Synthesis and chelation study of a fluoroionophore and a glycopeptide based on an aza crown iminosugar structure.

Capitalizing on a recently reported iminosugar-based aza-crown (ISAC) accessed by a double Staudinger azaWittig coupling reaction, we have expanded the structural diversity of this new family of sweet cyclam analogs. Replacement of the two secondary amines linking the iminosugar units by two amide bonds obtained a cyclodimerization by with BOP and DIPEA led to a macrocycle that did not demonstrate efficient Zn2+ chelation unlike the parent ISAC. Introduction of two pyrene moieties on the secondary amines of the parent ISAC yielded a new fluoroionophore that selectively binds Hg2+ in methanol.

Combined Effects of Confinement and Macromolecular Crowding on Protein Stability.

Confinement and crowding have been shown to affect protein fates, including folding, functional stability, and their interactions with self and other proteins. Using both theoretical and experimental studies, researchers have established the independent effects of confinement or crowding, but only a few studies have explored their effects in combination; therefore, their combined impact on protein fates is still relatively unknown. Here, we investigated the combined effects of confinement and crowding on protein stability using the pores of agarose hydrogels as a confining agent and the biopolymer, dextran, as a crowding agent. The addition of dextran further stabilized the enzymes encapsulated in agarose; moreover, the observed increases in enhancements (due to the addition of dextran) exceeded the sum of the individual enhancements due to confinement and crowding. These results suggest that even though confinement and crowding may behave differently in how they influence protein fates, these conditions may be combined to provide synergistic benefits for protein stabilization. In summary, our study demonstrated the successful use of polymer-based platforms to advance our understanding of how in vivo like environments impact protein function and structure.

Codeposition Modification of Cation Exchange Membranes with Dopamine and Crown Ether To Achieve High K+ Electrodialysis Selectivity.

Surface modification has been proven to be an effective approach for ion exchange membranes to achieve separation of counterions with different valences by altering interfacial construction of membranes to improve ion transfer performance. In this work, we have fabricated a series of novel cation exchange membranes (CEMs) by modifying sulfonated polysulfone (SPSF) membranes via codeposition of mussel-inspired dopamine (DA) and 4'-aminobenzo-15-crown-5 (ACE), followed by glutaraldehyde cross-linking, aiming at achieving selective separation of specific cations. The as-prepared membranes before and after modification were systematically characterized in terms of their structural, physicochemical, electrochemical, and electrodialytic properties. In the electrodialysis process, the modified membranes exhibit distinct perm selectivity to K+ ions in binary (K+/Li+, K+/Na+, K+/Mg2+) and ternary (K+/Li+/Mg2+) systems. In particular, at a constant current density of 5.0 mA·cm-2, modified membrane M-co-0.50 shows significantly prominent perm selectivity [Formula: see text] in the K+/Mg2+ system and M-co-0.75 exhibits remarkable performance in the K+/Li+ system [Formula: see text], superior to commercial monovalent-selective CEM (CIMS, [Formula: see text], [Formula: see text]). Besides, in the K+/Li+/Mg2+ ternary system, K+ flux reaches 30.8 nmol·cm-2·s-1 for M-co-0.50, while it reaches 25.8 nmol·cm-2·s-1 for CIMS. It possibly arises from the effects of pore-size sieving and the synergistic action of electric field driving and host-guest molecular recognition of ACE and K+ ions. This study can provide new insights into the separation of specific alkali metal ions, especially on reducing influence of coexisting cations K+ and Na+ on Li+ ion recovery from salt lake and seawater.

Sm(iii)[12-MCGa(III)shi-4] as a luminescent probe for G-quadruplex structures.

