the thermal decompositions were characterized as metallic palladium by X-ray powder diffraction (XRD).     

LC Method for Analysis of Three Flavonols in Rat Plasma and Urine after Oral Administration of Polygonum aviculare Extract

A high-performance liquid chromatographic method has been developed for the simultaneous analysis of the flavonols myricitrin (1), avicularin (2), and juglanin (3) in rat plasma and urine after oral administration of the total flavonoids from Polygonum aviculare. Samples were prepared by solid-phase extraction then separated on a C₁₈ reversed-phase column by use of a mobile-phase gradient prepared from methanol and aqueous formic acid solution. The flow rate was 1 mL min^?1. Detection was performed at 254 nm. The calibration range was 11–1,100 μg mL^?1 for both 2 and 3 in plasma; in urine the calibration ranges for 1, 2, and 3 were 32–1,600, 11–1,100, and 22–1,100 μg mL^?1, respectively. Intra-day and inter-day RSD were less than 4.33 and 3.62% for 2 and 3, respectively, in plasma, and no more than 4.03 and 2.22% for all the analytes in urine. The analytical sensitivity and selectivity of the assay enabled successful application to pharmacokinetic studies of flavonols 1–3 in rats.     

New copper(II) 2-(alkylamino)troponates

The copper aminotropones Cu[ON(R′)C₇H₄R-4]₂ [R = H, R′ = Me (13), Et (14), n-Pr (15), n-Bu (16), Bz (17), MenOCH₂CH₂ (20); R = i-Pr, R′ = Me (18), n-Pr (19), MenOCH₂CH₂ (21)] have been prepared from the corresponding aminotropones HN(R′)OC₇H₄R-4 (1–7) by reacting with copper(II) acetate in aqueous ethanol. 20, 21 contain the flavourant, menthol, as part of the ligand. The structures of 5 (R = H, R′ = Bz), a hydrogen-bonded dimer, 14 and 20, both incorporating square-planar, four-coordinate copper centres, have been determined by X-ray crystallography. The antibacterial activities of complexes 13, 17, 20 and 21 have been assayed against Staphylococcus waneri, an in vitro model of plaque inhibition effects, and found to be more active than a commercial toothpaste formulation, but less active than the O,O-chelated copper(II) complex of ethylmaltol.     

Excited state intramolecular hydrogen atom transfer of phenylethynyl-substituted 2′-hydroxychalcones

(E)-1-[2-Hydroxy-4-(phenylethynyl)phenyl]-3-[4-(phenylethynyl)phenyl]prop-2-en-1-one (1), (E)-1-[2-hydroxy-4-(phenylethynyl)phenyl]-3-phenylprop-2-en-1-one (2), and (E)-1-(2-hydroxyphenyl)-3-[4-(phenylethynyl)phenyl]prop-2-en-1-one (3), which belong to a new class of 2′-hydroxychalcones with phenylethynyl group(s) at the para position of the phenyl ring, were synthesized, and their photochemical properties were investigated. The lowest energy absorption band of 1 peaks at a longer wavelength (383 nm) with a much larger molar extinction coefficient (5.0 × 10⁴ M ^?1 cm^?1) than that of the parent 2′-hydroxychalcone (2′HC) (2.0 × 10⁴ M ^?1 cm^?1 at 318 nm). Upon photoexcitation, all three compounds underwent excited-state intramolecular hydrogen atom transfer (ESIHT) to produce an excited tautomer that emitted fluorescence with a large Stokes shift in the longer wavelength region at 600–700 nm. The quantum yield of the tautomer fluorescence of 1 was not high at 298 K (Φ _f = 9.1 × 10^?5), but was highest among 2′HC and its analogues. The Φ _f values of 1–3 increased 10–30 fold upon reducing the temperature from 298 to 77 K.     

