Hybrid Macrocycles Research Articles

BODIPY-phenylacetylene macrocycle motifs for enhanced light-harvesting and energy transfer applications

BODIPY-phenylacetylene macrocyclic hybrids are reported, where energy transfer is observed from the phenylacetylene unit to the BODIPY core.

Macrocyclic Salen–Bis-NHC Hybrid Ligands and Their Application to the Synthesis of Enantiopure Bi- and Trimetallic Complexes

Salen and NHC ligands are among the most important ligands for homogeneous catalysis. We have recently reported bimetallic complexes, in which both motifs have been merged for the first time. However, the intermetallic distances, which play a crucial role for cooperative bimetallic catalysis, were probably not appropriate in these first-generation hybrid catalysts. To generate heterobimetallic salen/NHC hybrid complexes with intermetallic distances suitable for cooperative catalysis, chiral macrocyclic hybrid ligands featuring a salen and two linked NHC donor moieties have been prepared in the present study. For the ligand formation, chiral enantiopure diamines as well as chiral enantiopure bisimidazoles were employed, and a matched/mismatched situation was found depending on the configuration of both chirality sources. Regioselective complexation of Zn(II), Ni(II), and Pd(II) by the salen N2O2 coordination sphere was efficiently accomplished. Subsequent coordination of the NHC units was achieved for Ag(I...

A Hybrid Macrocycle with a Pyridine Subunit Displays Aromatic Character upon Uranyl Cation Complexation

Reported here is a new hybrid macrocycle, cyclo[1]furan[1]pyridine[4]pyrrole (1), that bears analogy to the previously reported mixed heterocycle system cyclo[2]pyridine[4]pyrrole (2) and cyclo[6]pyrrole 3, an all-pyrrole 22 π-electron aromatic expanded porphyrin. The oxidized, dianionic form of 1, [1 - 4H](2-), has been characterized as its uranyl complex. In contrast to 2 and 3 and in spite of the presence of a 2,6-disubstituted pyridine subunit, the uranyl complex of [1 - 4H](2-) displays solid-state structural and solution-phase spectroscopic features consistent with contributions to the overall electronic structure that involve a conjugated, (4n + 2) π-electron aromatic periphery.

Synthesis and structure of expanded pyriporphyrins containing a dipyrrylpyridine unit

Expanded pyriporphyrins with five and ten nitrogens were prepared in 67% and 6.5% yield, respectively, by the reactions of bis(azafulvene) and dipyrrylpyridine. The minimum 17-membered non-aromatic macrocycle made of four pyrroles and one pyridine is highly non-planar in comparison with orangarin that contains a tripyrrole unit instead of a dipyrrylpyridine unit. This highly non-planar ring structure is basically unchanged in the complex with trifluoroacetic acid (TFA) where carboxylate anions are bound on both sides of the macrocyle plane by multiple hydrogen bondings. This monopyridine-tetrapyrrole hybrid macrocycle was able to act as a dianionic ligand for various metal ions including lanthanide ions. In contrast to the reported figure eight type X-ray structure of turcasarin that is a double sized macrocycle of orangarin, the pyridine-containing macrocycle analog of the same 34-membered ring size isolated in this study was found not to take a figure eight type conformation as evidenced by X-ray crystallography of the tetracation with TFA anions.

Synthesis and Structure of Calix[n]bifurano[n]thiophene (n = 2-5) Hybrid Macrocycles

Department of Chemistry, Gangneung-Wonju University, Gangneung 210-702, KoreaReceived December 26, 2010, Accepted January 10, 2011Key Words : Bifuran, Anion binding, Modified calixpyrrole Anion or neutral molecule recognition have been one ofthe important areas in the molecular recognitiondue totheir potential applications in biology and environmentalscience.

Helical binuclear Co II complexes of pyriporphyrin analogue for sensing homochiral carboxylic acids

A hybrid macrocycle composed of two bipyridines and two dipyrrins gave biscobalt complexes of figure eight macrocycle conformation with κ 2-carboxylate ligands and water ligands at the axial sites. The axial acetate ligands of the biscobalt complex are readily exchanged with carboxylates of α-hydroxyl acids and α-amino acids. The chiral center of the axial carboxylate ligands controls the helical handedness of the macrocycle as evidenced by a typical CD couplet at 550 nm. The substitution labile nature of the biscobalt complex plays a key role for helical chirality induction on the macrocycle upon co-ordination of chiral carboxylate anions.