G-quadruplexes (GQs), spatial assemblies of guanine-rich DNA strands, play an important role in the regulation of gene expression and chromosome stabilization. These structures are recognized to be useful in cancer therapies as the presence of multiple G-quadruplexes in a telomeric strand stops cancer cell proliferation. Metallacrowns of the type 12-MC-4 form planar structures that have remarkable similarity to G-tetrads in terms of dimension, shape and the ability to bind alkali metal and lanthanide cations in a central cavity. The interaction between the Sm(iii)[12-MCGa(III)shi-4] (SmMC) metallacrown (MC) and human telomeric G-quadruplex structures was examined using several methods including CD titrations, CD melting temperatures, fluorescence titration of SmMC with GQ/Na+, fluorescence intercalator displacement (FID) assays and methods measuring the MC quenching effect on the Tb3+/GQ luminescence. It was proven that the studied metallacrown acted as a sensing probe and interacted with quadruplex DNA. The Stern-Volmer quenching constant (Kas) of Tb3+/GQ luminescence was calculated to be 3.9 × 105 M-1. The binding constant using the indirect FID method gave the result of 1.3 × 105 M-1. CD melting temperature experiments reveal the following pattern - the higher the concentration of the complex the lower the registered Tm for quadruplex DNA, which indicates a destabilizing effect of SmMC at higher GQ : MC ratios. These data implicate a shape and size selective interaction between MCs and GQs that may be exploited for telomere detection.

Luminescent properties of 4-aminobenzo-15-crown-5 after preferential binding of ferric ions in aqueous solutions.

We report a combined approach that introduces the use of 4-aminobenzo-15-crown-5 (4AB15C5) for the detection of ferric(III) ions by colorimetric, ultraviolet (UV)-visible light absorption, fluorescence, and live-cell imaging techniques along with density functional theory (DFT) calculations. We have found that 4AB15C5 is sensitive and selective for binding ferric(III) ions in aqueous solutions. DFT calculations using the polarizable continuum model have been used to explain the strong binding of the ferric ion by 4AB15C5 in aqueous solutions. The detection limit in the fluorescence quenching measurements was found to be as low as 50 µM for the ferric ion with a determined Stern-Volmer constant of 1.52 × 104  M-1 . Fluorescence intensity did not change for other ions tested, Fe2+ , Co2+ , Mn2+ , Mg2+ , Zn2+ , Ca2+ , NH4+ , Na+ , and K+ ions. Live-cell fluorescence imaging was also used to check the intracellular variations in ferric ion levels. Our spectroscopic data indicated that 4AB15C5 can bind ferric ions selectively in aqueous solutions.

Antibiotic Potency against E.†coli Is Enhanced by Channel-Forming Alkyl Lariat Ethers.

Several N,N'-bis(n-alkyl-4,13-diaza[18]crown-6) lariat ethers were found to significantly enhance the potency of rifampicin and tetracycline, but not erythromycin and kanamycin, against the non-pathogenic DH5α and K-12 strains of Escherichia coli when administered at levels below their minimum inhibitory concentrations (MICs). The enhancements in antibiotic potency observed for the lariat ethers ranged from three- to 20-fold, depending on the strain of E. coli, the antibiotic, and the lengths of the alkyl chains attached at the macroring nitrogen atoms. The dialkyl lariat ethers, previously thought to only be cation carriers, formed well-behaved, ion-conducting pores in soybean asolectin membranes, as judged by planar bilayer conductance measurements. The ability of lariat ethers to form stable pores, which appeared to be aggregated, depended in part on alkyl chain length and in part on the composition of the bilayer membrane in which they were studied.

Pillar-Shaped Macrocyclic Hosts Pillar[n]arenes: New Key Players for Supramolecular Chemistry.

In 2008, we reported a new class of pillar-shaped macrocyclic hosts, known as "pillar[n]arenes". Today, pillar[n]arenes are recognized as key players in supramolecular chemistry because of their facile synthesis, unique pillar shape, versatile functionality, interesting host-guest properties, and original supramolecular assembly characteristics, which have resulted in numerous electrochemical and biomedical material applications. In this Review, we have provided historical background to macrocyclic chemistry, followed by a detailed discussion of the fundamental properties of pillar[n]arenes, including their synthesis, structure, and host-guest properties. Furthermore, we have discussed the applications of pillar[n]arenes to materials science, as well as their applications in supramolecular chemistry, in terms of their fundamental properties. Finally, we have described the future perspectives of pillar[n]arene chemistry. We hope that this Review will provide a useful reference for researchers working in the field and inspire discoveries concerning pillar[n]arene chemistry.

Cesium cation templated selective synthesis of a "cone-shaped" sugar macrotricyclic cryptand: A dual anion-cation molecular recognition of potassium tartrate.

