Assembly of a heterobinuclear 2-D network: a rare example of endo- and exocyclic coordination of Pd(II)/Ag(I) in a single macrocycle

The S3O2 macrocycle L1 was synthesized by a dithiol-dihalide coupling reaction under high-dilution conditions. The reaction of L1 with K2PdCl4 afforded an exocoordinated complex 1, [cis-Cl2Pd(L1)], which can then be manipulated to provide a heterobinuclear complex 3, {[Pd(L1)Ag(NO3)(2.5)](NO3)(0.5)}n, utilizing endocyclic Pd(II) and exocyclic Ag(I) in a single macrocycle through a successive reaction with AgNO3. The network of 3 contains a unique honeycomb-like 2-D sheet made up of the repeating unit [Ag6(NO3)6].     

Rearrangement of a cyclohexyl radical to a cyclopentylmethyl radical on the avermectin skeleton

The rearrangement of a substituted cyclohexyl radical to a cyclopentylmethyl radical on the skeleton of avermectin B1 was observed experimentally and explored computationally. The Stork-Nishiyama methodology was applied to the macrocycle of interest followed by a Tamao oxidation. The expected 5-6 fused ring product was observed in minor amounts. The major product was a 5-5 fused ring resulting from apparent conversion of the initially formed cyclohexyl radical to a cyclopentylmethyl radical. Preliminary computational results indicate that substituents in the macrocycle induce the rearrangement.     

Template synthesis of a huge macrocycle by olefin metathesis using easily accessible [Pt(PEt(3))(2)] templates

We have reported the template synthesis of a 90-membered macrocycle by olefin metathesis. The macrocycle 7 was prepared by an initial six-oxidative-addition reaction of 2 by [Pt(PEt(3))(4)]. The definite structure of a six-oxidative product was confirmed by the crystal structure. The coordination of 2,6-bis(hex-5-enyloxy)pyridine to 3 led to the hexacationic aryl complex of type 4. The metathesis of olefin-substituted pyridine with Grubbs catalyst ([PhCH==RuCl(2)(Cy(3)P)(2)]) formed the expected macrocycle 5. The olefin metathesis reaction was formed under high dilution to suppress intermolecular olefin metathesis polymerization. The detachment of the newly formed macrocycle 6, followed by reduction to alkane macrocycle 7 by using palladium on charcoal and hydrogen led to a huge macrocycle. The mild and easy access of the template protocol opens a host of potential subsequent transformations toward the construction of a variety of macrocycles.     

Binding of phosphate with a simple hexaaza polyammonium macrocycle

A mixture of dihydrogen phosphate and phosphoric acid has been crystallized with a hexaprotonated 26-membered polyammonium macrocycle, 1,4,7,14,17,20-hexaazacyclohexacosane, as the counterion. The complex crystallizes in the monoclinic space group P2(1)/c with unit cell parameters of a = 10.006(2) A, b = 12.525(1) A, c = 19.210(2) A, beta = 102.91(1) degrees, and V = 2346.6(5) A3. The hexaprotonated macrocycle is located on a crystallographic center of inversion and is surrounded by eight phosphate anions. Six of the phosphates are dihydrogen phosphates (H2PO4-), and the other two are neutral phosphoric acid molecules. Intricate hydrogen-bonding networks, involving the anionic and neutral phosphates and the protonated macrocycle, dominate the crystal lattice. Potentiometric studies using NaCl as the supporting electrolyte indicate high formation constants for the triprotonated macrocycle, H3L3+, with PO4(3-) at pH approximately 9.5 (log K = 4.55(4)), for the tetraprotonated macrocycle, H4L4+, with monohydrogen phosphate, HPO4(2-), at pH approximately 8.0 (log K = 6.01(3)), and for ditopic complexes with H5L5+ and H6L6+ and dihydrogen phosphate, H2PO4-, at pH approximately 4.0 (log K = 6.16(6)) and pH approximately 2.5 (log K = 6.44(5)), respectively. The ditopic behavior in the simple polyazamacrocycle receptor is a somewhat unusual occurrence, as is the finding of phosphoric acid species in the crystal structure.     

