Wide Rim Research Articles

Calixarenes functionalized with phosphine oxide and diamide functions as extractants and ionofores for rare-earth metals

Calixarene-based ligands with phosphine oxide and diamide functions at wide and narrow rims are synthesized and studied as extracting agents for liquid extraction and ionophores for polymeric electrochemical ion sensors. Calixarene ligands are compared with corresponding phosphine oxide and diamide ligands which are not attached to the calixarene platform. Extraction and sensor properties of the ligands were studied in different metal ion solution with special attention paid to rare-earth metals. Attachment of phosphine oxide groups to the calixarene platform leads to the sharp increase of both extraction and sensing ability of the corresponding systems comparing to non-bonded phosphine oxide. In case of the diamide derivatives attached to the calixarene performance of corresponding ligands was similar to those of non-bonded diamides.

Theoretical and experimental study of the inclusion complexes of ferulic acid with cyclodextrins

The inclusion complexation behaviour of ferulic acid (FA) with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated by UV–vis, fluorescence and 1H NMR spectroscopy. Since the guest may exist in either anionic or neutral form, the experiments were performed at different pH values. The stoichiometry and association constants of the complexes were determined by nonlinear regression analysis. The phase-solubility studies indicated that the water solubility of FA was improved through complexation with β-CD and HP-β-CD. An increase in the antioxidant reactivity was observed when inclusion complexes that FA formed with CDs were studied. Based on the NMR data, the spatial configurations of FA/β-CD and FA/HP-β-CD complexes were proposed, which suggested that FA entered into the cavity of β-CD from the narrow side, with the lipophilic aromatic ring and ethylenic moieties inside the CD cavity, and the –COOH group was close to the wider rim and exposed outside the cavity. A theoretical study of the complexes using molecular modelling gives the results in good agreement with the NMR data.

The dorsal root ganglion in Friedreich’s ataxia

Atrophy of dorsal root ganglia (DRG) and thinning of dorsal roots (DR) are hallmarks of Friedreich's ataxia (FRDA). Many previous authors also emphasized the selective vulnerability of larger neurons in DRG and thicker myelinated DR axons. This report is based on a systematic reexamination of DRG, DR and ventral roots (VR) in 19 genetically confirmed cases of FRDA by immunocytochemistry and single- and double-label immunofluorescence with antibodies to specific proteins of myelin, neurons and axons; S-100alpha as a marker of satellite and Schwann cells; laminin; and the iron-responsive proteins ferritin, mitochondrial ferritin, and ferroportin. Confocal images of axons and myelin allowed the quantitative analysis of fiber density and size, and the extent of DR and VR myelination. A novel technology, high-definition X-ray fluorescence (HDXRF) of polyethylene glycol-embedded fixed tissue, was used to "map" iron in DRG. Unfixed frozen tissue of DRG in three cases was available for the chemical assay of total iron. Proliferation of S-100alpha-positive satellite cells accompanied neuronal destruction in DRG of all FRDA cases. Double-label visualization of peripheral nerve myelin protein 22 and phosphorylated neurofilament protein confirmed the known loss of large myelinated DR fibers, but quantitative fiber counts per unit area did not change. The ratio of myelinated to neurofilament-positive fibers in DR rose significantly from 0.55 to 0.66. In VR of FRDA patients, fiber counts and degree of myelination did not differ from normal. Pooled histograms of axonal perimeters disclosed a shift to thinner fibers in DR, but also a modest excess of smaller axons in VR. Schwann cell cytoplasm in DR of FRDA was depleted while laminin reaction product remained prominent. Numerous small axons clustered around fewer Schwann cells. Ferritin in normal DRG localized to satellite cells, and proliferation of these cells in FRDA caused wide rims of reaction product about degenerating nerve cells. Mitochondrial ferritin was not detectable. Ferroportin was present in the cytoplasm of normal satellite cells and neurons, and in large axons of DR and VR. In FRDA, some DRG neurons lost their cytoplasmic ferroportin immunoreactivity, whereas the cytoplasm of satellite cells remained ferroportin positive. Ferroportin in DR axons disappeared in parallel with atrophy of large fibers. HDXRF of DRG detected regional and diffuse increases in iron fluorescence that matched ferritin expression in satellite cells. The observations support the conclusions that satellite cells and DRG neurons are affected by iron dysmetabolism; and that regeneration and inappropriate myelination of small axons in DR are characteristic of the disease.

