Design and synthesis of an aminobenzo-15-crown-5-labeled estradiol tethered with disulfide linkage

A novel measuring method (electroimmunoassay) of 17β-estradiol (E₂) in urine or blood was proposed on the basis of a competition between E₂ and a labeled E₂ against an immobilizing antibody. To evaluate the principle, 3-{4-[17β-hydroxy-1,3,5(10)-estratrien-3-yloxy]butyldisulfanyl}-N-(6,7,9,10,12,13,15,16-octahydro-5,8,11,14,17-pentaoxabenzocyclopentadecen-2-yl) succinamic acid (1) was designed and synthesized as a novel aminobenzo-15-crown-5-containing E₂ tethered with disulfide linkage. Two thiol-intermediates 5b and 19c were efficiently synthesized from mercaptosuccinic acid 7 and 4,4′-dithiodibutyric acid 12, respectively. Formations of disulfide linkages from less reactive thiols were examined and 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) could be employed for the formation of an unsymmetrical disulfide 20c from 5b and 19c. Then, removal of TMS- and allyl-protecting groups in 20c successfully afforded the crown ether-containing E₂1.     

Reversible nonlinear conduction behavior for high‐density polyethylene/graphite powder composites near the percolation threshold

The reversible nonlinear conduction (RNC) behavior of high‐density polyethylene/graphite powder composites with various graphite powder volume concentrations slightly above the threshold has been studied. The relationships between the current density (J) and electric field (E) of the composites, as shown in J(E) curves, can be well described by the scaling functions of J/J_c ～ (E/E_c) when E < E_c and J/J_c ～ (E/E_c) when E > E_c, where J_c is the crossover current density and E_c is the crossover electric field. The results indicate that J_c scales with the linear conductivity σ₀ as J_c ～ σ. It is believed that the macroscopic RNC is a combined result of the microscopic conduction processes, involving electronic transporting along carbon chains and tunneling or hopping across thin polymer bridges. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 2833–2842, 2001     

Preparation and reactivity of macrocyclic dienynes

(1E,5E)-Cyclopentadeca-1,5-dien-3-yne (1c), which represents the first macrocyclic 1,5-dien-3-yne, can be obtained by thermal- or butyllithium-induced fragmentation of the corresponding 1,2,3-selenadiazole 8. The (E,E)-dienyne functionality causes a geometrical strain E_g, which enhances the reactivity in addition (1c→12,13) and cycloaddition (1c→10) reactions and lowers the isomerization barrier to the unstrained (E,Z)-configuration 1d (E_g = 0). A slow process 1c→1d occurs even at ambient temperatures within several weeks.     

Synthesis and structures of π-allylpalladium(II) complexes containing bis(1,2,4-triazol-5-ylidene-1-yl)borate ligands. An unusual tetrahedral palladium complex

Four air stable, neutral π-allylpalladium(II) complexes containing bis(1,2,4-triazol-5-ylidene-1-yl)borate ligands [H₂B(RBTz)₂Pd(π-allyl)] (R = ⁿBu, 2a; ^tBu, 2b; 2,6-diisopropylphenyl, 2c; cyclohexyl, 2d) have been prepared and characterized. The molecular structures of 2c and 2d have been confirmed by single-crystal X-ray diffraction. To our surprise, the coordination geometry about the palladium atom in 2d is distorted tetrahedron, in which the allyl group is nearly perpendicular to the plane defined by the Pd and the carbene C atoms. To our knowledge, such configuration has not been reported for a four-coordinated palladium allyl complex.     

