Assembly Of Macrocycles Research Articles

Fusion of Coordination‐ and Polyoxometalate Chemistry – Chelated Cobalt(III) Centers as Structural Components of Polyoxomolybdates – [{Co(en)}4Mo10O38]4– and Macrocyclic [{CoII(H2O)2}­{Co(en)}8{Mo20O76}]6–

AbstractOn the basis of the argument that a monochelated octahedral transition‐metal unit is topologically analogous to the Type II (cis‐dioxo) metal center frequently observed in the structures of many polyoxometalates, we report the synthesis and structural characterization of salts of two polyoxomolybdate anions demonstrating this principle, [{Co(en)}4Mo10O38]4– (1) and [{CoII(H2O)2}{Co(en)}8{Mo20O76}]6– (2). Anion 1 has a structure of nominal Cs symmetry and consists of two blocks of seven edge‐shared metal‐centered octahedra linked by two corner‐shared junctions (Co–O–Mo). The four octahedra which contain {Co(en)}3+ instead of {MoO2}2+ are distributed unequally between the two blocks, three in one and the fourth in the other. The structure of 2 can be described as a chiral macrocyclic assembly (C4 symmetry) of four identical blocks of seven octahedra as observed in the structure of 1, but now containing two {Co(en)}3+ per block. As in 1 the blocks are linked by corner‐shared Co–O–Mo linkages. A trans‐diaquacobalt(II) cation occupies the center of the anion. The opportunities provided by the introduction of chelated metal centers, especially those with unsymmetrical diamines, into new polyoxometalates include the generation of resolvable and optically stable structures that have so far eluded polyoxometalate chemists.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Reversible constitutional switching between macrocycles and polymers induced by shape change in a dynamic covalent system

We report here the development of morphological switches as a new tool that can be used in constitutional dynamic chemistry (CDC) to control the constitution of the whole dynamic system. Molecules that have well-defined but switchable shapes were designed and synthesized. Their restrained conformational states were characterized both in the solid and in solution. The addition of metal ions induces a shape change through coordination; the shape generated was also fully investigated both in the solid and in solution. Such molecules constitute morphological switches, meaning that they can explore various shape states as a result of controlled well-defined shape changes triggered by an effector. These morphological switches were then integrated into covalent dynamic systems through formation of reversible imine bonds. Thermodynamic and kinetic analyses were performed in order to quantify the covalent equilibrium and to investigate the labile character of the covalent reversible link. It was then demonstrated that the molecular shape state of the morphological switches induces a well-defined constitution through covalent self-assembly, and that the system can be steered, quantitatively and reversibly without significant fatigue, between two different constitutional states, respectively, polymeric and macrocyclic assemblies. The dynamic covalent polymeric assemblies were analysed by DOSY NMR and small angle neutrons scattering (SANS). Their dynamic behaviour as a function of the concentration and the temperature was demonstrated and characterized.

A Biomimetic Approach for Polyfunctional Secocholanes: Tuning Flexibility and Functionality on Peptidic and Macrocyclic Scaffolds Derived from Bile Acids

Bile acids are important scaffolds in medicinal and supramolecular chemistry. However, the use of seco bile acids, i.e., bile acids with opened rings, as cores or building blocks for the assembly of complex peptide conjugates or macrocycles has remained elusive so far. A biomimetic approach to secocholanes, based on an oxidative ring-expansion/ring-opening sequence, offers efficient access to novel structures with tunable flexibility and functionality. The process preserves selected portions of the original stereochemical and functional information of the steroid, while additional structural elements are incorporated in further (diversity-generating) steps. The potential of these building blocks for peptide and macrocycle chemistry is exemplified by the attachment of relevant alpha-amino acids and by the production of various complex macrocycles obtained by conventional (e.g., macrolactonization and macrolactamization) and multicomponent (e.g., Ugi four-component) macrocyclizations. This combination of secocholanic skeleton manipulation with, e.g., varied types of macrocyclization protocols, produces high levels of skeletal diversity and complexity. Therefore, this approach may have applicability either for the synthesis of biologically active ligands or as artificial receptors ("hosts").