A convergent synthesis of Hexahomotriazacalix

A new, convergent synthesis of hexahomotriazacalix[3]arenes 1a-e is described. The key transformation in this synthesis involves the coupling of the triamines 4a-d with 2, 6-bis(chloromethyl)-4-methylphenol 5 and results in the formation of the hexahomotriazacalix[3]arenes 1a-d in 90-95% yield. The triamines 4a-d were constructed by the one-pot reaction of monochloroaldehyde 3 and a primary amine followed by reduction to yield the triamines 4a-d in 50-55% yield. Deallylation of macrocycle 1d was accomplished by palladium catalysis to obtain the N-unsubstituted macrocycle 1e, which has the potential to be a precursor to a variety of N-substituted hexahomotriazacalix[3]arenes.     

Extra large macrocycle: 40-membered macrocycle via 2:2 cyclization and its dimercury(II) complex

A large 40-membered N(4)O(4)S(4) macrocycle (L(2)) was obtained through a 2:2 cyclization of the corresponding dithiol and dichloride as a minor product during the preparation of a 20-membered N(2)O(2)S(2) macrocycle (L(1), 1:1 cyclization product). Each macrocycle was successfully separated from the mixed products and identified. The larger macrocycle L(2) allowed the preparation of its dimercury(II) complex, adopting a one-dimensional (1D) stairway-like polymeric chain linked with the anion. A monomercury(II) complex of the smaller macrocycle L(1) was also prepared. Both complexes and the larger macrocycle L(2) were structurally characterized by the single crystal X-ray analysis.     

Mild and selective reduction of imines: formation of an unsymmetrical macrocycle

During investigations of 5, a [3 + 3] Schiff-base macrocycle with six imines, a partially reduced Schiff-base macrocycle, 6, possessing one CH(2)NH and five imine groups was obtained. Control experiments and deuterium labeling indicate that the macrocycle is reduced by a benzimidazoline generated during the reaction. Benzimidazolines may be convenient reagents for the mild and selective reduction of imines.     

Interaction of Iodine with Hexaaza-18-crown-6 and Tetraaza-14-crown-4 in Chloroform Solution

Interactions of hexaaza-18-crown-6 (HA18C6) and tetraaza-14-crown-4 (TA14C4) with iodine have been investigated spectrophotometrically in chloroform solution. The observed time dependence of the charge-transfer band and subsequent formation of I₃ ^- in solution were related to the slow transformation of the initially formed 1:1 macrocycle. I₂ outer complex to an inner electron donor-acceptor (EDA) complex, followed by fast reaction of the inner complex with iodine to form a triiodide ion, as follows: macrocycle + I₂→_fast ^K _f macrocycle.I₂ (outer complex) macrocycle.I₂ (outer complex) →^slow (macrocycle.I⁺)I^- (inner complex) macrocycle.I⁺)I^- (inner complex) + I²→^slow (macrocycle.I⁺)I₃ ^-. The pseudo-first-order rate constants at various temperatures for thetransformation process were evaluated from the absorbance-time data. The activation parameters (E_a, Δ H^?, and Δ S^?) for thetransformation were obtained from the temperature dependence of the rate constants. The stoichiometry and formation constants of the resulting EDA complexes have also been determined. It was found that the (TA14C4.I⁺)I₃ ^- is more stable the (HA18C6.I⁺)I₃ ^- complex in chloroform solution.     

Anion-free bambus[6]uril and its supramolecular properties

Methods for the preparation of anion-free bambus[6]uril (BU6) are presented. They are based on the oxidation of iodide anion, which is bound inside the macrocycle, utilizing dark oxidation by hydrogen peroxide or photooxidation in the presence of titanium dioxide. Anion-free BU6 was found to be insoluble in any of the investigated solvents; however, it dissolves in methanol/chloroform (1:1) or acetonitrile/water (1:1) mixtures in the presence of the tetrabutylammonium salt of a suitable anion. The association constants with halide ions, BF(4)(-), NO(3)(-), and CN(-), were measured by (1)H NMR spectroscopy. The highest association constant (8.9×10(5) M(-1)) was found for the 1:1 complex of BU6 with I(-) in acetonitrile/water mixture. A number of crystal structures of BU6 complexes with various anions were obtained. The influence of the anion size on the macrocycle diameter is discussed together with an unusual arrangement of the macrocycles into separate layers.     