Synthesis and characterization of palladium(II) complexes [PdX2(p-diben)] (X = Cl,Br, I,N3, or NCO; p-diben = N,N′-bis(4-dimethylaminobenzylidene)ethane-1,2-diamine): crystal structure of [Pd(N3)2(p-diben)]

Five new complexes of general formula [PdX₂(p-diben)], where p-diben = N,N′-bis(4-dimethylaminobenzylidene)ethane-1,2-diamine) (1) and X = Cl (2), Br (3), I (4), N₃ (5), or CNO (6), were synthesized and characterized by physicochemical and spectroscopic methods. The crystal structure of compound (5) was determined by single-crystal X-ray diffraction. Complexes 2–6 were characterized as N,N-chelated products. The crystal structure confirmed this formulation for [Pd(N₃)₂(p-diben)], besides showing the isomerism inversion of one of the C=N bonds, caused by Pd(II) coordination.     

Further studies on the properties and effect of high energetic ionizing radiation on copper(II) complexes: 1H NMR,electronic absorption,ESR spectra and solid electrical conductivity

The effect of energetic γ-radiation on ¹H NMR, electronic absorption, ESR spectra, differential thermal analysis (DTA) and solid state dc electrical conductivity of the ligand N-phenyl-2-(2-(phenylamino)acetyl)hydrazine carbothioamide (H₂L) and its copper(II) complexes; Cu(HL)(OAc)H₂O, Cu(HL)BrH₂O and Cu(H₂L)₂(NO₃)₂?3H₂O before and after γ-irradiation (hereafter referred to as (B), (B ₁ ), (B ₂ ), (B ₃ ) and (A), (A ₁ ), (A ₂ ), (A ₃ ), respectively) has been studied. Electronic spectral bands of the complexes after irradiation exhibited some better resolved shapes with a remarkably higher absorbance, ESR spectrum of complex Cu(HL)BrH₂O (B ₂ ) before irradiation showed isotropic spectrum with g _iso = 2.075 however, after irradiation (A ₂ ) displayed axial ESR spectrum with g _∥ > g _⊥ > 2.0023 and d _(x2?y2) ground state. DTA of the compounds reveals that γ-irradiation induced generation of new peaks as well as changes in the peak intensities. Solid state dc electrical conductivity for complexes was investigated before and after γ-irradiation. Complexes were found to be semiconductors, the activation energies (E _a) were calculated for the complexes by using the Arrhenius plot.     

Ammonium carbamate type self-derivative salts of (R-)- and racemic α-methylbenzylamine

Two different compounds have formed from liquid enantiomeric (R-) and racemic α-methylbenzylamine (α-MBA, named also as 1-phenylethylamine, 1-FEA) with supercritical fluid CO₂. The crystalline solids have been characterized by elemental CHN analysis, X-ray diffraction (XRD), FTIR, ¹H, and ¹³C NMR spectroscopy, and found to be α-methylbenzylammonium α-methylbenzylcarbamate self-derivative ionic salts 1 (R/R) and 2 (rac RS), respectively, of the corresponding amines. Compound 2 (rac RS) has shown different XRD pattern from that of enantiomerically pure 1 (R/R), indicating a preferential formation of a 1:1 mixture of (R/S-) and (S/R-) or rather a racemate compound of (RS/SR-) ammonium carbamate salt (2 (rac RS)) from racemate. For thermal stability, the compounds have been checked by differential scanning calorimetry (DSC), simultaneous thermogravimetry and differential thermal analysis (TG/DTA), and in situ coupled evolved gas analysis by mass spectroscopy (TG/DTA?EGA?MS) and FTIR-gas cell (TG?FTIR). No melting point is observed because of the low thermal stability of the compounds. Decomposition stages are tried to be separated with using semi-closed (sealed with a pinhole on the top) crucibles, thus different evolution courses of CO₂ and organic vapors could be followed by MS and FTIR spectroscopy. The α-MBA vapors themselves, evolved from open crucibles could be identified by FTIR-gas cell, while vapors up to m/z = 164 have been detected by MS from semi-closed Al crucible.     

