Imidazolium-based macrocycles as multisignaling chemosensors for anions

A series of structurally novel anion receptors , , and in which a ferrocene unit and a fluorescent moiety are linked to two imidazolium rings have been designed and prepared from 1,1'-bis(imidazolylmethyl)ferrocene. Their crystal structures revealed that these receptors are capable of incorporating anions such as PF(6)(-) and Br(-). Consequently, the anion binding studies were carried out using various techniques including electrochemistry (CV and OSWV), fluorescence, UV-vis, and (1)H NMR spectroscopy. All the receptors showed a special electrochemical response to the F(-) anion with a remarkable cathodic shift of more than 260 mV and displayed a unique selectivity for F(-) and AcO(-) anions with fluorescence enhancement over various other anions of present interest (Cl(-), Br(-), I(-), HSO(4)(-), H(2)PO(4)(-)). In addition, for receptor , obvious absorption changes were observed when the H(2)PO(4)(-) anion was added while other anions (F(-), Cl(-), Br(-), I(-), AcO(-), HSO(4)(-)) showed only a minor influence on the UV-vis spectra. (1)H NMR titrations demonstrated that receptors and can bind anions through (C-H)(+)X(-) hydrogen bonds and showed strong affinity and high selectivity for the AcO(-) anion in acetonitrile.     

1,1'-Binaphthyl-substituted macrocycles as receptors for saccharide recognition

The preparation of receptors for saccharide recognition in a natural environment has been an unmet goal for a long time. We present herein the synthesis and binding properties of (R,S)-1,1'-binaphthyl-substituted macrocycles as receptors for saccharide recognition in water/acetonitrile (1:1) and in DMSO. Porphyrin and metalloporphyrin macrocycles with two to four 1,1'-binaphthyl substituents and multiple hydroxy groups generate a binding site for saccharides that incorporates hydrogen-bonding hydroxy groups together with the aromatic hydrophobic pocket. The specificity for di- and trisaccharides is governed by the cavity size. The mechanism of binding has been studied by 1H NMR spectroscopy and the role of H-bonding and CH-pi interactions has been evaluated; the ability to bind saccharides has been demonstrated by the surface plasmon resonance (SPR) technique. The application of these macrocyclic receptors to sensor development is also presented.     

Bridged peptide macrocycles as ligands for PDZ domain proteins

[reaction: see text] Conformationally constrained side chain-bridged cyclic peptides were prepared using bis-carboxylic acid ring spacers. These macrocyles were designed to inhibit protein-protein interactions mediated by the third PDZ domain (PDZ3) of a mammalian neuronal protein, PSD-95. Isothermal titration calorimetry (ITC) experiments measured dissociation constants in the low micromolar range. For each compound, the change in entropy (TdeltaS) of binding either is comparable in magnitude to the enthalpy change (deltaH) or is the predominant driving force for association.     

Aza-crown macrocycles as chiral solvating agents for mandelic acid derivatives

A series of new chiral macrocycles containing the trans-1,2-diaminocyclohexane (DACH) subunit and arene- and oligoethylene glycol-derived spacers has been prepared in enantiomerically pure form. Four of the macrocycles have been characterized by X-ray crystallography, which reveals a consistent mode of intramolecular N-H···N hydrogen bonding and conformational variations about the N-benzylic bonds. Most of the macrocycles were found to differentiate the enantiomers of mandelic acid (MA) by (1)H NMR spectroscopy in CDCl(3); within the series of macrocycles tested, enantiodiscrimination was promoted by (i) a meta-linkage geometry about the arene spacer, (ii) the presence of naphthalene- rather than phenylene-derived arene spacers, and (iii) increasing length of the oligoethylene glycol bridge. (1)H NMR titrations were performed with optically pure MA samples, and the data were fitted to a simultaneous 1:1 and 2:1 binding model, yielding estimates of 2:1 binding constants between some of the macrocycles and MA enantiomers. In several cases, NOESY spectra of the MA:macrocycle complexes show differential intramolecular correlations between protons adjacent to the amine and carboxylic acid groups of the macrocycles and MA enantiomers, respectively, thus demonstrating geometric differences between the diastereomeric intermolecular complexes. The three most effective macrocycles were employed as chiral solvating agents (CSAs) to determine the enantiomeric excess (ee) of 18 MA samples over a wide ee range and with very high accuracy (1% absolute error).     