Hydrazinocarben-Metallkomplexe—synthese aus allenylidenkomplexen und hydrazinen, umlagerung und cyclisierung

The diarylallenylidene pentacarbonyl complexes (CO)₅M=C=C=C(C₆H₄NMe₂-p)₂ (M = W (1), Cr (2)) add 1,2,-disubstituted hydrazines RNH-HNR to form alkenyl hydrazino carbene complexes (CO)₅M=C(C(H)=C(C₆H₄NMe₂-p)₂) NR-N(H)R (M = W, R = Bn (3b), ⁱPr (3c), ^cHex (3d); M = Cr, R = Me (4a), ⁱPr (4b)) in good yield. 3c and 4b are formed selectively as E-conformers (E arrangement of N_βHR and (CO)₅M with respect to the C(carbene)-N_α bond). In contrast, all other derivatives of 3 and 4 are obtained as a mixture of E/Z-isomers. On heating, E-3a and E-3b rearrange to give the acrylamidine complexes (CO)₅W-NR=C(NHR)C(H)=C(C₆H₄NMe₂-p)₂ (R = Me (5a), Bn (5b). The structure of complex 5b was established by X-ray analysis. Acid-catalyzed, the alkenyl hydrazino carbene complexes E-3a, E-3b and 3c are transformed by intramolecular cyclization into the pyrazolidinylidene complexes

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(R =Me (6a), Bn (6b), ⁱPr (6c)).

Zusammenfassung

Die Diarylallenyliden(pentacarbonyl)komplexe (CO)₅M=C=C=C(C₆H₄NMe₂-p)₂ (M = W (1), Cr (2)) addieren 1,2-disbustituierte Hydrazine RNH-HNR in guten Ausbeuten zu Alkenylhydrazinocarbenkomplexen (CO)₅M=C(C(H)=C(C₆H₄NMe₂p)₂) NR-N(H)R (M = W, R = Bn (3b), ⁱPr (3c), ^cHex (3d); M = Cr, R =Me(4a), ⁱPr (4b)). 3c und 4b entstehen hierbei selektiv in der E-Konformation (E-Anordnung von N_βHR und (CO)₅M bezülich der C(Carben)-N_α-Bindung). Alle anderen Derivate von 3 und 4 werden dagegen als E/Z-Isomerengemisch gebildet. E-3a und E-3b lagern sich beim Erwärmen in die Acrylamidinkomplexe (CO)₅W-NR=C(NHR)C(H)=C(C₆H₄NMe₂-p)₂ (R = Me (5a), Bn (5b)) um. Die Struktur von 5b wurde anhand einer Röntgenstrukturanalyse gesichert. Säurekatalysiert cyclisieren die Alkenylhydrazinocarbenkomplexe E-3a, E-3b und 3c zu den Pyrazolidinylidenkomplexen

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(R = Me (6b), ⁱPr (6c)).     

Temperature Dependence of the Ratios of C—H (C—D) Bond Breaking Rates in Reactions of Cycloalkanes C5H10, C6H12, C6D12 with Adamantyl Carbocations in Sulfuric Acid

We have determined the differences in the parameters log A and E of the Arrhenius equations for the kinetic isotope effect (KIE) (c-C₆H₁₂/c-C₆D₁₂) and the 5/6 effect (c-C₅H₁₀/c-C₆H₁₂) in reactions of the C—H bonds of cycloalkanes with adamantyl (Ad⁺) carbocations (1-adamantanol in 92.8% H₂SO₄, 40-97 °C). We have established the compensation relations between log A and E for the kinetic isotope effect and the 5/6 effect for anthracene (AH⁺), hydroxymethyl (CH₂OH⁺), Ad⁺ carbocations and the hypothetical "infinitely strong reagent," supporting a hydride transfer mechanism in such reactions.     

Substituted six-membered ring carbenes: the effects of amino and cyclopropyl groups through DFT calculations

DFT calculations are employed to compare and contrast six-membered ring carbenes including 1,3-dimethyltetrahydropyrimidin-2-ylidene (1a), 1-methyl-3-cyclopropyltetrahydropyridine-2-ylidene (2a), and 1,3-dicyclopropylcyclohexane-2-ylidene (3a) as well as their unsaturated analogues 1b, 2b, 3b, and 2c. The amino groups exert singlet-triplet energy separation (?E_s−t) of 60.9 kcal/mol to 1a while cyclopropyls induce a ?E_s−t of 14.8 kcal/mol to 3a. The simultaneous presence of amino and cyclopropyl in 2a leads to a ?E_s−t of 43.3 kcal/mol. Unsaturation slightly increases the ?E_s−t of 1a and 3a but not that of 2a. Our thermodynamic, kinetic, and reactivity results are compared with those of synthetic five-membered ring N-heterocyclic carbenes.     

