Macrocyclic Ethers Research Articles

Hexagonal wheel formation through the hydrogen-bonded assembly of cobalt Pacman complexes

A cobalt aquo-hydroxo complex of a ditopic Schiff-base pyrrole-crown ether macrocycle has been prepared and forms a rigid Pacman-clefted structure that assembles through hydrogen-bonding into a hexagonal wheel motif in the solid state.

ChemInform Abstract: Fluorinated Macrocyclic Ethers as Fluoride Ion Hosts. Novel Structures and Dynamic Properties.

ChemInform Abstract: Fluorinated Macrocyclic Ethers as Fluoride Ion Hosts. Novel Structures and Dynamic Properties.

A Convenient Approach to 16‐, 19‐, and 22‐Membered 2,2′‐Bipyridine Thiacrown Ethers and Their Conformation Preferences

AbstractA convenient, three‐step synthesis of 1:1 thiacrown ether macrocycles 5a–c containing a fused cyclopenteno[c]2,2′‐bipyridine subunit has been accomplished through first homocoupling of 1,2,4‐triazine bisulfides 3a–c tethered to poly(ethylene glycol) chains with potassium cyanide and secondDiels–Alder/retro‐Diels–Alder reaction of such obtained thiamacrocycles 4a–c with 1‐pyrrolidino‐1‐cyclopentene. Macrocycles 5a–c were oxidized to nonracemic monosulfoxides 6a–c by using Davis' oxaziridine and tested in the asymmetric addition of the diethylzinc to benzaldehyde. The crystal structure determinations of 5a–c and 6b and theoretical calculations at the DFT/B3LYP/6‐311G** level were used to establish their cis or trans conformations in the solid state and the gas phase.

Diaquabromidocopper(II)–18-crown-6–water (1/1/2)

In the title compound, [CuBr2(H2O)2]·C12H24O6·2H2O, the CuII atom, which is situated on an inversion centre and has a slightly distorted square-planar geometry, and the two coordinated water mol­ecules are linked to the 18-crown-6 macrocycles by O—H⋯O hydrogen bonds. The water mol­ecule of crystallization further links the metal complex and the crown ether macrocycles into a chain along the c axis.

ChemInform Abstract: The Synthesis of 14-Membered Macrocyclic Ethers.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Lectin-Targeted Crown Ethers. Part 1. Synthesis of Di- and Trisaccharides Incorporating a Crown Ether Macrocycle.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: [Ni(dmit)2] Salts with Supramolecular Cation Structure

Abstract The dithiolate complex, [Ni(dmit) 2 ] (dmit=2-thioxo-1,3-dithiol-4,5-dithiolate) is an organic π-molecule which gives highly conducting salts with closed shell cations or organic donors. We have found that crown ether macrocycles can be incorporated into the salts in which the crown ethers include alkali metal cations forming supramolecular cation (SC) structures. The SC structural diversity was observed to depend on the size of the crown ether and cation. Three kinds of crown ethers, 12-crown-4, 15-crown-5 and 18-crown-6 in addition to an acyclic polyether analog of pentaetyleneglycol were incorporated in the conducting [Ni(dmit) 2 ] crystals. The structure of these crystals will be described with emphasis on both the structures of SC and Ni(dmit) 2 conducting layers. In one example, the crown ether forms a channel in which the cation has a translational freedom. The cation, otherwise merely forms a periodic Coulomb potential in the crystal, can influence the electrical conduction through the motion in the channel. The monovalent [Ni(dmit) 2 ] salts, which are possible candidates for molecular magnets will be described on a salt having SC structure.

Recent advances in the synthesis of ammonium-based rotaxanes.

The number of synthetic methods enabling the preparation of ammonium-based rotaxanes has increased very rapidly in the past ten years. The challenge in the synthesis of rotaxanes results from the rather weak interactions between the ammonium-containing rod and the crown ether macrocycle in the pseudorotaxane structure that rely mostly on O·H hydrogen bonds. Indeed, no strong base or polar solvent that could break up H-bonding can be used during the formation of rotaxanes because the two components will separate as two distinct entities. Moreover, most of the reactions have to be performed at room temperature to favor the formation of pseudorotaxane in solution. These non-trivial prerequisites have been taken into account to develop efficient reaction conditions for the preparation of rotaxanes and those are described in detail along this review.