Total synthesis and biological evaluation of a series of macrocyclic hybrids and analogues of the antimitotic natural products dictyostatin, discodermolide, and taxol.

The design, synthesis, and biological evaluation of a series of hybrids and analogues of the microtubule-stabilizing anticancer agents dictyostatin, discodermolide, and taxol is described. A 22-membered macrolide scaffold was prepared by adapting earlier synthetic routes directed towards dictyostatin and discodermolide, taking advantage of the distinctive structural and stereochemical similarities between these two polyketide-derived marine natural products. Initial endeavors towards accessing novel discodermolide/dictyostatin hybrids led to the adoption of a late-stage diversification strategy and the construction of a small library of methyl-ether derivatives, along with the first triple hybrids bearing the side-chain of taxol or taxotere attached through an ester linkage. Biological assays of the anti-proliferative activity of these compounds in a series of human cancer cell lines, including the taxol-resistant NCI/ADR-Res cell line, allowed the proposal of various structure-activity relationships. This led to the identification of a potent macrocyclic discodermolide/dictyostatin hybrid 12 and its C9 methoxy derivative 38, accessible by an efficient total synthesis and with a similar biological profile to dictyostatin.

Control of Channel Size for Selective Guest Inclusion with Inlaid Anionic Building Blocks in a Porous Cationic Metal–Organic Host Framework

Step by step: By attaching anionic building blocks of variable bulk to a cationic metal-organic framework, stepwise channel-size adjustment of the resulting porous three-dimensional host framework is achieved (see picture). This method is a new and viable approach for materials with predesigned nanopores for application in molecular recognition and selective guest inclusion.Through the introduction of perfluorocarboxylates as counteranions that line the inner surface of each channel in a host cationic metal-organic open framework, stepwise channel-size control has been realized, resulting in wide guest compatibility for [{Ag(L)(CF(3)CO(2))}(6)6 G](infinity) (1 supersetG; G=guest, L=ligand), selective guest recognition for [{Ag(L)(C(2)F(5)CO(2))}(6)4 G'](infinity) (2 supersetG'), and a lack of inclusion behavior for [{Ag(L)(C(3)F(7)CO(2))}(6)](infinity) (3; G and G' represent the same or different guest molecules). The cationic frameworks in 1-3 are constructed from the linkage of hexameric inorganic-organic hybrid macrocycles through multiple argentophilic interaction plus pi-pi interactions between pyridyl rings and carbonyl-carbonyl interactions, to which corresponding counteranions are attached. With different anions as intrachannel arms, similar frameworks in complexes 1 supersetG, 2 supersetG', and 3 exhibit percentages of guest-accessible voids of approximately 30-35, 25, and 18 % for 1-3, respectively. The highly flexible framework 1 in 1 supersetG contains stretchable channels with up to 21.7 % effective-volume change of the solvent-accessible void for inclusion of various guest species in the series of solvates 1 a-m. The pair of complexes 1 supersetG and [Ag(L)(CF(3)CO(2))](infinity) (4), and likewise the pair 2 supersetG' and [Ag(L)(C(2)F(5)CO(2))](infinity) (5), are interconvertible through distinct controllable processes.

Phosphole-Containing Calixpyrroles, Calixphyrins, and Porphyrins: Synthesis and Coordination Chemistry