Cesium templated Staudinger-aza-Wittig tandem reaction (S.A.W.) has been used in the synthesis of a bis-diazacrown-bis-cellobiosyl-tetra-ureido cryptand. A novel macrotricyclic compound having a "cone-shaped" configuration was selectively obtained. Additionally, first results on potential recognition properties of the cryptand are also given.

Interaction of metallacrown complexes with G-quadruplex DNA.

Interactions of the G-quadruplex (GQ) DNA with two pentacoordinate lanthanide (III) metallacrown (MC) complexes containing phenylalanine hydroxamic acid (pheHA) and copper(II) ions of the formula Eu 15-[MCCu,pheHA]-5 (1) and Tb 15-[MCCu,pheHA]-5 (2) were investigated. Binding of both metallacrowns to human telomeric G-quadruplex DNA was followed using CD spectroscopy, DNA melting profiles, and fluorescent intercalator displacement (FID) assay. A new G-quadruplex binding assay based of quenching of Tb(III)-GQ luminescence was proposed and evaluated. All performed tests confirmed interactions of MCs with studied GQ structure. Binding affinities of MCs were appreciable (KMC ~2-5×10(5)M(-1)). Higher concentration of MCs (the ratio of GQ:MC above 2.5) caused destabilization of tetraplex structure of GQ as evidenced by CD spectroscopy, melting temperatures, and Tb(III)-GQ luminescence quenching results.

Engineered Ionic Gates for Ion Conduction Based on Sodium and Potassium Activated Nanochannels.

In living systems, ion conduction plays a major role in numerous cellular processes and can be controlled by biological ion channels in response to specific environmental stimuli. This article describes biomimetic ionic gates for ion conduction based on sodium and potassium activated nanochannels. The Na(+) activated ionic gate and K(+) activated ionic gate were developed by immobilizing the alkali metal cation-responsive functional molecules, 4'-aminobenzo-15-crown-5 and 4'-aminobenzo-18-crown-6, respectively, onto the conical polyimide nanochannels. When the ionic gate was in the presence of the specific alkali metal cation, positively charged complexes formed between the crown ether and the alkali metal cation. On the basis of the resulting changes in surface charge, wettability and effective pore size, the nanochannel can achieve reversible switching. The switching behaviors of the two complexes differed due to the differences in binding strength between the two complexes. The Na(+) activated ionic gate is able to open and close to control the ion conduction through the nanochannel, and the K(+) activated ionic gate enables selective cation and anion conduction through the nanochannel. The Na(+) and K(+) activated ionic gates show great promise for use in clinical medicine, biosensors and drug delivery based on their high sensitivity and selectivity of being activated, and good stability.

Improved selectivity for Pb(II) by sulfur, selenium and tellurium analogues of 1,8-anthraquinone-18-crown-5: synthesis, spectroscopy, X-ray crystallography and computational studies.

We report here a series of heteroatom-substituted macrocycles containing an anthraquinone moiety as a fluorescent signaling unit and a cyclic polyheteroether chain as the receptor. Sulfur, selenium, and tellurium derivatives of 1,8-anthraquinone-18-crown-5 (1) were synthesized by reacting sodium sulfide (Na2S), sodium selenide (Na2Se) and sodium telluride (Na2Te) with 1,8-bis(2-bromoethylethyleneoxy)anthracene-9,10-dione in a 1 : 1 ratio. The optical properties of the new compounds are examined and the sulfur and selenium analogues produce an intense green emission enhancement upon association with Pb(II) in acetonitrile. Selectivity for Pb(II) is markedly improved as compared to the oxygen analogue 1 which was also competitive for Ca(II) ion. UV-Visible and luminescence titrations reveal that 2 and 3 form 1 : 1 complexes with Pb(II), confirmed by single-crystal X-ray studies where Pb(II) is complexed within the macrocycle through coordinate covalent bonds to neighboring carbonyl, ether and heteroether donor atoms. Cyclic voltammetry of 2-8 showed classical, irreversible oxidation potentials for sulfur, selenium and tellurium heteroethers in addition to two one-electron reductions for the anthraquinone carbonyl groups. DFT calculations were also conducted on 1, 2, 3, 6, 6 + Pb(II) and 6 + Mg(II) to determine the trend in energies of the HOMO and the LUMO levels along the series.

A thiacalix[4]crown based chemosensor for Zn²âº and H2PO4⁻: sequential logic operations at the molecular level.