Photoswitchable ionophores based on 1,3-alternate calix[4]arenes bearing acridane units at the wide rim and bridged at the narrow rim by glycol chains

The complexation with alkali metal ions by calix[4]arenes with 1,3-alternate conformation bearing acridinium and acridane substituents at one rim and a glycol chain at the other rim has been studied by isothermal calorimetry. The thermodynamic parameters and the stoichiometry of the complexes are strongly influenced by the nature of the substituent (acridane or acridinium), by the solvent and by the length of the glycol chain. Both 9-methoxyacridane substituents are involved in the photoheterolysis leading to the corresponding acridinium calixcrowns. The nucleophilic attack of the methoxide leaving group reverses the reaction thermally. Therefore, the different complexation properties of acridane and acridinium calixcrowns can be switched on and off.

Photo, proton and metal ion responsive wide-rim acridane substituted calix[4]arenes

Calix[4]arenes bearing acridinium and acridane substituents at the wide rim and a short glycol chain and two OH-groups at the narrow rim have been prepared. The interaction with alkali metal ions can be identified with the naked eye by the change in solution color arising from deprotonation of the OH-groups. Unlike the acridane calixarenes, the acridinium-substituted calixarene-crown-4 binds sodium ions. Due to the photoheterolysis of the acridane, calixarene sodium ions are picked up from the acetonitrile solution due to the formation of acridinium calixarene.

Diffusion tensor magnetic resonance imaging of glial brain tumors

Aim To evaluate the author's experience with the use of diffusion tensor magnetic resonance imaging (DTI) on patients with glial tumors. Methods A retrospective evaluation of a group of 24 patients with glial tumors was performed. There were eight patients with Grade II, eight patients with Grade III and eight patients with Grade IV tumors with a histologically proven diagnosis. All the patients underwent routine imaging including T2 weighted images, multidirectional diffusion weighted imaging (measured in 60 non-collinear directions) and T1 weighted non-enhanced and contrast enhanced images. The imaging sequence and evaluation software were produced by Massachusetts General Hospital Corporation (Boston, MA, USA). Fractional anisotropy (FA) maps were calculated in all patients. The white matter FA changes were assessed within the tumorous tissue, on the tumorous borderline and in the normally appearing white matter adjacent to the tumor. A three-dimensional model of the white matter tract was created to demonstrate the space relationship of the tumor and the capsula interna or corpus callosum in each case using the following fiber tracing parameters: FA step 0.25 and a tensor declination angle of 45 gr. An additional assessment of the tumorous tissue enhancement was performed. Results A uniform homogenous structure with sharp demargination of the Grade II tumors and the wide rim of the intermedial FA in all Grade III tumors respectively, were found during the evaluation of the FA maps. In Grade IV tumors a variable demargination was noted on the FA maps. The sensitivity and specificity for the discrimination of low- and high-grade glial tumors using FA maps was revealed to be 81% and 87% respectively. If the evaluation of the contrast enhancement was combined with the evaluation of the FA maps, both sensitivity and specificity were 100%. Conclusion Although the evaluation of the fractional anisotropy maps is not sufficient for glioma grading, the combination of the contrast enhancement pattern and fractional anisotropy maps evaluation improves the possibility of distinguishing low- and high-grade glial tumors. Three-dimensional models of the white matter fibers in the corpus callosum and the internal capsule may be used in the presurgical planning.

Antioxidant and antiradical activities of resorcinarene tetranitroxides

Resorcinarene oxazines bearing four TEMPO fragments at the wide rim of the macrocycle were prepared through the aminomethylation of resorcinarene octols with 4-amino-TEMPO and formaldehyde. Tetra-TEMPO resorcinarenes are efficient scavengers of 1,1-diphenyl-2-picrylhydrazyl radicals. The model studies revealed that macrocyclic structure and intramolecular hydrogen bonding make considerable contribution to antiradical activity of these compounds. Tetra-TEMPO resorcinarenes show also superoxide dismutase-like activity and efficiently inhibit ABAP-induced peroxidation of linoleic acid.