6 + 6 Macrocycles derived from 2,6-diformylpyridine and trans-1,2-diaminocyclohexane

While the non-templated reaction of racemic trans-1,2-diaminocyclohexane with 2,6-diformylpyridine leads to a mixture of 2?+?2 and 4?+?4 macrocyclic imines, the reaction of the isolated 2?+?2 macrocycle with cadmium(II) chloride results in the fusion of three smaller macrocyclic units into a large 6?+?6 macrocycle. The X-ray molecular structures of the hexanuclear cadmium complex of this macrocycle as well as the derived 6?+?6 protonated amine reveal multiply folded macrocycles that adopt container-type conformations.     

High-yield synthesis of a novel water-soluble macrocycle for selective recognition of naphthalene

A novel good water-soluble macrocycle containing two pyridinium moieties was synthesized in high yield.It could form 1:1 complexes with neutral guests containing naphthalene or phenyl units in water.The water-soluble macrocycle can selectively encapsulate naphthalene to form a 1:1 complex over a variety of polycyclic aromatic hydrocarbons.     

Influence of charge on anion receptivity in amide-based macrocycles

Binding and structural aspects of anions with tetraamido/diquaternized diamino macrocyclic receptors containing m-xylyl, pyridine, and thiophene spacers are reported. (1)H NMR studies indicate that the quaternized receptors display higher affinities for anions compared to corresponding neutral macrocycles. The macrocycles containing pyridine spacers consistently display higher affinity for a given anion compared to those with either m-xylyl or thiophene spacers. The m-xylyl- and pyridine-containing receptors exhibit high selectivity for H(2)PO(4)(-) in DMSO-d(6) with association constants, K(a) = 1.09 × 10(4) and >10(5) M(-1), respectively, and moderate selectivity for Cl(-) with K(a) = 1.70 × 10(3) and 5.62 × 10(4) M(-1), respectively. Crystallographic studies for the Cl(-) and HSO(4)(-) complexes indicate that the m-xylyl-containing ligand is relatively elliptical in shape, with the two charges at ends of the major axis of the ellipse. The anions are hydrogen bonded with the macrocycle but are outside the ligand cavity. In the solid state, an unusual low-barrier hydrogen bond (LBHB) was discovered between two of the macrocycle's carbonyl oxygen atoms in the HSO(4)(-) complex. The pyridine-containing macrocycle folds so that the two pyridine units are face-to-face. The two I(-) ions are chelated to the two amides adjacent to a given pyridine. In the structure of the thiophene containing macrocycle with two BPh(4)(-) counterions, virtually no interaction was observed crystallographically between the macrocycle and the bulky anions.     

Disfavoring Macrocycle b Fragments by Constraining Torsional Freedom: The “Twisted” Case of QWFGLM b<Subscript>6</Subscript>

While recent studies have shown that for some peptides, such as oligoglycines and Leu-enkephalin, mid-sized b fragment ions exist as a mixture of oxazolone and macrocycle structures, other primary structure motifs, such as QWFGLM, are shown to exclusively give rise to macrocycle structures. The aim of this study was to determine if certain amino acid residues are capable of suppressing macrocycle formation in the corresponding b fragment. The residues proline and 4-aminomethylbenzoic acid (4AMBz) were chosen because of their intrinsic rigidity, in the expectation that limited torsional flexibility may impede “head-to-tail” macrocycle formation. The presence of oxazolone versus macrocycle b₆ fragment structures was validated by infrared multiple photon dissociation (IRMPD) spectroscopy, using the free electron laser FELIX. It is confirmed that proline disfavors macrocycle formation in the cases of QPWFGLM b₇ and in QPFGLM b₆. The 4AMBz substitution experiments show that merely QWFG(4AMBz)M b₆, with 4AMBz in the fifth position, exhibits a weak oxazolone band. This effect is likely ascribed to a stabilization of the oxazolone structure, due to an extended oxazolone ring-phenyl π-electron system, not due to the rigidity of the 4AMBz residue. These results show that some primary structures have an intrinsic propensity to form macrocycle structures, which is difficult to disrupt, even using residues with limited torsional flexibility.     