SYNTHESIS OF MACROCYCLIC ARYL ETHER KETONE SULFONE OLIGOMERS VIA ELECTROPHILIC REACTION AND THEIR THEIR RING-OPENING POLYMERIZATION

Under pseudo-high dilution conditions, two kinds of macrocyclic aryl ether ketone sulfone oligomers have been synthesized in high yield from phthaloyl dichloride and electron-rich aromatic hydrocarbons in the presence of Lewis base via electrophilic reaction. The presence of Lewis base NMP in this reaction is demonstrated to be advantageous for forming macrocyclic oligomers. Detailed structural characterization of the oligomers confirmed the cyclic nature by a combination of MALDI-TOF-MS, GPC, IR and H-1-NMR analyses. The cyclic ether ketone sulfone oligomers 3a readily undergo anionic ring-opening polymerization in the melt by using potassium 4,4'-biphenoxide as the initiator, producing linear, high molecular weight poly( ether ketone sulfone) with T-g of 221.8 degrees C and excellent thermal stability. Moreover, the isothermal chemorheology of the ring-opening polymerization of cyclic oligomers 3a was also investigated. The results show that the shear viscosity of the molten reactive mixture increases slowly and is lower than 10 Pa.s at a constant shear rate of 0.05 rad/s in the initial stage of ring-opening polymerization, and the length of the initial stage shortens as the content of initiator Increases.

Mn2+Complexes with Pyridine-Containing 15-Membered Macrocycles: Thermodynamic, Kinetic, Crystallographic, and1H/17O Relaxation Studies

Given its five unpaired d-electrons, long electronic relaxation time, and fast water exchange, Mn(2+) is a potential candidate for contrast agent application in medical magnetic resonance imaging. Nevertheless, the design of chelators that ensure stable Mn(2+) complexation and optimal relaxation properties remains a coordination chemistry challenge. Here, we report the synthesis of two pyridine-containing ligands L1 and L2, with 15-membered triaza-dioxa-crown and pentaaza-crown ether macrocycles, respectively, and the characterization of their Mn(2+) complexes. Protonation constants of the ligands and stability constants of various metal complexes were determined by potentiometry. The presence of the pyridine in the macrocyclic ring induces rigidity of the complexes which results in a greater thermodynamic stability with respect to the nonpyridine analogues. Solid-state structures of MnL1 and MnL2 confirmed seven-coordination of Mn(2+) with Cl(-) and H(2)O in axial positions. The dissociation kinetics of MnL2 in the presence of Zn(2+) were followed by relaxometric measurements. They proved the prime importance of the proton-assisted dissociation while the zinc(II)-assisted pathway is not important at physiological pH. For MnL1, the dissociation was too fast to be studied by conventional relaxivity measurements under pH 6. A combined (17)O NMR and (1)H NMRD study on MnL1 and MnL2 yielded the parameters that govern the relaxivity of these complexes. The water exchange rate for MnL1, k(ex)(298) = 0.38 x 10(7) s(-1), is the lowest value ever reported for a Mn(2+) complex, while a considerably higher value was obtained for MnL2 (k(ex)(298) = 6.9 x 10(7) s(-1)). Anion binding was studied by relaxometric titrations. They revealed weak interactions between MnL2 and phosphate or citrate, leading to the formation of monohydrated species. Overall, the incorporation of a pyridine into a polyaza macrocycle scaffold has several beneficial effects on the Mn(2+) chelates with respect to potential MRI contrast agent applications: (i) The thermodynamic and the kinetic stability of the complexes is increased. (ii) The rigidified ligand backbone results in higher coordination numbers of the metal ion, allowing for two inner-sphere water molecules in aqueous solution.