Synthesis and Resolution of a Multifunctional Inherently Chiral Calix[4]arene with an ABCD Substitution Pattern at the Wide Rim: The Effect of a Multifunctional Structure in the Organocatalyst on Enantioselectivity in Asymmetric Reactions

An efficient synthetic route to inherently chiral calix[4]arenes with an ABCD substitution pattern at the wide rim in the cone conformation was developed for the first time. For the synthesis of inherently chiral ABCD-type calix[4]arenes, first 5,11-dibromo-17-(3,5-dimethylphenyl)-25,26,27,28-tetrapropoxycalix[4]arene (9) was prepared as a key intermediate. Then, functionalization of the calix[4]arene 9 was examined, and highly regioselective monofunctionalization was achieved via selective monolithiation of bromo groups. Various multifunctionalized inherently chiral ABCD-type calix[4]arenes can be synthesized by using this method; thus, the synthesis of inherently chiral phosphine and carboxylic acid derivatives of ABCD-type calix[4]arene was demonstrated. In addition, the aminophenol derivative 1b of an ABCD-type calix[4]arene with a 3,5-dimethylphenyl group at the wide rim was synthesized and resolved into optically pure enantiomers. The chiral calix[4]arene 1b was used as an organocatalyst in asymmetric Michael addition reactions of thiophenols. The effect of the 3,5-dimethylphenyl group at the wide rim of calix[4]arene 1b on enantioselectivity was examined, and a positive effect of the 3,5-dimethylphenyl group was observed.

Complex chemical zoning in eclogite facies garnet reaction rims: the role of grain boundary diffusion

In metapelites of the Saualpe complex (Eastern Alps) continuous 10 µm to 20 µm wide garnet reaction rims formed along biotite-plagioclase and biotite-perthite interfaces. The pre-existing mineral assemblages are remnants of low pressure high temperature metamorphism of Permian age. The garnet reaction rims grew during the Cretaceous eclogite facies overprint. Reaction rim growth involved transfer of Fe and Mg components from the garnet-biotite interface to the garnet-feldspar interface and transfer of the Ca component in the opposite direction. The garnets show complex, asymmetrical chemical zoning, which reflects the relative contributions of short circuit diffusion along grain boundaries within the polycrystalline garnet reaction rims and volume diffusion through the grain interiors on bulk mass transfer. It is demonstrated by numerical modelling that the spacing of the grain boundaries, i.e. the grain size of the garnet in the reaction rim is a first order control on its internal chemical zoning.

A Convenient Preparation of C-Silylated Calixarenes

Calix[4]arenes having multiple silyl groups on the upper (wide) rim were prepared from the corresponding bromocalixarenes by halogen-metal exchange with t-BuLi followed by silylation. The best results were obtained using the clear supernatant from a mixture of chlorosilane and triethylamine. With the higher molecular weight chlorosilanes, an aqueous workup was replaced by a filtration through a column of silica gel. p-(Trimethylsilyl)calixarene 17, the silicon analogue of the well-studied p-tert-butylcalixarene 1, formed a crystalline complex with toluene having a toluene molecule in the cone cavity with the toluene methyl protruding out at an angle.

CMPO-calix[4]arenes and the influence of structural modifications on the Eu(III), Am(III), Cm(III) separation

The syntheses of new calix[4]arenes featuring CMPO groups on the wide rim are reported and the extraction of Am(III) and Eu(III) from concentrated HNO3 aqueous phases are discussed with reference to the properties of the symmetric tetra-CMPO derivative 1 . All extraction studies were conducted in the same experimental conditions which allows to directly compare the dependence of the distribution coefficients of various calixarenes on the acid concentration (0.1 M < [HNO3] < 5 M). Calix[4]arene 1 becomes a very poor extractant if the length of the aliphatic chain between the amide and phosphine oxide groups of CMPO is increased, if the bridging methylene groups are replaced by sulfur atoms or if the macrocyclic cavity size is increased. By contrast, mixed amide — CMPO calix[4]arenes are nearly as effective than 1 . Moreover, Am(III)/Cm(III) separation coefficients between 1.5 and 3 have been obtained with unsymmetrical calix[4]arenes of type 1 with different aliphatic chains grafted on the narrow rim. Guidelines to anticipate the extraction ability of calix[4]arenes remain elusive because of the intricate solution behavior of these compounds.

Selective Monofunctionalization of Tri-urea-mono-acetamides of ­Calix[4]arenes on the Narrow Rim

The synthesis of calix[4]arenes substituted at their wide rim by three 3-aryl-urea and one acetamide group and at their narrow rim by three alkyl ether groups and one ether group ending in a carboxy function is described. The reaction sequence ensures that these functional groups are attached to the same phenolic unit. Two key intermediates have been additionally characterized by X-ray crystal structure analysis.