Sequence of Metal‐Organic Oligomer‐Polymer Exchange Equilibria in Solution: Supramolecular Isomerism, Self‐Assembly Dynamics and Carboxylate Shift of Di‐n‐butyltin cis‐1,4‐Cyclohexanedicarboxylate

AbstractDi‐n‐butyltin dichloride (nBu2SnCl2) was treated with the potassium salt of cis‐1,4‐cyclohexanedicarboxylate (cis‐1,4‐chdcaK2) to give di‐n‐butyltin cis‐1,4‐cyclohexanedicarboxylate. In the solid state two supramolecular isomers coexist within the same crystal lattice, the 36‐membered macrocyclic tetranuclear complex [{nBu2Sn(cis‐1,4‐chdca)}4] and the analogous polymeric form [{nBu2Sn(cis‐1,4‐chdca)}n]. In solution, fast (on the NMR time scale) dynamic equilibria were detected. The supramolecular arrangement in the solid state consists of alternating macrocycle and polymer ribbons with different patterns of intermolecular Sn···O interactions that give rise to a total of four different types of supramolecular macrocyclic assemblies. They probably resemble local environments in the liquid phase and allow to propose a plausible mechanistic pathway for the ring‐chain rearrangement dynamics during which the macrocycle molecules are transformed into other macrocyclic and polymeric molecules.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Total Synthesis of Aigialomycin D: Surprising Chemoselectivity Dependence on Alkyne Structure in Nickel-Catalyzed Cyclizations

The total synthesis of aigialomycin D was carried out using a nickel-catalyzed ynal macrocyclization as a key step. This key step allowed macrocycle assembly and formation of a disubstituted alkene and a secondary hydroxyl stereocenter in a single step, although the stereocenter was formed unselectively. An interesting side reaction involving five-membered-ring synthesis by an aldehyde/styrene cyclization was observed when macrocyclization of an alkynyl silane was attempted. A mechanistic basis for this surprising process is provided.

Structurally-tolerant self-assembly of zinc pyridyl porphyrins

Zinc porphyrins equipped with pyridine ligands form macrocyclic assemblies in organic solvents. The assemblies have been characterised by 1H NMR, UV-visible spectroscopy, X-ray crystallography and vapour pressure osmometry. The self-assembly properties of six isomeric porphyrins are relatively insensitive to the geometry of the porphyrin monomer. Changes in the internal torsion angles allow all of the porphyrins to form macrocyclic dimers but with differences in the relative orientations of the porphyrin units. The associated strain reduces the effective molarities from the value of 6 M reported previously for an ‘ideal’ monomer to between 0.07 and 2 M leading to dimerisation constants in the 105–106 M−1 range. Only one isomer has a geometry that makes dimerisation impossible without severe distortion, and this compound self-assembles to give a tetrameric macrocycle at millimolar concentrations.

Programmed Dynamic Covalent Assembly of Unsymmetrical Macrocycles

Unsymmetrical shape-persistent macrocycles have been prepared from diphenylacetylene monomers using imine formation and metathesis. A sequence-directed approach, in which each monomer is uniquely labeled by its N-donor/C-donor sequence, has been used to control the self-assembly and makes possible an added level of complexity in the final structures. To illustrate the potential of this strategy, a series of macrocycles with different side-chain substitution patterns have been prepared, including monofunctionalized and Janus-type structures. We believe this to be the first example of sequence control of dynamic covalent self-assembly and that it will enable the fully covalent synthesis of more complex nanostructures.

The dynamic covalent chemistry of mono- and bifunctional boroxoaromatics

10-Hydroxy-10,9-boroxophenanthrene reacts rapidly and reversibly with both benzylic and alkane diols in non-polar solvents. The formation of 2:1 adducts between the boroxoaromatic and the diols is favoured. The diol component of the adduct can be exchanged readily and rapidly by treatment of the boroxoaromatic–diol adduct with an alternative diol in solution at room temperature. This reversible covalent chemistry would appear to be ideal for the dynamic assembly of more complex superstructures. However, attempts to extend this dynamic equilibrium to the assembly of macrocycles using the bifunctional boroxoaromatic 5,9-dihydroxy-5,9-dibora-4,10-dioxopyrene failed as a result of changes in the reactivity of the boron centre in the bifunctional boron-containing compound.