A thiacalix[4]crown based di-topic receptor 3 possessing two types of binding sites viz. crown-5 ring and imino moieties has been synthesized which undergoes fluorescence enhancement in the presence of Zn(2+) ions. The selective binding of Zn(2+) to compound 3 does not allow the K(+) ions to bind with the crown-5 ring and thus a negative allosteric behaviour has been observed between Zn(2+)/K(+) ions. In addition, the 3-Zn(2+) complex can be used for the detection of H2PO4(-) ions with a fluorescence "turn-off" response. Furthermore, based on the fluorescence response, a two input and one output sequential logic circuit has been constructed.

A thermodynamic insight into the recognition of hydrophilic and hydrophobic amino acids in pure water by aza-scorpiand type receptors.

Interactions of different hydrophilic (His, Asp, Glu,) and hydrophobic (Ala, Phe, Tyr, Trp) amino acids in water with a scorpiand aza-macrocycle (L1) containing a pyridine group in the ring and its derivative (L2) bearing a naphthalene group in the tail have been analysed by potentiometric and calorimetric measurements. Theoretical calculations corroborate that major attractive forces that hold the adduct together are hydrogen bonds and salt-bridges, even though other interactions such as π-stacking or NH(+)⋯π may contribute in the case of hydrophobic amino acids and L2. Calorimetric measurements indicate that the interactions between L1 and the different amino acids are principally driven by entropy, often associated with solvation/desolvation processes.

Direct and short construction of the ACDE ring system of daphenylline.

Daphenylline, a novel daphniphyllum alkaloid, boasts a fused and bridging ring system coupled with six stereogenic centers. Here we present a direct and short construction of the ACDE ring system of daphenylline from the known 3-(2-bromophenyl)propanal in 10 steps and 17 % overall yield. The synthesis features an iron(III)-catalyzed aza-Cope-Mannich reaction, a self-terminating 6-exo-trig aryl radical-alkene cyclization and an intramolecular Friedel-Crafts acylation.

Homochiral columns constructed by chiral self-sorting during supramolecular helical organization of hat-shaped molecules.

A library of dendronized cyclotriveratrylene (CTV) crowns substituted with chiral, racemic, or achiral peripheral alkyl chains, including enantiopure R and S branched alkyls, "racemic by mixture", "racemic by synthesis", n-octyl, and n-dodecyl groups was synthesized. In solvophobic solvents and in bulk they self-assemble in helical columns. Their solution and bulk shape-persistent supramolecular structures were determined by a complementary combination of circular dichroism (CD) and UV in solution and thin film, microspot CD in thin film, differential scanning calorimetry combined with fiber X-ray diffraction, computer simulation, and molecular models. In solution, self-assembly via a cooperative mechanism generates single-handed columns from enantiopure CTVs and mixtures of right- and left-handed columns from racemic by mixture, racemic by synthesis, other combinations of R and S, and even from achiral compounds. In bulk state all supramolecular columns form a 3D hexagonal crystalline phase, Φ(h)(k) (P63 symmetry), that can be obtained only from single-handed columns and a columnar hexagonal 2D liquid crystal, Φ(h). The highest order Φ(h)(k) consists of enantiopure single-handed columns that are slightly distorted 12-fold triple helices. The "hat-shaped" dendronized CTV assembles in bent-branch pine-tree columns that allow interdigitation of alkyl groups in adjacent columns regardless of their direction. Enantiomerically rich, racemic, and achiral compositions undergo deracemization in the crystal state by transfer of the transient disc-like conformer of dendronized CTV from column to column during crown inversion. Solid state NMR experiments identified motional processes that allow such transfer. This unprecedented supramolecular chiral self-sorting will impact the creation of functions in complex systems.

Understanding spin structure in metallacrown single-molecule magnets using magnetic compton scattering.