Self‐Assembled Chiral Dimeric Capsules from Difunctionalized N,C‐Linked Peptidocalix[4]arenes: Scope and Limitations

AbstractIn this paper we report the synthesis of the first examples of upper (wide) rim calix[4]arene amino acids 5 and 27, together with the conformational, self‐assembly and molecular inclusion properties of the N,C‐linked peptidocalix[4]arenes obtained from them. Whereas the dipropyl derivative 5 readily undergoes peptide synthesis allowing a small library of calix[4]arene pseudopeptides 12–21 to be obtained, the tetrapropoxy compound 27 preferentially gives upper‐rim‐bridged derivatives (e.g., 28) which are formed through an intramolecular condensation reaction. The tetrapropoxycalix[4]arene pseudopeptide 33 shows conformational and self‐assembly properties quite different to those of the dipropoxy derivatives 12–21. The observed differences are explained on the basis of the different conformational flexibilities of the two calix[4]arene scaffolds. Calixarene 5 is more rigid than 27 thanks to the presence of two OH groups at the lower (narrow) rim that are involved in strong intramolecular hydrogen bonds. Only peptidocalix[4]arenes 12–21 but not 33 form hydrogen‐bonded dimeric capsules in which the two macrocycles approach each other face‐to‐face and rotated by 180° with respect to the other in order to allow hydrogen‐bonding complementarity between the interacting peptide chains, which, in some cases (17–19), form an antiparallel β sheet enhancing the stability of the capsule. The structures of the chiral dimeric capsules were established by molecular modelling calculations and NOESY NMR experiments, which give consistent results, whereas their stability in CDCl3 (69 ≤ Kdim ≤ 950 M–1) was determined by dilution NMR experiments. Compound 12 forms both 1:1 and 2:1 [K11 = (7.8±1.2) × 102 M–1, K21 = (1.8±0.2) × 105 M–2] host:guest complexes with the methylpyridinium (MePy+) cation in CD2Cl2/CDCl3 (10:1, v/v). There is no evidence for a guest template effect in stabilizing the supramolecular capsule.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Anion Binding to Resorcinarene‐Based Cavitands: The Importance of CH⋅⋅⋅Anion Interactions

Anions rather than cations: While resorcinarenes bind cations through cation–π interactions, methylene-bridged cavitands surprisingly bind anions through CH⋅⋅⋅anion interactions with the acetal protons at the wider rim (see model of the complex in the scheme). Mass spectrometry, in agreement with theory, provides evidence for anion binding on the concave side of the cavitand bowl. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z703451_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Self-Assembled Polymers Based on bis-Tetra-Urea Calix[4]arenes Connected via the Wide Rim

Six double calixarenes were synthesised in which two tetra-urea calix[4]arenes are linked by a rigid spacer between the urea functions at their wide rim. The dimerisation of their tetra-urea parts leads to hydrogen-bonded polymeric assemblies in apolar solvents. The addition of the stoichiometric amount of a tetra-tosylurea calix[4]arene disrupts the polymeric structures due to the preferred formation of heterodimeric capsules between tetra-aryl and tetra-tosylurea calix[4]arenes. The existence of polymeric assemblies was further established by AFM studies on spin-coated samples.

Self-assembled dendrimers with uniform structure

Calix[4]arenes substituted at their wide rim by four aryl urea residues (1) form hydrogen-bonded dimers in apolar solvents. Replacement of one urea residue by an acetamido moiety leads to calix[4]arene derivatives (5) which form hydrogen-bonded tetramers under the same conditions. Both self-assembly processes occur independently. Therefore, molecules have been prepared in which a tetra-urea calix[4]arene and a tri-urea mono acetamide derivative are covalently connected between their narrow rims by a long, mainly aliphatic chain [-O-(CH(2))(n)-C(O)-NH-(CH(2))(m)-O-] (7). In the presence of an equimolar amount of tetra-tosyl urea calix[4]arene () they form dendritic assemblies since the well known heterodimerization of tetra-tosyl and tetra-aryl urea calix[4]arenes prevents the formation of a cross-linked structure. Covalent connection of adjacent urea residues leads to tetra-loop derivatives (3) that cannot form homodimers, but instead form heterodimers with tetra-aryl or tetra-tosylureas. Therefore, similar dendrimers should be available using the selective dimerization observed for 3. The formation of a single, structurally uniform dendrimer from eight building blocks is confirmed by (1)H NMR spectra, showing only peaks that are also found for respective model assemblies. Translational diffusion coefficients of the assemblies have been determined using (1)H DOSY NMR.

Calixarene receptors of environmentally hazardous and biorelevant molecules and ions

Abstract In the paper, a report on the rational design of the calixarene receptors bearing ligating, H-donor, H-acceptor fragments at the wide and/or narrow rim of the macrocycle is presented. The calixarenes form supramolecular complexes with various cations, anions, organic molecules, and biomolecules in solution, in the crystalline state and even in the gas phase. The calixarenes or their complexes can be used as materials for radionuclide extraction, construction of chemosensors, and drug design.

