Homooxacalix[3]arene Derivatives as Ionophores for Serotonin‐Selective Membrane Electrodes

Homooxacalix[3]arene derivatives are effective ionophores for constructing serotonin‐selective membrane electrodes. An electrode based on one of the derivatives, tris(methoxyphenylpropyloxy)hexahomooxacalix[3]arene‐triethyl ether, with potassium tetrakis(p‐chlorophenyl)borate (20 mol% relative to the ionophore) as an ionic additive and bis(2‐ethylhexyl) sebacate as a solvent mediator in a poly(vinyl chloride) membrane matrix, displayed much better selectivity for serotonin than for various organic ammonium ions and inorganic cations. The electrode exhibited a near‐Nernstian response to serotonin in the concentration range of 2×10^?4 to 1×10^?2 M with a slope of 56.4 mV per concentration decade in physiological saline containing 150 mM NaCl and 10 mM Na₂HPO₄/NaH₂PO₄ (pH 7.4). The limit of the detection was 8×10^?5 M. The selectivity pattern of this electrode was quite different from that of an electrode using calix[6]arene‐hexaacetic acid hexaethyl ester, a well‐known ionophore for primary organic ammonium ions, which did not induce an enhanced response to serotonin. The developed electrode was used for the active loading of serotonin in liposomes induced by transmembrane pH gradients.     

Imidazo[2,1-b]benzothiazoles. II. Synthesis and antiinflammatory activity of some imidazo[2,1-b]benzothiazoles

3-[2-[p-(Un)substituted phenyl]imidazo [2,1-b]benzothiazol-3- yl]propionic acid derivatives (2a--e) were prepared via the interaction of the corresponding 2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazoles (1a--e) with acrylic acid in the presence of acetic anhydride and acetic acid. Esterification of 2a--e produced methyl esters (3a--e). Upon the interaction of 3a with m-chloroperbenzoic acid, the S-dioxide (4a) was obtained. Compound 5a was prepared from 4a by alkaline hydrolysis. Vilsmeier formylation for 1a--e produced novel [2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazol-3- yl]formaldehyde derivatives (6a--e). Derivatives 6a--e reacted with ethyl bromoacetate to give ethyl 3-hydroxy-3-[2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazol- 3-yl]propionate esters (7a--e). Compound dl-7a was resolved with l-(+)-tartaric acid. Compounds 2a--e showed weak or no activity in the carrageein-induced paw edema assay. Compound 4a significantly inhibited the leakage of pontamine-sky blue dye into the peritoneal cavity of mice, in the capillary permeability inhibition assay. Compound 5a inhibited the writhing by 62% in the acetic acid-induced writhing assay.     

Reverse phase high pressure liquid chromatography for the separation of peptide hormone diastereoisomers

Diastereoisomers of specifically labeled oxytocin derivatives were resolved using reverse phase high pressure liquid chromatography. The peptides [1-hemi-DL-[alpha-2H]cystine]oxytocin, [6-hemi-DL-[alpha-2H]cystine]oxytocin, [2-DL-[alpha-2H]tyrosine]oxytocin and[8-DL-[2-13C]leucine]oxytocin were readily separated using the conditions described. The diastereoisomers of the oxytocin analog [3-DL-[2-13C]leucine]oxytocin also demonstrated baseline resolution under the same conditions. The procedure offers the investigator a rapid method for screening synthetic oxytocin peptides for undesirable diastereoisomeric by-products.     

Structural investigation of the bridged activated complex in the reaction between hexachloroiridate(IV) and pentacyanocobaltate(II)

Time resolved energy dispersive X-ray absorption spectroscopy has been used to follow the structural evolution of the inner-sphere electron transfer reaction between [IrCl6]2- and [Co(CN)5]3-, and to characterise the local structure of the iridium metal centre in the bridged activated complex formed during the reaction.     