Anion-Directed Assembly of Macrocycle and Helix

Self-assembly of the flexible ligand N,N‘-bis(3-pyridylmethyl)thiourea (bpt) with ZnCl2 and CdCl2 in the absence and presence of KSCN yielded a short series of novel complexes (1−4) with macrocyclic, helical, double-helical, and 1D polymeric structures. Different metal ions, hydrogen bonds, and counteranions play significant roles in the final crystal structures. The NCS- anion was found to favor the formation of helical structures, whereas the Cl- anion favored macrocycle formation in the present system. Photoluminescence (PL) measurement results revealed that complex 2 (Zn(bpt)(SCN)2) with a helical structure exhibits enhanced emissions compared to those of the ligand and other complexes. The anion-directed assembly as well as the interesting emissions may provide useful information for further design of metal−organic compounds with novel structures and properties.

Solid support synthesis of 15-membered macrocycles containing a serotonin unit

Efficient assembly of 15-membered macrocycles utilizing the S NAr of fluorine in 3-fluoro-4-nitrobenzoic acid with the OH functionality of serotonin on solid support is reported. This flexible synthesis yields a set of title macrocycles with good purity (>90%).

A functionalized noncovalent macrocyclic multiporphyrin assembly from a dizinc(II) bis-porphyrin receptor and a free-base dipyridylporphyrin.

The bis-porphyrin system ZnP(2), in which two zinc porphyrins are connected by a phenanthroline linker in an oblique fashion, acts as a bifunctional receptor towards the complexation of free-base meso-5,10-bis(4'-pyridyl)-15,20-diphenylporphyrin (4'-cis DPyP). In solution, NMR spectroscopy evidenced quantitative formation of the tris-porphyrin macrocyclic assembly ZnP(2)(4'-cis DPyP), in which the two fragments are held together by two axial 4'-N(pyridyl)-Zn interactions. The remarkable stability of the edifice (an association constant of about 6x10(8) M(-1) was determined by UV/Vis absorption and emission titration experiments in toluene) is due to the almost perfect geometrical match between the two interacting units. The macrocycle was crystallized and studied by X-ray diffraction, which confirmed the excellent complementarity of the two components. Photoinduced energy transfer from the singlet excited state of the zinc porphyrin chromophores to the free-base porphyrin occurs with an efficiency of 98 % (k(en)=2x10(10) s(-1) in toluene, ambient temperature) with a mechanism consistent with a dipole-dipole process with a low orientation factor.

Big macrocyclic assemblies of carboranes (big MACs): synthesis and crystal structure of a macrocyclic assembly of four carboranes containing alternate ortho- and meta-carborane icosahedra linked by para-phenylene units

The macrocyclic compound, [1,2-C 2B 10H 10-1,4-C 6H 4-1,7-C 2B 10H 10-1,4-C 6H 4] 2 ( 5)—a novel cyclooctaphane, was prepared by condensation of the C,C′-dicopper(I) derivative of meta-carborane with 1,2-bis(4-iodophenyl)- ortho-carborane. The X-ray crystal structure of 5·C 6H 6·6C 6H 12 was determined at 150 K, revealing an extremely loose packing mode. Molecule 5 has a crystallographic C s and local C 2 v symmetry; the macrocycle adopts a butterfly (dihedral angle 143°) conformation with the ortho-carborane units at the wingtips and the phenylene ring planes roughly perpendicular to the wing planes. Multinuclear NMR spectra suggest that molecule 5 in solution inverts rapidly via the planar D 2 h geometry, which (from ab initio HF/6-31G* calculations) is only 1 kcal mol −1 higher in energy than the C 2 v one. An attempt to prepare an even larger macrocycle, comprising three para-carborane and three ortho-carborane units linked by six para-phenylene units, was unsuccessful.

Solid support synthesis of 14- and 17-membered macrocycles via the S NAr methodology

Efficient assembly of 14-membered macrocycles utilizing the S NAr of fluorine in 3-fluoro-4-nitrobenzoic acid with the OH of 3-hydroxytyrosine on solid support is reported. The flexibility of this synthesis, as well as the excellent purity (>90%) of the final products are the distinctive characteristic of the resultant library.

