Electroinitiated Polymerization of 3,3-BIS(N-Carbazolylmethyl)Oxetane

Abstract

3,3-Bis(N-carbazolylmethyl)oxetane, a cyclic compound with carbazolyl substituents closely linked to the oxetane ring, was polymerized by electrochemical initiation in aprotic polar solvents using a quaternary ammonium salt as electrolyte. Colored polymers were obtained as thin films deposited on the anode and were characterized by IR, ¹H NMR, and thermogravimetry. The data obtained refute the classical cationic polymerization of oxetanes.     

Polybenzimidazole-Ester-Imides

Thermostable heterocyclic polymers containing benzimidazole and imide rings, as well as flexible ester groups, have been synthesized by solution polycondensation of diaminobenzimidazoles with dianhydrides incorporating preformed ester linkages. The thermal stability and the electrical insulating properties of these products are discussed and compared with related heterocyclic polymers.     

Interaction of Naproxen with Crystalline and Amorphous Methylated β-Cyclodextrin in the Liquid and Solid State

Abstract

Interactions of naproxen (NAP) with amorphous, randomly methylated β-cyclodextrin at a degree of substitution per anhydroglucose unit of 1.8 (RAMEB) and with crystalline heptakis-(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) were studied in aqueous solution and in the solid state using, respectively, phase-solubility analysis (at 25 °C, 37 °C and 47 °C) and differential scanning calorimetry (DSC) supported by X-ray powder diffractometry. RAMEB and DIMEB displayed similar solubilizing and complexing abilities towards NAP, suggesting analogous inclusion modes of the drug in the host cavity in aqueous solution. Differences were instead observed in interactions in the solid state, where the amorphizing capacity of RAMEB toward NAP (evaluated by DSC) was about twice that of DIMEB at each drug-to-carrier ratio. Assuming that inclusion complexation is also involved in solid-state interactions, molecular modelling accounted for the experimental results in terms of structural features of DIMEB, i.e. the particular inwards orientation of O-6-C-8 groups of three alternate glucoses on the primary hydroxyl side which hampers a deep penetration of NAP in the DIMEB cavity in the solid state. On the contrary, no obstruction of the cavity apparently occurs with RAMEB due its noncrystalline state. The aqueous dissolution rate of NAP from NAP-RAMEB and NAP-DIMEB blends containing 0.59, 0.73, 0.85, and 0.92 mass fraction of carrier linearly increased at decreasing drug-to-carrier ratios. The improvement was 5 to 20 times (from powders) and 50 to 200 times (from discs) the dissolution rate of NAP alone for both carrier. Therefore the choice of the amorphous RAMEB in pharmaceutical formulations can be recommended mainly for economic reasons, though the anhydrous and non-hygroscopic nature of crystalline DIMEB might be of particular advantage in case of moisture sensitive formulations.     

Synthesis,binding and fluorescence studies of a new neutral H-bonding receptor for anions based on 3,5-bis(trifluoromethyl)phenylurea

The synthesis and anion binding studies of the new neutral receptor 1,1′-(2,2′-(4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diyl)bis(2-oxoethane-2,1-diyl))bis(3-(3,5-bis(trifluoromethyl)phenyl)urea) (L1) are reported. L1 is a macrocyclic ligand containing the 3,5-trifluoromethylphenylureido-binding fragment attached as a side arm on the tetraazacyclododecane. L1 is soluble in numerous organic solvents; the binding properties of L1 towards several simple anions (G) were investigated by NMR, UV–vis and fluorescence techniques in DMSO and CH₃CN solutions. L1 is able to bind F^? , Cl^?  and AcO^?  in both solvents; in addition, it binds Br^?  in CH₃CN. Fluoride shows the highest constant values in the halide series (F^?  > Cl^?  > Br^? ) and AcO^?  is the most strongly bound among all the anions investigated. L1 is able to signal the presence of the anions in solution by fluorescence change; in the case of acetate, this occurs in the visible range.     