Synthesis of 1,1′-methylenedi[(1R,1′R,3R,3′R,5R,5′R)-8-oxabicyclo[3.2.1]oct-6-en-3-ol] and derivatives: precursors of long-chain polyketides

Racemic 1,1′-methylene[(1RS,1′RS,3RS,3′RS,5RS,5′RS)-8-oxabicyclo[3.2.1]oct-6-en-3-ol] ((±)-6) derived from 2,2′-methylenedifuran has been resolved kinetically with Candida cyclindracea lipase-catalysed transesterification giving 1,1′-methylenedi[(1R,1′R,3R,3′R,5R,5′R)-8-oxabicyclo[3.2.1]oct-6-en-3-ol] (−)-6 (30% yield, 98% ee) and 1,1′-methylenedi[(1S,1′S,3S,3′S,5S,5′S)-8-oxabicyclo[3.2.1]oct-6-en-3-yl] diacetate (+)-8, (40% yield, 98% ee). These compounds have been converted into 1,1′-methylenedi[(4S,4′S,6S,6′S)- and (4R,4′R,6R,6′R)-cyclohept-1-en-4,6-diyl] derivatives.     

Synthesis and characterization of 1,8-naphthalimide with [6]helicene skeleton

A 1,8-naphthalimide with [6]helicene derivative scaffold has been designed and synthesized. The (P)- and (M)-enantiomers of the [6]helicene derivative were resolved by HPLC on a chiral column. The single crystal of the [6]helicene derivative exhibits an intermolecular interactions of the 1,8-naphthalimide units.     

Synthese der enantiomeren 1,6-Spiro[4.4]nonadiene

Two new syntheses of spiro[4.4]nonane-1, 6-dione (I) are described: one by rearrangement of 1,6-epoxy-bicyclo[4.3.0]-nonane-2-one (IV) with boron trifluoride, the other by an acid catalyzed, intramolecular Claisen condensation of 4-(2-oxocyclopentyl)-butyric acid. Spiro[4.4]-nonane-1,6-dione is converted into trans, trans-spiro[4.4]nonane-1,6-diol which is resolved into enantiomers via the diastereomeric esters with (?)-camphanic acid. (+)-(5S)-Spiro[4.4]nona-1,6-diene (III) is prepared from (1R, 6R)-trans,trans-spiro[4.4]nonane-1,6-diol (II) by pyrolysis of the corresponding bis-4-methylphenyl-thionocarbonate. This modification of the Chugaev reaction is particularly useful with sterically hindered alcohols which cannot be converted into S-me-thylxanthates. The circular dichroism, UV.- and NMR.-spectrum of optically active spiro[4.4]-nonane-1,6-diene are discussed.     

Efficient resolution of a dinuclear triple helicate by asymmetric extraction/precipitation with TRISPHAT anions as resolving agents

Tetradentate 1,2-bis[4-(4'-methyl-2,2'-bipyridyl)]ethane ligand (3) and Fe(NH4)2(SO4)2.6H2O combine in a 3:2 ratio to form the racemic helicate [Fe2L3]4+ (4), as reported by Elliott et al. We now show that the enantiomeric purity of 4 can be efficiently measured by 1H NMR by the use of the TRISPHAT (1) salt as a chiral shift reagent. Large differences in chemical shifts (deltadeltadelta of up to 0.3 ppm, 20% [D6]DMSO in CD3CN) are observed between the enantiomers of 4 upon addition of [nBu4N][delta-1]. The resolution of 4 by asymmetric extraction was attempted: addition of an organic solution of [cinchonidinium][delta-1] salt (2 equiv) to an aqueous solution of helicate 4-(SO4)2 led, after vigorous stirring, to the extraction of the homochiral diastereomer [P-4][delta-1]4 into the organic layer along with the precipitation of the heterochiral diastereomer [M-4][delta-1]4 at the interface (diastereomeric ratio>49:1 for both processes). An enantioenriched fraction of [P-4][SO4]2 remained in the aqueous layer. To obtain only two fractions of resolved helicate and develop this procedure into an efficient resolution protocol, four equivalents of [cinchonidinium][delta-1] salt were used as the resolving agent. Chemically and diastereomerically pure [P-4][delta-1]4 and [M-4][delta-1]4 helicate salts were then obtained in excellent yields.     