Phase transitions in K3AlF6

Phase transitions in the elpasolite-type K₃AlF₆ complex fluoride were investigated using differential scanning calorimetry, electron diffraction and X-ray powder diffraction. Three phase transitions were identified with critical temperatures , and . The α-K₃AlF₆ phase is stable below T₁ and crystallizes in a monoclinic unit cell with a=18.8588(2)Å, b=34.0278(2)Å, c=18.9231(1)Å, β=90.453(1)° (a=2a_c−c_c, b=4b_c, c=a_c+2c_c; a_c, b_c, c_c—the basic lattice vectors of the face-centered cubic elpasolite structure) and space group I2/a or Ia. The intermediate β phase exists only in very narrow temperature interval between T₁ and T₂. The γ polymorph is stable in the T₂<T<T₃ temperature range and has an orthorhombic unit cell with a=36.1229(6)Å, b=17.1114(3)Å, c=12.0502(3)Å (a=3a_c−3c_c, b=2b_c, c=a_c+c_c) at 250 °C and space group Fddd. Above T₃ the cubic δ polymorph forms with a_c=8.5786(4)Å at 400 °C and space group . The similarity between the K₃AlF₆ and K₃MoO₃F₃ compounds is discussed.     

Study of non-isothermal crystallization of amorphous Cu<Subscript>50</Subscript>Ti<Subscript>50</Subscript> alloy

The crystallization kinetics of amorphous Cu₅₀Ti₅₀ has been studied using differential scanning calorimetry (DSC) under non-isothermal conditions. The curves at different linear heating rates (2, 4, 8 and 16 K min^–1) show sharp crystallization peaks. The crystallization peak shifts to higher temperatures with increasing heating rate. The Kissingers method of analysis of the shift in the transformation peak is applied to evaluate the activation energy (E _c). The KJMA formalism, which is basically developed for isothermal experiments, is also used to obtain E _c and the Avrami parameter (n).The DSC data have been analysed in terms of kinetic parameters, viz. activation energy (E _c), Avrami exponent (n) and frequency factor K ₀ using three different theoretical models. It is observed that the activation energy values derived from KJMA approach and modified Kissinger equation agree fairly well with each other. The activation energy values obtained from normal Kissinger method, and Gao and Wang expression underestimate the activation energy.The financial support provided by All India Council for Technical Education (AICTE), New Delhi (Govt. of India) is gratefully acknowledged.     

Highly stereoselective and efficient synthesis of ω-heterofunctional di- and trienoic esters for Horner-Wadsworth-Emmons reaction via alkyne hydrozirconation and Pd-catalyzed alkenylation

In situ OH metalation with ⁱBu₂AlH and hydrozirconation with HZrCp₂Cl of HOCH₂CCH, (E)-HOCH₂CHCHCCH, and HOCH₂CCCH₃ followed by Pd-catalyzed alkenyl-alkenyl coupling with (E)-BrCHCHCO₂Et and (E)-BrCHC(Me)CO₂Et using PEPPSI-IPr (7) as a catalyst provides a highly efficient and selective (?98% all-E) route to ω-hydroxy di- and trienoic acid esters (1a-6a). The corresponding phosphonate esters (1c-4c) of ?98% isomeric purity can be obtained via conventional bromination-phosphonation in >80% yields. As expected, their carbonyl olefination is ca. 85-90% E-selective with alkyl aldehydes but ?98% E-selective with PhCHO and some α,β-unsaturated aldehydes under the conditions used.     