Penta-coordinated transition metal macrocycles as electrocatalysts for the oxygen reduction reaction

Journal of Solid State Electrochemistry - The oxygen reduction reaction (ORR) is a highly important reaction in electrochemistry. The following short review details recent advances in novel...     

Zn(II) Robson macrocycles as templates for chelating diphosphines

Chelating diphosphines were constructed using dinuclear Zn(II) complexes of Robson macrocycles (Zn-RMCs) as templates. The assembly process is driven by the interaction between the metal centers (Lewis acids) with anionic and neutral Lewis base-functionalized monophosphines. The stability of the final structure depends on the geometry and the affinity of the functional groups of the ditopic phosphines and on the structure of the RMC. In the free ligand the ditopic phosphines coordinate at opposite faces of the pseudo-planar macrocycle as is shown in the molecular structure of several of the assemblies, according to X-ray diffraction. Pre-organization of the system by coordinating the phosphorus atoms to a transition metal center enforced coordination of the functional groups at the same face of the RMC. For several templated diphosphines cis-PtCl(2) complexes were identified by NMR. The in situ assembled diphosphines showed a chelating effect in the rhodium catalyzed hydroformylation of 1-octene. Combination of Zn-RMC 3 and phosphine A gave the highest l/b ratio (13) in acetonitrile.     

Calixarenes and related macrocycles as gene delivery vehicles

The success of gene therapy depends largely on the development of new efficient gene delivery vehicles. The emerging class of molecules for this application is macrocycles that feature persistent shape, thus ensuring higher level of supramolecular organization of the DNA complexes. The review focuses on recently developed calixarenes and close analogues as gene delivery vectors, their chemistry, ability to compact nucleic acids, transfection ability in vitro and cytotoxicity. Their fixed conformation with the possibility of multiple functional groups at the upper and lower rims allows preparation of cone-shaped macromolecules capable of programmed hierarchical assembly in the presence of DNA. It is shown that specially designed calixarenes, particularly those having amphiphilic structure with clustered DNA binding units, can form small virus-sized DNA nanoparticles with well-defined architecture, high transfection efficiency and low toxicity. The field is still largely underexplored so that there is a lot of room for further improvement of the molecular design of calixarenes. Moreover, their evaluation in vivo on animals will be an important step towards their validation for gene therapy.     

C-substituted diethyleneimides of acids of phosphorus

Conclusions We have obtained the hitherto undescribed 2,2-dimethyl- and 2-ethylethyleneimides of alkylphosphorous acids and, by addition of sulfur and selenium to these compounds, the corresponding ethyleneimldes of alkylthio-and selenophosphoric acids.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1143–1144, May, 1968.     

Strained aromatic oligoamide macrocycles as new molecular clips

Can one join both ends of a helix? A helical aromatic oligoamide was macrocyclized into a saddle-shaped bifunctional clip molecule that self-assembles into discrete circular dodecamers in the solid state and shows great potential for binding aromatic acid guests in solution. The cyclization step requires that the helix is only partly denatured in the reaction medium.     

Strain visualization for strained macrocycles

Strain has a unique and sometimes unpredictable impact on the properties and reactivity of molecules. To thoroughly describe strain in molecules, a computational tool that relates strain energy to reactivity by localizing and quantifying strain was developed. Strain energy is calculated local to every coordinate in the molecule and areas of higher strain are shown experimentally to be more reactive. Not only does this tool directly compare strain energy in parts of the same molecule, but it also computes total strain to give a full picture of molecular strain energy. It is freely available to the public on GitHub under the name StrainViz and much of the workflow is automated to simplify use for non-experts. Unique insight into the reactivity of curved aromatic molecules and strained alkyne bioorthogonal reagents is described within.

Strain has a unique and sometimes unpredictable impact on the properties and reactivity of molecules.     

Asymmetric oxadiazole mesogens as candidates for low-temperature biaxial nematics

We report the synthesis and properties of a homologous series of asymmetric, mesogenic derivatives of 2,5-bis-(p-hydroxyphenyl)-1,3,4-oxadiazole (ODBP). Benzyloxy (BnO-), alkoxy benzoate ester derivatives BnO-ODBP-Ph-O-C _n , where n?=?4, 5, 6, 7, 8, 9, 12, were studied by ²H-NMR, X-ray diffraction and polarising microscopy in order to ascertain if the lower temperature nematic phases exhibited biaxiality. Deuterium nuclear magnetic resonance (NMR) of labelled probes in these asymmetric mesogens does not show evidence of biaxiality. The absence of biaxiality is discussed in terms of the statistical non-linearity of these asymmetric ODBP mesogens.     