Porphyrins are large heterocyclic macrocycles that bind metals to form complexes such as heme and chlorophyll. Porphyrinogens are related macrocycles in which the meso-carbons, the carbon atoms connecting the pyrroles or the related five-atom heterocycles, are all or partially reduced to methylene, disrupting the pi-electron conjugation. Both porphyrins and porphyrinogens are important components of natural and synthetic systems, and they have completely different coordination behavior. Consequently, the coordination chemistry of the entire porphyrin family, including regular porphyrins, porphyrinogens, and their expanded analogs, has been extensively investigated. Core modification, namely, replacing one or more pyrrole rings with other heterocyclic or carbocyclic rings, is a highly promising approach for creating unprecedented coordination properties in the porphyrin family. The size, shape, charge, and binding ability of the core-modified porphyrin platforms are readily tunable by variation of the heterole subunits. Until recently, however, the only atoms that could be incorporated into the core were carbon and chalcogens (the oxygen family). Phosphole, the phosphorus isologue of pyrrole, is considered a nonaromatic heterole because of insufficient pi-conjugation between the cis-dienic pi-system and the lone electron pair of the phosphorus atom. As a consequence, phospholes behave not only as efficient pi-conjugative frameworks but also as ordinary phosphine ligands for transition metals. With this in mind, we started a research project on core-modified porphyrins in which the phosphole subunit plays a crucial role in providing characteristic coordination environments. In this Account, we describe our efforts to explore the utility of phosphole-containing porphyrins and porphyrinogens as macrocyclic, mixed-donor ligands. We have established convenient methods for the synthesis of calixpyrroles, calixphyrins, and porphyrins with P and either O or S substitutions, that is, P,X,N(2)-hybrids, as well as the phosphatripyrrane precursors. We also have investigated the effects of varying the combination of core heteroatoms (P, N, S, and O) on the coordination properties of the hybrid macrocycles. Our recent investigations have shown that (1) the P,S,N(2)-calixpyrroles behave as monophosphine ligands while maintaining the hosting functions that originate from the pyrrole subunits, (2) the P,X,N(2)-calixphyrins behave as neutral, monoanionic, or dianionic tetradentate ligands with electronic structures that vary widely depending on the combination of heterole subunits, and (3) the P,S,N(2)-porphyrin behaves as a redox-active pi-ligand for group 10 (the Ni family) metals, affording a novel class of core-modified isophlorin complexes. As a whole, the incorporation of the phosphole subunit into the macrocyclic framework provides unprecedented coordinating properties for the porphyrin family, affording exceptional synthetic control over the behavior of these important macrocycles.

Design and Synthesis of Thiazoline—Thiazole Hybrid Macrocycles Possessing Strong Binding Affinity to Pb2+ and Cd2+.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of novel steroid-peptoid hybrid macrocycles by multiple multicomponent macrocyclizations including bifunctional building blocks (MiBs).

Two new groups of cholane-peptoid hybrid macrocycles were produced by implementing novel combinations of the MiB methodology. Steroid-based hybrid macrolactams including heterocycle and aryl moieties were obtained by utilizing cholanic dicarboxylic acids and diamines in a bidirectional double Ugi-Four-Component (Ugi-4CR) based macrocyclization protocol. Alternatively, N-substituted cyclocholamides were produced from a cholanic pseudo-amino acid by an Ugi-4CR-based cyclooligomerization approach. Both types of macrocycles are steroid-peptoid hybrid macrocycles containing exocyclic peptidic chains. These novel frameworks are a result of the use of bile acids bifunctionalized with carboxylic and amino functionalities as bifunctional building blocks of the Ugi-MiB approach.

Bipyrrole- and Dipyrromethane-Based Amido-imine Hybrid Macrocycles. New Receptors for Oxoanions

Three new amido-imine-type hybrid macrocycles based on substituted pyrrole units have been synthesized and shown to act as effective receptors for oxoanions in the solid state and in acetonitrile solution. One of the macrocycles in question, compound 15, was characterized by X-ray diffraction analysis as the free macrocycle and as a complex with sulfuric acid. A comparison of the resulting structures reveals that this receptor is capable of undergoing a conformational change and, as a consequence, varying the number of donor sites that can interact with a bound substrate. This system and the other two new receptors described in this work (macrocycles 14 and 16, respectively) display a high affinity toward oxoanions (studied as their tetrabutylammonium (TBA) salts), with association constants on the order of 10(7) M-1 being determined in acetonitrile solution using standard UV-vis spectroscopic titration methods. A competitive titration method was used to determine affinity constants in excess of ca. 10(6) M-1. Two of the receptors (14 and 15) were found to bind acetate, hydrogen sulfate, and dihydrogen phosphate anion well, and the bipyrrole-based receptor (14) was also found to bind the perrhenate anion. In contrast, the bis-dipyrromethane-derived receptor (16) was found to bind chloride anion preferentially. The unusual selectivity displayed by 16 for this spherical anion was rationalized on the basis of single-crystal X-ray diffraction data and DFT modeling calculations, which revealed a rigid structure appropriately suited for chloride anion recognition.