Trinuclear Double Helicates of Iron(II) and Nickel(II): Self-assembly and resolution into helical enantiomers

The synthesis of the linear tris[terpyridine] 1 with three tridentate binding sites is described. The reaction with metal ions of octahedral coordination geometry, such as Fe^II or Ni^II, leads to the self-assembly of trinuclear complexes [M₃( 1 )₂]⁶⁺, which display properties in agreement with a double helical structure. The trinuclear iron (II) helicate has been resolved into its enantiomers.     

Stereoselective synthesis and optical resolution of chiral calix[4]arenes with mixed ligating functionalities

Exhaustive alkylation of syn-proximal bis[(2-pyridylmethyl)oxy]calix[4]arene 1 with t-butyl bromoacetate or 2-(chloromethyl)quinoline hydrochloride in the presence of Cs₂CO₃ affords selectively a new type of inherently chiral calix[4]arenes 2a,b in the partial cone conformation. (±) 2b has been resolved into its optical antipodes by an HPLC method.     

Racematspaltung und Bestimmung der absoluten Konfiguration von 2, 6-disubstituierten Bicyclo [3.3.1]nonanen

Resolution and Determination of the Absolute Configuration of 2,6-Disubstituted Bicyclo[3.3.1]nonanes (±)-endo, endo-Bicyclo [3.3.1]nonane-2,6-diol was resolved via diastereomeric camphanic acid esters. Conversion of the (+)-enantiomer 2 via (+)- 5 and (+)- 6 as key intermediates gave (+) methyl 3-(3-oxocyclohexyl)-propionate ( 7 ) which independently could be prepared also from the known (+)-(R)-3-oxo-cyclohexane-carboxylic acid ( 8 ). These chemical correlations establish the absolute configuration of (+) -2 , (+) -5 and (+) -6 as well as that of (+)-bicyclo [3.3.1]nonane-2,6-dione ( 1 ) obtained by oxidation of (+) -2 . The chiroptical properties of 1 and 6 are discussed.     

Synthesis and cytotoxic activity of benzo[a]pyrano[3,2-h] and [2,3-i]xanthone analogues of psorospermine, acronycine, and benzo[a]acronycine

Condensation of 2-hydroxy-1-naphthalenecarboxylic acid with phloroglucinol afforded 9,11-dihydroxy-12H-benzo[a]xanthen-12-one (6). Construction of an additional dimethylpyran ring onto this skeleton, by alkylation with 3-chloro-3-methyl-1-butyne followed by Claisen rearrangement, gave access to 6-hydroxy-3,3-dimethyl-3H,7H-benzo[a]pyrano[3,2-h]xanthen-7-one (12) and 5-hydroxy-2,2-dimethyl-2H,6H-benzo[a]pyrano[2,3-i]xanthen-6-one (13), which were methylated into 6-methoxy-3,3-dimethyl-3H,7H-benzo[a]pyrano[3,2-h]xanthen-7-one (14) and 5-methoxy-2,2-dimethyl-2H,6H-benzo[a]pyrano[2,3-i]xanthen-6-one (15), respectively. Osmium tetroxide oxidation of 14 and 15 gave the corresponding (+/-)-cis-diols 16 and 17, which afforded the corresponding esters 18-21 upon acylation. Similarly, condensation of 2-hydroxy-1-naphthalenecarboxylic acid with 3,5-dimethoxyaniline gave 11-amino-9-methoxy-12H-benzo[a]xanthen-12-one (23) which was converted into 11-amino-9-hydroxy-12H-benzo[a]xanthen-12-one (24) upon treatment with hydrogen bromide in acetic acid. Alkylation with 3-chloro-3-methyl-1-butyne followed by Claisen rearrangement afforded 6-amino-3,3-dimethyl-3H,7H-benzo[a]pyrano[3,2-h]xanthen-7-one (25) and 5-amino-2,2-dimethyl-2H,6H-benzo[a]pyrano[2,3-i]xanthen-6-one (26). The new benzopyranoxanthone derivatives only displayed marginal antiproliferative activity when tested against L1210 and KB-3-1 cell lines. The only compounds found significantly active against L1210 cell line, 16 and 20, belong to the benzo[a]pyrano[3,2-h]xanthen-7-one series, which possess a pyran ring fused angularly onto the xanthone basic core.     