Solvent effect on the blue shifted weakly H-bound F3 CH…FCD3 complex

Solvent effect on the ν^c frequency of CH stretching vibration of the blue shifted F₃CH…FCD₃ complex has been studied in liquefied N₂, CO, Ar, Kr and Xe. In the case of Xe, the spectroscopic measurements have also been extended to the solid state. It was found that the ν^c position of the complex in the solutions studied lowers with respect to the value in the gas phase. In liquid Xe, characterized by the largest permittivity, this effect reaches its maximum value of −14.5 cm⁻¹. The ν^c frequency begins to grow again just below the freezing point of Xe, where a noticeable (15%) increase of the density of Xe occurs. The experimental results obtained for the liquid phase have been analyzed in the framework of the Onsager-like reaction field model and Polarizable Continuum Model (PCM) implemented into a standard Gaussian 98 Program.     

Oxazoline Chemistry. Part 11: Syntheses of natural and synthetic isoflavones, stilbenes and related species via C-C bond formation promoted by a Pd-oxazoline complex

The complex trans-[PdCl₂(2-ethyl-2-oxazoline-κ¹N)₂] (1) is shown to be an active and oxidatively robust catalyst for C-C bond forming reactions (Heck, Sonogashira, Ullmann, Miyaura-Suzuki, etc.). These reactions can be carried out in air without rigorous solvent/substrate purification and in the absence of additional free ligand. The general methodology described above has been applied to the high yield and regio-selective formation, via Miyaura-Suzuki coupling, of natural and synthetic isoflavones (i.e., isoflavone, 2′-methylisoflavone [7b], 3′-methylisoflavone [7c] and 3′,4′-benzoisoflavone: [7d]). Compounds 7c and 7d are previously unknown. In addition, the synthesis of (E)-tris-O-methylresveratrol and (E)-3,5-dimethoxystilbene is also described; the former is a recognized anti-cancer agent while the latter is a biologically active extract from the bark of the conifer species Pinus armandii. Both of these latter products are produced as a result of a Heck coupling reaction promoted by 1.     

New stable germylenes, stannylenes, and related compounds. 5. Germanium(II) and tin(II) azides [N3-E-OCH2CH2NMe2]2 (E = Ge, Sn): synthesis and structure

New stable azido derivatives of divalent germanium and tin [N₃-E¹⁴-OCH₂CH₂NMe₂]₂ (E¹⁴ = Ge (1), Sn (2)) have been synthesized by use of the β-dimethylaminoethoxy ligand that forms the intramolecular E¹⁴ ← N coordination bond. Their crystal structures have been determined by X-ray diffraction analysis. Compounds 1 and 2 are centrosymmetric dimers via two intermolecular dative E¹⁴ ← O interactions with essentially linear monodentate azide ligands. The dominant canonical form of the E¹⁴-azide moieties is E¹⁴-N-NN.     

Methylene-2-ethynylcyclopropanes: synthesis and biological activity of (Z)- and (E)-9-{[2-ethynyl-2-(hydroxymethyl)cyclopropylidene]methyl}adenine and -guanine

Synthesis of methylene-2-ethynylcyclopropane analogues of nucleosides 12a, 12b, 13a, and 13b is described. Ethyl methylenecyclopropane carboxylate 14 was hydroxymethylated to give alcohol 15, which was reduced to diol 16. Selective protection with tert-butyldimethylsilyl group gave derivative 17, which was oxidized to aldehyde 18. Wittig reaction with CBr₄ gave dibromoalkene 19. Elimination of both bromine atoms afforded methylene-2-ethynylcyclopropane 20. Bromoselenenylation using N-bromosuccinimide and diphenyldiselenide gave intermediate 21. Alkylation of adenine and 2-amino-6-chloropurine with 21 provided the Z,E-isomeric mixtures 22a and 22c. Oxidation afforded selenoxides 23a and 23c. Mild thermolysis furnished methylenecyclopropanes Z-24a, E-24a, and 24c. Deprotection and separation of Z,E-isomers gave adenine analogues 12a and 13a, and 2-amino-6-chloropurine intermediates 12c and 13c. Hydrolytic dechlorination of 12c and 13c afforded guanine analogues 12b and 13b. Adenine Z-isomer 12a inhibits replication of Epstein-Barr virus through its cytotoxicity. The E-isomer 13a is a substrate for adenosine deaminase.     