Evaluation of nanopores as candidates for electronic analyte detection

In an effort to increase throughput and decrease the cost of electrophoretic separation of DNA and proteins, various groups are developing highly parallel, miniaturized separation devices based on capillaries etched into silicon, glass or plastic substrates. To date, these miniaturized devices have relied on optical detectors, thus placing a lower limit on instrument size, and complicating the incorporation of an entire DNA analyzer instrument on a chip. To address this limitation, we are evaluating nanopores as candidate Coulter counters for purely electronic detection of analytes in miniaturized electrophoresis and similar separation devices. To establish feasibility of this detection scheme, we have investigated the detection sensitivity of a nanopore sensor through experiments with the alpha-hemolysin (alpha-HL) ion channel, and through a Monte Carlo (MC) model of polymer capture rate with a cylindrical nanopore under an applied voltage. Experimental and model results are extrapolated to predict the capture rate of synthetic pores operating at higher voltages than presently achievable with protein pores.     

Resorcinarenes as templates: a general strategy for the synthesis of large macrocycles

The concept that resorcinarenes can be used as templates for the synthesis of large macrocycles is introduced. By way of example, previously inaccessible, aromatic crown ethers compounds are synthesized.     

Acridine-based macrocycles as potential probes for studies of the structures of nucleic acids

The possibility of the use of bis- and tris-acridine macrocycles as photoactivated reagents, which are sensitive to the DNA and RNA secondary structures, was examined. The bis- and tris-acridine macrocycles can induce photomodification (in the case of DNA) and photocleavage (in the case of RNA). Both processes occur predominantly at the purine residues located in loops or at the junction of the RNA and DNA hairpins.     

Polyazaphosphorus macrocycles

Abstract

A general way of preparation of phosphorus macrocycles is reported. Their chemical properties are described.     

188Re-labeled hyperbranched polysulfonamine as a robust tool for targeted cancer diagnosis and radioimmunotherapy

Hyperbranched polysulfonamine (HPSA) is a promising biomaterial due to its highly branched spherical architecture and efficient intracellular translocation. To realize the functionalization of HPSA, both N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) for tethering the human-mouse chimeric monoclonal antibody CH12 and N-hydroxy succinimidyl S-acetylmercaptoacetyltriglycinate (NHS-MAG₃) for labeling ¹⁸⁸Re were sequentially grafted onto the primary amine terminals of HPSA via covalent linkages, attaining the SPDP-HPSA-MAG₃ intermediate. In order to reserve the structural integrity of CH12, the fragment crystallizable (Fc) region was also processed by oxidation of oligosaccharide moieties with sodium periodate and then reacted with N-(κ-maleimidoundecanoic acid) hydrazide (KMUH). After chelating ¹⁸⁸Re with MAG₃ group, the SPDP was reduced to PDP and connected onto the maleinimide group at the Fc region. As a result, both the epidermal growth factor receptor vIII (EGFRvIII) targeted monoclonal antibody CH12 and the radionuclide ¹⁸⁸Re were conjugated to the HPSA-based vehicles, forming the ¹⁸⁸Re-labeled and CH12-tethered HPSA (CH12-HPSA-¹⁸⁸Re). The molecular weight and in vitro stability of CH12-HPSA-¹⁸⁸Re were evaluated by gel electrophoresis and paper chromatography. On one hand, the CH12-HPSA-¹⁸⁸Re could specifically bind to the EGFRvIII-positive human hepatocarcinoma cells in vitro. On the other hand, it could also target at the tumor tissue of nude mice in vivo. Hence, the CH12-HPSA-¹⁸⁸Re could effectively target at the human hepatocarcinoma and facilitate the tumor detection and targeted radioimmunotherapy.     

Pseudo-halogen behavior of thiophosphoryl azides as a tool for the functionalization of phosphorus macrocycles

Phosphoryl azides are known as azide-transfer agents in organic chemistry; such behavior denotes the pseudo-halogen character of the azide group when linked to a tetracoordinated phosphorus atom, but it was considered up to now only for the functionalization of organic substrates by N₃. We show in this paper that the azide can also be considered as a good leaving group, which facilitates the functionalization of the phosphorus atom which bore it. This reaction is first demonstrated on a small thiophosphoryl azide, then applied to the functionalization of more complex macromolecules, i.e. macrocycles incorporating in their structure thiophosphoryl azido groups.