Some new energetic benzaldoximes

5-Nitro-2-hydroxy benzaldoxime (I), 3-nitro-4-hydroxy benzaldoxime (II), 3,5-dinitro-2-hydroxy benzaldoxime (III), and 3,5-dinitro-4-hydroxy benzaldoxime (IV) were prepared from their respective nitrated aldehydes. Prepared oximes were characterized by IR spectroscopy, elemental analysis, and mass spectrometry. Suitable crystals of compounds II and III were obtained and molecular structures were determined by means of the single crystal XRD method. All benzaldoximes were investigated by TG. At temperatures above 140 °C, it was observed that compounds II and IV lost one H₂O and was converted to the respective benzonitriles. Only thermal analysis peaks of 3,5-dinitro-4-hydroxy benzonitrile (V) were found proper for both experimental and theoretic calculations; whereas, compounds I and III were converted to phenoxazines by Beckmann rearrangement along with dehydration. Beckmann product of compound III is referred as compound VI and its tautomer as compound VII. Similarly only 3,5-dinitro phenoxazine (VIII) was investigated experimentally and theoretically since its thermal analysis peaks were proper for the purpose. DFT-based structure optimizations and frequency analyses were performed at the B3LYP/cc-pVDZ level of theory. The enthalpies of formation for compounds III–VIII were calculated by means of the complete basis set (CBS-4M) method of Petersson and coworkers to obtain accurate energies. The enthalpies of decomposition for compounds III and IV were obtained from calculated enthalpies of formation according to Hess’ law and were compared with the experimental values which were available from DSC analyses and were found to be in good agreement with the theoretic values.     

Non-aqueous synthesis of nano-sized aluminium(III) isopropoxide derivatives with 8-hydroxyquinoline and their sol–gel transformation to nano-sized δ-alumina

Non-aqueous reactions of aluminum isopropoxide with 8-hydroxyquinoline (Hq = HONH₆C₉) in 1:1, 1:2 and 1:3 molar ratios in anhydrous benzene yield complexes of the type [q_nAl(OPrⁱ)_3?n] {where n = 1 (1), n = 2 (2), n = 3 (3)}. Progress of the reactions were monitored by estimating liberated 2-propanol in benzene-2-propanol azeotrope by oxidimetric method. All the products were fluorescent green powders, sparingly soluble in CHCl₃. They were characterized by elemental analysis, FT-IR and (¹H, ¹³C and ²⁷Al) NMR studies. The ESI mass spectral studies indicate dimeric nature for (1) and (2) and monomeric nature for the compound (3). The XRD spectra of (1–3) showed crystalline nature with the average particle size of 45, 32 and 27 nm respectively, as evaluated from Debye–Scherrer equation. The XRD spectrum of (3) also suggests the formation of β-crystalline polymorphs of Alq₃. The SEM images appear to indicate granular morphology for (1) and formation of cylindrical shaped rods for (2) and (3). Sol–gel hydrolysis of (1), (2) or (3) in presence of a strong acid as well as of the precursor, Al(OPrⁱ)₃,without acid or base catalyst, followed by sintering at 950 °C yielded tetragonal primitive phase of nano-sized δ-alumina in all the cases, as reflected by their powder X-ray diffraction pattern. The IR, SEM and EDX studies also support the formation of transition alumina.     

Microwave Promoted Oxidative Addition Reactions of Os3(CO)12: Efficient Syntheses of Triosmium Clusters of the Type Os3(μ-X)2(CO)10 and Os3(μ-H)(μ-OR)(CO)10

Microwave heating allows for the high-yield, one-step synthesis of the known triosmium complexes Os₃(μ-Br)₂(CO)₁₀ (1), Os₃(μ-I)₂(CO)₁₀ (2), and Os₃(μ-H)(μ-OR)(CO)₁₀ with R = methyl (3), ethyl (4), isopropyl (5), n-butyl (6), and phenyl (7). In addition, the new clusters Os₃(μ-H)(μ-OR)(CO)₁₀ with R = n-propyl (8), sec-butyl (9), isobutyl (10), and tert-butyl (11) are synthesized in a microwave reactor. The preparation of these complexes is easily accomplished without the need to first prepare an activated derivative of Os₃(CO)₁₂, and without the need to exclude air from the reaction vessel. The syntheses of complexes 1 and 2 are carried out in less than 15 min by heating stoichiometric mixtures of Os₃(CO)₁₂ and the appropriate halogen in cyclohexane. Clusters 3–6 and 8–10 are prepared by the microwave irradiation of Os₃(CO)₁₂ in neat alcohols, while clusters 7 and 11 are prepared from mixtures of Os₃(CO)₁₂, alcohol and 1,2-dichlorobenzene. Structural characterization of clusters 2, 4, and 5 was carried out by X-ray crystallographic analysis. High resolution X-ray crystal structures of two other oxidative addition products, Os₃(CO)₁₂I₂ (12) and Os₃(μ-H)(μ-O₂CC₆H₅)(CO)₁₀ (13), are also presented.     