Induced‐Fit Binding of π‐Electron‐Donor Substrates to Macrocyclic Aromatic Ether Imide Sulfones: A Versatile Approach to Molecular Assembly

Novel macrocyclic receptors that bind electron-donor aromatic substrates through pi-stacking donor-acceptor interactions are obtained by cycloimidisation of an amine-functionalised aryl ether sulfone with pyromellitic and 1,4,5,8-naphthalenetetracarboxylic dianhydrides. These macrocycles can form complexes with a wide variety of pi-donor substrates, including tetrathiafulvalene, naphthalene, anthracene, pyrene, perylene and functional derivatives of these polycyclic hydrocarbons. The resulting supramolecular assemblies range from simple 1:1 complexes to [2]- and [3]pseudorotaxanes and even (as a result of crystallographic disorder) an apparent polyrotaxane. Direct five-component self-assembly of a metal-centred [3]pseudorotaxane is also observed on complexation of a macrocyclic ether imide with 8-hydroxyquinoline in the presence of palladium(II) ions. Binding studies in solution were carried out by using (1)H NMR and UV/Vis spectroscopy, and the stoichiometries of binding were confirmed by Job plots based on the charge-transfer absorption bands. The highest association constants were found for strong pi-donor guests with large surface areas, notably perylene and 1-hydroxypyrene, for which K(a) values of 1.4x10(3) and 2.3x10(3) M(-1), respectively, were found. Single-crystal X-ray analyses of the receptors and their derived complexes reveal large induced-fit distortions of the macrocyclic frameworks as a result of complexation. These structures provide compelling evidence for the existence of strong attractive forces between the electronically complementary aromatic pi systems of host and guest.

Enthalpies of solvation of macrocyclic ether of dibenzo-24-crown-8 in solvents of different polarity

Enthalpies of solution of dibenzo-24-crown-8 in tetrachlormethane, benzene, chloroform, pyridine, acetone, acetonitrile, DMF, DMSO and propylene carbonate have been determined by calorimetric method at 298.15 K. The changes in enthalpy of solute-solvent interaction for the transfer the ether from inert tetrachlormethane into various solvents have been calculated from the obtained data. The thermochemical characteristics obtained for dibenzo-24-crown-8 have been compared with similar ones for dibenzo-18-crown-6 having a smaller cycle size. It has been found that an exothermicity of solute-solvent interaction changes to a lesser extent for transfer of the larger cyclic ether into polar solvents. But the effect increases more sharply for the transfer to chloroform. It has been concluded that the contribution from electrostatic interaction with solvent decreases with an increase of the cycle size as result of the increasing structural flexibility and decreasing polarity of cycle. But the contribution from hydrogen bonding with chloroform becomes larger due to an increase in the number of donor atoms of the ether molecules. It was ascertained that the ability to bind specifically acetonitrile molecules disappears in going from 18-merous to 24-merous cycle.

Efficient synthesis of a hetero[4]rotaxane by a “threading-stoppering-followed-by-clipping” approach

A "threading-stoppering-followed-by-clipping" approach was used for the synthesis of a hetero[4]rotaxane, in which one cucurbit[6]uril (CB[6]) and two hetero crown ether macrocycles are threaded onto one dumbbell-shaped molecule. The process involves three steps: (1) threading of a CB[6] macrocycle onto a thread containing two dialkylammonium sites to form a CB[6]-based pseudo[2]rotaxane; (2) stoppering of the as-formed pseudo[2]rotaxane by imine condensation reaction followed by reduction/protonation to afford a CB[6]-based [2]rotaxane with two new dialkylammonium sites; and (3) selective clipping of two hetero crown ether macrocycles onto the newly-formed ammonium sites and subsequent reduction of the imine bonds in each crown ether to afford the final hetero[4]rotaxane in good yield. The whole process was followed by NMR spectroscopy and the structure of the hetero[4]rotaxane was confirmed by NMR spectroscopy, elemental analysis and mass spectrometry.