Design and synthesis of thiazoline–thiazole hybrid macrocycles possessing strong binding affinity to Pb2+ and Cd2+

Thiazoline-thiazole hybrid macrocycles were synthesized via head-to-tail cyclooligomerization. The macrocycle consisting of eight heterocyclic subunits displays high binding affinity to the heavy metal toxins Pb(2+) and Cd(2+).

Synthesis, structure, and complexing properties of macrocyclic receptors for anions

Abstract Understanding of structure-affinity relationships is crucial for rational receptor design, however, such studies for anion receptors are still limited. Therefore, we investigated this issue in the case of amide-based macrocyclic receptors derived from aromatic diacids (i.e., isophthalic and dipicolinic). Using these model compounds, we examined the macrocyclic effect, the influence of intramolecular hydrogen bonds, and the correlation between the ring size and anion affinity. We found that in contrast to what was known for acyclic diamides, macrocyclic isophthalamide receptors bind anions more weakly than their dipicolinic analogs. Comprehensive structural studies revealed that such behavior is due to intramolecular hydrogen bonds present in isophthalamide receptors. Furthermore, we demonstrated how this obstacle can be overcome by the preparation of a hybrid macrocycle based on both building blocks.

A versatile building block for pyrazole–pyrrole hybrid macrocycles

This contribution describes the synthesis of a novel pyrazole-pyrrole building block and its use in the formation of a non-aromatic, Schiff base-type macrocycle incorporating a chromophore and H-bonding donor and acceptor functionalities inside and outside of the macrocycle, which makes it predestined for molecular recognition systems.

Synthesis and Structure of Non‐Aromatic Porphyrinoid Schiff‐Base Macrocycles Bearing Thiophene.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of Steroid−Biaryl Ether Hybrid Macrocycles with High Skeletal and Side Chain Variability by Multiple Multicomponent Macrocyclization Including Bifunctional Building Blocks

Utilizing the multiple multicomponent macrocyclization including bifunctional building blocks (MiB) strategy, a library of nonracemic, nonrepetitive peptoid-containing steroid-biaryl ether hybrid macrocycles was built. Up to 16 new bonds, including those of the macrocyclization, can be formed in one pot simultaneously while introducing varied elements of diversity. Functional diversity is generated primarily by choosing Ugi-reactive functional building blocks, bearing the respective recognition or catalytic motifs. These appear attached to the peptoid backbone of the macrocyclic cavity, similar to side chains of amino acids found in enzyme active sites. Likewise, skeletal diversity is based on the variation of defined bifunctional building blocks which allow the parallel formation of macrocyclic cavities that are highly diverse in shape and size and thus perspectively in function. This straightforward approach is suitable to generate multifunctional macrocycles for applications in catalysis, supramolecular, or biological chemistry.

Synthesis and Structure of Non-aromatic Porphyrinoid Schiff-base Macrocycles Bearing Thiophene

Expanded porphyrins and their metal complexes have shown considerable potentials in medicinal applications such as diagnostic or treatment tools for various deseases. The hybrid macrocycles composed of the combination of part of the porphyrin and part of the Schiff-base have shown interesting physico-chemical properties. Since the report of the synthesis of fully aromatic expanded porphyrins and their metal complexes by Sessler et al., many new macroaromatic porphyrinoids consisted with tripyrromethanes and imines have been synthesized and studied for potential biological applications. For example, some of the lanthanide complexes of the expanded porphyrins have been used for enhancing images in MRI or for selective anion binding agents. The unusual contractive cyclization accompanying with C-C bond cleavage was reported in some condensation reactions. Here, we extend the reactions further and report the identification and solid state structure of the synthesized macrocycles. Results and Discussions

Mono-palladium(ii) complexes of diamidopyridine–dipyrromethane hybrid macrocycles

The reaction of diamidopyridine-dipyrromethane or dipyrromethene hybrid macrocycles with palladium(II) affords mono-metalated complexes, wherein the metal centre is coordinated to the macrocycle exclusively through pyrrolic nitrogen donor atoms.

New Polydentate Macrocyclic Ligands of Hybrid Amine‐Imine and Amide‐Imine Types as Artificial Anion Receptors. Synthesis and Study of Anion Binding.

AbstractFor Abstract see ChemInform Abstract in Full Text.