A New Phosphonium Calix[4]arene for Selective Anion Recognition: Synthesis and Studies in Solution and in Ion Selective Electrodes

The synthesis and characterization of a new tetra (triphenylphosphonium) p-tert-butylcalix[4]arene 2 is presented. Its interactions with anions were studied by ¹H and ³¹P NMR and UV absorption spectrophotometry, showing the biggest interaction with ClO₄ ^? , I^?  and SCN^? . Anion selectivity in ion-selective PVC-membrane electrodes (ISEs) plasticized with o-NPOE containing ionophore 2 was also investigated. Compound 2 shows a potentiometric response for various anions with the following selectivity pattern: ClO₄ ^?  > SCN^?  > I^?  > Cr₂O₇ ^2 ?  > NO₃ ^?  > Br^?  > Cl^? .     

Design,Synthesis and Structural Analysis of New Macrocycles Containing Dispiro-1,3-dioxane Units

The synthesis and the structure of new macrocycles containing semiflexible dispiro-1,3-dioxane units is reported. The structural analysis of the compounds is performed by high field NMR spectra, mass spectrometry investigations (MALDI, ESI-MS) and the solid state molecular structure obtained for two compounds by single crystal X-ray diffractometry. The dynamics of the macrocycles promoted by the flipping of the middle cyclohexane ring of the dispirane units is investigated using low temperature NMR experiments.

New macrocycles containing dispiro-1,3-dioxane units were investigated by NMR, X-ray diffractometry and mass spectrometry     

Pyridyl-, bipyridyl-, and terpyridyl-functionalised azamacrocycles

Abstract

A series of azamacrocycles which have been N-functionalised with pendent pyridylmethyl-(pyCH₂-), bipyridylmethyl-(bipyCH₂-) and terpyridylmethyl- (terpyCH₂-) arms have been synthesised and characterised, and some of their coordination chemistry with transition metal ions is reported. By attaching the pendent-arms at the 5- rather than the 6-position of the py, bipy and terpy, new ligands are generated which can be used to form polynuclear metal complexes in a controlled and systematic fashion. Fluorescent pH and transition metal ion sensors have been developed by reacting the azamacrocyclic N-pendent bipyCH₂ arm(s) with cis-[Ru(bipy)₂Cl₂], to give macrocycles with up to four attached [Ru(bipy)₃]²⁺ groups. That based on 1,4,7-triazacyclononane (9N3), with three attached [Ru(bipy)₃]²⁺ groups, has a first photo excited state pK_a of 7.1, and is a useful fluorescent sensor for physiological pH at below micromolar concentrations. The analogous derivative of cyclam (1,4,8,11-tetraazacyclotetradecane) carrying four [Ru(bipy)₃]²⁺ groups has a first photo excited state pK_a of 5.7, allowing kinetic and thermodynamic fluorescence studies of metal ion uptake by an azamacrocycle at neutral pH without complications from protonated species. A pre-organised hexadentate tris(2,2′-bipyridyl) chelating ligand, 1,4,7-tris(2′,2″-bipyridyl-5′-ylmethyl)-1,4,7-triazacyclononane (L) has been developed, and crystal structures of mononuclear complexes [M(LH)]³⁺ (M = Ru, Cu) are reported. In [M(LH)]³⁺ the azamacrocyclic N-atoms are non-coordinating to M, but have a very high affinity for a single proton trapped in the macrocyclic cavity. An analogous and potentially nonadentate ligand has been developed based on 9N3 with three N-pendent terpyCH₂-arms.     

New artificial receptors from selectively functionalized calix[4]arenes

Abstract

The development of new synthetic methods for the monoalkylation of calix[4]arenes at the lower rim allows the synthesis of a new class of trihydroxamate siderophores. Three chelating hydroxamic acid units are introduced through a sequence of reactions which blocks the macrocycle in the cone conformation. The new ligands obtained form neutral 1:1 complexes (FeL) with iron (III), which are stable in EtOH/H₂O 9:1 at pH 2–7. Calix[4]arene bis-crown ethers are prepared by exploiting the selective 1,2-(proximal) functionalization of calix[4]arenes at the lower rim. These ligands are, however, less effective in complexing alkali metal cations compared with the 1,3-calix[4]arene crown-ethers which, in their partial cone structure, offer a better shielding for the complexed cations. Rigid upper rim-bridged calix[4]arenes potentially useful for the inclusion of neutral molecules are prepared by exploiting the selective 1,3-diformylation of calix[4]arene at the upper rim. Finally a new chloromethylation method for calix[4]arenes blocked in the cone conformation is described together with the synthesis of new cavitands.     