Cyanometallate incorporated supramolecular networks based on a nitroalkyl-substituted CuN4 precursor: Synthesis, crystal structure, thermal and electrochemical studies

Two new copper(II) complexes, viz. [Cu(nelin)(H₂O)₂]₂[Fe(CN)₆] · 6H₂O (2) and [{Cu(nelin)}₂Ni(CN)₄](ClO₄)₂ · 2H₂O (3), have been synthesized using [Cu(nelin)](ClO₄)₂ (1) (nelin = 1,9-diamino-5-methyl-5-nitro-3,7-diazanonane) as a nitroalkyl-substituted Cu^IIN₄ precursor, and their structures and supramolecular networks have been fully explored using the single crystal X-ray diffraction technique. The H-bonded 1D chains of 2 run along the a-axis, being generated from supramolecular synthons using cations and anions, and are further propagated into a 3D array to form irregular honeycomb-like channels which are divided into two halves, with each half accomodating a helical water chain running in opposite directions to each other. In complex 3, the trinuclear units are arranged in successive rows in a herringbone fashion and bifurcated hydrogen bonding through the uncoordinated terminals of the [Ni(CN)₄]²⁻ units give rise to a supramolecular (4,4) network. A comparison of the PXRD pattern of complex 2 and its dehydrated form indicate marked changes in the diffraction pattern with the development of a quasi glassy nature in the dehydrated form. The electrochemical properties of 1, 2 and 3 have been investigated in comparative ways using the cyclic voltammetric technique in aqueous and MeCN solutions with Ag/AgCl as a reference electrode. Electrochemical reduction generates the one-electron reduced nitro-radical anion. In water–alcohol glass at 77 K complex 2 exhibits a typical four-line hyperfine EPR spectra with g_|| = 2.11, g = 2.02, A_|| = 150 Oe and A = 5 Oe at ν = 9.45 MHz.     

Conformational space of tetrakis(2-naphthalenyl)ethene: a naphthologous AIE luminogen

The AIE luminogen tetrakis(2-naphthalenyl)ethene (2-NA ₄ E) was synthesized by Barton’s double extrusion diazo-thione coupling method from 2,2′-dinaphthyl thioketone and 2,2′-(diazomethylene)bisnaphthylene in 77 % yield. The structure of 2-NA ₄ E was confirmed by its ¹H NMR and ¹³C NMR spectra with full assignments. 2-NA ₄ E and its parent tetraphenylethene (Ph ₄ E) have been subjected to a comprehensive computational DFT study, in search of their conformational spaces. Seven conformers and two transition states of 2-NA ₄ E have been located. Four conformers and one transition state of Ph ₄ E have been located. The conformers of 2-NA ₄ E and Ph ₄ E are not overcrowded, as indicated by the contact distances in the fjord and cove regions. The relative free energies (ΔG ₂₉₈) of the six most stable conformers of 2-NA ₄ E are in the narrow range of 2.3 kJ/mol; they make comparable contributions (12–29 %) to the equilibrium mixture. The energy barriers for the diastereomerization D ₂-Z,Z,Z,Z $ \rightleftharpoons $ ? D ₂-E,E,E,E via the transition state C ₁-Z,E,E,Z and for the enantiomerization C ₂-Z,Z,E,E $ \rightleftharpoons $ ? C ₂-E,E,Z,Z via the transition state C _i -Z,E,Z,E are only 29.8 and 29.0 kJ/mol, respectively, indicating very rapid rates of diastereomerization and enantiomerization at room temperature. The values of naphthalenyl torsion angles and ethenic twist angles in 2-NA ₄ E are almost identical to those in the parent Ph ₄ E. The previously proposed “bulkiness” of the naphthalenyl substituents and the validity of the restriction of naphthalenyl rotation are challenged. The analysis of the AIE effect in 2-NA ₄ E should take into account the intermolecular homochiral and heterochiral interactions between the conformers.     