Complexation of Mercury(I) and Mercury(II) by 18-Crown-6: Hydrothermal Synthesis of the Mercuric Nitrite Complex

A dimercury(I) 18-crown-6 complex is isolated, and its possible role in the hydrothermal preparation of the mercuric nitrite complex is discussed. The reported structures are of [Hg(2)(18-crown-6)(2)(H(2)O)(2)](ClO(4))(2) (1), monoclinic, C2/c, a = 21.0345(9), b = 12.1565(5), c = 16.8010(7) A, beta = 113.2000(10) degrees , V = 3948.7(3) A(3), Z = 16, R = 0.0230; [Hg(18-crown-6)](NO(2))(2) (2), monoclinic, P2(1)/c, a = 8.027(5), b = 14.437(9), c = 7.827(5) A, beta = 95.165(11) degrees , V = 905.6(10) A(3), Z = 2, R = 0.0175. The complex cation in compound 1 consists of a mercurous dimer exhibiting a Hg-Hg bond length of 2.524(2) A. Non-bonding interactions between adjacent crown ether macrocycles across the Hg-Hg bond result in large variations in mercury to oxygen distances within equatorial coordination sites. At low pH compound 1 is proposed to be preferentially formed under hydrothermal conditions affording compound 2 upon disproportionation. Nitrite ions ligate via a unidentate nitrito (cis to metal) coordination mode as interpreted using vibrational (infrared) spectroscopy. The conformation adopted by 18-crown-6 in compounds 1 and 2 is closely related to a D(3d) conformation as evidenced by X-ray crystallography. Band splitting readily observed in vibrational spectra of the metal free crown ether, attributed to vibrational modes of oxyethylene fragments, is absent in spectra of 1 and 2 confirming a regular D(3d) macrocyclic orientation. Short Hg-O bonds observed for axially coordinated water molecules in 1 and coordinated nitrite ligands in 2, illustrate the prevalence of relativistic effects commonly observed in mercury complexes.

Synthesis of novel C2-symmetric chiral crown ethers and investigation of their enantiomeric recognition properties

A series of new C 2-symmetric chiral aza crown ether macrocycles 1– 4 have been synthesized from ( S)-3-aryloxy-1,2-propanediol and ( S)-1,2-propanediol for the enantiomeric recognition of amino acid ester derivatives. These new macrocycles have been shown to be strong complexing agents for primary organic ammonium salts (with K up to 176.93 M −1 and Δ G° up to 12.81 kJ mol −1) by 1H NMR titration. These macrocyclic host exhibited enantioselective bonding toward the d-enantiomer of phenylalanine methyl ester hydrochloride with K D/ K L up to 6.87 in CDCl 3 with 0.25% CD 3OD.

A New Access to 16-Membered Macrocycles: Synthesis of the Model C-O-D Ring System of Vancomycin

A simple methodology for construction of the C-O-D diphenyl ether 16-membered ring system present in vancomycin by an intramolecular O-arylation reaction of arylboronic acid with substituted phenol for formation of the macrocyclic biaryl ether is described.

Docking in Metal-Organic Frameworks

The use of metal-organic frameworks (MOFs) so far has largely relied on nonspecific binding interactions to host small molecular guests. We used long organic struts (approximately 2 nanometers) incorporating 34- and 36-membered macrocyclic polyethers as recognition modules in the construction of several crystalline primitive cubic frameworks that engage in specific binding in a way not observed in passive, open reticulated geometries. MOF-1001 is capable of docking paraquat dication (PQT2+) guests within the macrocycles in a stereoelectronically controlled fashion. This act of specific complexation yields quantitatively the corresponding MOF-1001 pseudorotaxanes, as confirmed by x-ray diffraction and by solid- and solution-state nuclear magnetic resonance spectroscopic studies performed on MOF-1001, its pseudorotaxanes, and their molecular strut precursors. A control experiment involving the attempted inclusion of PQT2+ inside a framework (MOF-177) devoid of polyether struts showed negligible uptake of PQT2+, indicating the importance of the macrocyclic polyether in PQT2+ docking.