Assembly and Binding Properties of Osmate Ester-Bridged Binuclear Macrocycles

Osmium (VI)-bridged macrocycles 1a−c, 2, and 3 assemble spontaneously when osmium tetraoxide, olefins, and L-shaped bispyridyl ligands are mixed in CHCl3. The macrocycles possess well-defined square or rectangular cavities enclosed by aryl walls and act as host molecules. Hydrogen-bond donors on the inner surface of the hosts offer binding sites to acceptors of guests with complementary dimensions. The host 1a binds adipamide G2 (Ka = 3.6 × 104 M-1) and terephthalamide G6 (Ka = 2.0 × 104 M-1), while it binds negligibly (Ka < 10 M-1) benzamide G5, isophthalamide G9, or 1,4-naphthalenedicarboxamide G10. The larger hosts 2 and 3 bind the longer guests biphenyldicarboxamide G12 and terphenyldicarboxamide G17, respectively, but shorter guests such as adipamide G2 and terephthalamide G6 are not well-bound (Ka < 10 M-1). Hosts 1a−c with different remote substituents (H, OMe, NO2) but identical cavity size were prepared and their binding affinities were measured. The relative binding affinities of the hosts 1a−c ...

Solid support synthesis of 14-membered macrocycles via S NAr methodology on acrylate resin

Efficient assembly of 14-membered macrocycles utilizing S NAr of fluorine in 3-fluoro-4-nitrobenzoic acid with the OH of 3-hydroxytyrosine on the solid support is reported. The flexibility of this synthesis, as well as the excellent purity (>90%) of the final products are the distinctive characteristics of the resulting library.

Solid support synthesis of 14-membered macrocycles containing the thioether bridge via S NAr methodology

An efficient assembly of 14-membered macrocycles utilizing the S NAr of fluorine in 3-fluoro-4-nitrobenzoic acid with the SH of cysteine on solid support is reported. The flexibility of this synthesis, as well as the excellent purity (>90%) of the final products, are the distinctive characteristics of the resulting library.

A New Staining Method for Cyclic Peptides After Thin-Layer Chromatography

This article focuses on the development of design strategies and self-assembly pathways of metal-based systems incorporating Schiff base ligands. Versatility in Schiff base ligand design provides the possibility of straightforward modulation of a variety of structural features that dictate the properties of corresponding molecular metal complexes and supramolecular assemblies. First, mononuclear metal complexes are characterized in general terms, which is followed by a description of their application as building blocks of functional macromolecular/supramolecular structures. The metal-directed self-assembly of Schiff bases has also experienced considerable attention in offering a route toward the fabrication of multinuclear assemblies. By using different rigid or semirigid Schiff base-based scaffolds, numerous types of metallacycles have been constructed, either through stepwise or one-step procedures; triangles, square, and rectangular boxes, cages, and hexagon rings are some of the assemblies that have resulted from these approaches. Macrocyclic assemblies based on Schiff bases were shown to generate various types of mechanically interlocked molecular architectures, such as catenanes, Borromean rings, and knots. Additional structural and functional properties have also been created using Schiff base-based metalloligands, which offer structural rigidity and additional functional groups to a preorganized conformation. This type of metalloligand is particularly prone to be further involved in the assembly of coordination polymers of various dimensionalities and functionalities.

Structural features of solid-state calix[4]arene in the cone conformation

A statistical analysis of cone-shaped calix[4]arene structural features derived from the Cambridge Structural Database is presented. The mean, standard deviation and range of values for lengths, angles, and dihedrals for the monomers and for the macrocyclic assembly as a whole are provided. A comparison of native, near-native, and derivatized calix[4]arenes is made. Semiempirical molecular orbital theories and empirical force field calculations, both in gas and solution phase, are inconsistent with experimentally known conformer populations of a tetramethyl ether derivative of p-tert-butylcalix[4]arene. A reason for the inability of these computational methods to give correct answers is given, and extreme caution is urged when using these tools to predict calixarene structure and energy