Elusive 6-exo-Hydroxybicyclo[2.2.2]octan-2-ones from the corresponding acetates by methanolysis in the presence of CH(3)ONa/La(OTf)(3)

[reaction: see text] A series of 6-exo-acetoxybicyclo[2.2.2]octan-2-ones were converted into the corresponding 6-exo-hydroxybicyclo[2.2.2]octan-2-ones by methanolysis in the presence of CH(3)ONa/La(OTf)(3). Under the given conditions, epimerization at C(6) of the latter led in the least favorable cases only to traces of the more stable 6-endo-hydroxybicyclo[2.2.2]octan-2-ones. This procedure, when combined with the described conversion of easily available 6-endo-hydroxybicyclo[2.2.2]octan-2-ones into the corresponding 6-exo-acetoxy derivatives, provides a convenient route to elusive 6-exo-hydroxybicyclo[2.2.2]octan-2-ones. Applications to total synthesis are shown and envisaged.     

Efficient syntheses and resolutions of inherently chiral calix[4]quinolines in the cone and partial-cone conformation

[structure: see text] The syntheses of five pairs of novel inherently chiral calix[4]arenes are described. Two synthetic routes were adopted to generate racemic 3-carboxylic or 2-carboxylic group substituted calix[4]quinolines in the cone or the partial-cone conformation, respectively. The chiral products were thoroughly characterized by various spectroscopic methods. The optical resolutions of chiral calix[4]quinolines 5, 6, 11, and 17 were successfully achieved through the separation of their diastereomers using common column chromatography or preparative TLC. The chirality of compound 20 was proven by the splitting of the 1H NMR signals in the presence of Pirkle's reagent. The 1H NMR features of the diastereomers are discussed. The CD spectra of each pair of enantiomers showed excellent mirror images. The experimental results disclose that 3-carboxylic calix[4]quinolines can be resolved more easily than the 2-carboxylic ones in both the cone conformation and the partial-cone conformation.     

Mercury bis(phenyltellurolate) as a precursor for the synthesis of binary and ternary nanoclusters

The reaction of Hg(TePh)2 with AgX (X = Cl, NO3) in the presence of PPh3 and PMePh2 in dimethylformamide (DMF) affords the cluster [Hg6Ag4(TePh)16] (1) at room temperature or [Hg6Ag4Te(TePh)14]2 (2) with heating. When Hg(TePh)2 is reacted with [Co(PPh3)2Cl2] or [Ni(PPh3)2Cl2], the clusters [Hg8Te(PhTe)12Cl4]Q [3; Q = [Co(DMF)6]2+ (3a), [Ni(DMF)6]2+ (3b)] are formed. The syntheses of 1 and 2 occur with the incorporation of AgI into the cluster, and the single-crystal analyses show that the two ternary clusters consist of Hg, Ag, and Te centers occupying well-defined positions. Compounds 3a and 3b do not show the incorporation of the metal into the cluster, but the CoII and NiII salts provide the Cl atom to generate the anionic cluster 3 stabilized by the [Co(DMF)6]2+ or [Ni(DMF)6]2+ ion.     

Synthesis,chiroptical properties and absolute configuration of spiro[1,3-benzodioxole-methanocyclooct[b]indole

The synthesis of chiral 1'H-spiro[1,3-benzodioxole-2,12'-[6',10']methanocyclooct[b]indole] 3, a fused polycyclic structure derived from bicyclo[3.3.1]nonane, was accomplished via the Fisher indolization reaction. Enantiomers of this structure were obtained by chiral HPLC enantiomer separation on a swollen microcrystalline triacetylcellulose column. Chiroptical properties of the resolved enantiomers containing indole and 1,2-methylenedioxybenzene chromophores were studied. Application of the sector rule to the 1,2-methylenedioxybenzene chromophore to establish the absolute configuration of this polycyclic structure did not lead to an unequivocal conclusion which is likely to be due to the transannular interaction of the chromophores. The enantiospecific synthesis from enantiomerically enriched (-)-(1R,5S)-bicyclo[3.3.1]nonane-2,9-dione 1 was performed to prove unequivocally the (+)-(6'R,10'S)-configuration of the title structure. This study demonstrates that semiempirical rules should be applied cautiously to the determination of the absolute configuration of molecules containing several chromophores.     