A β-Secretase (BACE1)-inhibiting C-Methylrotenoid Induced by Yeast Elicitation in Abronia nana Suspension Cultures

Suspension cultures of Abronia nana were established to produce C-methylisoflavones. Treatment of the A. nana cultures with yeast elicitor induced boeravinone E (1), with maximum induction at 24 h after elicitor treatment. Of the biotic and abiotic elicitors tested, yeast extract gave the strongest induction of 1. The IC₅₀ value of 1 against β-secretase (β-amyloid cleaving enzyme-1) was 5.57 μM. Other proteases such as trypsin, chymotrypsin, and elastase were not inhibited by concentrations up to 1.0 mM, indicating that inhibition of β-secretase was specific. 1 was noncompetitive in Dixon plot, and Ki value was 3.79 μM.     

A study on thermal behaviors of mono ethyl ester azocalix[4]arene derivatives

In the present study, thermal stabilities of five new family of azocalix[4]arene mono ethyl ester derivatives, 4a–e, were investigated using thermogravimetry, differential thermogravimetry, and differential thermal analysis methods. It was found that all compounds showed thermal stability up to 236 °C averagely. After this temperature, decomposition of compounds starts gradually. The decomposition routes of 4a–c compounds are similar and occur with two stages. Ester alkyl groups decompose and remove from the structure in the first stage. Second stage corresponds to rest of structure decomposition. The decomposition routes of the 4d–e compounds are different from the decomposition routes of the 4a–c compounds. These compounds include halogen, and decomposition reactions realize with three and four stages respectively.     

Synthesis,characterization, and thermal behavior of palladium(II) complexes containing 4-iodopyrazole

The mononuclear pyrazolyl complexes [PdCl₂(HIPz)₂] (1), [PdBr₂(HIPz)₂] (2), [PdI₂(HIPz)₂] (3), [Pd(SCN)₂(HIPz)₂] (4), and [Pd(NHCOIPz)₂] (5) have been prepared. Compound 1 was obtained from the displacement of acetonitrile from [PdCl₂(CH₃CN)₂] precursor by the 4-iodopyrazole (HIPz) ligand, whereas 2–5 were synthesized by substitution of the chlorido in 1 by the respective anionic group. The compounds were characterized by elemental analysis, infrared spectroscopy, and ¹H NMR spectroscopy. The thermal behavior of 1–5 has been studied by TG and DTA. The thermal stability of [PdX₂(HIPz)₂] compounds varies according to the trends X = Cl^? < I^? ? SCN^?< Br^?. No stable intermediates were isolated during the thermal decompositions due to the overlap of the degradation processes. The final products of the thermal decompositions were characterized as metallic palladium by X-ray powder diffraction.     

Thermal studies and decomposition kinetics of alkaline earth metal trichloroacetates

Alkaline earth metal trichloroacetates M(O₂CCCl₃)₂·nH₂O, where M = Be (1), n = 4; M = Mg (2), n = 6; M = Ca (3) or Sr (4) or Ba (5), n = 4, were synthesized and their thermal behavior analyzed using thermogravimetric analysis (TG/DTG/DSC). A critical examination was made for the apparent activation energy by means of non-isothermal kinetic methods employing multiple heating rates. A systematic and comparative study of thermal decomposition was carried out at different heating rates i.e., 5, 10, 15, and 20 °C min^?1 for various trichloroacetates synthesized. It was observed that the Ca, Sr, and Ba trichloroacetates decompose preferentially to respective metal halides while Be and Mg compounds decompose to metal and metal oxide, respectively. The composition of the final residues was also confirmed using FT-IR spectroscopy. The activation energy follows the order: Mg > Ca > Sr > Ba, Be being the exception. Results reveal that each metal trichloroacetate decomposes through its unique thermolysis mechanism.     