The 3d-4f mixed metallacrowns frequently show single-molecule magnetic behavior. We have used magnetic Compton scattering to characterize the spin structure and orbital interactions in three isostructural metallacrowns: Gd2Mn4, Dy2Mn4, and Y2Mn4. These data allow the direct determination of the spin only contribution to the overall magnetic moment. We find that the lanthanide 4f spin in Gd2Mn4 and Dy2Mn4 is aligned parallel to the Mn 3d spin. For Y2Mn4 (manganese-only spin) we find evidence for spin delocalization into the O 2p orbitals. Comparing the magnetic Compton scattering data with SQUID studies that measure the total magnetic moment suggests that Gd2Mn4 and Y2Mn4 have only a small orbital contribution to the moment. In contrast, the total magnetic moment for Dy2Mn4 MCs is much larger than the spin-only moment, demonstrating a significant orbital contribution to the overall magnetic moment. Overall, these data provide direct insight into the correlation of molecular design with molecular magnetic properties.

Synthesis and characterization of novel macroporous silica-polymer-calixcrown hybrid supramolecular recognition materials for effective separation of cesium.

Two novel macroporous silica-polymer-calixcrown hybrid supramolecular recognition materials, 25,27-bis(n-octyloxy)calix[4]arene-crown-6 (BnOCalix[4]C6)/SiO2-P and 25,27-bis(i-octyloxy)calix[4]arene-crown-6 (BiOCalix[4]C6)/SiO2-P were synthesized by in situ polymerization and impregnation techniques. The obtained materials were characterized by scanning electron microscope (SEM), particle size distribution, nitrogen adsorption-desorption isotherms, thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, (29)Si solid-state NMR, and powder X-ray diffraction (XRD). The adsorption of some typical fission and non-fission products Na(I), K(I), Rb(I), Cs(I), Sr(II), Ba(II), La(III), Y(III), Pd(II), Ru(III), Zr(IV), and Mo(VI) onto BnOCalix[4]C6/SiO2-P and BiOCalix[4]C6/SiO2-P in HNO3 solution was investigated. The bleeding of the materials in HNO3 solution was evaluated by analysis of total organic carbon (TOC). BnOCalix[4]C6/SiO2-P and BiOCalix[4]C6/SiO2-P exhibited excellent adsorption ability and high selectivity for Cs(I) over all the other tested metals.

Thiacalix[4]crown based optical chemosensor for Fe3+, Li+ and cysteine: a Fe3+/Li+ ion synchronized allosteric regulation.

A heteroditopic chemosensor 2 based on a thiacalix[4]crown with a 1,3-alternate conformation has been synthesized and shows a selective fluorescence turn-off response with Fe(3+) ions in mixed aqueous media. Furthermore, the 2-Fe(3+) complex can be used as a chemosensing system for the detection of Li(+) and cysteine based on two different approaches. Moreover, the sequence addition of Fe(3+) and Li(+) triggers an Fe(3+)/Li(+) switchable on-off-on fluorescence chemosensor with negative allosteric regulations.

Rigid Mn(II) chelate as efficient MRI contrast agent for vascular imaging.

The aza-semi-crown pentadentate ligand rigidified by pyridine and piperidine rings was designed and synthesized. It can react with Mn(II) in water to form complex with improved longitudinal relaxivity, leading to efficient signal intensity enhancement of vascular vessels under a clinical magnetic resonance imaging scanner.

A new ion selective electrode for cesium (I) based on calix[4]arene-crown-6 compounds.

A polyvinylchloride (PVC) based liquid membrane ion selective electrode (ISE) for cesium has been developed. 25,27-Dihydroxycalix[4]arene-crown-6 (L1), 5,11,17,23-tetra-tert-butyl-25,27-dimethoxycalix[4]arene-crown-6 (L2) and 25,27-bis(1-octyloxy)calix[4]arene-crown-6 (L3) were investigated for their use as ionophores. The cation exchange resin DOWEX-50W was used to maintain low activity Cs+ in inner filling solution to improve the performance. The best response for cesium was observed with L3 along with optimized membrane constituents and composition. Excellent Nernstian response (56.6 mV/decade of Cs(I)) over the concentration range 10(-7) to 10(-2)M of Cs(I) was obtained with a fast response time of less than 10s. Detection limit for Cs(I) using the present ISE is 8.48×10(-8) M Cs(I). Separate solution method (SSM) was applied to ascertain the selectivity for Cs(I) over alkali, alkaline earth and transition metal ions. The response of ISE for Cs(I) was fairly constant over the pH range of 4-11. The lifetime of the electrode is 10 months which is the highest life for any membrane based Cs-ISE so far developed. The concentration of cesium ion in two simulated high level active waste streams was determined and results agreed well with those obtained independently employing AAS.