Lanthanide complexes of the heterochiral nonaaza macrocycle: switching the orientation of the helix axis

The La(III), Ce(III), Pr(III), Nd(III), Sm(III), and Eu(III) complexes of the racemic heterochiral nonaaza macrocyclic amine L have been synthesized and characterized by spectroscopic methods. The X-ray crystal structures of the [PrL][Pr(NO(3))(6)].CH(3)OH and the isomorphic [NdL][Nd(NO(3))(6)].CH(3)OH complexes show that all nine nitrogen atoms of the macrocycle coordinate to the Ln(3+) ion, completing its coordination sphere. The macrocycle wraps tightly around the metal ion in double-helical fashion. The structures reveal the RRRRSS/SSSSRR configuration at the stereogenic carbon atoms of the three cyclohexane rings, confirming the heterochiral nature of the parent 3 + 3 macrocycle obtained in the condensation of racemic trans-1,2-diaminocyclohexane and 2,6-diformylpyridine. The NMR spectra of the isolated complexes indicate the presence of low C(1) symmetry [LnL](3+) complexes. The same symmetry is indicated by the X-ray crystal structures of Pr(III) and Nd(III) complexes, which show that for the RRRRSS enantiomer of the macrocycle L, the helix axis passes through the cyclohexane ring of RR chirality and the opposite pyridine ring. The NMR studies of complex formation in solution by the paramagnetic Pr(3+) and Eu(3+) ions indicate that the initially formed [LnL](3+) complexes are of C(2) symmetry. For the RRRRSS enantiomer of the macrocycle L in the C(2)-symmetric species, the helix axis passes through the cyclohexane ring of SS chirality and the opposite pyridine ring. The C(1)-symmetric and C(2)-symmetric forms of the [LnL](3+) complexes constitute a new kind of isomers and the conversion of the kinetic complexation product of C(2) symmetry into the thermodynamic product of C(1) symmetry corresponds to an unprecedented switching of the orientation of the helix axis within the macrocycle framework.     

Rigid macrocyclic triamides as anion receptors: anion-dependent binding stoichiometries and 1H chemical shift changes

The cyclic triamide of 3'-amino-3-biphenylcarboxlic acid is readily synthesized in a stepwise manner and represents a novel class of anion receptors with a large central cavity. This macrocycle binds more strongly to tetrahedral anions than spherical or planar anions in organic solvents. The binding stoichiometries for anions with symmetrical charge distribution depend on the solvent polarity, while tetrahedral p-tosylate binds to the macrocycle with 1:1 stoichiometry in all solvents studied. The (1)H NMR chemical shift changes of the protons lining the interior of the macrocycle's central cavity also depend on the geometry of the bound anion. The importance of the convergent array of hydrogen bond donors for anion binding by the macrocycle was confirmed by control studies with an acyclic triamide and a macrocycle with intramolecular hydrogen bonds.     

Binding of inorganic oxoanions to macrocyclic ligands: effect of the degree of protonation on supramolecular assemblies formed by phosphate and [18]aneN(6)