Determination of polycyclic aromatic hydrocarbons with molecular weight 302 in water samples by solid-phase nano-extraction and laser excited time-resolved Shpol'skii spectroscopy

Monitoring of high-molecular weight polycyclic aromatic hydrocarbons (HMW-PAH) via simple and cost effective methods still remains a challenge. In this article, we combine solid-phase nano-extraction (SPNE) and 4.2 K laser-excited time resolved Shpol'skii spectroscopy (LETRSS) into a valuable alternative for the water analysis of dibenzo[a,l]pyrene, dibenzo[a,h]pyrene, dibenzo[a,i]pyrene and naphtho[2,3-a]pyrene. In comparison to the original SPNE procedure, the present method improves PAH recoveries and reduces extraction time from 30 to 20 min per sample. Quantitative release of HMW-PAH into the Shpol'skii matrix (n-octane) is best accomplished with a mixture of 48 μL of methanol and 2 μL of 1-pentanethiol. Their migration into the 50 μL layer of n-octane provides highly resolved spectra with distinct fluorescence lifetimes for unambiguous isomer determination. Complete analysis takes less than 30 min per sample and consumes only 100 micro-liters of organic solvents. 500 μL of water are sufficient to obtain limits of detection ranging from 16 ng L(-1) (dibenzo[a,l]pyrene) to 55 ng L(-1) (dibenzo[a,i]pyrene), relative standard deviations better than 3% and analytical recoveries above 90%. Although a straightforward comparison to chromatographic methods is not possible because of the lack of analytical figures of merit on HMW-PAH, the excellent precision of measurements, limits of detection and overall recoveries makes SPNE-LETRSS an attractive approach to water analysis of HMW-PAH.     

pH-dependence of the aqueous electrochemistry of the two-electron reduced alpha-[Mo18O54(SO3)] sulfite Dawson-like polyoxometalate anion derived from its triethanolammonium salt

The electrochemistry of the Dawson-like sulfite polyoxometalate anion alpha-[Mo18O54(SO3)2]6-, derived from the TEAH6{alpha-[Mo18O54(SO3)2]} salt (TEAH+ is the triethanolammonium cation; pKa=7.8), has been investigated in aqueous media using cyclic and rotated disk voltammetry at glassy carbon electrodes and bulk electrolysis, with a focus on the pH-dependence for oxidation to alpha-[Mo18O54(SO3)2]4-. In buffered media at pH>or=4, the cyclic voltammetric response for alpha-[Mo18O54(SO3)2]6- reveals two partially resolved one-electron oxidation processes corresponding to the sequential generation of alpha-[Mo18O54(SO3)2]5- and alpha-[Mo18O54(SO3)2]4-. At lower pH, using electrolytes containing sulfuric acid, the two waves coalesce but the individual apparent E0' reversible formal potential values for the two processes can be extracted down to pH 2 by assuming that reversible protonation accompanies fast electron transfer. The results for 2相似文献   

Room-temperature phosphorescence and energy transfer in luminescent multinuclear platinum(II) complexes of branched alkynyls