Solvent extraction of europium trifluoromethanesulfonate into nitrobenzene by using three electroneutral receptors

From extraction experiments and $ \gamma $ -activity measurements, the extraction constants corresponding to the general equilibrium Eu³⁺(aq) + 3 A^?(aq) + L(nb) $ \Leftrightarrow $ EuL³⁺(nb) + 3A^?(nb) taking place in the two-phase water–nitrobenzene system ( $ {\text{A}}^{ - } = {\text{CF}}_{ 3} {\text{SO}}_{3}^{ - } $ ; L = electroneutral receptors denoted by 1, 2, and 3 – see Scheme 1; aq = aqueous phase, nb = nitrobenzene phase) were evaluated. Further, the stability constants of the EuL³⁺ complexes in nitrobenzene saturated with water were calculated; they were found to increase in the series of 3 < 2 < 1.

Naphthologs of overcrowded bistricyclic aromatic enes: (E)-bisbenzo[a]fluorenylidene

(E)-11H-Bisbenzo[a]fluorenylidene (E-6) was synthesized by Barton’s double extrusion diazo-thione coupling method from 11H-benzo[a]fluoren-11-thione (11) and 11-diazo-11H-benzo[a]fluorene (13). The reaction is probably thermodynamically controlled; in the event that the less stable Z -6 is also formed, it would rapidly undergo Z → E diastereomerization to give E -6. The B3LYP/6-311G(d,p) calculated diastereomerization barrier for Z -6 → E -6 is ΔG ₂₉₈ = 57.0 kJ/mol (13.6 kcal/mol). The calculated equilibrium constant K _eq(E -6 → Z -6) = 92:8 (at 298 K) is indicative of a marked diastereoselectivity of the reaction leading to E -6. The structure of E-6 was established by ¹H-NMR and ¹³C-NMR spectroscopies and by X-ray analysis. PAE E-6 crystallizes in the monoclinic space group C2/c. The unit cell of the crystal structure E -6 contains eight molecules, arranged as four pairs of enantiomers. PAE E -6 adopts a twisted conformation with the pure twist of the central C¹¹=C^11′ bond ω = 39°. The dihedral angle ν in E -6 is 60.6°, which is significantly higher than the respective dihedral angle in PAEs Z -6, 2, E -7, Z -7, 14, and 15. The large syn-pyramidalization angles at C¹¹ and C^11′ (χ = 12.6° and 14.8°) of E-6 indicates the enhanced strain in the fjord regions of the molecule. The enhanced twist is primarily attributed to the double benzo[a]annelation of the bifluorenylidene moiety at the fjord regions. The B3LYP/6-311G(d,p) calculated structure of E -6 is in a very good agreement with the experimental X-ray structure. PAE E -6 adopts a twisted conformation in solution, with the downfield chemical shift of H¹/H^1′ (8.31 ppm); H¹⁰/H^10′ (δ = 7.20 ppm) and H⁹/H^9′ (δ = 6.86 ppm) in E -6 are positioned above the planes of the opposing naphthalene rings. PAEs E -6 and Z -6 are significantly higher in energy than their corresponding benzo[b]annelated isomers E -7 and Z -7.     

Dependence of the basic properties of meso-nitro-substituted derivatives of β-octaethylporphyrin on the nature of substituents

Spectrophotometric titration is used to study the basic properties of a series of porphyrins with a continuously increasing degree of macrocycle deformation resulting from the introduction of strong electron-withdrawing substituents: 2,3,7,8,12,13,17,18-octaethylporphyrin (I), 5-nitro-2,3,7,8,12,13,17,18-octaethylporphyrin (II), 5,15-dinitro-2,3,7,8,12,13,17,18-octaethylporphyrin (III), 5,10,15-trinitro-2,3,7,8,12,13,17,18-octaethylporphyrin (IV), and 5,10,15,20-tetranitro-2,3,7,8,12,13,17,18-octaethylporphyrin (V). It is found that the values of logK _b (total basicity constants) obtained for the investigated compounds consistently diminish with an increase in the number of meso-substituents: 11.85 (I) > 10.45 (II) > 10.31 (III) > 10.23 (IV) > 9.56 (V). It is shown that two opposing factors, the steric and electronic effects of the substituents, change the basic properties of the above series of compounds.