From calixfurans to heterocyclophanes containing isopyrazole units

Cyclic poly-1,4-diketones 2, obtained by the oxidation of the furan units present in calix[4]furan 1a and calix[6]furan 1c have been converted into the novel heterocyclophanes 4a and 4c containing four and six isopyrazole units, respectively. Solution studies have demonstrated the ability of 4a and 4c to act as ligands for transition metals. The crystal structures of 4a and the coordination compound formed by 4c with 2 equiv. of cis-PtCl₂(DMSO)₂ have been determined. In the solid state 4c is shown to bind aromatic substrates within its cavity.     

Temperature Dependences of the Kinetic Isotope Effect and the Ratio of the Reaction Rates for Reaction of Cyclopentane and Cyclohexane with HOCl in Water

We have determined the activation parameters logA and E for the Arrhenius equations for the kinetic isotope effect (c-C₆H₁₂/c-C₆D₁₂) and the 5/6 effect (c-C₅H₁₀/c-C₆H₁₂) in reactions of the C—H bonds of cycloalkanes with HOCl in aqueous solutions in the interval 30-90 °C. The data obtained are consistent with a chlorination mechanism including a pre-activation step with formation of an HO^· ... Cl^· pair, linear abstraction of the H atom by the OH group and angular attack by the Cl atom "at a distance" on the carbon atom.     

Synthesis, characterization and potential biomedical applications of N-succinimidyl ester functionalized, polypyrrole-coated polystyrene latex particles

N-Succinimidyl ester functionalized polypyrrole-coated polystyrene latex particles (PS_E-PPyNSE) were prepared by the in situ copolymerization of pyrrole and the active ester-functionalized pyrrole (pyrrole-NSE) in the presence of polystyrene latex particles. Polystyrene microspheres were prepared by emulsion polymerization (PS_E) leading to particles having a diameter of 450 nm. These PS_E particles were precoated with poly(N-vinylpyrrolidone) prior to the in situ copolymerization of pyrrole and pyrrole-NSE. The initial comonomer concentration fractions were 25/75, 50/50 and 75/25 for pyrrole and pyrrole-NSE, respectively. The PPy-coated PS_E particles were characterized in terms of morphology, particle size, electrophoretic mobility and chemical composition. The study of morphology by means of scanning electron microscopy showed roughening of the underlying PS_E particles owing to the addition of PPyNSE, the overlayer thickness of which was estimated to be around 7 nm. Moreover, loading PPyNSE overlayers resulted in a shift of the electrophoretic mobility from –5.31 m cm/V s to a very small but positive value (0.082–0.112 m cm/V s). X-ray photoelectron spectroscopy and IR spectroscopy permitted the detection of pyrrole-NSE repeat units at the surface indicating that pyrrole and pyrrole-NSE did indeed copolymerize. The PS_E-PPyNSE particles were further evaluated as bioadsorbents of human serum albumin used as a test protein. For this study, PS_E-PPyNSE₅₀ particles, synthesized from a comonomer feed ratio of 50/50 in pyrrole/pyrrole-NSE, were used and were shown to attach efficiently human serum albumin macromolecules with a maximum amount of 0.2 mg m^–2.

New strained ferrocenophane-based receptors for the selective electrochemical recognition of Mg in the presence of Ca cations

Ferrocenophane derivatives 3 act as electrochemical sensors of Mg²⁺ ions: a new redox peak appears in the CVs anodically shifted compared to the E_1/2 of the free receptors by 268-382 mV. Receptors 3a, 3c and 3d are selective for Mg²⁺, whilst 3b is also responsive to Ca²⁺ ion (302 mV shift). Receptor 3c also gave a highly visual output response in the presence of Mg²⁺ consisting of a deep purple colour.