Nucleophile Assisting Leaving Groups: A Strategy for Aliphatic 18F-Fluorination

A series of arylsulfonate nucleophile assisting leaving groups (NALGs) were prepared in which the metal chelating unit is attached to the aryl ring via an ether linker. These NALGs exhibited significant rate enhancements in halogenation reactions using metal halides. Studies with a NALG containing a macrocyclic ether unit suggest that rate enhancements of these nucleophilic halogenation reactions are facilitated by stabilization of charge in the transition state rather than through strong precomplexation with metal cation. In several cases, a primary substrate containing one of the new leaving groups rivaled or surpassed the reactivity of triflates when exposed to nucleophile but was otherwise highly stable and isolable. These and previously disclosed chelating leaving groups were used in (18)F-fluorination reactions using no-carrier-added [18F]fluoride ion (t(1/2) = 109.7 min, beta+ = 97%) in CH3CN. Under microwave irradiation and without the assistance of a cryptand, such as K2.2.2, primary substrates with select NALGs led to a substantial improvement (2-3-fold) in radiofluorination yields over traditional leaving groups.

Sensing Abilities of Crown Ether Functionalized Polythiophenes

Tuning sensing abilities! The affinity of three different [15]crown-5 ether functionalized polythiophenes for alkali ions has been explored (see figure). Ab initio and DFT quantum mechanical calculations show that the binding energy between neutral conducting polymers and metallic ions, which interact attractively, decreases as the size of the ion increases. Oxidation of these polythiophene derivatives significantly reduces their affinity towards alkali ions, becoming low or even nonexistent.This work reports a theoretical study of the affinity of three different [15]crown-5 ether functionalized polythiophenes for alkali ions. Ab initio and DFT quantum mechanical calculations have evidenced that the binding energy between neutral conducting polymers and metallic ions, which interact attractively, decreases as the size of the ion increases. However, the preferences of these polythiophene derivatives have been found to be influenced by the entropic contribution, which favors binding with Na(+) in preference to Li(+). Molecular dynamics simulations have shown that this behavior can be accounted for on the basis of the large fluctuations that Li(+) undergoes when it is contained in the cavity of the [15]crown-5 ether macrocycle. In contrast, the fluctuations detected for complexes with Na(+) and K(+) were particularly low, even though only the former ion fits into the center of the macrocyclic cavity. Oxidation of these polythiophene derivatives produces a drastic change in their sensing abilities, their affinities towards alkali ions becoming low or even nonexistent. Moreover, calculations indicate that the presence of unsubstituted thiophene rings directly attached to a functionalized thiophene modulates the strength of the binding in the oxidized state by reducing the repulsive interaction between the metallic cation and the pi-conjugated system. On the other hand, the influence of alkali ions on the electronic properties, in particular, on the ionization potentials and the lowest pi-pi* transitions, of both the neutral and oxidized polythiophenes is discussed.

Acid Promoted Cinnamyl Ion Mobility within Peptide Derived Macrocycles

We are developing methods that restrict the conformational mobility of peptides and related heteropolymers while simultaneously altering their properties. Our experiments occur as processes wherein a conserved, lipophilic reagent is activated in stages to form composite products with unprotected polyamides in parallel. For each starting oligomer, the goal is to create not one, but rather a collection of products. The intent is for those materials to retain molecular recognition elements of the biopolymer, yet display that functionality as part of stable, cyclic structures having defined shapes and enhanced membrane solubility/permeability. Here we describe reagent 2 and its two-step integration into peptides to afford macrocyclic ethers (e.g., 4 when starting with W-W-Y). When those materials are treated with protic acid in anhydrous solvent, the cinnamyl unit migrates from the oxygen of tyrosine to distribute throughout the structure, forming new products via carbon/carbon bonding. These changes occur concomitantly with acid-promoted rearrangements/cyclizations of the dienyne appendage to generate mixtures containing unique macrocycles such as 15. Similar amalgamations of 2 with more diverse peptides is a means to begin accessing complex peptidomimetics systematically. From a library of screening fractions generated in this way, we have identified a small molecule that selectively promotes hippocampal neurogenesis in the adult mouse brain.