Spectrofluorometric, thermal, and molecular mechanics studies of the inclusion complexation of selected imidazoline-derived drugs with β-cyclodextrin in aqueous media

The inclusion complexes of selected imidazoline-derived drugs, namely Antazoline (AN), Naphazoline (NP) and Xylometazoline (XM) with β-cyclodextrin (β-CD) were investigated using steady-state fluorescence spectroscopy, differential scanning calorimetry (DSC), and molecular mechanics (MM) calculations and modeling. The modified form of the Benesi-Hildebrand relation was employed for estimating the formation constant (Kf) of the 1:1 inclusion complexes, which was applied based on measuring the variation in the fluorescence intensity of the guest molecule as a function of growing β-CD concentration. On the other hand, the formation of the inclusion complexes was verified by analyzing solid samples of the complexes using DSC. The thermodynamics of the inclusion complexation, standard enthalpy (ΔH°) and entropy changes −(ΔS°) were obtained from the temperature-dependence of Kf. Obtained values of ΔH° and ΔS° indicated that the inclusion process favorably proceeds through enthalpy changes that was sufficiently predominant to compensate for the unfavorable entropy changes. MM calculations revealed that the proposed drugs molecules can form 1:1 inclusion complexes with β-CD that are stabilized predominantly through van der Waals forces. In addition, MM calculation provided the energetically favored configuration of the inclusion complexes, where NP and XM can be included inside the β-CD cavity through its wide rim, whereas AN can penetrate through the narrow rim of the β-CD cavity.

Effect of state of compensation on the relaxation of crustal plateaus on Venus

Building on Nunes et al. (2004), which examined the end‐member case of viscous relaxation of fully compensated crustal plateaus on Venus, we now investigate viscous relaxation for the other end‐member case of uncompensated topography. The approach consists of modeling viscous flow in a crust‐mantle system by means of analytic and finite element methods. Differential stresses produced by uncompensated plateau topography concentrate beneath the entire domain of the plateau and extend deep into the mantle. Loss of topography occurs via fast subsidence due to isostatic adjustment, and a slower lateral flow due to spreading of the thickened crust. Rims arise from the isostatic adjustment, and rim dimensions depend on the thickness of the competent layer, controlled by the thermal state of the system. Rim dimensions after 1 Myr are ∼1 km high and ∼300 km wide for a surface temperature of 740 K and thermal gradient of <10 K/km, and ∼600 m high and ∼100 km wide for hotter crustal conditions. Although models predict the marginal circumferential (hoop) folding observed at crustal plateaus, they do not account for the large radial grabens also observed. Adding a subcrustal zone of time‐dependent buoyancy causes a delay in the isostatic adjustment. During this period of delay, viscous flow in a relatively hot crust leads to a reduction in rim amplitude once isostatic adjustment takes place. Only cooler conditions in this model can reproduce the wide and high rims observed at crustal plateaus on Venus. Consequently, phase transitions in the lower crust may produce sufficiently large variations in buoyancy to affect the surface topography and are more compatible with a cooler thermal state, but they cannot explain the thickened crust or the interpretation of gravity data showing current isostatic support. Lateral variation in heat flow (and thickness of the competent layer) may help address the latter and needs to be explored through both lithospheric and mantle convection models.

Calix[4]arene‐Based Bis[2]catenanes: Synthesis and Chiral Resolution

The exclusive formation of hydrogen-bonded dimers between tetraaryl and tetratosylurea calix[4]arenes has been used to prepare a series of ten "bisloop" tetraurea calix[4]arenes 3, in which adjacent phenylurea groups are covalently linked through alpha,omega-dioxyalkane chains. This dimerization with tetratosylurea 2 as template preorganizes the alkenyl residues of tetra(m-alkenyloxyphenyl) ureas 1 and enables their selective connection in high yield (up to 95 %) by olefin metathesis followed by hydrogenation. The "bisloop" calixarenes 3 also exclusively form heterodimers with 1. Thus, in a separated metathesis/hydrogenation sequence, a series of 14 cyclic bis[2]catenanes 4, in which two calix[4]arenes are connected through their wide rims by two pairs of interlocked rings (total size 29 to 41 atoms), were prepared in yields of up to 97 %. Optical resolution of these chiral bis[2]catenanes was studied by HPLC on chiral stationary phases. The single-crystal X-ray structure of one example (4(P,10)) confirmed the interlocking rings and revealed that the hydrogen-bonded dimeric capsule of the calix[4]arene can be "completely" opened.