A series of luminescent branched platinum(II) alkynyl complexes, [1,3,5-{RC[triple bond]C(PEt3)2PtC[triple bond]C-C6H4C[triple bond]C}3C6H3] (R=C6H5, C6H4OMe, C6H4Me, C6H4CF3, C5H4N, C6H4SAc, 1-napthyl (Np), 1-pyrenyl (Pyr), 1-anthryl-8-ethynyl (HC[triple bond]CAn)), [1,3-{PyrC[triple chemical bond]C(PEt3)2PtC[triple bond]CC6H4C[triple bond]C}2-5-{(iPr)3SiC[triple bond]C}C6H3], and [1,3-{PyrC[triple bond]C(PEt3)2PtC[triple bond]CC6H4C[triple bond]C}2-5-(HC[triple bond]C)C6H3], was successfully synthesized by using the precursors [1,3,5-{Cl(PEt3)2PtC[triple bond]CC6H4C[triple bond]C}3C6H3] or [1,3-{Cl(PEt3)2PtC[triple bond]CC6H4C[triple bond]C}2-5-{(iPr)3SiC[triple bond]C}C6H3]. The X-ray crystal structures of [1,3,5-{MeOC6H4C[triple bond]C(PEt3)2PtC[triple bond]CC6H4C[triple bond]C}3C6H3] and [1,8-{Cl(PEt3)2PtC[triple bond]C}2An] have been determined. These complexes were found to show long-lived emission in both solution and solid-state phases at room temperature. The emission origin of the branched complexes [1,3,5-{RC[triple bond]C(PEt3)2PtC[triple bond]CC6H4C[triple bond]C}3C6H3] with R=C6H5, C6H4OMe, C6H4Me, C6H4CF3, C5H4N, and C6H4SAc was tentatively assigned to be derived from triplet states of predominantly intraligand (IL) character with some mixing of metal-to-ligand charge-transfer (MLCT) (dpi(Pt)-->pi*(C[triple bond]CR)) character, while the emission origin of the branched complexes with polyaromatic alkynyl ligands, [1,3,5-{RC[triple bond]C(PEt3)2PtC[triple bond]CC6H4C[triple bond]C}3C6H3] with R=Np, Pyr, or HC[triple bond]CAn, [1,3-{PyrC[triple bond]C(PEt3)2PtC[triple bond]CC6H4C[triple bond]C}2-5-{(iPr)3SiC[triple bond]C}C6H3], [1,3-{PyrC[triple bond]C(PEt3)2PtC[triple bond]CC6H4C[triple bond]C}2-5-(HC[triple bond]C)C6H3], and [1,8-{Cl(PEt3)2PtC[triple bond]C}2An], was tentatively assigned to be derived from the predominantly 3IL states of the respective polyaromatic alkynyl ligands, mixed with some 3MLCT (d(pi)(Pt)-->pi*(C[triple bond]CR)) character. By incorporating different alkynyl ligands into the periphery of these branched complexes, one could readily tune the nature of the lowest energy emissive state and the direction of the excitation energy transfer.     

When is a metallopolymer not a metallopolymer? When it is a metallomacrocycle

We report reactions of cobalt(II) acetate with a series of ditopic bis(tpy) ligands (tpy = 2,2':6',2'-terpyridine) containing flexible polyethyleneoxy spacers (tpy-4'-O{(CH(2))(2)O}(n)-4'-tpy, n = 2, 3, 4 or 6 ligands 1-4, respectively) which result in the formation of complicated mixtures of species, presumed to be both open chain and cyclic species. Well resolved paramagnetically shifted (1)H NMR spectra are a powerful tool for the analysis of these solution systems. Upon equilibration, [n + n] metallomacrocycles are isolated as the dominant (thermodynamic) species in some cases, and the single crystal X-ray structures of [Co(2)(3)(2)][PF(6)](4)·6MeCN and [Co(2)(4)(2)][PF(6)](5)·2MeCN (a mixed cobalt(ii)/cobalt(iii) species) are presented. Oxidation of the equilibrated cobalt(II) mixtures to kinetically inert cobalt(III) species provides additional evidence for the formation of metallomacrocycles as the thermodynamic products. Single crystal structural data for [Co(3)(2)(3)][PF(6)](9)·2MeCN·3.5H(2)O, [Co(2)(3)(2)][PF(6)](6)·10MeCN and [Co(2)(4)(2)][PF(6)](6)·6MeCN confirm the assembly of [2 + 2] and [3 + 3] metallomacrocycles. PGSE NMR spectroscopy has been used to determine the hydrodynamic radii of the solution species.