Five macrocycle-oxoanion adducts have been isolated from aqueous solutions containing 1,4,7,10,13,16-hexaazacyclooctadecane ([18]aneN(6), L) and phosphoric acid whose pH had been adjusted to selected values in the 1-8 range. Four products, (H(6)L)(H(2)PO(4))(6).2H(3)PO(4) (1), (H(6)L)(H(2)PO(4))(6) (2), (H(4)L)(H(2)PO(4))(4).2H(2)O (4), and (H(4)L)(HPO(4))(2).7H(2)O (5) crystallized from aqueous solutions at pH 1, 3, 6, and 8, respectively, while (H(4)L)(H(2)PO(4))(4) (3) crystallized on diffusion of EtOH into an aqueous reaction mixture at pH 6. Single-crystal X-ray structure determinations enabled an examination of supramolecular interactions between protonated forms of [18]aneN(6), phosphoric acid and its conjugate bases, and water of solvation. The macrocycle adopts a variety of conformations in order to accommodate the supramolecular constructs formed by the oxoanions and solvent molecules as the relative proportions of interacting species are altered. At pH 1 and 3, the fully protonated macrocycle, [LH(6)](6+), is found with six H(2)PO(4)(-) anions. At pH 6 and 8, the tetraprotonated macrocycle, [LH(4)](4+), crystallizes with four H(2)PO(4)(-) and two HPO(4)(2)(-), respectively. Variations in the solute of crystallization are evident, with phosphoric acid being present at the lowest pH and water at pH 6 and 8. In 5, the seven unique water molecules form a string-of-pearls motif within which a new heptameric isomer, consisting of a water pentamer that uses a single water to interact with the other two unique water molecules, is found. Structures 1, 2, 4, and 5 exhibit eta-3 H-bonding of ammonium protons to a single oxygen of the guest phosphates located above and below the macrocyclic ring. In 3, two phosphate oxygens of the cavity anion interact with the macrocycle, one of which participates in eta-2 H-bonding with ammonium groups.     

Phenylacetylene macrocycles with two opposing bipyridine donor sites: syntheses, X-ray structure determinations, and Ru complexation

Reaction of the known macrocycle 1a, which contains two bipyridine units in opposing sides, with two equivalents of [Ru(bipy)2Cl2] furnishes the doubly exocyclically complexed macrocycle 8a in 55% yield. Synthesis of the shape-persistent macrocycle 1c by Hagihara-Sonogashira cross-coupling chemistry of suitably functionalized building blocks is reported. This macrocycle was also converted into a Ru complex (8c). X-ray analysis of single crystals of 1b and 1c shows a layered structure that contains "channels" filled with solvent molecules and parts of the flexible chains, with which the cycle is decorated for solubility reasons.     

Synthesis of triazolium-based mono- and tris-branched [1]rotaxanes using a molecular transporter of dibenzo-24-crown-8

We report a diverted route to [1]rotaxane and tris-branched [1]rotaxane that are devoid of any efficient template and which could not be obtained by classical straightforward strategies. The described chemical route relies on the utilization of a “macrocycle transporter”, which is able first to bind a macrocycle, second to link temporarily a triazolium-containing molecular axle, and third to deliver the macrocycle around the new docked axle through molecular machinery in a [1]rotaxane structure. The extended encircled thread is eventually cleaved by an amine or a triamine to afford the triazolium-containing [1]rotaxanes, releasing at the same time, the macrocycle transporter as a recyclable species.     

A new type of insulated molecular wire: a rotaxane derived from a metal-capped conjugated tetrayne

The platinum butadiynyl complex trans-(C(6)F(5))(p-tol(3)P)(2)Pt(C≡C)(2)H and a CuI adduct of a 1,10-phenanthroline based 33-membered macrocycle react in the presence of K(2)CO(3) and I(2) or O(2) to give a rotaxane (ca. 9%) in which the macrocycle is threaded by the sp carbon chain of trans,trans-(C(6)F(5))(p-tol(3)P)(2)Pt(C≡C)(4)Pt(Pp-tol(3))(2)(C(6)F(5)). The crystal structure and macrocycle/axle electronic interactions are analyzed in detail.     

Kinetically-Locked Metallomacrocycle for Host-Guest Chemistry with Bulky Anions

As a robust and large molecular receptor, a kinetically-locked trinuclear Co(III) macrocycle was synthesized with bis(β-diketone) ligands having large π-panels of 9,10-diphenylanthracene moieties via a combination of Co(II)-assisted self-assembly and subsequent oxidation of the metal centers. The X-ray structure revealed that the macrocycle had a discrete nanocavity of more than 300 ų, which was surrounded by three anthracenyl panels in the middle. As the macrocycle has three cationic centres on each metal ion and a large cavity, it acts as a guest receptor for sodium tetraphenylborate. The binding constant was estimated to be 4.0×10⁻² M⁻¹ from ¹H NMR titration experiments, whereas no interaction was observed between the macrocycle and potassium 1-adamantanecarboxylate.