Structure‐oriented UHPLC‐LTQ Orbitrap‐based approach as a dereplication strategy for the identification of isoflavonoids from Amphimas pterocarpoides crude extract

Hyphenated techniques and especially ultra‐high performance liquid chromatography‐mass spectrometry (UHPLC‐MS) are nowadays widely employed in natural products research. However, the complex nature of plant extracts complicates considerably the analysis and the identification of their constituents. Nevertheless, new MS analyzers with increased resolving power and accuracy such as the orbital trap (Orbitrap) could facilitate drastically this process. The objective of this study is the development of a new structure‐oriented approach based on fast UHPLC‐high‐resolution (HR)MS and HRMS/MS methodologies for the identification of isoflavonoids in crude extracts. In addition, aims to assist dereplication procedures, to decrease the laborious isolation steps and orient the focused isolation of compounds of interest. As a proof of concept, the methanol extract of the stem bark of Amphimas pterocarpoides (Leguminosae) was selected. Based on chromatographic (retention time, polarity) and spectrometric features (ultraviolet spectra, accurate m/z, proposed elemental composition, ring double bond equivalent, and relative isotopic abundance) as well as HRMS/MS spectra, several isoflavonoids were identified. In order to verify the proposed structures, 11 isoflavonoids were selectively isolated and unambiguously identified using 1&2D nuclear magnetic resonance techniques. Moreover, the isolated isoflavonoids were studied in HRMS/MS level, employing electrospray ionization and atmospheric pressure chemical ionization sources, in both modes. Useful information regarding their fragmentation patterns was obtained, and characteristic diagnostic ions were defined for the identification of methoxylated isoflavones, dihydroisoflavones and 5‐hydroxylated isoflavonoids. Based on the current results, the proposed dereplication strategy was verified and could comprise a novel approach for the analysis of crude extracts in the future not only for isoflavonoids but also for other chemical classes of natural products. Copyright © 2013 John Wiley & Sons, Ltd.     

Sodiation as a tool for enhancing the diagnostic value of MALDI‐TOF/TOF‐MS spectra of complex astaxanthin ester mixtures from Haematococcus pluvialis

The microalga Haematococcus pluvialis produces the pigment astaxanthin mainly in esterified form with a multitude of fatty acids, which results in a complex mixture of carotenol mono‐ and diesters. For rapid fingerprinting of these esters, matrix‐assisted laser desorption ionization time of flight mass spectrometry (MALDI‐TOF/TOF‐MS) might be an alternative to traditional chromatographic separation combined with MS. Investigation of ionization and fragmentation of astaxanthin mono‐ and diester palmitate standards in MALDI‐TOF/TOF‐MS showed that sodium adduct parent masses [M + Na]⁺ gave much simpler MS² spectra than radical / protonated [M]^+● / [M + H]⁺ parents. [M + Na]⁺ fragments yielded diagnostic polyene‐specific eliminations and fatty acid neutral losses, whereas [M]^+● / [M + H]⁺ fragmentation resulted in a multitude of non‐diagnostic daughters. For diesters, a benzonium fragment, formed by polyene elimination, was required for identification of the second fatty acid attached to the astaxanthin backbone. Parents were forced into [M + Na]⁺ ionization by addition of sodium acetate, and best signal‐to‐noise ratios were obtained in the 0.1 to 1.0 mM range. This method was applied to fingerprinting astaxanthin esters in a crude H. pluvialis extract. Prior to MALDI‐TOF/TOF‐MS, the extract was fractionated by normal phase Flash chromatography to obtain fractions enriched in mono‐ and diesters and to remove pheophytin a, which compromised monoester signals. All 12 types of all‐trans esterified esters found in LC were identified with MALDI‐TOF/TOF‐MS, with the exception of two minor monoesters. Copyright © 2013 John Wiley & Sons, Ltd.